[Senate Hearing 110-341]
[From the U.S. Government Publishing Office]



                                                        S. Hrg. 110-341
 
         PANDEMIC INFLUENZA: PROGRESS MADE AND CHALLENGES AHEAD

=======================================================================

                                HEARING

                                before a

                          SUBCOMMITTEE OF THE

            COMMITTEE ON APPROPRIATIONS UNITED STATES SENATE

                       ONE HUNDRED TENTH CONGRESS

                             FIRST SESSION

                               __________

                            SPECIAL HEARING

                    JANUARY 24, 2007--WASHINGTON, DC

                               __________

         Printed for the use of the Committee on Appropriations


  Available via the World Wide Web: http://www.gpoaccess.gov/congress/
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                               __________
                      COMMITTEE ON APPROPRIATIONS

                ROBERT C. BYRD, West Virginia, Chairman
DANIEL K. INOUYE, Hawaii             THAD COCHRAN, Mississippi
PATRICK J. LEAHY, Vermont            TED STEVENS, Alaska
TOM HARKIN, Iowa                     ARLEN SPECTER, Pennsylvania
BARBARA A. MIKULSKI, Maryland        PETE V. DOMENICI, New Mexico
HERB KOHL, Wisconsin                 CHRISTOPHER S. BOND, Missouri
PATTY MURRAY, Washington             MITCH McCONNELL, Kentucky
BYRON L. DORGAN, North Dakota        RICHARD C. SHELBY, Alabama
DIANNE FEINSTEIN, California         JUDD GREGG, New Hampshire
RICHARD J. DURBIN, Illinois          ROBERT F. BENNETT, Utah
TIM JOHNSON, South Dakota            LARRY CRAIG, Idaho
MARY L. LANDRIEU, Louisiana          KAY BAILEY HUTCHISON, Texas
JACK REED, Rhode Island              SAM BROWNBACK, Kansas
FRANK R. LAUTENBERG, New Jersey      WAYNE ALLARD, Colorado
BEN NELSON, Nebraska                 LAMAR ALEXANDER, Tennessee
                    Charles Kieffer, Staff Director
                  Bruce Evans, Minority Staff Director
                                 ------                                

 Subcommittee on Departments of Labor, Health and Human Services, and 
                    Education, and Related Agencies

                       TOM HARKIN, Iowa, Chairman
DANIEL K. INOUYE, Hawaii             ARLEN SPECTER, Pennsylvania
HERB KOHL, Wisconsin                 THAD COCHRAN, Mississippi
PATTY MURRAY, Washington             JUDD GREGG, New Hampshire
MARY L. LANDRIEU, Louisiana          LARRY CRAIG, Idaho
RICHARD J. DURBIN, Illinois          KAY BAILEY HUTCHISON, Texas
JACK REED, Rhode Island              TED STEVENS, Alaska
FRANK R. LAUTENBERG, New Jersey      RICHARD C. SHELBY, Alabama
                           Professional Staff
                              Ellen Murray
                              Erik Fatemi
                              Mark Laisch
                            Adrienne Hallett
                             Lisa Bernhardt
                       Bettilou Taylor (Minority)
                    Sudip Shrikant Parikh (Minority)

                         Administrative Support
                              Teri Curtin
                         Jeff Kratz (Minority)


                            C O N T E N T S

                              ----------                              
                                                                   Page

Opening statement of Senator Arlen Specter.......................     1
Opening statement of Senator Tom Harkin..........................     2
    Prepared statement...........................................     3
Statement of Dr. Gerald W. Parker, D.V.M., Ph.D. Principal Deputy 
  Assistant Secretary, Office of the Assistant Secretary for 
  Preparedness and Response, Department of Health and Human 
  Services.......................................................     5
    Prepared statement...........................................     7
Statement of Dr. Julie L. Gerberding, M.D., Director, Centers for 
  Disease Control and Prevention, Department of Health and Human 
  Services.......................................................    14
    Prepared statement...........................................    16
Statement of Dr. Anthony S. Fauci, M.D., Director, National 
  Institute of Allergy and Infectious Diseases, National 
  Institutes of Health, Department of Health and Human Services..    25
    Prepared statement...........................................    27
Statement of Dr. John Jay Treanor, M.D., director, Vaccine 
  Treatment and Evaluation Unit, University of Rochester Medical 
  Center.........................................................    32
    Prepared statement...........................................    34


         PANDEMIC INFLUENZA: PROGRESS MADE AND CHALLENGES AHEAD

                              ----------                              


                      WEDNESDAY, JANUARY 24, 2007

                           U.S. Senate,    
    Subcommittee on Labor, Health and Human
     Services, and Education, and Related Agencies,
                               Committee on Appropriations,
                                                    Washington, DC.
    The subcommittee met at 9:50 a.m., in room SD-124, Dirksen 
Senate Office Building, Hon. Tom Harkin (chairman) presiding.
    Present: Senators Harkin, Reed, Durbin, and Specter.


               opening statement of senator arlen specter


    Senator Specter. Good morning, ladies and gentlemen. On a 
conspiracy, secret conspiracy, which is about to be made 
public, the chairman and I have been conferring and he handed 
me the gavel so that we could have a ceremonial shift in gavel.
    Senator Harkin and I, who have traded positions as the 
powers have flowed, have always talked about it being a 
seamless change in the gavel. So I want to express my 
appreciation to Senator Harkin for handing me the gavel and to 
announce publicly that I'm not going to give it back.
    But on a serious level, it doesn't happen too often in the 
Senate, Tom Harkin and Arlen Specter have worked very closely 
together for more than two decades, since Senator Harkin was 
elected in 1984, and I think that has benefited the American 
people and the health community and the education community and 
worker safety and labor, where those three departments are 
under the funding of this subcommittee. In a contentious 
political climate in Washington, this is we think the way it 
ought to be operated.
    So here comes the seamless transfer, Mr. Chairman.
    Senator Harkin. Well, thank you. Thank you, Arlen, very 
much. Let me thank my friend and colleague for his kind words, 
and for 22 years of very close cooperation and a great working 
relationship.
    It has been, I was just counting up, this is the fourth 
time, Arlen, that this thing has gone back and forth between 
us, and it has been great working together. Even our staffs, I 
mean, I think if I'm not mistaken, I think because of the shift 
and all that kind of stuff and the reallocation and all that, I 
think some of his staff have just come over to my staff. It's 
hard to say where one leaves and one takes off, and I think 
that's the way it ought to be because we're all sort of in the 
same boat here, trying to do the same job.
    I just want to thank you, Senator Specter, for your great 
leadership in the last--well, there's been so many breaks 
here--the last 4 years, and then before that 10 years on this 
committee. It was under your leadership that we were able to 
double the funding for NIH, more than double it, as a matter of 
fact. It was under your leadership that we accomplished that, 
and you did it through two different administrations, one 
Democrat, one Republican.
    It's been under your leadership that we have begun to 
address a lot of the real issues, health issues confronting the 
American people, one of which we're going to discuss here this 
morning. I would say without any hesitation, if there is one 
person who has really pushed hard on basic medical research, 
and here I talk about stem cell research and really taking the 
lead in that and getting the public informed, Arlen Specter has 
been on the head of that.
    So I hope you will all join me in thanking Senator Specter 
for his great leadership and our continued working relationship 
on this committee. Thank you, Arlen.
    Senator Specter. Thank you.


                opening statement of senator tom harkin


    Senator Harkin. I guess, since I've got the gavel, the 
Subcommittee on Labor, Health and Human Services, and 
Education, and Related Agencies, Appropriations Subcommittee, 
will come to order. Again, I want to welcome all of you to this 
hearing titled ``Pandemic Flu: Progress Made and Challenges 
Ahead.''
    As you all know, the threat of pandemic flu has not abated. 
It may have fallen briefly from the headlines, but the problem 
remains. Bird populations across Asia have been infected by the 
H5N1 strain of avian influenza. The virus has spread as far as 
Eastern Europe. Hundreds of people have died.
    It may be only a matter of time before this virus mutates 
and sustained human-to-human transmission occurs. If this virus 
is able to do this, achieve this, which has been the history of 
viruses, millions of people may die worldwide, rivaling the 
Spanish Influenza outbreak of 1918 and 1919. The CDC has 
estimated that a medium level pandemic could kill over 200,000 
Americans and sicken a third of our population.
    Now just a little history here. The President's original 
request to combat the pandemic threat was $7.1 billion in 2005. 
To date, this committee, again under Senator Specter, 
appropriated $6.1 billion for pandemic flu preparedness, 
including $600 million for State and local preparedness. This 
money has gone to build vaccine capacity, purchase egg-based 
vaccines, accelerate cell-based vaccine capability, stockpiling 
antivirals, improving lab capacity at the CDC, and improving 
surveillance.
    In addition, Congress has given HHS new authority to 
develop the tools we need to respond to mass casualty events. 
Last year we passed and the President signed into law the 
Pandemic and All Hazards Preparedness Act that was led by my 
friend Senator Burr, who led that effort in the authorizing 
committee, the Health Committee, and I was proud to work with 
him on that.
    Both Congress and the administration are responding to this 
threat, but our activities raise new questions. Are we 
investing in the right vaccine technology? Should we invest in 
other capabilities beyond cell-and egg-based vaccines? How will 
this new barter, as it's called, within HHS change the way we 
develop vaccines? Are we doing all we can to make sure State 
and local agencies have the ability to respond?
    So those are some of the questions that I would pose, and 
to answer these questions and to bring us up to date we have a 
very distinguished panel. I thank them all for being here.


                           prepared statement


    Dr. Anthony Fauci, of course, serves as the Director of the 
National Institute of Allergy and Infectious Diseases at the 
National Institutes of Health. Dr. Gerald Parker serves as the 
Principal Deputy Assistant Secretary in the Office of the 
Assistant Secretary for Preparedness and Response at HHS. Dr. 
Julie Gerberding has served as the Director of the Centers for 
Disease Control and Prevention since July 2002. So we are just 
very grateful for all of your leadership, look forward to your 
testimony, but before that I would yield to Senator Specter.
    [The statement follows:]
                Prepared Statement of Senator Tom Harkin
    Good Morning. I want to welcome you all to this Labor, Health, 
Human Services, and Education Appropriations Subcommittee hearing 
entitled: ``Pandemic Flu: Progress Made and Challenges Ahead.''
    As you all know, the threat of pandemic flu has not abated. It may 
have fallen briefly from the headlines, but the problem remains. Bird 
populations across Asia have been infected by the H5N1 strain of avian 
influenza and the virus has spread as far as Eastern Europe. Hundreds 
of people have died and it may be only a matter of time before the 
virus mutates and sustained human-to-human transmission occurs. If the 
virus is able to achieve this, millions of people may die worldwide, 
rivaling the Spanish Influenza outbreak in 1918-1919. The CDC estimates 
that a ``medium-level pandemic'' could kill over 200,000 Americans and 
sicken one-third of the U.S. population.
    The President's original request to combat the pandemic threat was 
$7.1 billion in 2005. To date, we have appropriated $6.1 billion for 
pandemic flu preparedness, including $600 million for state and local 
preparedness. This money has gone to build vaccine capacity, purchase 
egg based vaccines, accelerate cell-based vaccine capability, stockpile 
anti-virals, improve lab capacity at the CDC, and improve surveillance. 
But there is still more to do.
    In addition, Congress has given HHS new authority to develop the 
tools we need to respond to mass casualty events. Last year, we passed, 
and the President signed into law, the Pandemic and All-Hazards 
Preparedness Act. My good friend Senator Burr led the effort in the 
HELP Committee and I was proud to work with him on the legislation. 
Importantly, part of this bill changed the way the government works 
with the private sector to develop countermeasures to biological 
threats, including avian flu.
    Both Congress and the administration are responding to this threat. 
But our activities also raise new questions. Are we investing in the 
right vaccine technology? Should we invest in other capabilities beyond 
cell and egg based vaccines? Also--How will the Biomedical Advanced 
Research and Development Authority within HHS change the way we develop 
vaccines? In addition, are we doing all we can to make sure State and 
local governments have the ability to respond?
    To answer these questions we have a distinguished panel.
    Anthony S. Fauci, M.D. serves as the Director of the National 
Institute of Allergy and Infectious Disease at the National Institutes 
of Health. He oversees an extensive research portfolio of basic and 
applied research to prevent, diagnose, and treat infectious diseases 
such as HIV/AIDS and other sexually transmitted infections, influenza, 
tuberculosis, malaria and illness from potential agents of 
bioterrorism. He received his M.D. degree from Cornell University 
Medical College in 1966. He then completed an internship and residency 
at The New York Hospital-Cornell Medical Center.
    Dr. Gerald W. Parker serves as the Principal Deputy to the 
Assistant Secretary, Office of the Assistant Secretary for Preparedness 
and Response at the Department of Health and Human Services. Prior to 
joining the Department of Health and Human Services in July 2005, Dr. 
Parker was at the Department of Homeland Security from April 2004 to 
July 2005, and he had 26 years of active U.S. Army service as a 
researcher. Dr. Parker graduated from Texas A&M University with a 
Bachelors of Science in Veterinary Medicine and with a degree of Doctor 
of Veterinary Medicine. He holds a Doctorate in Physiology from Baylor 
College of Medicine in Houston, Texas and a Masters of Science in 
Resourcing the National Strategy from the Industrial College of the 
Armed Forces.
    Dr. Julie Gerberding has served as the Director of the Centers for 
Disease Control and Prevention since July 2002. Prior to taking over 
CDC, Dr. Gerberding was Acting Deputy Director of the National Center 
for Infectious Diseases (NCID), where she played a major role in 
leading CDC's response to the anthrax bioterrorism events of 2001. She 
earned a B.A. magna cum laude in chemistry and biology and an M.D. at 
Case Western Reserve University in Cleveland, Ohio. Dr. Gerberding then 
completed her internship and residency in internal medicine at UCSF, 
where she also served as Chief Medical Resident before completing her 
fellowship in Clinical Pharmacology and Infectious Diseases at UCSF. 
She earned an M.P.H. degree at the University of California, Berkeley 
in 1990.
    Dr. John Treanor is Professor of Medicine, and of Microbiology and 
Immunology at the University of Rochester. He has done novel research 
on inhibitors to the influenza virus and on antivirals. He earned his 
M.D. from the University of Rochester in 1979.

    Senator Specter. Thank you very much, Mr. Chairman. We have 
a very distinguished panel here today. When we talk about 
congressional oversight, when we deal with the National 
Institutes of Health and the Centers for Disease Control, they 
don't have to have anybody looking over their shoulders on what 
they're doing on medical research and protecting public health.
    But what the Congress needs to do is to be in close touch 
with those key health agencies to find out what they need to do 
their job, and funding is extraordinarily difficult. In fact, 
that is an understatement. It's close to impossible.
    Here we are at the end of January 2007, and we do not have 
a budget for the Department of Health and Human Services for 
the period beginning October 1, 2006. That's just totally 
unacceptable. We're still dealing with a continuing resolution. 
Under a continuing resolution, what happens is that NIH and CDC 
lose funds.
    Beyond the problem of a continuing resolution, we've had 
cuts. To cut the National Cancer Institute by $50 million, 
which was done last year, is really scandalous. In 1970 
President Nixon declared war on cancer, and had we prosecuted 
that war with the same attention that we prosecute other wars, 
a lot of people who have suffered from cancer might have been 
spared, including Arlen Specter.
    Now we look at the pandemic, and Senator Harkin saw this 
first last year and came up with a proposal for $8 billion, and 
he was a pretty good negotiator to ask for $8 billion and come 
up with $7.1 billion. That's pretty good negotiations, but all 
the funds haven't been forthcoming.
    But when you look at the history of this issue and you look 
back to 1918, when between 500,000 and 670,000 people died in 
the United States--we can't be exactly sure because that can't 
be quantified with precision--and 40 million to 100 million 
died worldwide, and then the very heavy loss of life in 1957 
and 1968, you can see how pandemic flu can spread around the 
world.
    We have to be very vigilant, and the vigilance starts right 
here with the Department of Health and Human Services and the 
NIH and the CDC, and Tom Harkin and Arlen Specter. So I'm glad 
to see this is the first hearing that the recycled chairman has 
called, and it couldn't be for a more important subject, so 
thank you, Mr. Recycled.
    Senator Harkin. That term applies to you, too, you know.
    Senator Specter. I wear that term proudly and am waiting 
for the next recycling.
    Senator Harkin. Hopefully it's a long cycle.
    I recognize Senator Reed for any opening statement.
    Senator Reed. Mr. Chairman, thank you and thank Senator 
Specter. I don't have a statement for the record. I just want 
to welcome the panelists, and particularly thank Dr. Gerberding 
for her assistance recently, CDC to Rhode Island. We had what 
the clinicians say is a Mycoplasma event, and your help was 
deeply appreciated. Thank you, doctor, and thank you for your 
hospitality in Atlanta. Thank you.
    Senator Harkin. Thank you, Senator Reed.
    Senator Durbin.
    Senator Durbin. Thank you very much, Mr. Chairman. I 
apologize for just walking in at the last minute, and I'm 
looking forward to the testimony. I'll waive my opening 
statement.
    Senator Harkin. Thank you very much.
    I was told there's a certain protocol, and I do adhere to 
protocol sometimes. If we could ask Dr. Treanor, who is a 
professor of medicine and microbiology and immunology at the 
University of Rochester Medical Center, who will also be 
testifying, to come up and take the table, we'll do the 
administration first and then we'll follow up with Dr. Treanor 
at the end, but no use your sitting out there someplace, Dr. 
Treanor. Thanks for being here this morning.
    So to kick this all off, and again I'm hopeful that--I've 
got the clock set for 5 minutes--if you could just give us sort 
of a summation, a 5-minute summation of your testimony, I would 
be most appreciative. Your full statements will be made a part 
of the record in their entirety, and we'll start first of 
course with Gerald Parker. Dr. Parker.

STATEMENT OF DR. GERALD W. PARKER, D.V.M., Ph.D. 
            PRINCIPAL DEPUTY ASSISTANT SECRETARY, 
            OFFICE OF THE ASSISTANT SECRETARY FOR 
            PREPAREDNESS AND RESPONSE, DEPARTMENT OF 
            HEALTH AND HUMAN SERVICES
    Dr. Parker. Thank you, Mr. Chairman and members of the 
subcommittee. I am honored to be here today to describe for you 
how HHS is working to improve the preparedness for a potential 
influenza pandemic, specifically by pursuing a strategic and 
comprehensive approach for the development and acquisition of 
medical countermeasures including vaccines----
    Senator Harkin. I don't think your mike is on.
    Dr. Parker. I'm sorry. Is that better? Okay.
    We are working collaboratively, this is very important, 
because we are working very collaboratively as an enterprise 
with in the department and with our industrial partners on this 
medical countermeasures program and the program goals that we 
have established for an influenza pandemic.
    We very much appreciate the support from this subcommittee 
and Congress during fiscal year 2006 for the emergency 
supplemental, and I thank you very much for this opportunity 
today to at least give you a brief overview of the progress 
that we've made to date on the medical countermeasures 
development and acquisition programs and on the whole 
enterprise, from R&D to advanced development to procurement to 
distribution and so forth. I will focus my remarks really on 
the medical countermeasures, to include the vaccines, advanced 
development, acquisitions, antivirals, and just briefly, 
diagnostics, and then a conclusion.
    Our goals, I think they've been articulated before but 
there are really two primary goals with the vaccines, and that 
is to establish a dynamic pre-pandemic vaccine stockpile for 20 
million persons and, two, to be able to provide pandemic 
vaccine to all U.S. citizens within 6 months of a pandemic 
declaration. As far as antivirals, our two goals are to provide 
influenza antiviral stockpiles for pandemic treatment for 25 
percent of the U.S. population, and to provide influenza 
antivirals for a strategic containment strategy. Then, finally, 
diagnostics are to develop point-of-care medical diagnostics.
    The Pandemic Influenza Medical Countermeasures Program now 
includes 25 contracts that have obligated over $3 billion to 
date. This table illustrates the multipronged approach and 
diversified portfolio of programs that have been established to 
help us achieve the implementation program for the medical 
countermeasures program.
    I would now like to take the opportunity to talk in a 
little bit more detail about some of these programs. First, 
vaccines are the optimal way to control the spread and 
associated morbidity and mortality of seasonal epidemics or 
pandemics. The HHS strategy is to simultaneously stockpile a 
limited amount of pre-pandemic vaccine, build vaccine 
manufacturing capacity so that we can quickly produce pandemic 
vaccine should a pandemic occur, and explore approaches using 
adjuvants. This approach has utility to help strengthen and 
integrate both the seasonal and pandemic influenza preparedness 
needs.
    We have aggressively established a vaccine advanced 
development portfolio that includes 4 projects with 10 
contracts and obligations of over $1.3 billion to date. These 
projects support new influenza vaccine technologies and are 
precursors to enhancing vaccine manufacturing capacity.
    First, cell-based. HHS has awarded more than $1 billion to 
six manufacturers to accelerate the development and production 
of new technologies for influenza vaccines within the United 
States. These contracts provide support for advanced 
development of cell-based production technologies for seasonal 
and pre-pandemic influenza vaccines.
    Additionally, these contracts are facilitating the 
modernization and strengthening of the Nation's influenza 
vaccine production by creating an alternative to producing 
influenza vaccines in eggs. Notably, these contracts required 
commitments by each manufacturer to establish U.S.-based 
manufacturing facilities with a vaccine production capacity of 
at least 150 million doses within 6 months of a pandemic. 
Currently, six manufacturers are in clinical studies in the 
United States to determine the safety and immunogenicity of 
these cell-based products.
    Antigen-sparing. Earlier this month, HHS announced the 
award of contracts totaling $132 million to three vaccine 
manufacturers for the advanced development of H5N1 influenza 
vaccines using an immune system booster called an adjuvant. In 
the event of an influenza pandemic, a vaccine that uses an 
adjuvant could provide a way to extend a limited supply to more 
people.
    Another key feature of these adjuvants is that early 
studies indicate that they may confer cross-protection 
properties upon influenza vaccines to afford efficacy against 
``antigenic drift'' variants. That is, an H5N1 vaccine made 
against the circulating strain in 2006 may offer cross-
protection against new strains in the future.
    The addition of these adjuvants to candidate vaccines has 
been shown, in initial European clinical studies, to reduce by 
10-to-20 fold the amount of antigen per dose needed to achieve 
effective individual protection. If these studies are confirmed 
in larger clinical studies, then these adjuvants may make 
reaching the goal of United States and global vaccine 
preparedness faster and more feasible, and help to achieve 
pandemic vaccine goals number 1 and 2.
    Senator Harkin. Can you start to wrap it up?
    Dr. Parker. Yes, sir. As far as vaccine acquisitions, we 
are currently in procurement of H5N1. We currently have 1.3 
million doses of H5N1 Clade 1 vaccine filled in vials. We have 
more than 6 million doses of H5N1 Clade 1 vaccine in bulk form, 
awaiting final instructions for filling. We have approximately 
5 million doses of Clade 2 vaccine currently under production.
    Then a key part of our strategy is to increase the surge 
capacity, and we really have two main approaches there. One is 
to look for retrofitting existing manufacturing facilities, 
either egg-based or cell-based. We anticipating awarding a 
contract very soon. Then a real key strategy is a follow-on to 
the cell-based, and that is looking at actually building 
manufacturing capacity, and we anticipate going out with an RFP 
for that in fiscal year 2007.
    Then, finally, antiviral drugs. We have two major 
components there, an advanced development effort, and we just 
recently awarded a contract for an advanced development; and we 
are very close, we are on track as far as pursuing our strategy 
for the procurement both for the Federal and the State 
subsidized component of the antiviral stockpile.

                           PREPARED STATEMENT

    Then finally I will leave discussion on diagnostics to Dr. 
Gerberding, and I'd just like to conclude that we have moved 
out aggressively. We appreciate the support from this 
subcommittee, but I want to emphasize that it is a total team 
effort within the department and with our Federal interagency 
partners in this endeavor. We are taking the concept of working 
as an enterprise very seriously, again from the research and 
development all the way to distribution. Thank you for this 
opportunity to give you this brief summary.
    [The statement follows:]

               Prepared Statement of Dr. Gerald W. Parker

    Mr. Chairman and Members of the Subcommittee, I am honored to be 
here today to describe for you how the Department of Health and Human 
Services is working to improve preparedness for a potential human 
influenza pandemic, specifically by pursuing a strategic and 
comprehensive approach to the development and acquisition of medical 
countermeasures including vaccines, antivirals, diagnostics, and 
through building domestic manufacturing infrastructure for influenza 
vaccines. We are working cooperatively to leverage resources throughout 
the Department and with industry to meet the program goals. We recently 
formalized linkages within HHS through the establishment of the Public 
Health Emergency Medical Countermeasures Enterprise, led by the leaders 
of the Office of the Assistant Secretary for Preparedness and Response, 
the Centers for Disease Control and Prevention, the National Institutes 
of Health, and the Food and Drug Administration. Thank you for the 
invitation to testify on this topic which Secretary Mike Leavitt has 
made a top priority.
    On November 1, 2005, the President requested $7.1 billion in 
emergency funding for the National Strategy for Pandemic Influenza, of 
which $6.7 billion was designated for HHS. Congress appropriated $3.8 
billion in December 2005 as the first installment of the President's 
request to begin these priority activities, and of this amount, $3.3 
billion was provided to HHS. The second appropriation in June 2006 
provided HHS with $2.3 billion. We appreciate the action of Congress on 
these appropriations, as it takes us an essential step forward in 
becoming the first generation in history to be prepared for a possible 
pandemic.
    The potential for a human influenza pandemic is a current public 
health concern with an immense potential impact. We know that the 
influenza virus has the potential to cause a pandemic but we don't know 
when a pandemic will occur. We don't know how severe a pandemic might 
be and we don't know which influenza virus will be the one that 
develops the ability to spark a pandemic. However, we do know that the 
H5N1 strain of avian flu has spread to more than 50 countries and has 
led to the deaths of hundreds of millions of birds, and that more than 
260 human cases of avian influenza (so called ``bird flu'') have 
occurred in 10 countries. More than half of those persons infected have 
died. This has heightened global concern about the possibility of a 
human flu pandemic. To date, H5N1 avian influenza has remained 
primarily an animal disease, but should the virus mutate further and 
acquire the ability for sustained transmission among humans, a severe 
influenza pandemic could result that may have grave consequences for 
global public health. And while a mild pandemic would be primarily a 
public health problem, the consequences of a severe pandemic on the 
global economy and on the functioning of society could be enormous.

           national and hhs-specific pandemic influenza plans

    On November 1, 2005, the President announced the National Strategy 
for Pandemic Influenza, with the three pillars of Preparedness and 
Communications, Surveillance and Detection, and Response and 
Containment.
    The day after the release of the President's National Strategy for 
Pandemic Influenza, Secretary Leavitt announced the HHS Pandemic 
Influenza Plan--a blueprint for all HHS pandemic influenza preparedness 
and response planning--and released Parts 1 and 2. Part 1, the HHS 
Strategic Plan, outlines Federal plans and preparation for public 
health and medical support in the event of a pandemic. It identifies 
the key roles of HHS and its agencies in a pandemic and provides 
planning assumptions for federal, state and local governments and 
public health operations plans. Part 2, Public Health Guidance for 
State and Local Partners, provides detailed guidance to state and local 
health departments in 11 key areas.
    In May 2006, the National Strategy for Pandemic Influenza 
Implementation Plan was released. It translated the National Strategy 
for Pandemic Influenza into more than 300 actions, timelines, and 
metrics for Federal departments and agencies and set clear expectations 
for State and local governments and other non-Federal entities. One of 
the Federal priority actions was to ``Accelerate the Development of 
Medical Countermeasures'' and included these efforts:
  --Establish stockpiles of vaccine and antiviral medications
  --Advance technology and production capacity for influenza vaccine
  --Develop rapid diagnostics
    Cascading from the National Strategy and National Implementation 
Plan, one of the key components of the HHS plan called for increasing 
capacity to produce pandemic influenza antivirals and vaccines, and 
increasing stockpiles of these countermeasures. Specific strategic 
goals for pandemic medical countermeasures are displayed in Table 1.

           TABLE 1.--HHS PANDEMIC MEDICAL COUNTERMEASURE GOALS
------------------------------------------------------------------------

------------------------------------------------------------------------
Vaccine Goal #1..............  To establish and maintain a dynamic pre-
                                pandemic influenza vaccine stockpile
                                sufficient for 20 million persons (at 2
                                doses/person): H5N1 vaccine stockpiles.
Vaccine Goal #2..............  To provide pandemic vaccine to all U.S.
                                citizens within 6 months of a pandemic
                                declaration: 600 million doses pandemic
                                vaccine.
Antivirals Goal #1...........  To provide influenza antiviral drug
                                stockpiles for pandemic treatment of 25
                                percent of U.S. population: 75 million
                                treatment courses.
Antivirals Goal #2...........  To provide an influenza antiviral drug
                                stockpile for strategic limited
                                containment at onset of pandemic: 6
                                million treatment courses
Diagnostics Goal #1..........  To develop new high throughput laboratory
                                and Point of Care (POC) influenza
                                diagnostics for pandemic virus
                                detection.
------------------------------------------------------------------------

    The Pandemic Influenza Medical Countermeasure Program now includes 
25 contracts obligating over $3 billion. Table 2 illustrates the multi-
pronged approach and diversified portfolio of programs that have been 
established to help us achieve the Implementation Plan's medical 
countermeasure goals.

                        TABLE 2.--HHS PANDEMIC INFLUENZA MEDICAL COUNTERMEASURE PROGRAMS
----------------------------------------------------------------------------------------------------------------
                                                Vaccines                    Antivirals           Diagnostics
----------------------------------------------------------------------------------------------------------------
Advanced Development...........  Cell-based...........................  Peramivir.........  High Throughput.
                                 Antigen-sparing......................                       Point of Care.
                                 Next Generation......................                       Clinical Lab.
                                 Egg-based Supply.....................
Acquisitions...................  H5N1 Vaccine Stockpiles..............  Tamiflu &
                                                                         Relenza
                                                                          Federal
                                                                         Stockpiles
                                                                          State Stockpiles
Infrastructure Building........  Retrofit Existing Mfg Facilities
                                 Build New Cell-based Mfg Facilities
----------------------------------------------------------------------------------------------------------------

    I would now like to take this opportunity to provide details about 
the substantive progress toward meeting our public health emergency 
preparedness goals in each of these medical countermeasure programs.

                                vaccines

    Vaccines are the optimal way to control the spread and associated 
morbidity and mortality of seasonal epidemics or pandemics. Broadly 
speaking, our approach to developing vaccines for a pandemic may be 
divided into two categories: those that are developed against strains 
of animal influenza viruses that have caused isolated infections in 
human, which may be regarded as ``pre-pandemic'' vaccines; and those 
that are developed against strains that have evolved the capacity for 
sustained and efficient human-to-human transmission (``pandemic'' 
vaccines). Because emergence in human populations necessarily reflects 
genetic changes within the pandemic virus, pre-pandemic vaccines may be 
a good or poor match for--and offer greater or lesser protection 
against--the pandemic strain that ultimately emerges. Thus, the HHS 
strategy is to simultaneously stockpile a limited amount of pre-
pandemic vaccine, build vaccine manufacturing capacity so that we can 
quickly produce pandemic vaccine should a pandemic occur, and explore 
approaches utilizing adjuvants to enhance the likelihood that a vaccine 
administered prior to a pandemic will provide useful protection during 
a pandemic. Further, this approach will strengthen and integrate both 
the seasonal and pandemic influenza preparedness needs.

                     vaccines--advanced development

    The Office of the Assistant Secretary for Preparedness and Response 
(ASPR) supports vaccine advanced development and is currently managing 
a program that includes 4 projects with 10 contracts and obligations 
over $1.3 billion (Table 3). These projects support new influenza 
vaccine technologies and are precursors to enhancing vaccine 
manufacturing capacity.

                               TABLE 3.--HHS ADVANCED DEVELOPMENT VACCINE PROJECTS
----------------------------------------------------------------------------------------------------------------
              Projects                Contracts          Awarded           Duration          Goals/Results
----------------------------------------------------------------------------------------------------------------
Cell-based.........................            6  $1.1 billion.........    2005-2011  Expand domestic flu
                                                                                       vaccine mfg.
                                                                                      Capacity to produce 475 M
                                                                                       doses pandemic vaccine by
                                                                                       2013.
Antigen-sparing....................            3  $133 million.........    2007-2012  Reduce amount of vaccine
                                                                                       antigen needed in order
                                                                                       to increase the number of
                                                                                       doses that can be
                                                                                       produced.
Next Generation....................      ( \1\ )  ( \2\ )..............    2007-2012  Diversify flu vaccine mfg.
                                                                                      Reduce mfg. time
Egg-based Supply...................            1  $43 million..........    2004-2008  Provide year-round egg
                                                                                       supply for flu vaccine
                                                                                       mfg.
                                                                                      Provide clinical study
                                                                                       vaccines.
----------------------------------------------------------------------------------------------------------------
\1\ RFP in fiscal year 2007.
\2\ To be determined.

                          cell-based projects

    As part of the President's plan to prepare for a pandemic, HHS 
awarded in May 2006 more than $1 billion to accelerate development and 
production of new technologies for influenza vaccines within the United 
States. These five contracts and an additional contract awarded in 2005 
provided support for the advanced development of cell-based production 
technologies for seasonal and pre-pandemic H5N1 influenza vaccines. 
Additionally, these contracts facilitated the modernization and 
strengthening of the Nation's influenza vaccine production by creating 
an alternative to producing influenza vaccines in eggs. Notably, these 
contracts required commitments by each manufacturer to establish U.S.-
based manufacturing facilities with a vaccine production capacity of at 
least 150 million doses within 6 months of a pandemic.
    Accelerating the development of this vaccine technology and 
enhancing domestic production capacity are critical enhancements of our 
public health emergency preparedness efforts. Cell-based vaccine 
manufacturing--a technology that is used for the manufacturing of many 
other modern vaccines--holds the potential of a reliable, flexible, and 
scalable method of producing influenza vaccines.
    Using a cell culture approach to produce influenza vaccines offers 
a number of benefits. Currently licensed influenza vaccines are 
produced in embryonated hens' eggs in a technique that has changed 
little in the past 50 years. With increasing demand for seasonal 
influenza vaccine and with the looming threat of a pandemic, a system 
that allows surge capacity in an emergency is needed. Vaccine 
manufacturers utilizing cell-culture technology may be able to bypass 
the steps needed to adapt the virus strains to grow in eggs, which may 
save weeks in vaccine production during a pandemic. Since cell-culture 
technology is used to produce other licensed biologicals, emergency 
usage of such facilities for pandemic vaccine production is more 
feasible than with egg-based vaccine manufacturing, which requires 
highly specialized equipment for egg handling. Further, manufacture of 
influenza vaccines produced by cell culture also will provide security 
against risks associated with egg-based production, such as the 
potential for egg supplies to be unavailable as a result of various 
poultry-based diseases. Finally, the new cell-based influenza vaccines 
will provide an option for people who are allergic to eggs and 
therefore unable to receive the currently licensed vaccines.
    Currently, six manufacturers are in Phase 1 clinical studies in the 
United States to determine the safety and immunogenicity of these cell-
based products; however, several of these seasonal influenza vaccine 
products have already been evaluated clinically in Europe and have been 
shown to be well-tolerated, immunogenic, and efficacious. H5N1 vaccine 
products under development in these contracts include inactivated split 
and whole virion vaccine candidates formulated with adjuvants and live, 
attenuated virus vaccine candidates. In pursuit of Pandemic Vaccine 
Goal 2, the impact of these contracts on domestic surge capacity is 
forecasted to begin by 2009, and will grow through 2013.

                        antigen-sparing projects

    Earlier this month, HHS announced the award of contracts totaling 
$132.5 million to three vaccine manufacturers for the advanced 
development of H5N1 influenza vaccines using an immune system booster 
called an adjuvant, which is a substance that may be added to a vaccine 
to increase the body's immune response to the vaccine's active 
ingredient, called an antigen. In the event of an influenza pandemic, a 
vaccine that uses adjuvant could optimize utilization of the vaccine 
stockpile and could provide a way to extend a limited vaccine supply to 
more people. Another key feature of these adjuvants is that early 
studies indicate that they may confer cross protection properties upon 
influenza vaccines to afford efficacy against ``antigenic drift'' 
variants--that is, an H5N1 vaccine made against the circulating strain 
in 2006 may offer cross protection against new H5N1 virus strains 
emerging in future years.
    The contracts provide support for advanced development of antigen-
sparing pandemic vaccine with adjuvants through U.S. clinical trials 
towards U.S-licensure. Further, these contracts facilitate the 
establishment of manufacturing capabilities for these adjuvants and 
development of delivery devices, including adjuvant containing patches 
which could similarly extend a limited vaccine supply.
    Under the contracts, each company will build up to a capacity to 
produce, within 6 months after the onset of an influenza pandemic, 
either 150 million doses of an adjuvant-based pandemic influenza 
vaccine or enough adjuvant to be stockpiled for 150 million doses of a 
pandemic influenza vaccine. In addition to supporting the development 
of each company's antigen-sparing vaccine candidate, the contracts also 
require each company to provide its proprietary adjuvant for U.S. 
Government-sponsored, independent evaluation with influenza vaccines 
from other manufacturers.
    Initial clinical studies conducted by NIH on antigen-alone H5N1 
vaccine candidates in humans have shown that two 90-microgram doses of 
the vaccine are required to stimulate a level of immune response that 
researchers anticipate would provide protection for an individual 
against the H5N1 strains that have been spreading among birds in Asia. 
However, the addition of adjuvant to these candidate vaccines has been 
shown, in initial European clinical studies, to reduce by 10-to-20-fold 
the amount of antigen per dose needed to achieve effective individual 
protection. Phase 1 and 2 clinical studies for safety, immunogenicity, 
and cross protection are planned in 2007 for the H5N1 vaccine products 
with the each of the three new adjuvants. If these results are 
confirmed in larger clinical studies, then these adjuvants may make 
reaching the goal of United States and global pandemic vaccine 
preparedness faster and more feasible, and help to achieve Pandemic 
Vaccine Goals 1 and 2.

                            egg-based supply

    To be able to manufacture flu vaccines in the event of a pandemic 
flu outbreak or future vaccine shortages, HHS awarded a contract in 
November 2004 for $43 million to develop and implement an egg supply 
plan for transition to a secure, year-round egg supply, stockpile other 
vaccine manufacturing supplies, such as vials, caps, and stoppers, and 
to develop and manufacture pandemic vaccine candidates for clinical 
investigation. In April 2005 a secure year-round egg supply for 
domestic influenza vaccine manufacturing was realized, and two pandemic 
vaccine candidates--H5N1 clade 2 and H7N7--have been produced for NIH 
clinical investigations under this contract.
    Vaccines--Acquisitions
    ASPR currently has a vaccine acquisition program that includes four 
projects with six contracts and obligations over $500 million to 
procure pre-pandemic vaccine (Table 4).

                                 TABLE 4.--HHS H5N1 VACCINE ACQUISITION PROJECTS
                                              [Dollars in millions]
----------------------------------------------------------------------------------------------------------------
                 Projects                    Contracts      Award       Duration           Goals/Results
----------------------------------------------------------------------------------------------------------------
H5N1 Vaccine Clade 1--2004................            1          $21    2004-2008  Provide 0.47 million doses @
                                                                                    90 mg/dose
H5N1 Vaccine Clade 1--2005................            2          243    2005-2008  Provide 8.0 M doses @ 90 mg/
                                                                                    dose
H5N1 Vaccine Clade 2--2006................            3          241    2006-2008  Provide 4.9 million doses @
                                                                                    90 mg/dose
H5N1 Vaccine 2007.........................      ( \1\ )      ( \1\ )    2007-2009  Provide doses for pre-
                                                                                    pandemic stockpile (H5N1)
----------------------------------------------------------------------------------------------------------------
\1\ To be determined.

    Manufacturing these pre-pandemic vaccines not only provides the 
industry experience in producing novel influenza vaccine candidates at 
a commercial scale, but also provides a foundation for pre-pandemic 
vaccine stockpiles. In the early stages of a severe pandemic, and 
before a well-matched vaccine is available, pre-pandemic vaccines may 
be used in selected populations to mitigate disease, support essential 
operations, and maintain social and economic systems.
    Currently, 1.3 million doses of H5N1 Clade 1 vaccine (90 mg/dose) 
have been filled in vials. More than 6 million doses (90 mg/dose) of 
H5N1 Clade 1 vaccine remain in bulk form and await instructions for 
formulation into final vaccine vials. Additionally, approximately 5 
million doses of H5N1 Clade 2 vaccine are currently under production.

                   vaccines--infrastructure building

    In order to achieve pandemic preparedness, the influenza vaccine 
surge capacity needs to be expanded. Expansion of commercial scale egg- 
or cell-based production could be accomplished by renovation of 
existing domestic manufacturing facilities already licensed for 
approved biologicals. Furthermore, pandemic vaccine surge capacity 
required extension of the time dedicated to its production, as H5N1 
vaccine stockpile manufacturing was limited to the 3 months each year 
when influenza manufacturers are not producing seasonal flu vaccine. 
Therefore, in July 2006, HHS issued a solicitation for proposals to 
retrofit or remodel these existing domestic manufacturing facilities 
and establish warm-base capabilities for the emergency production of 
pandemic vaccine. HHS plans to award these contracts in February 2007 
(Table 5).. These contracts will not only increase domestic pandemic 
influenza vaccine capacity, but will also allow year-round production 
of pre-pandemic stockpiles.
    To further capitalize on the promise of cell-based influenza 
vaccines, HHS plans to issue an RFP later this year to assist in the 
establishment of new U.S.-based vaccine manufacturing facilities for 
the production of cell-based seasonal and pandemic influenza vaccines 
(Table 5), helping us achieve Pandemic Vaccine Goal 1.

                 TABLE 5.--HHS INFLUENZA VACCINE MANUFACTURING INFRASTRUCTURE BUILDING PROJECTS
----------------------------------------------------------------------------------------------------------------
               Projects                         Contracts           Award   Duration         Goals/Results
----------------------------------------------------------------------------------------------------------------
Retrofit existing manufacturing         Active RFP; contract       ( \1\    2007-2013  Increase domestic flu
 facilities.                             awards expected Feb.           )               vaccine capacity to
                                         2007.                                          produce 125 M doses of
                                                                                        egg-based pandemic flu
                                                                                        vaccine.
Build new cell-based vaccine            RFP expected in fiscal     ( \1\    2008-2013  Build domestic cell-based
 facilities.                             year 2007.                     )               flu vaccine mfg.
                                                                                        capacity to support
                                                                                        pandemic needs.
----------------------------------------------------------------------------------------------------------------
\1\ To be determined.

                            antiviral drugs

    Antivirals are principally used to treat influenza infections. 
Under certain circumstances, antivirals may also reduce transmission of 
the influenza virus or even prevent infection. Two antiviral drugs were 
effective against the H5N1 virus in laboratory testing. In the event of 
a pandemic, antiviral drugs may be a key line of defense before a well-
matched pandemic vaccine is available.
    HHS funding was therefore allocated to acquire antiviral drugs. 
Currently two drugs, oseltamivir (Tamiflu) and zanamivir (Relenza) 
may provide clinical benefit against most H5N1 virus strains currently 
circulating in Asia; however, several cases of drug-resistant H5N1 
viruses in humans have been identified. Accordingly HHS is stimulating 
the development of new and more promising influenza antivirals and 
establishing antiviral drug stockpiles to achieve antiviral goals #1 
and #2.

                 antiviral drugs--advanced development

    ASPR has an antiviral advanced development program that earlier 
this month awarded a $102 million contract for the development of a new 
influenza antiviral--Peramivir, which is a member of the neuraminidase 
inhibitor class of influenza antiviral drugs (Table 6). The drug 
resistant profile for Peramivir is dissimilar to those of the licensed 
antiviral drugs. While the other antiviral drugs in this class are 
either taken orally (oseltamivir/Tamiflu) or by an inhaler (zanamivir/
Relenza), peramivir is being studied as a drug that can be 
administered parenterally, that is through intravenous or intramuscular 
injection.

                       TABLE 6.--HHS INFLUENZA ANTIVIRAL DRUG ADVANCED DEVELOPMENT PROJECT
                                              [Dollars in millions]
----------------------------------------------------------------------------------------------------------------
                  Project                     Contracts     Award      Duration            Goals/Results
----------------------------------------------------------------------------------------------------------------
New influenza antiviral drugs..............            1       $102    2007-2011  Expand and diversify flu
                                                                                   antivirals.
                                                                                  Develop peramivir for IM/IV
                                                                                   administration.
----------------------------------------------------------------------------------------------------------------

    Funding in this contract over the next 4 years will support 
manufacturing of clinical investigational and consistency lots; Phase 2 
and 3 clinical studies to evaluate safety and efficacy in support of 
product approval in the United States; manufacturing process 
validation; and other product approval requirements.

            antiviral drugs--federal and state acquisitions

    Another key goal in the HHS Pandemic Influenza Plan is to ensure 
the availability of antiviral treatment courses for 25 percent of the 
population, or 75 million individuals. By fiscal year 2008, the Federal 
government will complete the 20 million course antiviral stockpile 
purchase to maintain the function of the health care system and protect 
first responders, and stockpile an additional 24 million treatment 
courses for treatment of pandemic influenza, for a total of 44 million 
treatment courses. In addition, the Federal government plans to 
stockpile 6 million treatment courses to attempt to contain no more 
than two local outbreaks at the outset of a pandemic in the U.S. To 
date, HHS has ordered more than 36 million courses of influenza 
antivirals for which 26 million courses have been delivered to the 
Strategic National Stockpile for pro rata distribution to States during 
a pandemic (Table 7). A small portion of the Federal stockpile has been 
deployed to eastern Asia to help contain a potential outbreak.

                            TABLE 7.--HHS INFLUENZA ANTIVIRAL DRUG STOCKPILE PROJECTS
----------------------------------------------------------------------------------------------------------------
               Projects                Contracts            Award             Duration        Goals/Results
----------------------------------------------------------------------------------------------------------------
Federal pan flu antivirals stockpiles          2  $587 million............    2004-2008  Build federal stockpile
                                                                                          of pan flu antivirals
                                                                                          for containment &
                                                                                          treatment (50 million
                                                                                          treatment courses
                                                                                          total).
State pan flu antivirals stockpiles..          2  $170 million budget.....    2006-2008  Subsidize purchase of
                                                                                          pan flu antivirals by
                                                                                          States and other
                                                                                          entities to build
                                                                                          stockpile of 31
                                                                                          million treatment
                                                                                          courses.
----------------------------------------------------------------------------------------------------------------

    Additionally, the Implementation Plan calls for States to purchase 
31 million antiviral treatment courses, for which the Federal 
government subsidizes at 25 percent of the cost ($170 million total).
    In summer 2006, HHS announced two-year contract awards totaling 
$166 million that provided discounted prices for all 50 States, the 
District of Columbia, five U.S. territories, and the three Freely 
Associated States of the Pacific to purchase influenza antiviral drugs 
for State pandemic stockpiles. At the time, Secretary Leavitt 
commented, ``Our ultimate goal is to stockpile sufficient quantities of 
antiviral drugs to treat 25 percent of the U.S. population. Helping the 
states develop their own medical stockpiles will facilitate quicker 
distribution of antiviral drugs in the event of a pandemic influenza 
outbreak.''
    To date 43 States have ordered 11 million treatment courses and are 
committed to purchasing 30.6 million treatment courses by 2008. A 
complete table of projected antiviral purchases and subsidized 
allocations for all jurisdictions is posted online at http://
www.pandemicflu.gov/state/antivirals.html.

                              diagnostics

    Funding has been designated for the advanced development of rapid 
detection tests for avian influenza in humans. CDC, with the assistance 
of ASPR, currently has an advanced development program for point of 
care diagnostics that includes four contracts and obligations over $11 
million (Table 8).

                          TABLE 8.--HHS PANDEMIC RAPID DIAGNOSTICS DEVELOPMENT PROJECTS
----------------------------------------------------------------------------------------------------------------
               Projects                Contracts            Award             Duration        Goals/Results
----------------------------------------------------------------------------------------------------------------
POC flu diagnostics..................          4  $11.4 million for year 1    2006-2007  Facilitate development
                                                                                          of point of care
                                                                                          diagnostics towards
                                                                                          U.S.-approval for
                                                                                          detection of pandemic
                                                                                          flu viruses.
----------------------------------------------------------------------------------------------------------------

    In December 2006, HHS announced $11.4 million in new contracts to 
four companies working to develop new point of care diagnostic tests 
that doctors and field epidemiologists could eventually use to quickly 
and accurately test patients for avian influenza H5N1, other emerging 
influenza viruses, as well as more common influenza viruses. The tests 
could provide public health experts worldwide with critical information 
on the influenza viruses circulating and help monitor for viruses that 
could cause a global influenza pandemic.
    During the next year, the four companies will work to create tests 
that would detect seasonal human influenza viruses and differentiate 
within 30 minutes influenza A H5N1 from seasonal human influenza 
viruses. These contracts, in support of diagnostics goal #1, will 
stimulate development of promising technology that could help doctors 
treat their patients faster and help public health authorities track 
influenza viruses that could spur a pandemic, and may be used at points 
of entry for screening. In addition to these contracts, CDC will 
provide funding for a repository of influenza reagents and other 
materials to aid with the advanced development of these point-of-care 
diagnostics.

       non-pharmaceutical medical supplies and response capacity

    HHS is expanding medical infrastructure and response capacity 
during an influenza pandemic by stockpiling non-pharmaceutical medical 
supplies for distribution to States in the event of a pandemic. HHS has 
purchased over 155 million masks to reduce the spread of disease. In 
addition, HHS has obligated $100 million for the purchase of 
ventilators, intravenous antibiotics, syringes and needles. Of the $170 
million allocated, over $156 million has been obligated for medical 
supplies.
    HHS has also directed funding to increase State and local capacity, 
enhance international surveillance, expand clinical research capacity 
Southeast Asia, and implement rapid outbreak response in currently 
affected countries. HHS has also allocated funds for risk communication 
strategies and other domestic preparedness activities. Lastly, ASPR has 
provided grants in 2006 for $11 million to Vietnam and the World Health 
Organization for in-country development of H5N1 vaccine candidates.

                               conclusion

    I hope my testimony today has provided you a summary of the 
tremendous progress that has been made by the Department of Health and 
Human Services' enterprise and its industrial partners to develop and 
acquire medical countermeasures to improve our preparedness for an 
influenza pandemic. As described:
  --HHS initiated and/or awarded contracts for all of the first phase 
        medical countermeasure development and acquisition programs 
        within one year of the initial appropriation in December 2005,
  --HHS is managing a robust and comprehensive portfolio with over two 
        dozen contracts, and
  --HHS is initiating phase 2 initiatives for vaccine infrastructure 
        building and managing vaccine and antiviral stockpiles.
    Although much has been accomplished, continued vigilance and 
preparation are needed for us to be ready for Influenza--seasonal 
epidemics and Pandemics.
    Thank you for the opportunity to share this information with you. I 
am happy to answer any questions.

    Senator Harkin. Thank you, Dr. Parker.
    Dr. Gerberding.

STATEMENT OF DR. JULIE L. GERBERDING, M.D., DIRECTOR, 
            CENTERS FOR DISEASE CONTROL AND PREVENTION, 
            DEPARTMENT OF HEALTH AND HUMAN SERVICES
    Dr. Gerberding. Good morning. I'm very pleased to have an 
opportunity to testify before the subcommittee, and I just 
personally thank both of you, Senator Specter and Senator 
Harkin, for your ongoing interest and the detailed effort that 
you make to understand the pandemic and why that's important. I 
really appreciate being here.
    I am going to do two things. First, I would just like to 
give a brief situation report on the status of the H5N1 avian 
problem that we're experiencing, and then summarize for you the 
pandemic preparedness efforts that CDC is leading on behalf of 
Secretary Leavitt and the department.
    So I have a graph that I think even from a distance you can 
see has a lot more color on it than it did a year ago. These 
are all the countries that have had poultry outbreaks. The 
orange countries are countries where the problem has been 
primarily in domestic poultry. The yellow countries have not 
had domestic outbreaks but have had cases detected in wild 
birds.
    You can see that this really involves many continents, and 
what we've learned from watching this, number one, is that 
there is seasonality to the outbreaks. We're in high season 
right now in Asia. So we see a cyclical pattern. We also know 
that this is very lethal for birds. Broad species die.
    Most importantly, we know this virus is not just moving 
geographically but it's moving biologically. It's mutating and 
evolving. We now have two main families of virus, and the 
second family has split off into three sub-families. So we're 
watching the inevitable evolution of the H5N1 virus over time, 
and that of course makes it more challenging for us to develop 
seed viruses for vaccines, and for Dr. Fauci and others to stay 
on top of the vaccine development.
    On the next graphic I have a map that sadly has many red 
areas. These are the countries that have had human cases where 
the virus has spilled over, and you can see again this map is 
much redder than it was a year ago because more countries, more 
cases.
    What we've learned from this experience is that this 
remains a very unusual event, for people to pick up the virus. 
Most of this has occurred from bird to human, but we have had 
small clusters of human-to-human transmission that have been 
well documented, and sadly, very high fatality rates here. 
We're still seeing, of the 269 cases, the mortality rate is 
much greater than 50 percent.
    Just in the first 24 days of January we've had seven new 
cases in India and Egypt. Six of those seven patients died from 
H5N1 influenza.
    On the next graphic I'm showing geographically where CDC 
along with other Federal partners is investing effort to try to 
stay on top of the global situation. The green countries are 
basically places where CDC has provided resources to the 
ministries of health or indirectly through other cooperative 
agreements. All of the little dots on this map are places where 
CDC either has people or where we have supported the training 
and development of in-country availability along with our 
collaborators in USAID.
    The good news is, this is a much greener map than it was 
the last time we were here, but the problem remains. There are 
still countries that aren't involved in the surveillance, and 
we still have some black boxes where we just don't get 
information about evolving health situations, including 
pandemic.
    On the next graphic I have just summarized for you some of 
the highlights of the progress that we have made in the last 
year. When we talk about pandemic preparedness, we are not 
talking about just H5N1. We are talking about any virus that 
has the potential to move rapidly from human to human and cause 
deadly outbreaks.
    We need four things to be prepared. We need products, and 
Dr. Parker and Dr. Fauci will talk more specifically about the 
vaccine and the antivirals, but we need other products like 
diagnostic tests. You can see that we're on our way now to 
develop a rapid diagnostic test through some cooperative 
agreements and contracts.
    We also need plans. CDC has developed a flu operation plan 
to carry out the Secretary's strategy. We have about 1,000 
tasks in that plan, and we have more than 150 people who are 
working their hearts out, trying to make sure that we 
accelerate our preparedness not just at CDC but throughout the 
State and local health departments, the business community, the 
educational community, and so on and so forth.
    So that's plans and products. We also need people, and we 
have got to invest in the scientists and the preparedness 
experts at every element of the preparedness network if we want 
to be successful. CDC is recruiting and developing a much 
broader cadre of expertise in this area, thanks to the support 
that we have gotten so far from the supplemental.
    The fourth thing we need is practice, and what you're going 
to see in the next year is a great deal of practice of all of 
this planning that has gone on in the States and at CDC. You'll 
be seeing not just tabletops but what we call ``crawl walk 
run'' exercise regimens where we gradually scale up our ability 
to act out our responses in the pandemic and to understand what 
we need to continue to improve. That is a requirement. That is 
part of what we're using the resources that Congress has 
appropriated to the States to accomplish this year, and we 
think this ultimately is the best way to end up the kind of 
preparedness we need.

                           PREPARED STATEMENT

    So people, plans, products, and practice is really what 
we're doing with the investment that you have made in us, and 
we're very grateful for it.
    Senator Harkin. Thank you very much, Dr. Gerberding.
    [The statement follows:]

             Prepared Statement of Dr. Julie L. Gerberding

    Mr. Chairman and members of the subcommittee: I am pleased to be 
here today to provide an update on cross-cutting preparations the 
Centers for Disease Control and Prevention (CDC) and our many partners, 
collaborators, and other organizations are undertaking for the next 
influenza pandemic. Secretary Michael O. Leavitt, Secretary of the 
Department of Health and Human Services (HHS), is strongly committed to 
preparing for a pandemic. An influenza pandemic would have a profound 
impact on almost every sector of society, both in the United States and 
globally. I would like to emphasize the importance of this consolidated 
approach not only within the realm of public health but across all 
sectors of society in readiness for the next influenza pandemic. CDC is 
committed to improving the health of our Nation and the world. Our 
longstanding emphasis on cooperative action has allowed the public 
health community to accomplish a great deal since I testified before 
the Subcommittee last January, and much more needs to be done. I will 
focus my testimony today on three areas: ongoing domestic and 
international surveillance, other preparedness initiatives in 2006, and 
examples of CDC actions planned for 2007 and beyond. I will also 
describe the agency's progress towards the President's National 
Strategy for Pandemic Influenza.
    Before continuing my testimony, I would like to thank this 
subcommittee and the Congress for providing Fiscal Year 2006 Emergency 
Supplemental funding for pandemic preparedness.
    CDC recognizes the continuing threat of avian influenza A/H5N1 as 
well as other influenza strains that could evolve into a pandemic, and 
we are committed to take steps necessary for effective preparedness and 
response. Work clearly must continue to ensure sustained actions that 
will minimize the morbidity, mortality, economic burden, and social 
disruption that an influenza pandemic could cause. To put this 
imperative into perspective, I'd like to share a few comparisons 
between 2005 and today.
    In January 2005, 10 countries that had reported detection of highly 
pathogenic avian influenza A (H5N1) viruses in wild birds or domestic 
poultry to World Organization for Animal Health (OIE) (including both 
China and the Hong Kong Special Administrative Region of China). By 
January 22, 2007, 56 countries had reported H5N1 in birds (including 
both China and the Hong Kong Special Administrative Region of China). 
In January 2005, the World Health Organization (WHO) confirmed 47 human 
cases with 34 fatalities in two countries. As of January 22, 2007, WHO 
had confirmed 269 human cases with 163 fatalities in 10 countries.

            ongoing international and domestic surveillance

    One of CDC's most important roles in protecting the nation's health 
is to provide an ongoing assessment of the threat of an influenza 
pandemic. We collect and disseminate surveillance information for 
influenza strains circulating throughout the world, including those 
with a high possibility of evolving into an influenza pandemic. As one 
of four World Health Organization Global Collaborating Centers for 
Influenza, CDC is responsible for detecting and reporting predominant 
influenza strains and coordinating development of annual influenza 
vaccines for the Northern and Southern Hemispheres.
    Our agency is especially focused on monitoring changes in the avian 
influenza A/H5N1 virus. We are carefully monitoring changes in the H5N1 
virus that might allow it to evolve into a strain that could result in 
a pandemic. Our work in this area is highly collaborative, involving 
global and regional non-governmental organizations, ministries of 
health in countries across the world, CDC offices in selected 
countries, and other United States Government agencies such as Naval 
Medical Research Units (NAMRU). This extensive surveillance network has 
made it possible for CDC to closely track the geographic spread of the 
H5N1 viruses in 2006 and to identify and analyze several subtle changes 
in the virus. Fortunately, at present, these changes do not appear to 
have increased the virus' capability for efficient human-to-human 
transmission. CDC also has been able to identify changes in the 
composition of H5N1 virus samples that could affect its susceptibility 
to antiviral medications. A recent example appeared in an H5N1 virus 
sample from Egypt, initially indicating a change in susceptibility to 
oseltamivir, better known as TamifluTM. As WHO has stated, 
at this time there is no indication that oseltamivir resistance is 
widespread in Egypt or elsewhere.
    Influenza surveillance within the United States is closely linked 
with seasonal influenza activities. The established domestic 
surveillance network provides a solid foundation on which CDC and our 
partners are building the real-time human surveillance that will be 
vital when an influenza pandemic appears in the United States. We also 
are working closely with agencies such as the U.S. Geological Survey 
and the United States Department of Agriculture (USDA) to maintain 
integrated surveillance of animals infected by avian influenza strains. 
CDC is cooperating with public and private organizations to monitor 
migratory wild birds that carry numerous strains of avian influenza. We 
have strengthened agreements with our neighbors in Canada and Mexico to 
identify highly pathogenic H5N1 and other potential pandemic strains 
quickly.
    International and domestic surveillance is vital if the United 
States is to contain viruses that cause influenza pandemics and slow 
the spread of infection to allow the most time possible for development 
and dissemination of a pandemic vaccine. If an influenza pandemic 
expands in the United States, CDC's surveillance efforts will shift 
focus to supplying the necessary data to track the extent and severity 
of infection and inform response and recovery efforts.

                 other preparedness initiatives in 2006

    CDC's preparedness initiatives can be grouped under the agency's 
Health Preparedness Goals. Many of the agency's accomplishments in 2006 
bridge these goals, including the completion and implementation of a 
comprehensive Pandemic Influenza Operations Plan, an examination by 
nationally recognized ethicists of ethical issues in the decisions that 
must be made to achieve preparedness for an influenza pandemic, and the 
implementation of a cross-cutting Pandemic Influenza Task Force that is 
focusing on CDC's responsibilities related to the President's Pandemic 
Influenza National Response Plan.

                               prevention

    In 2006, CDC completed several important preparedness actions 
related to prevention, in cooperation with parts of the HHS and other 
organizations.
  --CDC played a lead role in most State Influenza Summits coordinated 
        by HHS and has continued follow-up with the States.
  --CDC has prepared and disseminated guidance, recommendations and 
        initial funding to the 62 States, localities, territories, and 
        tribal nations that are receiving HHS funding for pandemic 
        influenza preparedness. This guidance included templates for 
        operational drills of influenza immunization clinics and table-
        top exercises for community-based school-closing decision 
        processes as well a model contract for engaging pertinent 
        private-sector entities in receipt, storage and emergency 
        intra-state distribution of antiviral drugs when an influenza 
        pandemic seems imminent.
  --To strengthen seasonal vaccination and prepare a foundation for 
        promotion and distribution of a pandemic influenza vaccine upon 
        availability, CDC held two National Vaccine Summits with 
        partners in 2006 and conducted the first National Influenza 
        Vaccination Week.
  --CDC completed its Pandemic Influenza Operations Plan in 2006 and 
        began implementing the plan. As part of this initiative, the 
        agency has begun a systematic series of preparedness exercises.
  --CDC and other WHO Global Collaborating Reference Laboratories 
        isolated and characterized strains of avian influenza and with 
        this information recommended representative strains for use in 
        avian influenza vaccines.
  --CDC laboratories employed reverse genetics methods to rapidly 
        develop safer strains of newly identified avian influenza 
        viruses for use in vaccine production.
  --CDC's 2006 research on the deadly 1918 pandemic influenza increased 
        understanding about the challenges in preventing or minimizing 
        the impact of pandemics.
  --As part of United States global cooperation, CDC in collaboration 
        with other parts of HHS, had worked with other agencies to pre-
        position antiviral regimens overseas to support international 
        containment efforts. This activity is closely coordinated with 
        WHO.

                        detection and reporting

    In 2006, CDC made considerable progress in its detection and 
reporting goals related to pandemic influenza preparedness.
  --CDC awarded four contracts to biotechnology companies to develop 
        easy to use rapid diagnostic tests for detecting avian 
        influenza. These tests can diagnose influenza within 30 minutes 
        and will be used at the point of care such as in doctor's 
        offices, in emergency rooms, or at ports of entry.
  --Research accomplishments ranged from development, production and 
        dissemination of new rapid diagnostic tests to development of 
        tests to distinguish H5 viruses from other strains, which now 
        are being used by 113 certified laboratories in the Laboratory 
        Response Network (LRN). These labs have reagents on hand to 
        perform the H5N1 test (assay). Of these, 107 are domestic labs 
        and six are international labs. CDC also conducted extensive 
        research on viral samples to identify changes in the structure 
        of H5N1 subtypes that might indicate greater ability for 
        person-to-person transmission or increased severity of 
        infection.
  --To help ensure the prompt identification and containment of people 
        infected by H5N1 and other viruses that could result in an 
        influenza pandemic, CDC and the Council for State and 
        Territorial Epidemiologists (CSTE) continued our cooperative 
        work to make all laboratory-confirmed influenza 
        hospitalizations notifiable. In addition, CSTE recently has 
        recommended that infection with novel influenza viruses be 
        nationally reportable.

               timeliness and accuracy of communications

    Risk communication planning is critical to pandemic influenza 
preparedness and response. HHS and CDC are committed to the 
scientifically validated tenets of outbreak risk communication: 
comprehensive information shared across diverse audiences, information 
tailored according to need, and information that is consistent, frank, 
transparent, and timely.
  --CDC developed a comprehensive pandemic influenza risk communication 
        plan based on its nationally recognized risk communications 
        training program. This plan is included in the agency's 
        Pandemic Influenza Operations Plan and will be modified as 
        needed based in part on scheduled pandemic influenza exercises.
  --In 2006, CDC developed preparedness checklists and other practical 
        guidance for targeted groups, including the business community 
        and healthcare facilities.
  --CDC has contributed substantial information to the national 
        pandemic preparedness web site, www.pandemicflu.gov, including 
        information, education, or guidance documents.
  --The agency also enhanced its speaker's bureau and hotline to 
        accommodate increased requests for presentations about pandemic 
        influenza preparedness. Since February 2006, the CDC Speaker's 
        Bureau has recorded as accepted more than 115 presentations to 
        groups in the United States and internationally on pandemic 
        influenza.

                       investigation and control

    CDC's investigation and control efforts focus on decreasing the 
time needed to identify causes, risk factors, and appropriate 
interventions for those affected by the threat of pandemic influenza. 
These efforts include activities that support rapid outbreak response 
and purchasing and stockpiling of antiviral medications and other 
materiel.
  --Rapid response to international outbreaks has been a part of CDC's 
        mandate for decades, but recently published work suggesting 
        challenges involved in slowing or containing an influenza 
        pandemic clarifies the importance of such response 
        capabilities. For optimal response, an emerging influenza 
        pandemic outbreak anywhere in the world must be recognized 
        within 1 to 2 weeks and investigated and virologically 
        confirmed within days. An unprecedented and well-coordinated 
        containment effort must be launched in stages in response to 
        pre-planned trigger points, including deployment of dozens of 
        trained teams, public health messages, social isolation 
        measures, movement restriction considerations, treatment of 
        patients, and tracing and prophylaxis of contacts. During an 
        international training meeting in Bangkok, Thailand in July 
        2006, CDC unveiled a new, one-week standard curriculum to train 
        local rapid response teams throughout the world. This program 
        was developed in collaboration with the University of North 
        Carolina School of Public Health and provides essential 
        response skills to Rapid Response Teams composed of medical 
        doctors, epidemiologists, veterinarians, nurses, laboratorians, 
        communications specialists and other health responders.
  --In 2006, CDC awarded a total of 21 new Cooperative Agreements 
        supporting avian and pandemic influenza detection and response 
        to all six WHO regional offices and countries throughout the 
        world, bringing the total number of grantees supported by CDC 
        to 47.
  --The agency deployed investigative teams to many countries that 
        experienced H5N1 outbreaks, including Indonesia, Turkey, 
        Azerbaijan, Djibouti, Nigeria, and Sudan. These teams often 
        contributed to investigations coordinated by WHO or requested 
        specifically by ministries of health. Other teams were part of 
        multi-agency U.S. Government initiatives. For example, in 
        Azerbaijan, CDC subject matter experts visited as part of the 
        Department of State visit and advised on outbreak control. In 
        addition, CDC staff that are stationed in China, Thailand, 
        Cambodia, and Laos have participated in investigations.
  --CDC also collaborated with USDA and numerous other Federal partners 
        to develop a playbook that systematically addresses scenarios 
        and roles for responding to the introduction of H5N1 and other 
        avian influenza viruses by wild birds and domestic animals.
  --CDC developed a comprehensive Global Disease Detection (GDD) 
        strategy and in 2006 expanded its international surveillance, 
        diagnosis, and epidemic investigations, which are integrated 
        with WHO and other international partners.
  --In 2006, in collaboration with WHO and other partners, CDC enhanced 
        sharing of influenza virus genetic sequences as part of an 
        international effort to increase information for research into 
        pandemic influenza.
  --Last year, CDC significantly increased supplies in the Strategic 
        National Stockpile, including antiviral medications, personal 
        protective equipment, and other vital material, which will be 
        used in the event of a pandemic.
  --The agency has worked extensively with sister-agencies, partners, 
        and public groups to develop health guidance specifically for 
        pandemic influenza. This includes development of technical 
        guidance for health-care workers on the use of personal 
        protective equipment.

                         response and recovery

    The U.S. healthcare system will be severely stressed by an 
influenza pandemic. In addition to critical preparation needed to 
respond successfully to the acute medical care needs of the population, 
the healthcare system will also need to resume normal services as 
rapidly as possible. Among its actions, the Pandemic Influenza Task 
Force in 2006 enhanced planning for recovery of vital public health 
services.
  --CDC has developed, with input from State and local health 
        departments, healthcare partners, and other Federal agencies, 
        guidance to assist healthcare facilities in developing and 
        implementing plans to respond to an influenza pandemic, 
        including guidance on the use of appropriate infection control 
        measures to minimize transmission during patient care.
  --Participation in tabletop exercises during the past year has helped 
        facilities identify gaps and improve their readiness to respond 
        and recover after a pandemic, as an integrated part of the 
        overall planning and response efforts of their local and State 
        health departments.

             cdc actions for 2007 and beyond for continuing

    The following highlights some of the actions in which CDC now is 
engaged.
    1. CDC will continue ongoing activities with State, local, 
territorial, and tribal nation grantees. These activities will include 
review and monitoring of preparedness efforts, technical assistance and 
guidance on exercise programs, analysis of potential gaps in 
preparedness plans, and promotion of best practices among grantees.
    2. A large CDC internal pandemic influenza preparedness exercise is 
scheduled for January 31-February 1, 2007. Additional exercises that 
will include other agencies and groups will be scheduled as the year 
progresses.
    3. CDC, building on its successful 2006 National Influenza 
Vaccination Week, and in collaboration with HHS and others, will make 
this an annual event for promoting the importance of influenza 
vaccination.
    4. CDC, in partnership with the Council for State and Territorial 
Epidemiologists (CSTE) is overseeing adaptation of the international 
Rapid Response curricula for use domestically in each state. CD-ROM and 
web-based versions of the trainings are in development for use by field 
staff and other partners as a self-study curriculum.
    5. CDC is working with HHS to develop and implement a National 
Education Campaign for Pandemic Preparedness, which will include a 
focus on vulnerable populations.
    6. CDC will provide training and support to other countries to 
improve avian and pandemic influenza preparedness and response.
    7. CDC laboratories will rapidly characterize avian and other 
influenza viruses to monitor for emergence of potential pandemic 
strains and to develop strains for use in vaccine production.
    8. CDC will complete the collaborative guidance document on the use 
of personal protective equipment by the public. CDC also will publish 
preliminary guidance on community mitigation strategies to educate the 
public, private sector, and our state and local partners about use of 
non-pharmaceutical interventions, which will be especially important in 
the initial months of an influenza pandemic. This guidance will be 
refined and updated as necessary.
    9. CDC continues toward the goal of developing the coordinated 
quarantine and screening capacity. This will include efforts in a range 
of areas, including continued strengthening of quarantine stations at 
major ports of entry, initiatives with border security as part of our 
discussions with public health counterparts in Mexico and Canada, and 
addressing possible legal and ethical questions regarding isolation and 
quarantine measures in communities to impede the spread of viral 
infection.

                               conclusion

    Although CDC and its many partners accomplished much for pandemic 
influenza preparedness and response during 2006, from a public health 
standpoint much more preparation is needed. CDC greatly appreciates the 
support of this Subcommittee and others in 2006 and looks forward to 
working with you to sustain these accomplishments.
    Thank you for the opportunity to share this information with you. I 
am happy to answer any questions.














    Senator Harkin. Dr. Fauci.

STATEMENT OF DR. ANTHONY S. FAUCI, M.D., DIRECTOR, 
            NATIONAL INSTITUTE OF ALLERGY AND 
            INFECTIOUS DISEASES, NATIONAL INSTITUTES OF 
            HEALTH, DEPARTMENT OF HEALTH AND HUMAN 
            SERVICES
    Dr. Fauci. Thank you very much, Mr. Chairman, Senator 
Specter, members of the committee. I appreciate the opportunity 
to meet with you today and to discuss very briefly with you the 
NIH's biomedical research efforts to attain some of the goals 
that have just been articulated by Dr. Parker and Dr. 
Gerberding.
    As you know from other testimonies before this committee, 
what we do at NIH is based fundamentally on sound basic 
research principles which we rapidly try to extrapolate into 
clinical and applied research for the development and testing 
of the products that were just mentioned. In the case of flu, 
those products are therapeutics, diagnostics, and vaccines as 
you just heard. I've discussed those in detail in my written 
statement. What I'd like to concentrate on in the next couple 
of minutes is the area of vaccine preparedness for influenza.
    The point I want to underscore is that which was alluded to 
just a moment ago by Dr. Gerberding. When we talk about 
preparedness, we talk about preparedness for influenza with 
very little distinction between seasonal and pandemic 
influenza. We're not talking about only H5N1 today. We're 
talking about our capability to respond to influenza, be it a 
seasonal influenza--which, I might add, and we've discussed 
this in the past, is not taken as seriously by society as it 
should be, and for that reason our preparedness has not gone 
into the 21st century where it belongs, but we're getting 
there. This is closely related, so that everything we do with 
pandemic influenza applies to seasonal influenza and vice 
versa.
    Let's talk a bit now specifically about the current threat 
of H5N1. When we talk about making a vaccine, it's important to 
talk about a pre-pandemic versus a pandemic vaccine. Right now 
we're looking at H5N1s that are circulating, multiple clades. 
We spoke about the Vietnam clade 1. There's the Indonesian 
Clade c.
    We've done clinical trials which I'll talk about briefly, 
and you'll hear from Dr. Treanor, about developing a vaccine to 
have available, to be able to get a head start. If in fact we 
do, and we hope we never do get a pandemic, we need the 
capability of what Dr. Gerberding just said, of being able to 
rapidly use what we've developed to get the doses available 
within a reasonable period of time of several months.
    Let's move on to the next slide, and we look at the trial 
that has gotten some attention, and that is looking at the 
Vietnam strain H5N1 I presented to this committee several 
months ago. Let me just tell you where we are today.
    This is a vaccine in which there is good news and sobering 
news. The good news is that it induces an immune response that 
you would predict by laboratory parameters to be protective. 
The sobering news is that this occurs in about 50 percent of 
people, not enough, and the dose that's required to get us 
there is prohibitively high. So we need to figure out a way, 
how we can get those doses expanded and how we could learn from 
this.
    So what are we doing from a research standpoint? What we're 
doing is that we are adddressing major challenges. One you've 
heard of. We have got to get the technology of upsurging. We've 
got to move from egg-based to cell-based production, but we've 
got to go beyond that. We've got to develop novel vaccine 
approaches, recombinant approaches, synthetic approaches, 
vector approaches, the kinds of things that are in the research 
stage right now, that need to be rapidly moved into 
practicality.
    You've heard about dose-sparing strategies such as 
adjuvants, and also we need to optimize what we do with live 
attenuated vaccines. Let's just spend a half a minute on 
adjuvants. What is an adjuvant? We talk about it a lot. It's a 
compound that enhances or amplifies the body's natural immune 
response to what you challenge it with. It is given in several 
other vaccines. We have never used it effectively in influenza.
    So what we're trying to say is that when you use an 
adjuvant, you give it together with the vaccine, it can reduce 
the amount of antigen needed, which can get us out of the 
impracticality of the high dose. It promotes earlier, stronger, 
and more durable responses, and it may actually--we're working 
on that now--increase the cross-protection, so that this is 
what you might get without an adjuvant and this is what you get 
with an adjuvant.
    Very briefly, next slide, the concept of a universal 
vaccine, what do we mean by that? Each year as the virus 
changes a bit in seasonal influenza, to get optimum protection 
we need to get a new vaccine that's slightly modified. Why? 
Because what changes are these two. I know this is a complex 
slide, and I apologize for it, but actually it is simple if I 
can just walk through in about 15 seconds with you.
    The H and the N are the flagship signatures of the virus, 
we call it H5N1, H3N2, this is what we make our vaccines 
against. It changes a little bit from year to year, and a lot 
from pandemic to pandemic. There are components of the vaccine, 
such as the nuclear protein, the matrix proteins, which change 
hardly at all from season to season, and also very little from 
pandemic to pandemic.
    So we're putting a lot of resources right now into trying 
to get a vaccine that would induce an effective response 
against those components of the vaccine that don't change. Now 
you might ask, ``Why doesn't that happen naturally?'' The 
reason is, when the body sees these proteins, it sees it in a 
form that's very poorly immunogenic. In other words, it doesn't 
make a good response against it. Our task, from a research 
standpoint, is to make the body see that as something that it 
really wants to respond to, and we could talk about that more 
in the question period.

                           PREPARED STATEMENT

    Final slide, getting back to the theme, everything that I 
spoke about in the few minutes I had applies to both seasonal 
and pandemic influenza. If we succeed, both from a production 
capability and a fundamental concept research standpoint, it 
will benefit the preparedness for both seasonal and pandemic 
influenza.
    Thank you, Mr. Chairman. I'd be happy to answer questions 
later.
    [The statement follows:]

               Prepared Statement of Dr. Anthony S. Fauci

    Mr. Chairman and members of the subcommittee, thank you for the 
opportunity to speak to you today about the ongoing threat of a human 
influenza pandemic, the immediate threat from H5N1 avian influenza, and 
research being conducted and supported by the National Institutes of 
Health (NIH) that is improving our ability to respond effectively not 
only to an influenza pandemic, but to seasonal influenza epidemics as 
well.
    Seasonal outbreaks of influenza occur almost every year in the 
United States and impose a substantial burden of morbidity and 
mortality on the population. Influenza viruses circulate constantly 
around the globe, and influenza cases occur sporadically throughout the 
year. Influenza epidemics, in which the number of cases peaks sharply, 
usually occur in winter months. These seasonal epidemics cause an 
annual average of about 200,000 hospitalizations and 36,000 deaths in 
this country, mostly among people aged 65 years and over and those with 
chronic health conditions. Globally, an estimated 250,000 to 500,000 
influenza-related deaths occur each year.
    As influenza viruses circulate, the genes that determine the 
structure of their surface proteins undergo small changes called 
mutations. As these mutations accumulate (a process called ``antigenic 
drift''), the immunity created by prior exposure to older circulating 
influenza viruses or by prior vaccination no longer can reliably 
prevent infection. Antigenic drift is thus the basis for the 
predictable patterns of seasonal influenza seen in most years and is 
the reason that we must update influenza vaccines annually.
    Influenza viruses also can change more dramatically. For example, 
viruses sometimes emerge that can infect species other than their 
natural animal reservoirs, typically migratory waterfowl. These avian 
viruses may begin to infect domestic poultry, farm animals such as 
pigs, or, very rarely, humans. When an avian influenza virus develops 
the ability to infect humans, the result is usually a ``dead-end'' 
infection that cannot readily spread further in the human population. 
However, the virus could mutate in ways that allow human-to-human 
transmission to occur more easily. Furthermore, if an animal influenza 
virus and a human influenza virus were to simultaneously co-infect a 
person or animal, the two viruses could exchange genes--a process known 
as reassortment--resulting in a virus that may be readily transmissible 
between humans and against which the human population may have no pre-
existing immunity. When such an ``antigenic shift'' occurs by either of 
these mechanisms, mutation or reassortment, a global influenza pandemic 
can result.
    Historically, pandemic influenza is a proven threat. In the 20th 
century, influenza pandemics occurred in 1918, 1957, and 1968. The 
pandemics of 1957 and 1968 were serious infectious disease events that 
killed approximately two million and 700,000 people worldwide, 
respectively. The 1918-1919 pandemic, however, was catastrophic: 
epidemiologists estimate that it killed more than 50 million people 
worldwide, including more than 500,000 people in the United States, and 
caused enormous social and economic disruption. In all three of these 
pandemics, for reasons that remain unclear, a much greater proportion 
of young adults were killed than is typical of seasonal influenza. 
Given this history, we can expect that a new influenza virus will 
emerge and another pandemic will occur at some point in the future. 
Although the precise timing of the next pandemic remains unknown, when 
it arises it is likely to spread rapidly in our modern society. The 
consequences likely will be severe throughout the world, in developed 
nations but especially in poor countries that do not have adequate 
public health systems.
    Of known influenza viruses, the highly pathogenic H5N1 avian 
influenza virus currently spreading among domestic and migratory birds 
in Asia, Africa, and the Middle East is of greatest concern. Although 
the H5N1 virus remains primarily an avian pathogen, 269 people are 
known to have been infected, usually from direct contact with infected 
poultry; 163 of the people diagnosed with H5N1 avian influenza 
infection have died. At this time, the virus does not efficiently 
spread from birds to humans, and transmission from one person to 
another is rare. However, if the H5N1 virus mutates further or 
exchanges genes with a human influenza virus to acquire the ability to 
spread from person to person as efficiently as the viruses that cause 
seasonal influenza epidemics, a human pandemic could become a reality. 
The degree of threat from such a virus would depend on the extent to 
which the virus retained its current virulence and how transmissible it 
became.
    In late 2005, the President announced the National Strategy for 
Pandemic Influenza, and U.S. Department of Health and Human Services 
(HHS) Secretary Michael O. Leavitt released the HHS Pandemic Influenza 
Preparedness and Response Plan, an integral component of the National 
Strategy. These two documents are part of a blueprint for a coordinated 
national effort to prepare for and respond to a human influenza 
pandemic that includes a National Implementation Plan and preparedness 
and response plans from other federal agencies. Within HHS, the 
National Institutes of Health, and the National Institute of Allergy 
and Infectious Diseases (NIAID) in particular, were given primary 
responsibility for the conduct of scientific research and clinical 
trials to foster development of therapies, diagnostic tests and 
devices, and vaccines to help prepare for a potential human influenza 
pandemic.
    In my testimony today, I will present an overview of the ongoing 
scientific research and development efforts of NIH and our progress and 
priorities in creating the countermeasures needed to reduce the threat 
posed by both seasonal and pandemic influenza.

                             basic research

    NIH supports numerous basic research projects intended to increase 
our understanding of how influenza viruses replicate, interact with 
their hosts, stimulate immune responses, and evolve into new strains. 
Although many questions remain unanswered, results from these basic 
research studies are laying the foundation for the design of new 
antiviral drugs, diagnostics, and vaccines, and are applicable to 
seasonal epidemic and pandemic strains alike. For example, NIH-
supported scientists recently used a massive database to complete the 
most comprehensive analysis to date of the critical sites on influenza 
viruses that are recognized by the immune system. Because the work 
reveals at the molecular level exactly where the immune system targets 
the viruses, it will help scientists design new vaccines, diagnostics 
and immune-based therapies against influenza. Moving from the molecular 
to the population level, NIH-supported modeling studies of the dynamics 
of influenza infection in large human populations are providing 
important insights into how the virus spreads, the effects of air 
travel and commuting patterns on how fast epidemics move, and the 
potential value of antiviral drugs and nonpharmaceutical interventions 
in controlling outbreaks. In addition, several NIH programs are 
describing the detailed immune responses to seasonal influenza 
vaccination in humans to define the immune correlates of protection and 
to understand the lack of efficacy in the elderly and other 
immunocompromised individuals.
    To better understand the varied and ever-changing genetic 
blueprints of influenza viruses, NIH launched the Influenza Genome 
Sequencing Project in the fall of 2004. The goal of this collaboration 
between NIH (NIAID and the National Library of Medicine), St. Jude 
Children's Research Hospital, the Wadsworth Center, the Institute for 
Genomic Research, the Centers for Disease Control and Prevention (CDC), 
and several other organizations is to determine the complete genetic 
sequences of different influenza viruses from around the world and to 
rapidly provide these sequence data to the scientific community. The 
project has determined genomic sequences of close to 2,000 animal and 
human influenza viruses, all of which are freely available to 
researchers via the NIH website; more than 200 new sequences are being 
added every month. The data flowing from this program will enable 
scientists to track how influenza viruses evolve as they spread through 
their host populations and across geographic regions, and to match 
viral genetic characteristics with virulence, ease of transmissibility, 
and other clinical properties. The end result will be a clearer 
understanding of how influenza epidemics and pandemics emerge.
    Scientists also are working to understand the virus that caused the 
devastating 1918 pandemic, and in the process are gaining new insights 
into what might happen with the H5N1 avian influenza virus. Using 
pathology samples from victims of the 1918 pandemic, NIH intramural and 
extramural scientists and their collaborators have determined the 
complete genetic sequence of this virus, and have assembled viruses 
that bear some or all of these genes. The sequence revealed that the 
pandemic virus probably did not arise through a reassortment of animal 
and human viruses but rather was an entirely avian-like virus that 
adapted to infect humans. Infection of mice and non-human primates with 
the complete 1918 virus resulted in a damaging inflammatory response in 
the lungs, with aberrant levels of expression of immune regulatory 
molecules. This result might explain the extraordinary mortality among 
young adults in the 1918 pandemic because young adults have a strong 
and robust immune system and a stronger immune response would lead to 
increased pathological consequences. Of note, immunological responses 
similar to those seen with reconstructed 1918 viruses in animals have 
been seen with recent H5N1 virus infections in humans.
    Ongoing sequence analysis of human influenza viruses from before 
and after 1918 seeks to place the emergence of the 1918 virus in its 
historic context. Understanding how long the pandemic virus circulated 
in humans before it emerged in full force in 1918 has important 
implications for pandemic planning, including more effective 
nonpharmaceutical interventions. Knowledge of how highly virulent 
influenza viruses kill could lead to new strategies for the development 
of novel antiviral drugs and other therapies.

                                vaccines

    Vaccines are essential tools for the control of influenza. NIH 
efforts to facilitate the creation of effective H5N1 influenza vaccines 
are based on isolates of the currently circulating H5N1 virus. Since 
there is no H5N1 pandemic among humans at this time, such vaccines are 
referred to as pre-pandemic H5N1 vaccines. Should an H5N1 virus emerge 
that can be easily transmitted among humans, a vaccine based on the 
newly emerged strain would need to be developed. However, development 
of pre-pandemic H5N1 vaccine candidates, which is proceeding rapidly, 
serves two important purposes. As the H5N1 virus mutates, even 
imperfectly matched prototype vaccines may prime the immune system to 
respond to related H5N1 viruses and offer enough protection to reduce 
the severity of disease, and therefore serve as an important 
preliminary component of pandemic control. In fact, recent results from 
a small study indicated that a previously administered dose of H5N1 
vaccine successfully served as immunologic priming for a vaccine 
against an antigenically drifted strain given seven to eight years 
later. Such a strategy could buy precious time while a vaccine that 
more closely matches the pandemic strain is produced and distributed. 
Producing prototype H5N1 vaccines also provides an opportunity to 
create the infrastructure, processes, and production capacity to 
manufacture enough vaccine should a worldwide pandemic ensue.
    In early 2004, NIH-supported researchers used a technology called 
reverse genetics to create an H5N1 reference vaccine strain from a 
Vietnamese H5N1 isolate. NIH then contracted with sanofi pasteur and 
Chiron Corporation to use this reference strain to manufacture small-
scale lots of inactivated virus vaccine for use in clinical trials. 
These pre-pandemic vaccine candidates have now been clinically tested 
in healthy adults, elderly people, and children, and the results 
provided both good and sobering news. The good news is that the vaccine 
is well tolerated, and induces an immune response that is similar in 
all age groups and is suggestive of protection against infection with 
the immunizing strain. The sobering news is that the doses of vaccine 
needed to elicit the levels of immune responses usually thought to 
predict protection were larger than those used for seasonal influenza 
vaccines. In addition, these predictably protective responses were 
elicited in only approximately half of the vaccinated individuals. The 
need for larger doses of vaccine reduces the number of people who could 
be immunized with the amount of vaccine that can be produced in a given 
timeframe. In addition, it is important to elicit a protective immune 
response in a greater percentage of vaccinated individuals.
    We, therefore, have pursued the use of vaccine additives called 
adjuvants that amplify the immune response. Results from a Phase I 
clinical trial of a candidate vaccine for H9N2 influenza--another avian 
virus that has caused human deaths--indicated that an adjuvant called 
MF59 increases the immune response and could thus reduce the required 
dose. In 2006, GlaxoSmithKline announced encouraging results indicating 
that its H5N1 influenza vaccine, using a proprietary adjuvant, achieved 
a high immune response at a low dose of antigen. Preliminary results 
from NIH-supported clinical trials of H5N1 pre-pandemic vaccine with 
adjuvants will soon be available. In addition, NIH-supported basic 
research into a family of immune system proteins called Toll-like 
receptors--molecules that are among the immune system's ``first 
responders''--is providing important insights into how adjuvants work, 
and may illuminate new opportunities for improved dose-optimization 
strategies. In addition, recent research has shown non-Toll-like 
receptors to be potential new targets for adjuvant function. This 
finding and other promising approaches to developing new vaccine 
adjuvants are being studied by NIH-supported innate immunity research 
programs.
    Most current seasonal influenza vaccines are based on an 
inactivated influenza virus grown in fertilized chicken eggs. 
Unfortunately, the domestic capacity for the manufacture of influenza 
vaccines using egg-based technology can meet only a small fraction of 
the expected demand should a pandemic virus emerge today. For this 
reason, we are conducting research that will help to increase U.S.-
based pandemic influenza vaccine production capacity, and lead to the 
further development of new vaccines and manufacturing methods that are 
faster and more flexible for influenza vaccine production. The ultimate 
goal is to have the capacity to produce sufficient quantities of 
effective and safe pandemic influenza vaccine to protect every American 
within six months of the emergence of a new pandemic virus.
    Although egg-based manufacturing methods have served us well for 
more than 40 years, they are logistically complex, can lead to delays 
if the vaccine strain of influenza virus will not grow efficiently, and 
cannot be rapidly expanded in response to increased demand for vaccine. 
To build a more reliable domestic manufacturing capacity that could be 
rapidly mobilized in response to the emergence of a pandemic virus, we 
are working to expand and accelerate the development of additional 
manufacturing methods, such as growing the vaccine strain in cell 
culture. New technologies for producing influenza vaccines in cell 
cultures are promising and such technologies are currently used in 
licensed vaccines for other diseases. However, the successful 
development of production methods and licensure of influenza cell-based 
products are likely several years in the future, and therefore, support 
for current egg-based technologies should also continue.
    Our strategic plans have articulated the goal of developing the 
capacity to provide 300 million people in the United States with the 
needed doses of pandemic vaccine within a six-month time frame. Our 
success in reaching this goal will depend to some extent on the success 
of efforts to understand and expand the use of effective and safe 
adjuvants and other dose-optimization strategies, and efforts to 
develop other technologies for vaccine preparation.
    In this regard, NIH is collaborating with industry to pursue 
several other vaccine strategies in addition to inactivated virus H5N1 
vaccines. From the mid-1970s to the early 1990s, NIH intramural and 
extramural researchers developed a cold-adapted, live attenuated 
influenza vaccine strain that led to the product now marketed by 
MedImmune, Inc. as FluMist. NIH intramural researchers are now working 
with colleagues from MedImmune Vaccines under a Cooperative Research 
and Development Agreement to produce and test a library of similar live 
vaccine candidates against all known influenza subtypes with pandemic 
potential, allowing a head start and faster response should a strain 
from any of these subtypes emerge as a pandemic threat. Tests in mice 
and ferrets showed that two doses of a live attenuated H5N1 candidate 
vaccine protected the animals from infection and death by a wide array 
of H5N1 isolates--an encouraging result indicating that this type of 
vaccine might protect even if not precisely matched to the circulating 
strain. Human studies of candidate cold-adapted, live attenuated H5N1 
vaccines are underway.
    Other strategies under development include recombinant subunit 
vaccines, in which cultured cells are induced to make various influenza 
virus proteins that are then purified and used in a vaccine; DNA 
vaccines, in which influenza genetic sequences are injected directly 
into a person to stimulate an immune response; and approaches that 
insert the genes of influenza virus into a different, harmless virus (a 
``vector'') that is used as a vaccine. A human trial of a DNA vaccine, 
developed at the NIAID Vaccine Research Center and designed to prevent 
H5N1 infection, began last month at the NIH Clinical Center. Planning 
is also underway to test intradermal injection as an alternate delivery 
technique for this vaccine, and to evaluate alternative vaccine 
candidates, such as recombinant adenoviral vectors containing H5N1 
genetic sequences and recombinant H5N1 proteins.
    An important NIH research goal is to develop a vaccine that raises 
immunity to parts of the influenza virus--so called epitopes--that vary 
little from season to season and from strain to strain. This is a 
challenging task because the invariant epitopes of influenza viruses 
generally do not elicit a vigorous immune response. Nonetheless, there 
is a great deal of interest in so-called Vaccine Common Epitope (VCE) 
vaccines against influenza, especially based on the influenza M2 
protein. The fundamental strategy is to present the common antigen to 
the immune system in a way that stimulates a robust and protective 
immune response. Such a vaccine might not only provide continued 
protection over multiple seasons but also might offer considerable 
protection against a newly emerged pandemic influenza virus. This would 
substantially increase the overall immunity of the population to 
influenza A, and make the country far less vulnerable to a new 
influenza A virus.

                          antiviral therapies

    Antiviral medications are an important counterpart to vaccines as a 
means of controlling influenza outbreaks, both to treat infection after 
it occurs and under certain circumstances to prevent infection prior to 
or immediately after exposure. Four drugs currently are available for 
the treatment of influenza, three of which are also licensed in the 
United States for influenza prevention in certain populations. Efforts 
to test and improve these existing anti-influenza drugs are in 
progress. H5N1 strains circulating in Southeast Asia, Africa, and 
elsewhere are generally resistant to two older drugs--rimantadine and 
amantadine--but the majority of isolates are sensitive to a newer class 
of drugs, called neuraminidase inhibitors. This class of drugs includes 
oseltamivir (marketed as Tamiflu), currently approved for treatment 
and prophylaxis of individuals older than one year. Studies to test the 
efficacy of higher doses of neuraminidase inhibitors, and to further 
characterize the safety profile of oseltamivir in very young children, 
are in the advanced planning stages. NIH is also collaborating with the 
Department of Defense and Department of Veterans Affairs (VA) in a VA-
funded research project to examine if probenecid co-administration with 
oseltamivir can increase the effective supply of oseltamivir. In 
addition, NIH has collaborated with the World Health Organization, the 
Wellcome Trust, and other institutions in Indonesia, Thailand, Vietnam, 
and the United Kingdom to develop the South East Asia (SEA) Influenza 
Clinical Trial Network, which is developing in-country research 
capacity in a region directly affected by the H5N1 influenza outbreak 
and conducting studies of antivirals in people infected with the H5N1 
virus.
    NIH-supported research to identify additional anti-influenza drugs 
that work through a variety of mechanisms is progressing rapidly. An 
NIH program that screens both licensed compounds and new drug 
candidates--first in cell culture systems and then in animal models--
has identified several promising anti-influenza candidates. NIH is 
collaborating with the private sector to further develop three 
promising candidates out of the 32 that were screened in mice in 2006:
  --FluDase binds host cell receptors to prevent viral entry;
  --T-705 inhibits replication of viral RNA; and
  --Peramavir inhibits viral neuraminidase.
    Furthermore, NIH is collaborating with industry to develop novel, 
broad-spectrum therapeutics that might work against many influenza 
virus strains; some of these target viral entry into human cells, while 
others specifically attack and degrade the influenza virus genome. In 
animal models, treatment with a monoclonal antibody is effective 
against what would otherwise be a lethal dose of H5N1 virus, even if 
given up to three days after infection, indicating that passive 
administration of antibodies might be a useful strategy to contain an 
H5N1 pandemic. NIH is exploring the possibility that one may be able to 
develop a high-titer anti-H5N1 antibody preparation as a treatment for 
patients with avian influenza through the hyperimmunization of healthy 
volunteers. Studies are also in progress to evaluate long-acting next-
generation neuraminidase inhibitors. The development and testing in 
animals of combination antiviral regimens against H5N1 and other 
potential pandemic influenza strains is also a top research priority.

                              diagnostics

    Inexpensive, fast, accurate, and precise methods to diagnose 
influenza infection in its earliest stages continue to be a focus of 
ongoing research. If a pandemic influenza virus were to emerge, 
diagnostic tools capable of quickly and definitively identifying 
infected people would be extremely valuable, helping to slow the spread 
of the virus and maximizing the efficiency with which stockpiled 
antivirals are used. If available for routine use, such diagnostics 
would also help to diagnose and treat seasonal influenza, which 
clinically can mimic many other diseases.
    Recently, NIH-supported scientists from the University of Colorado 
at Boulder, working in collaboration with researchers at the CDC, 
showed that a potentially revolutionary diagnostic device, called the 
MChip, is capable of quickly identifying many influenza viruses, 
including H5N1 avian influenza. The MChip has a number of strengths 
that could allow it to become a valuable tool in global influenza 
control efforts. The materials for each chip cost less than ten 
dollars. It tests for the influenza matrix gene, which varies 
relatively little between strains and over time, so the test likely 
would not have to be updated as frequently as tests based on other 
genes. The researchers already have automated the process of reading 
the test's output, allowing accurate assessment of many samples in a 
short time. Discussions are already under way to commercialize its 
manufacture, and in the future researchers hope to adapt this 
technology for handheld field use.

                               conclusion

    In closing, I would like to emphasize that our efforts to 
successfully prepare for an influenza pandemic--with a sufficient 
supply of effective vaccines and antiviral drugs, efficient infection 
control, and clear public communication--will benefit our ability to 
cope with seasonal influenza. It is clear, however, that we have not 
yet optimized our preparedness and responsiveness to this recurring 
disease. There is a pressing need to move toward adoption of newer 
vaccine manufacturing techniques and other strategies that can improve 
the surge capacity, flexibility, and speed with which vaccines are 
made. Moreover, increasing the proportion of the population that is 
vaccinated annually with seasonal influenza vaccine will help to pave 
the way for the more intense vaccination effort that would accompany an 
influenza pandemic.
    Fortunately, much of the research on influenza vaccines and 
antivirals that has been undertaken in response to the emergence of 
H5N1 avian influenza is directly applicable to both seasonal and 
pandemic preparedness, and efforts to improve our response to one will 
invariably improve our ability to manage the other.
    Thank you for the opportunity to testify before you today. I would 
be pleased to answer any questions that you may have.

    Senator Harkin. Thank you, Dr. Fauci. I do want to follow 
up on that. I don't understand all that, but I want to get a 
better understanding before we leave today on this ``universal 
vaccine'' and how that might work.
    Dr. Treanor, thank you very much for being here today, and 
we'll turn to you now.

STATEMENT OF DR. JOHN JAY TREANOR, M.D., DIRECTOR, 
            VACCINE TREATMENT AND EVALUATION UNIT, 
            UNIVERSITY OF ROCHESTER MEDICAL CENTER
    Dr. Treanor. Thank you very much, Chairman Harkin and 
Ranking Member Specter and other distinguished members of the 
subcommittee. I want to thank you for allowing me to testify 
today and for your leadership in calling this hearing on a 
very, very important topic.
    Now, most of my comments will simply echo what Dr. Fauci 
has just said. I would like to tell you about the University of 
Rochester Vaccine and Treatment Evaluation Unit, which is one 
of seven NIH-sponsored units throughout the country that 
perform clinically related research on novel vaccines and other 
control measures for human infectious diseases.
    This NIH-supported research has included studies of viral 
diarrhea, whooping cough, genital herpes, cervical cancer, 
respiratory viruses in children, pneumococcus, malaria, 
smallpox, and anthrax, among others, and has been particularly 
focused recently on the development of vaccines for both 
seasonal and pandemic influenza. I think that while this 
research has made substantial progress in guiding the use of 
currently-available measures, it's clear that we have a lot 
more to learn to be able to effectively deal with both seasonal 
and pandemic flu. I would certainly echo what Dr. Fauci has 
just said, that what we learn about seasonal and pandemic flu 
are intrinsically linked to each other.
    Now, as you have heard, the initial approach to developing 
a vaccine was really focused on using something similar to what 
we used for conventional flu, because we know those vaccines 
are safe and do have some efficacy in reducing flu. But we have 
also learned that in the case of H5, relatively high doses are 
required. This would be a strategy that would be effective in 
selective groups, but to provide protection for a large 
population we need to find ways to use lower doses, and one of 
those ways is through the use of adjuvants.
    Aluminum is the most commonly used adjuvant for vaccines 
now, but through these NIH studies we've learned that aluminum 
does not appear to substantially improve the response to an 
influenza H5 vaccine. So attention has been turned to other 
adjuvants and some promising candidates have been identified, 
including the adjuvant MF-59, which has been demonstrated in 
the VTEU studies to effectively increase the response to both 
H5 vaccines as well as another pandemic candidate, H9.
    Now, one of the other interesting things we've learned is, 
as you know, with the regular flu vaccines we only need to give 
a single dose and we get a fairly good response. With H5 that 
doesn't work, and one of the reasons is that for regular flu 
vaccines the immune response has been primed by multiple 
previous exposures to related viruses.
    We found that when we looked at people who had been 
vaccinated against H5 viruses back in 1998 and gave them a 
single additional dose of the H5 vaccine in 2005, they had a 
very vigorous immune response, suggesting that they had been 
primed. These sort of prime-boost strategies would be another 
way potentially to vaccinate at least selected populations who 
are at high risk of exposure prior to a pandemic.
    Now, as you have heard, one of the dreams of influenza 
researchers for many years has been development of a universal 
flu vaccine that would be able to provide protection against 
all strains of influenza, and there has been substantial 
progress in this area. At least one of these vaccines, based on 
the M2 protein, is in active clinical development.
    But all of the data that supports the use of a universal 
vaccine has really been generated in animal models of 
influenza. We do know from prospective studies in families that 
some degree of cross-protection between strains does occur, but 
we don't understand completely the immune mechanisms which are 
responsible for those cross-protective responses.
    One of the things we'd like to learn a lot more about is 
the immune response to the very first exposure to influenza in 
children and how that modifies subsequent responses when people 
are reexposed. These kinds of studies would have been very 
difficult to do many years ago, but NIH-supported advances in 
the ability to study the human immune response I think now 
create the possibility to learn much, much more about the 
immune response to flu and how to manipulate this to create a 
truly universal vaccine.
    So, in summary, I think research supported by NIH has led 
to developments that will significantly enhance our ability to 
respond to a pandemic in the short term, and much more work is 
needed for long-term approaches. I don't think there is a clear 
leader or an ultimate long-term solution at this time, although 
many promising methodologies are being developed.
    I think the most effective long-term strategy for improved 
influenza vaccination for both pandemic and seasonal flu is 
continued investment in basic research in both virology and 
immunology of influenza, with rapid translation of lead 
candidates into well designed and carefully controlled clinical 
studies.

                           PREPARED STATEMENT

    I'd like to thank the committee and sincerely let you know 
how much we in the research community appreciate the support 
that you've shown us with your continued appropriations and 
support for the struggle to battle both seasonal and potential 
pandemic influenza. Thank you.
    [The statement follows:]

               Prepared Statement of Dr. John Jay Treanor

    Chairman Harkin, ranking member Specter and other distinguished 
members of the subcommittee: Thank you for allowing me the opportunity 
to testify today. I would also like to thank you for your leadership in 
calling this hearing on this very important topic.
    I would like to begin by briefly presenting our work at the 
University of Rochester Vaccines and Treatment Evaluation Unit (VTEU) 
related to vaccines for pandemic influenza and some of the issues to 
consider in this context. The University of Rochester VTEU is one of 7 
NIH-sponsored units in the United States that perform clinically 
oriented research on novel vaccines and other control measures for 
human infectious diseases. This NIH-supported research has included 
studies of rotavirus (the most important cause of diarrhea in 
children), pertussis or whooping cough, genital herpes, human 
papillomavirus (the cause of cervical cancer), respiratory syncytial 
virus, pneumococcus, malaria, smallpox, and anthrax. In addition, the 
unit at Rochester has been intensively involved in studies of influenza 
vaccines in infants and young children, healthy and elderly adults, 
including candidate vaccines for pandemic varieties of influenza A 
virus. This research has helped guide the use of the currently 
available vaccines, and has also identified that while progress has 
been made, we have a long way to go to be fully prepared for the next 
pandemic.
    Inactivated H5 Vaccine Requires High Doses.--Two types of influenza 
vaccine have been convincingly demonstrated to actually protect humans 
against influenza: inactivated influenza vaccines, and live attenuated 
influenza vaccine. Our evaluation efforts for H5 have focused on 
inactivated vaccines made using standard technology, because such 
vaccines are effective for prevention of conventional or inter-pandemic 
influenza and are used safely and effectively each year. We have 
learned that inactivated vaccines for H5N1, while well tolerated, are 
poorly immunogenic and require high doses to elicit the types of immune 
responses likely associated with protection. The reasons for these 
relatively poor immune responses are unclear, but the results have been 
replicated over many studies. While a high dose inactivated H5 vaccine 
could be an effective tool for controlling pandemic influenza in 
selected groups, strategies using much lower doses would be required to 
provide enough vaccine for effective pandemic control in the general 
population.
    Enhancing the Response With Adjuvants.--One approach to dose-
sparing is the use of additional components, called adjuvants, which 
are designed to improve the response to a co-administered vaccine. 
Aluminum salts are commonly used adjuvants for many current vaccines, 
but our studies suggest that aluminum hydroxide is not able to 
significantly enhance the immune response to existing formulation of H5 
vaccine. Studies of aluminum with other types of inactivated H5 
vaccines are in progress. There is an urgent need to develop and 
clinically validate effective and safe adjuvants for use with pandemic 
vaccines, and a number of promising candidates have been identified. 
One candidate, the oil-in-water emulsion MF-59, has already been shown 
to significantly improve the response to an H5 vaccine as well as an 
additional strain, H9, in clinical trials conducted by NIH VTEUs, and 
other adjuvant trials are being planned.
    Revaccination and Priming Doses.--Unlike the H5 vaccine, regular 
influenza vaccines are given as a single dose each year, and elicit 
vigorous immune responses. In part, this difference is because the 
immune system has been primed to respond to regular flu vaccines by 
repeated prior exposures to related viruses. The pre-pandemic use of an 
H5 vaccine might prime the population to respond to a subsequent single 
lower dose, greatly facilitating a pandemic vaccination campaign. In a 
very small, preliminary study, we found that adults who had received an 
experimental H5 vaccine in 1998 had a much more vigorous immune 
response to a subsequent H5 vaccine in 2005 than did adults who had not 
been previously vaccinated. Similar results have been reported by 
workers in the United Kingdom, and suggest that a pre-priming strategy 
could be considered, particularly in high-risk populations. These two 
strategies, dose-sparing with adjuvants, and prime-boost strategies 
using conventional vaccines, probably represent the most promising 
short-term solutions to pandemic influenza.
    A Universal Influenza Vaccine.--Influenza viruses continually 
evolve their outer coat proteins to evade the immune system, making 
both minor and major changes that can severely limit the effectiveness 
of a vaccine made against the ``wrong'' strain. This is an issue each 
year for conventional vaccines, but is also an important consideration 
for the H5 viruses, which are in a state of rapid evolution. For many 
years, influenza researchers have dreamed of a vaccine that would not 
be affected by these changes and could provide protection against all 
strains of influenza. A handful of potential targets for such a vaccine 
have been identified in animal studies, and one of these, the M2 
protein, has reached the stage of active clinical development at 
Rochester and elsewhere. However, the degree to which these vaccines 
will provide cross-protection in humans is still unknown.
    A Better Understanding of the Human Immune Response is Needed.--
Almost all of the potential targets for a universal flu vaccine have 
been identified in studies in animal models of influenza. We know from 
observations in families many years ago that cross protection in humans 
can occur, but the immune mechanisms responsible for cross protection 
in humans have not been identified. Defining the immune responses of 
humans that could be manipulated to make an effective universal flu 
vaccine will require careful, prospective studies to examine both the B 
cell as well as the T cell components of the primary response to 
infection, and the consequences of these responses upon subsequent 
exposures to virus. The work will be expensive and tedious, but is now 
quite feasible with modern technologies of human immunology.
    Developing a more detailed understanding of cross-protective 
immunity in humans could lead to significant advances in our ability to 
control both conventional and pandemic influenza. However, these 
efforts will take time, so that development of a universal influenza 
vaccine is best seen as a more long-term (8 to 10 year) approach to 
pandemic influenza.
    Summary.--Research sponsored by NIH has led to developments that 
can significantly enhance our ability to respond to a pandemic in the 
short-term, but much more work is clearly needed. There is no clear 
leader for an ultimate long-term solution at this time, although many 
promising technologies are being developed. I believe that the most 
effective long-term strategy for improved influenza vaccination for 
both pandemic and inter-pandemic influenza will be continued investment 
in basic research in both the virology and immunology of influenza, 
with rapid translation of lead candidates into well designed and 
carefully conducted clinical studies.
    In the appendix to this testimony I have outlined some additional 
areas of active research in the development of a pandemic flu vaccine. 
Again, thank you for allowing me this opportunity to testify and thank 
you for the continued support and resources this Subcommittee allocates 
to the NIH and others to help up us prepare for the predictable annual 
severe impact of interpandemic flu, and the unpredictable, potentially 
catastrophic impact of an avian flu pandemic.

                                Appendix

    Antibody Tests for H5 Influenza are Not Robust.--A large number of 
inactivated influenza vaccines are currently in clinical trials 
throughout the world. It is important to recognize in interpreting the 
results of these trials that the assays used to assess immune responses 
work well for determining relative responses within the same study, but 
are much less well suited for comparing results between laboratories. 
This means that one must exercise caution when comparing the results of 
trials done by different groups. In addition, there is no absolute 
level of antibody that has been validated as a specific correlate of 
protection against H5 influenza in man.
    Animal Models are Not Perfect.--Several animal models can be used 
for pre-clinical evaluation of influenza vaccines, including the mouse, 
ferret, hamster, guinea pig, and monkeys. With the exception of the 
ferret, none of these animals are natural hosts of influenza, and all 
of them have significant imperfections for testing the efficacy of 
candidate influenza vaccines. Many different kinds of vaccines have 
been shown to protect mice against lethal influenza, but it is unclear 
to what extent this model is predictive of protection in humans.
    Adjuvants Hold Promise for Dose Sparing.--There are a multitude of 
promising adjuvants in active clinical development. Some adjuvants rely 
on changing the formulation to improve presentation to the immune 
system, for example mixing the antigen with an oil, formulating the 
antigen in a lipid membrane, or adding irritants to the antigen to 
recruit immune cells to the site of injection. Other adjuvants directly 
engage the toll-like receptors (TLRs), a family of receptors that 
recognize molecules typically found in pathogens and serve as an early 
warning mechanism for the immune system. For example, we have recently 
noted dramatic enhancement of the immune response to a malaria vaccine 
when the TLR-9 agonist CPG was added to the vaccine. Combinations of 
both approaches may be the most promising strategy. Recently, several 
groups have reported that systems that physically link the antigen to 
the adjuvant, rather than simply mixing them together, may be even more 
effective.
    However, none of the adjuvants tested to date has shown a dramatic 
effect on the response to conventional influenza vaccine in human 
trials. In addition, most adjuvants are associated with some increase 
in local pain on administration, which might make them less acceptable 
for routine use. Unless an adjuvanted influenza vaccine were to have a 
clear advantage over a more conventional vaccine for interpandemic 
influenza, it may be difficult to build the capacity for such a vaccine 
to use for pandemic influenza. In addition, there are no studies 
currently evaluating adjuvanted influenza vaccine in young children, 
who will be an important target group for a pandemic vaccine. Finally, 
almost all adjuvants are proprietary but would need to be shared among 
many manufacturers in order to be used effectively in a pandemic 
situation.
    Alternatives to Egg Based Production are Desirable but not 
Sufficient.--Current vaccines are manufactured in eggs, but there is a 
large-scale effort underway to move this manufacturing to a cell-
culture based system. Systems which involve either growing influenza 
viruses in cell culture or using recombinant DNA techniques to produce 
the relevant influenza virus proteins in a cell culture system are both 
in active development. While these new procedures may result in a more 
stable vaccine supply and one which could be increased more rapidly in 
response to a pandemic they do not intrinsically improve either the 
safety or the efficacy of the vaccine itself. These systems do 
represent a potential short term advantage for pandemic vaccine 
production. If in addition, these production methods resulted in 
significantly greater yields, then routine use of higher doses of 
vaccine associated with improved immune responses might be practical.
    Live Attenuated Vaccines Mimic the Response to the Pathogen.--
Fundamentally, a live attenuated vaccine consists of an influenza virus 
that has been genetically altered in such a way as to reduce or 
eliminate its ability to cause disease in the recipient. In the case of 
influenza, this has been done by reducing the replication fitness of 
the virus, and requires a careful titration to achieve a virus that 
replicates enough to generate an immune response, but not enough to 
cause symptoms. Because live vaccines amplify themselves in a 
susceptible host, they might be especially effective in response to a 
pandemic, and carefully controlled clinical trials to evaluate pandemic 
vaccines based on the licensed live attenuated influenza vaccine are 
currently underway. It is too early to tell whether these vaccines will 
generate good immune responses to the H5 viruses. Multiple other 
potential live attenuated vaccine viruses are in various stages of 
development.
    A Replicating Antigen Triggers a Different Response.--When a 
vaccine antigen is actually synthesized in the cells of the recipient, 
as would be the case upon exposure to the pathogen, the antigens are 
presented to the immune system in a fundamentally different way than an 
inactivated vaccine. In addition to using a live vaccine, this can be 
accomplished by cloning the gene for the relevant protein into another 
attenuated virus or bacteria and using that agent as a vector for 
delivery of the vaccine. Several approaches for using vectors for 
delivery of influenza antigens to the immune system have shown 
promising results in various animal models. Vectored vaccines can be 
problematic for use in a situation where vaccines must be periodically 
readministered because development of immunity to the vector can limit 
their effectiveness. Vectors which simply deliver the gene and undergo 
limited replication in the host can circumvent this problem in some 
cases. Vectored influenza vaccines are promising but have not been 
validated in studies to show that they can prevent influenza in humans.
    DNA Can Stimulate an Immune Response.--An alternative to using a 
vectored approach is the use of DNA encoding the antigen of interest. 
Because DNA is relatively easy to synthesize, these vaccines could 
theoretically be produced in large quantity and quite rapidly. DNA 
vaccines in humans have generally been more effective at generating 
cellular immune responses than at generating antibody, and this is a 
major drawback for a disease like influenza where the principal 
modality of protective immunity is felt to be antiviral antibody. 
However, recent results using powder delivery of the DNA into the skin 
has been reported to generate detectable antibody responses to 
influenza in phase I studies and additional clinical trials including 
studies of DNA vaccines for H5 influenza are underway in both the 
United States and the UK. Significantly more data will be required 
before these vaccines can be considered a mainstream approach for 
pandemic control.
    Induction of Mucosal Immunity May Provide Enhanced Protection.--
Influenzavirus replication in man is restricted to mucosal surfaces, an 
area of the body served by a specialized immune system. Approaches to 
specifically target mucosal immunity are highly effective in animal 
models, and provide good cross protection through poorly understood 
mechanisms. Live vaccines are one approach to inducing mucosal immunity 
against influenza. Other approaches which couple intranasal 
administration of protein antigens or virus-like particles with mucosal 
adjuvants are also in development, but several years away from clinical 
deployment.
    Pandemic Approaches Must Also Work for Conventional Influenza.--A 
major challenge for the sustained development of a pandemic vaccine is 
that in order for these vaccines to be produced in quantity, they 
likely must be commercially viable for seasonal use. This important 
issue must be considered for all of the experimental approaches 
currently in development for a pandemic vaccine.

    Senator Harkin. Dr. Treanor, thank you very much. Thank you 
all very much.
    I just got notice that there's going to be two rollcall 
votes starting around 11:30, so we'll try to wrap up everything 
in the next hour or so. We'll do 5-minute rounds of questions, 
then we'll come back around for the second round. I'll start my 
5 minutes right now.
    Dr. Gerberding, you've traveled a lot in Asia. You showed 
us the slides up there. I hear bits and pieces of conversation. 
People wonder, well, you know, you get a flu shot, you get a 
flu shot and that's fine, and there seems to be a lessening of 
any kind of real concern about this avian flu. Again, tell us, 
why is this avian flu different than what we know of as the 
flu? You know, people get the flu and they say, well, you get 
over it, or you get a shot. Why is this different? Is it more 
virulent? Why is that?
    Dr. Gerberding. This is a very virulent flu. When we have 
seasonal flu, the mortality rate is certainly less than 3 
percent. We're talking here about a virus that when it does 
affect people, has a mortality rate of greater than 50 percent, 
so that is in and of itself a reason for great concern.
    But, more importantly, people do not have any immunity to 
the H5 virus, so we have to assume that basically everyone in 
the world is susceptible. That means if it did evolve to be 
efficiently spread, we would all be at risk for disease and 
potential death if we had a mortality rate that was anywhere 
near what it currently is. Generally, as viruses evolve, they 
adapt to people and they become less deadly, but there's no 
guarantee that that would be the case. So it's alarming, we're 
not protected from it, and it's alarming because it is so 
deadly.
    Senator Harkin. In these areas where we've had this 
outbreak in humans, have we had any experience with using any 
antivirals afterward, and have they been successful?
    Dr. Gerberding. It's very difficult to say how well the 
families, the two families of antivirals work for H5N1 in 
people because they're not coming to treatment early enough to 
expect a benefit. Even for regular flu, you have to treat 
within the first 48 hours of feeling sick before you get any 
benefit, so these are late treatments. There's some suggestion 
that they may be helpful. There's also a suggestion that if you 
treat people, their virus can develop a resistance to the 
drugs. So we have a lot to learn about the role of antivirals 
for avian flu.
    Senator Harkin. A more general question, Dr. Gerberding, 
and that is I guess back to developing the capacity. We're 
spending money, a lot of money, on that. My concern is, what's 
going to happen if we create the capacity but there is no 
demand out there for the annual flu shot?
    Now, I hear you on the radio advising people to get their 
flu shots. I followed your advice and got my flu shot, but 
there seems to be some reticence among a lot of people in this 
country at getting their flu shots. If you're going to build 
the capacity, then you want to get people to get their annual 
flu shots, and I just wonder if you have any thoughts on that 
next step and what we can do besides your urging everyone.
    Dr. Gerberding. I think we have every year expanded the 
number of people that we know can benefit from a flu shot, so 
the number of people who need to be vaccinated based on science 
has continuously grown. In fact we have continuously increased 
the number of people that we vaccinate, but we're not anywhere 
near the number that need to be vaccinated.
    Senator Harkin. Are you experimenting with any new delivery 
type systems?
    Dr. Gerberding. We are not experimenting with new delivery 
for seasonal influenza.
    Senator Harkin. That's what I mean, just for seasonal.
    Dr. Gerberding. We have some progress underway with an NIH 
study to look at better ways of delivering H5 vaccine, but 
right now with the licensed products they're being delivered 
conventionally.
    Senator Harkin. Okay. Thank you.
    Again, Dr. Fauci, again I want to get a better 
understanding of this universal vaccine and priming. Tell me 
again what it means to be primed.
    Dr. Fauci. Sure. To be primed is when you--there are 
several ways of priming. You can be primed naturally, in the 
sense of what Dr. Gerberding mentioned. So let's say 3 years 
ago I got exposed to an H3N2 seasonal influenza, got mildly ill 
because I had some background immunity, and then this year I 
get exposed, without necessarily being vaccinated, to a related 
H3N2 seasonal influenza. I likely would do much better than 
someone who had never before been exposed to an H3 because I 
was naturally primed with a previous infection.
    When you deliberately, artificially prime somebody, it 
refers to what Dr. Treanor was mentioning, that you give a shot 
which is a first or prime shot. It sort of revs up the immune 
system so that when you get the next shot, which is the boost, 
or you get exposed and get boosted, then you already have what 
we call immunological memory to allow you to respond more 
quickly to something that you've already seen before. That's 
exactly what priming means.
    Now, with regard to the universal vaccine, this is not 
going to be an easy thing, because if just mere exposure to 
those components of the virus that don't change was going to 
protect you, then everyone who was previously exposed to 
influenzas would be protected.
    So what happens is that if you look at the virus, if you 
blow it up--and that's what I try to do with that schematic--
and you look at all the different proteins, which are the 
things that the body sees, when the body sees those proteins it 
makes a response against it, so that the next time you get 
exposed to the real virus it will rapidly respond. It relates 
to your first question about priming.
    There are components of that virus that change naturally 
from year to year. It's called drift. They change a little bit, 
not enough to make it a different virus but enough to require 
that if you want optimum protection, you're going to have to 
change your vaccine to look a lot more like the virus. Yet 
there are also components to the virus that just don't change 
from one season to another, or even from one pandemic strain to 
another, such as the NP--it doesn't mean anything to anybody 
except as a designation, nuclear protein--and M for matrix. 
They stay relatively the same.
    So you ask a logical question: Now, wait a minute. If this 
doesn't change, why don't we make that the target of our 
vaccine? That's exactly what we're doing, but the issue is that 
the way the body naturally sees it, it just doesn't make a good 
immune response against it because the way it's programmed, it 
doesn't recognize it in what we call--a big word--an 
immunogenic form, in a form that would really tell the body, 
``Hey, make a response against me.''
    So we manipulate that molecule, present it to the body, and 
say we're going to see what happens if you make a very good 
response against that antigen that doesn't change from virus to 
virus. If it does make a good response, then you have the 
possibility of protection against all the strains, hence you 
use the word ``universal'' vaccine.
    Senator Harkin. Very enlightening. Thank you very much, Dr. 
Fauci.
    Senator Specter.
    Senator Specter. Thank you, Mr. Chairman.
    I'm concerned that there is not as much public awareness or 
concern today as there was a year ago. A year ago we had John 
Barry talking about his book, ``The Great Influenza,'' and 
there were a great many articles. There was a great deal of 
publicity, and that was helpful in getting the significant 
appropriation, but now the matter has tapered off. There is not 
the public awareness. You see an occasional article, but I 
don't think the public understands how serious the potential 
for it is, and that's why this hearing is so important.
    When you take a look at the charts, and I thank you, Dr. 
Gerberding, you see the impact on humans, relatively small, in 
red, 269 cases since 2003 and 163 deaths, but the potential 
where the birds have been affected is much, much greater. So I 
think it would be useful if there was an assessment as to how 
serious is the risk.
    Now I know that that's very difficult to answer in a 
scientific way and you don't want to unduly alarm people, but 
on this state of the record I think people are now unconcerned, 
and I think that there needs to be some practical information 
put out as to what people do. Should we store water in our 
homes? Should we have staple foods? What is the extent of the 
risk if you leave your house to go to the grocery store?
    We've had advice that you ought not to go to the movies or 
you ought not to go where there are large groups of people. 
Should employers start to make plans to communicate with their 
employees at home through their Blackberrys, to try to keep the 
Senate and the House going, businesses going?
    Then there is the question as to when do we get the shot. 
You can't get the shot now because you don't know what the 
strain is, but when will we know the strain?
    Now I know I've asked a whole series of questions, but 
within 5 minutes you can't cover all the questions and get 
answers, but those are questions which I would like you four 
professionals to address. C-SPAN is a good medium. People will 
be watching this. You have to be an insomniac. They always play 
the Harkin-Specter hearings at 3 a.m.
    But let me ask you, Dr. Gerberding, and you, Dr. Fauci, 
what can be done by way of addressing the risk assessment so 
that it is both realistic and it alerts people to the danger? 
Then what can be done by way of something that is written and 
in simple form to tell people what they ought to do now, if 
anything, for prevention. When they ought to start to look for 
a vaccination, and what employers ought to do and organizations 
ought to do to try to keep functioning if it does strike? Dr. 
Gerberding, would you start, please?
    Dr. Gerberding. Thank you. Thank you because you're right, 
that having an opportunity to be on C-SPAN or to know that 
Congress is paying attention to this really helps us. People 
who fail to prepare for a flu pandemic are going to be 
tragically mistaken in retrospect. It's inevitable that we will 
have a pandemic. It may have nothing to do with H5N1 virus, and 
that----
    Senator Specter. Dr. Gerberding, let me interrupt you there 
where you say it is inevitable. That is pretty stark. That 
means it's going to happen.
    Dr. Gerberding. It will happen, I believe. I don't know 
when, and I don't know what virus will be the culprit. H5 is 
one possibility, but there are many other possibilities.
    Senator Specter. All right. When you talk about 
inevitability, that's a good warning. That's not a shot across 
the bow; that's a shot into the ship. How serious will it be? 
Will it be like 1918? What's your professional judgment on 
that?
    Dr. Gerberding. My professional judgment is that I can't 
tell you, and I don't know, and I don't think anyone does. 
We've had a 1918 pandemic. That's probably not as bad as it 
could get. But we've also had very mild pandemics. For example, 
in 1957 it was not much different than a regular seasonal flu 
year, which is bad enough. Thirty-six thousand people die every 
year from regular flu.
    Senator Specter. My red light is on and I will not go 
further. I would conclude with this comment. Don't wait for us 
to call hearings. Call us. Don't wait for us to call you. We 
will call you with some regularity, as you've seen. But if 
something comes up, we want to know about it and you should 
tell us what needs to be done, because when you talk about a 
problem of this magnitude, we can attract the attention. We can 
push the key buttons if we have the information.
    So let us know what Congress needs to do to respond, and 
you're going to have to undertake the job of quantifying, to 
the extent you can, the kinds of questions which I have asked. 
I'd like you to report back in 30 days, if you would, about 
what you can do in putting out information in a simplified form 
that can be transmitted to the public so they'll know how to 
respond.
    Dr. Gerberding. Thank you. May I just add one thing?
    Senator Specter. Sure.
    Dr. Gerberding. There is a very important web site, 
pandemicflu.gov, and on that web site you can go to the 
information that individual citizens need. What we need to be 
able to do is get that out more generally, but we're making a 
start at what you're asking for and I'll be happy to provide 
you with some of the specifics.
    Also, in a week or so we will be releasing an update on 
information that will describe better what communities need to 
do to protect their citizens at the local level if we have a 
pandemic with flu or some other virus. So there will be more 
information coming, and I'll make sure that you get it as it's 
available.
    Senator Specter. Thank you very much.
    Thank you, Mr. Chairman.
    Senator Harkin. Thanks, Senator Specter.
    Senator Reed.
    Senator Reed. Thank you very much, Mr. Chairman, and thank 
you for your excellent testimony.
    Dr. Parker and Dr. Gerberding, part of this national 
strategy involves the participation of States. Can you give us 
insight as to both their level of preparedness and the 
resources they're committing to this effort? Dr. Parker first.
    Dr. Parker. Well, first of all, it's just absolutely 
critical that individuals, localities, States, and that the 
Federal level have got huge responsibilities, and we have to be 
cognizant of the issue of complacency. We continue to take this 
threat very seriously and we're moving out aggressively on a 
number of fronts. But State preparedness is going to be 
absolutely critical to do the necessary planning and 
preparedness, and to include things like the antiviral 
procurements.
    But most importantly, one of the things that we're going to 
need to be doing is exercising, testing the plans that are 
forthcoming and have come from the States. It's one thing to 
plan, have a written document, but it's a whole other thing 
that we exercise those plans, exercise those plans within a 
regional basis, and how those State and regional bases also 
function in a broader national response plan.
    Senator Reed. I appreciate your comments. I think they're 
exactly on target. But do you have an idea at this point of the 
level of preparedness? Alternatively, do you have a plan going 
forward to do these tests and the funding to do it? Third 
point, do you see clearly, or let me ask directly, whose 
responsibility is it to generate these tests, evaluate the 
State response? Dr. Gerberding.
    Dr. Gerberding. It is CDC's responsibility to provide the 
leadership for that part of State preparedness, and certainly 
the network of public health is much broader than just CDC and 
the State and local health departments, because we've had to 
involve all of the important leaders at the community level.
    When the flu summits occurred in every State, Secretary 
Leavitt brought together with the Governor the leaders of 
businesses and universities and churches and educational 
institutions and health care organizations and public health at 
the table, to really develop the network of planning that needs 
to happen to really penetrate all the different parts of 
society that would be affected by a pandemic. The Congress has 
appropriated $350 million in one supplemental to help States 
begin that process of planning and identifying what's missing. 
What do we need? Where are the gaps in people, the plans, the 
products, and the practice?
    The next $250 million that they will be getting soon is 
specifically, primarily going to focus on practicing, and we 
have a curriculum of exercises that we will be expecting the 
States to conduct on their six key objectives, and sort of in a 
``crawl walk run,'' 18 different levels of activity that we 
will be monitoring their success in completing. We will be able 
to report to you at the end of that time, which will be many, 
many months from now, exactly who has achieved those objectives 
and who is still lagging behind. It's a process, but it is 
underway.
    Senator Reed. So in 18 months, for want of a better term, 
we can expect a report card from you on the capabilities of the 
States and localities?
    Dr. Gerberding. We hope that we will be able to provide 
more updated information than that. We're developing 
measurement tools, and we'd like to be able to have more 
regularized reporting of the status of our preparedness. But we 
are working on that now, and I'll be happy to make it available 
when we get the first draft of that.
    Senator Reed. Thank you. Just an observation, but one of 
the consistent problems at the State level, and I'll speak for 
my State, is the under funding of our public health agencies, 
not just with respect to this planning for pandemic flu but for 
a whole range of issues. They seem to be always towards the end 
of the line when there's issues of budgets at States and 
localities, and those issues obviously are with us again today.
    Dr. Gerberding. You are absolutely right. Part of the 
confusion I think people have about why aren't we more prepared 
as we should be, it's because we were in a very deep hole at 
the State and local level. People were starting from behind, 
and it's going to take a sustained investment over a long time 
to get us where we need to be in 2007.
    Senator Reed. Dr. Fauci, most commentators suggest that the 
arrival of avian flu will be inevitable, and the question is 
when. I wonder, does your research give us an idea of how much 
time we have to work through these issues?
    Dr. Fauci. I agree completely with Dr. Gerberding's 
assessment that it is really impossible to predict, Senator. 
You can't tell. We don't even know, though we have some 
suggestions of what the molecular changes that would require 
something that is now extremely inefficiently going from 
chicken to human, and even less efficiently from human to human 
in the rare so-called clusters. We have some hints at the 
molecular level about what, if mutations occur, would make it 
more or less likely, but it's such a complex process that we 
just can't give you an answer.
    We would love to say, ``Well, there's a this percent 
chance,'' but it's impossible to do that. Which is the reason 
why, Senator, I emphasized with very predetermined purpose, the 
seasonal basis and the pandemic basis, because we can't tell 
you when the pandemic will be.
    It may not even be an avian. It may be an H2N2 that people 
have already responded to, because the last time we had a 
problem with that was in 1957, so that as younger people enter 
the scene and older people die off, you may have a population 
that is naive to what is really a human variant. So when Dr. 
Gerberding and I and Dr. Treanor and Dr. Parker talked about 
pandemic, it doesn't necessarily have to be the bird flu. It's 
just something that has (a) never been seen before by the 
cohort that exists now and (b) that's quite virulent. That's 
how you get a pandemic.
    So to just reemphasize what I was saying, if we take very 
seriously seasonal flu, all the ingredients that go into that, 
you know, people getting vaccinated more, having the production 
capacity, then we don't have to start from behind, as Dr. 
Gerberding said. We have a head start on it.
    Senator Reed. Well, thank you, Dr. Fauci. Just one final. 
My time has expired. Thank you. This is a follow-on to the 
issue of the State effort, and you mentioned it, Dr. Parker, 
about the antivirals.
    Dr. Parker. Yes.
    Senator Reed. We have made provisions to subsidize the 
acquisition, to also encourage States, but it seems that the 
take-up rate is very low relative to what we need. This would 
be, I assume, one of the first lines of defense if a pandemic 
strikes before----
    Dr. Parker. Actually I'll get the specific data State-by-
State to you, but actually the information we have is that the 
take-up rate, at least the commitment to purchase, is actually 
quite high. In fact, upwards of or close to the total is 
already committed. Now, only 11 million has been purchased----
    Senator Reed. Right.
    Dr. Parker [continuing]. But there are at least commitments 
for the delta.
    Senator Reed. So we have goodwill but not product.
    Dr. Parker. That's correct. I think a lot of it, though, is 
dependent upon the availability, the right timing of the 
funding that the State will have, but at least there are 
commitments to purchase. But we'll get you a breakdown State-
by-State so you can see the latest information and the latest 
data that we have.
    Senator Reed. Thank you.
    Thank you, Mr. Chairman.
    Senator Harkin. Thank you.
    Senator Durbin.
    Senator Durbin. Thank you, Mr. Chairman.
    My question will betray my age. Last week I read a book by 
Bill Bryson about growing up in Des Moines, Iowa, in the 
1950's, and he reminded me of my youth and of our fear of polio 
and our misunderstanding about what caused it, our knowledge 
that many children my age were afflicted by it with varying 
results, some extremely serious and some not so serious.
    Then came that wondrous day when Jonas Salk, a name I had 
never heard before, became the savior for children across 
America, and Dr. Sabin as well, and we ran as quickly as we 
could to get this vaccine, knowing that we needed it, that we 
were exposed and needed that help. It may have created a 
mindset among people of my generation that you can work a 
miracle, that you can find this cure and somehow we can 
distribute it in time to save these lives. It's a very 
optimistic view of medical research. I hope it's realistic to 
some extent.
    But as I listen to Dr. Gerberding speak about the three P's 
that she mentioned, I want to focus on the third one, people, 
and I want to ask this question: Do we have the capacity, do we 
have the people to do this basic research? Are people moving 
into the fields where we need them to move into, making a life 
commitment that they may need to make for us to find these 
cures, not just for pandemic flu but for many other things? I 
hope the answer is yes. If it isn't, I'd like to know what we 
could do to change it.
    The second part of the question is, once we have found it, 
that vaccine, and I pray we will, do we have the capacity to 
distribute it in America at the level that we want to or need 
to? I think about our shortages of nurses and medical 
professionals. Last year in the State of Illinois we turned 
away 2,000 qualified applicants for nursing school, 2,000 
qualified applicants, facing an overwhelming nursing shortage 
that we know is coming, because we don't have nursing faculty. 
We haven't invested in creating the faculty at these schools 
and the clinical opportunities.
    So I want to go to the people issue and ask you, is that 
budding Jonas Salk in the wings, and many like him, many 
scientists and researchers like him? Once having found this 
vaccine, and I pray we will, do we have the capacity to 
distribute it, even in our own country, in an effective way?
    Dr. Fauci. Well, let me answer the people research 
component. There's also people health care delivery components, 
and I'll ask Dr. Gerberding to talk about the capacity of 
distribution.
    At the NIH over the years we, with regard to training 
researchers, largely through the efforts of this committee and 
other committees, we have done very well. We've had a doubling 
from 1999 to 2003. At that time there was a great deal of 
enthusiasm about getting into the field of great opportunities, 
and we see and have seen researchers, young people who are 
getting in very excited about what they are doing, and we still 
have that. So this is not a complaint at all.
    What happens, though, when you get into the vicissitudes 
that we have seen over the last couple of years, in which we 
have had flat budgets, has been a signal to the bright young 
people that maybe that's not the field necessarily that I want 
to go into. I don't think we're at a point of a crisis there in 
the sense that we've fallen back seriously, but I think we 
can't look at flat budgets when you have research which by its 
very nature creates opportunity that begets more opportunity.
    So the answer is, we have a lot of good people. I think 
we'll continue to get a lot of good people. We're doing a lot 
with the money we've gotten. But we've got to be careful that 
we don't send a signal to the bright young people about whether 
or not the opportunities are shrinking in this field.
    Dr. Gerberding. I have a somewhat less optimistic point of 
view about the work force at CDC. We are shrinking in our 
ability to be able to support our scientists. They've got 
wonderful space now, thanks to Congress, but we are not looking 
at an optimistic pipeline.
    In part, in Federal Government there is the aging of the 
work force, and more than 20 percent of CDC's work force is 
eligible for retirement, so we have a very grave concern, and 
that is echoed throughout the State and local health agencies 
that are responsible for vaccine delivery and vaccine programs. 
So we are worried about the work force, and we are worried 
about it in many lanes, including the bench but also in the 
other public health sciences that are critical.
    In terms of our ability to deliver a promising vaccine, I 
think we can handle that. We vaccinate the cohort of children 
every year who need all of their childhood vaccines, and that's 
a long list now, many appointments. So I think that we can 
build from what we know about immunizing children to develop a 
similar robust system for immunizing adults.
    It will be much easier if we only have to do it once or 
twice. If we have to do the entire adult population every year, 
we need to change the way we think about adult immunization 
programs, and we've got some work to do on that.
    Senator Durbin. If I could ask one followup question, in 
the dismal world of budgets we are facing in 2 weeks this 
continuing resolution, and some have said that if we are not 
careful, that we could end up creating some serious problems in 
the commitments that have been made for research. Do you have 
any observation of what a continuing resolution at last year's 
number would mean to this effort in terms of research for a 
pandemic flu vaccine?
    Dr. Gerberding. I would say one of the flu-specific 
concerns we have is that our resources have come as 
supplements. That's one-time funding, and so you need a 
sustained engagement in order to be able to recruit and hire 
people into permanent career development opportunities.
    So the good news is we have the supplement, and we're doing 
a lot with it and we're very excited about the progress that it 
has allowed us to accomplish, but it's that sustaining effort. 
You know, this isn't just we're preparing this year or next 
year. This is a long-term commitment for exactly the reason Dr. 
Fauci has emphasized, because with this investment we will save 
lives from seasonal flu. People don't need to die from 
influenza in the United States, but we have got to get this 
done and sustain the effort so that we can get into a polio-
like situation instead of this ongoing tragedy that we have 
every year from seasonal flu.
    Senator Durbin. Thank you.
    Dr. Fauci. Senator, you asked the question about a 
continuing resolution, what it would do to, for example, the 
granting, the fundamental basic research grants. We fund by 
peer review, and we measure what we call a success rate, namely 
what is the percentage of people who put a grant in who get 
funded.
    If we stay at a continuing--and these are just facts, 
numbers, this is not opinion--if you look at a continuing 
resolution at the current level, the success rate for our 
people who are putting in grants, new grants, young people 
getting excited, will be the lowest that I've seen it since I 
have been there. So those numbers just speak for themselves.
    Senator Durbin. Thank you.
    Thank you, Mr. Chairman.
    Senator Harkin. Let me just say to my friend from Illinois 
that last year, as a result of hearings like this and beginning 
to look at what we needed for infrastructure in this country, 
it occurred to me, and I had my staff look at the expense of 
it, what it might cost to introduce legislation, which I will 
again soon, and I invite the Senator's participation in that, 
and that is to provide a free flu shot to every American every 
year, just free. Right now they are, what, $10, $15, $18, 
something like that, and most people go to a doctor's office or 
someplace like that.
    But by providing a free flu shot for seasonal flu you 
accomplish a number of things. Aside from the 36,000 deaths 
every year, you'll cut down on a lot of lost work days that you 
won't have anymore, plus you build up the infrastructure. The 
idea was to find outlets where people could get free flu shots: 
Wal-Mart, grocery stores, churches, after church on Sunday 
here, that type of thing, to set up. That way you train people. 
You train a whole cadre of people in this country that know how 
to give a shot, and you have a structure set up, an 
infrastructure set up, so that if or when this pandemic hits, 
then you've got a system set up to distribute it and get people 
vaccinated in a hurry.
    I forget the cost of it. I think it was, if I remember 
right, it was less than $1 billion a year. But when you 
factored in what you would save in terms of work days, 
unnecessary deaths, that kind of cost, it really dwindles into 
a very small amount of money. So I'm going to ask the panel a 
question, but to my way of thinking that was one way that we 
could start to move in that direction.
    I don't know if you have any comments on that at all, any 
of the panel members, but the idea of giving a free flu shot to 
everybody in America, we have discussed this before. I don't 
know if you have any thoughts or anything beyond what I just 
said about it. If not, I'll move on.
    Dr. Parker. Before you move on, I really would like to 
emphasize the personnel and the expertise issue that you 
brought up just before. That is absolutely critical, and time 
and time again, having personnel and the scientific expertise, 
not only at the NIH and at the CDC but also I need to speak up 
for my colleagues at the FDA, to have the folks at the FDA that 
have the regulatory, the manufacturing experience. We need the 
scientific expertise in academia. We need the multidisciplinary 
expertise.
    We have a strong bench right now. It is absolutely 
phenomenal working with all the scientists at the NIH and the 
CDC and academia and FDA. But I'm not sure we have a deep 
bench. I'm very concerned about that.
    Senator Harkin. I think, if I remember, on the polio shots, 
I think they were free. I think when kids got polio shots, I 
remember when we got our shot, I don't think we were charged 
for those. I don't know. I'm going to find out about that.
    Dr. Gerberding. They were free. I remember standing in line 
and getting it.
    Senator Harkin. They were free. There you go. They were 
free.
    Yes, Dr. Treanor.
    Dr. Treanor. I would just point out that the free flu shot 
idea, which I think is a really good one, would also provide a 
platform that could greatly facilitate the delivery of other 
important vaccines, and that would be a real advantage.
    Senator Harkin. Not just flu, it could be other things, 
too. You would start building up the system. Smallpox, yes, 
other things like that. Thanks very much, sir.
    Well, I wanted to ask a question before we leave, a couple 
or three. I understand there are some trials on universal 
vaccines going on in Europe right now.
    Dr. Fauci. Yes.
    Senator Harkin. What do we know about that?
    Dr. Fauci. Well, they have started. Again, they are 
inducing an immune response. They appear to be safe. We can't 
say. They are too early, Senator. I mean, we always get that 
question. When a trial starts, they want to know how they're 
going. The trials are going well.
    The question is, we don't have the answers yet as to 
whether or not it's going to be effective. We have animal 
studies that have looked really good, where you use the 
principle, the concept of for example an M protein in an 
animal, and you challenge the animal and you get good 
protection. But you've always got to be careful when you try 
and directly extrapolate, for example, a mouse study to a 
human. But thus far everything we've seen looks like it's on 
track.
    Senator Harkin. All this talk about a pandemic, can you 
give us some idea, how soon will it happen? I mean, if it 
happens, what kind of warning will we have? How rapidly will it 
spread? How much time will we have? Is this something that is 
going to flow through the populace in a matter of days, weeks, 
months? What's your best analysis of that? What kind of warning 
would we have? How much time would we have?
    Dr. Gerberding. It depends. The short answer is, we don't 
know, and the things that are most likely to influence that are 
where does it emerge. If it emerges in Atlanta, we'll probably 
know it fairly soon, but if it emerges in one of those 
countries that we haven't been able to support or invest or 
engage, then we're in trouble.
    It may emerge slowly. It may gradually move from being in 
one species, chickens or pigs, for example, and then evolve 
gradually to adapt to humans, and we'll have time to recognize 
it and try to quench it before it goes too far. Or it may 
happen like SARS, where literally overnight that virus moved 
from a hotel in Hong Kong to the rest of the globe. We don't 
know, and we have to be prepared for the worst.
    Senator Harkin. But you were very successful on the SARS. 
You were very successful in containing that.
    Dr. Gerberding. In retrospect, we were I believe partially 
successful and partially fortunate. But we had a virus in that 
case that actually wasn't very transmissible unless you were 
very ill, and flu is not like that. Flu is sometimes 
transmissible before you even know you have it.
    Senator Harkin. Right.
    Dr. Gerberding. So it's a much different risk, and we think 
a much higher risk.
    Senator Harkin. Because the scenarios I've read about, 
heard about but mostly read about, is that a traveler goes to 
one of these countries, you pick up this flu strain. You get on 
a plane. You're in a closed environment. You don't know you 
have it. It gets circulated in the airplane. Others may pick it 
up. You come back to the States. You go to your community, and 
bit by bit all of a sudden it just starts to spread almost in a 
geometric fashion.
    Dr. Gerberding. There are several things that we're doing 
to rehearse for that situation. One of them, thanks to our 
appropriation, we have been able to now have 20 quarantine 
stations at major airports around the country that would be 
dealing with those planes full of passengers but also a number 
of other activities to try to protect our country from 
introduction.
    But also we are working on the ability to rapidly diagnose 
a new strain, not in a laboratory but at the bedside or 
wherever the first point of contact with an individual who is 
suspicious for illness, so that we can speed up our recognition 
and then the quarantine that would be necessary to isolate that 
person and protect others. So there are a lot of scenarios like 
the one you've described.
    I think it's fair to point out, however, that many people 
believe the 1918 pandemic started in the United States, so it's 
not just about something over there. We're all in this global 
network together, and it could happen anywhere.
    Senator Harkin. Dr. Fauci.
    Dr. Fauci. Just to amplify very briefly on everything that 
Dr. Gerberding said, ditto to everything she said, but we get 
uncomfortable when we get asked questions by people like you 
who we know, we've been dealing with so long. ``Why don't you 
have a precise answer for us?'' is what you're probably saying 
to yourself.
    Senator Harkin. I'm only asking you the questions my 
constituents ask me.
    Dr. Fauci. We appreciate that, but the issue, in addition 
to everything that Dr. Gerberding said, is that there are many 
variables to this. You're asking a precise question, and in 
order to give an answer you have to put all the variables in. 
I'll give you two of those variables.
    One, that Dr. Gerberding alluded to, we're talking about, 
let's take H5N1, and it may not even be H5N1, is that the 
evolution to go efficiently from human-to-human as efficiently 
as the seasonal flu goes is a big, big spectrum. It could start 
to go human-to-human but very, very inefficiently. That will 
have enormous impact on how long it takes to develop the 
efficiency, if it ever does. So it can go from extremely 
inefficient to very, very efficient but there's a wide 
spectrum. That completely impacts all of the questions you ask 
about speed.
    The other question that is very closely related to that is, 
how devastating would it be? You have again, within what we 
already know about pandemics, a big spectrum. You have the 1918 
pandemic with more than 50 million people killed, and then you 
get 1968 which, although it's officially categorized as a 
pandemic, was not historically significantly different than 
what you actually see with a seasonal pandemic.
    So you have these crossover, confounding variables which 
make it very, very difficult to give a precise answer to the 
question. We don't want to give a precise answer if we don't 
have the science to back it, because it will come back to bite 
us and it will come back to bite you.
    Dr. Gerberding. It's like preparing for a hurricane. You 
know they will occur but you just can't say when, where, how 
bad, or who will be affected.
    Senator Harkin. Fair enough, but you do know that 
hurricanes hit the coast. They don't hit Iowa.
    Dr. Gerberding. Yet.
    Senator Harkin. You know basically where they're going to 
hit, so you can kind of plan for that. You know how buildings, 
we know from history building codes and how you build and how 
you plan for things like that. So there are a lot of things we 
can do to mitigate the damage done by hurricanes.
    Well, we've got a lot of historical analysis here on 
medicine and pandemics. We've had them before. We know 
basically how they spread, the mechanisms thereof.
    Now, I understand that you can have one hurricane hit 
that's 70 miles an hour wind, and then you can have another one 
that's 150 mile an hour wind, so you can't plan for everything. 
But there are certain basics that you can do, and that is to 
set up an infrastructure so that you can take care of the mild 
to the strong. You can do research and find out what are the 
best buildings that you can build and how you build them 
safely. In this case it's the vaccines and the adjuvants and 
the antivirals that we have.
    Dr. Fauci. That's what we're doing, right.
    Senator Harkin. I don't mean to take this analogy beyond 
any reasonable comparisons, but it would seem to me that--I 
know you can't say precisely, but within that broad spectrum, 
what can we do to make sure that we respond to the needs of our 
society, to prepare for it?
    Now, the reason I asked about the time frame has to do with 
vaccines. I am told that from the outbreak of a pandemic or 
something like this, it might take 4 months, 6 months to 
develop the vaccine once you isolate the virus, develop the 
vaccine.
    Well, again, we're putting money into these building 
blocks, into research on vaccines. Egg-based, we know that. 
That seems to be a well understood science. Then there's cell-
based, which is maybe not quite so well understood. I don't 
know. You can correct me on that. But we have put money into 
cell-based, which they tell me would be a shorted period of 
time than egg-based production.
    Then I have people come to my office last year telling me 
about RNA vaccine, and then there's something called a 
synthetic vaccine. They're all telling me the time gets shorter 
and shorter and shorter to be able to isolate the virus and 
develop that kind of vaccine.
    Well, I mean, this all gets rather confusing after a while. 
So from our standpoint, from a public policy standpoint, what 
should we be doing in terms of developing or helping you all 
develop these other systems? Is an RNA-based system the way we 
ought to go because it would be so rapid? Will it have more 
applicability to various strains that may come up, rather than 
an egg-based? So that's why I ask you, how much time do we 
have?
    Dr. Fauci. Well, your question is a great question, and I 
can tell you very briefly that what you're talking about was 
the second bullet on one of my slides, with the development now 
of alternative platforms, we call them, or alternative vaccine 
candidate types, a DNA vaccine, a vector vaccine, all of those. 
Number two, develop novel vaccine approaches.
    So we're doing that now. I can't answer your question of 
when we're going to get a pandemic, but I can answer number 
two. I can tell you that no matter what happens, we are going 
to assume--and that I think answers the question that was 
implied in your statement--we are assuming that the worst is 
going to happen. Not only that, we're assuming that the science 
and the public health preparedness--now, if you do that in a 
vacuum, Senator, and it doesn't happen, you are very, very open 
to the justifiable criticism that it was a scare tactic and 
what you did is, you got everybody exercised about it and 
nothing happened.
    That's the reason why we're all linking it to seasonal 
influenza, because a DNA vaccine, a vector vaccine, a vaccine 
that is grown in cells, a vaccine that you could turn over in 2 
months instead of 6 months, all of that is going to help the 
seasonal flu. Developing the capacity to be able to make 
hundreds of millions of doses as opposed to trying to squeeze 
it out, as we've had to do for the past few years, will happen 
if we're treating seasonal influenza in a way in which we're 
getting as many people who should be vaccinated, vaccinated.
    The CDC, and Julie can speak to that much better than I, 
have been going in that direction for the past several years. 
So even though we can't give you an answer precisely when, we 
are acting like we're going there by what we're doing from a 
research and a preparatory standpoint. Julie?
    Dr. Gerberding. I think one thing to remember is that our 
science is better now. We do have much better global detection 
capability than we even had a decade ago. So if something 
emerges, our ability to know it sooner is certainly a major 
step forward to us, and it allows us to have a more rapid time 
frame between the virus appears and we have the vaccine.
    But it's not short enough to save all of the lives that we 
will be accountable for, and that's why all the other building 
blocks, just like--again, not to dwell on the hurricane 
analogy, but we're doing all of those things. We're doing 
things that would harden communities. We've got to do more to 
build the capacity to take care of sick people. We need more 
studies of how to use antivirals. We need more antivirals.
    We need a whole lot of things that are the building blocks 
of preparedness. Even though we can't say exactly when we would 
need to use them, we believe we will be using them, and these 
investments that we're making now are a big part of that but 
we've got a long way to go. I think we're kind of giving a 
mixed message here because that's the situation we're in. We've 
made a lot of progress but we all are sobered by the 
unpredictability of the problem and the number of steps that we 
have to go before we've really got the job done that we feel 
would be the optimal preparedness.
    Senator Harkin. I guess what we need to do here on this 
committee is to, again with the help of our staff and 
contacting your staff, you know, we've put all this money into 
it, how much was it, now? $6.1 billion, but some of that was 
for State and local preparedness, about $600 million, so we're 
$5.6 billion. So that's somewhat less than the $7.1 billion 
that we initially requested.
    I think what we need to get a better handle on is. We 
started all this stuff last year, developing more vaccine 
supply, to do more research I guess into adjuvants. I guess we 
need to know where are we on that road, and do we need to do 
anything more this year to enhance that, or are we okay where 
we are, or have we been lulled a little bit?
    I think that's where we started this whole hearing off. 
We've been sort of lulled into a sense of complacency. Is what 
we did last year fine, we don't have to worry about anything, 
or is there something else happening that we need to pay 
attention to again this year in our next budget cycle? That's 
really what we're groping for here. That's what we're trying to 
find out. Or are we just fine and we can coast for a couple of 
years?
    Dr. Fauci. I don't think we could ever say fine. Whenever 
you're dealing with a threat to the public health and you're 
dealing with trying to push research, push public health, push 
infrastructure maximally, we never accept that we're fine. We 
could always do better and we could always do more.
    But the feeling of complacency is not what's going on in 
the preparedness. For example, the last thing you just 
mentioned, the Secretary just signed contracts to $132.5 
million, just a little while ago, a few days ago, on the 
adjuvant dose-sparing technologies for three separate 
companies, one of which has a novel way of using a patch 
component to make an adjuvant essentially be easily 
administered.
    So these things are going on. You may not be hearing about 
it. The things that we spoke about at the hearing last year, 
and we said this is about to happen, they're happening now. The 
clinical trials that I promised you would go on, Dr. Treanor 
and his colleagues are already implementing many of them, so 
things are happening. Can we do better? Can we do more? Can we 
use more resources? Of course.
    Dr. Parker. I think it's really a multipronged approach 
here. That is, we have to go with the technology that's 
available today. We have harnessed actually a lot of the 
information that has already been invested in, say for the 
cell-based approach, and we're continuing the basic discovery 
so we can get to reliable, scalable, rapid vaccine candidates 
and platforms that we need.
    So the infrastructure and the investments we're making 
today are also looking with an eye to what's going to be coming 
out of the research base, and we're not, as Dr. Fauci said, we 
don't suffer the complacency internally. We will work with you 
to see how we can better do that communication on the risk 
assessment.
    But I would also like to perhaps invite--sometime perhaps 
our collective staffs can come over and give you a little bit 
more detail on that multipronged approach, when we have more 
time to go into more depth, and I'd be glad to do that.
    Senator Harkin. We'll follow up with you on that.
    Okay, from the broad, we started with the narrow on bird 
flu, broad, and now let's come back to the narrow on the bird 
flu itself. That's what gained a lot of attention last year, 
and still does periodically, not as much. But as you point out, 
Dr. Gerberding, over 50 percent of the people who get it die.
    My question on bird flu has to do with this. Is it, is the 
mortality rate the same among all age groups? Is it older 
people get it? Is it younger people? What kind of data? We've 
had, what, 3 or 4 years now of looking at this and examining 
the people who got it and have died. What do we know about it? 
I forget the word, but what do we know about how that operates 
among various age groups?
    Dr. Gerberding. The major determinant of who is getting it 
probably has to do with who has contact with birds in the 
family environment.
    Senator Harkin. There's no difference on age? If young 
people have contact, they----
    Dr. Gerberding. Exactly, so young children and young adults 
are probably disproportionately affected because they're the 
most likely to be either playing with chickens or handling 
chickens that are being tended by family members. There does 
not seem to be much difference in mortality once you get it. It 
is so fatal that, you know, whether you're a young, healthy 
child or not, you still have a greater than 50 percent chance 
of dying.
    Senator Harkin. Now last year Senator Stevens, I know, was 
talking about this, about the Alaskan flyway. We saw data where 
this was spreading up into Japan, Siberia, up that way, and he 
thought, well, the birds will be flying across there and 
bringing it down in the United States. Is our surveillance very 
good? I mean, nothing has come. We've not picked up one yet in 
the United States. Is our surveillance good enough to pick up 
something right away?
    Dr. Gerberding. We've made amazing progress in the United 
States. The Geological Survey and the USDA scientists have 
created a sentinel system where they're screening wild birds 
and also any domestic bird in a commercial flock who dies. 
There's a complicated surveillance system already in place for 
them. They are including, obviously, H5 screening in that 
assay.
    I don't think any of us would say that a bird is not going 
to sneak through the cracks and get into the United States. 
That would be naive, given the tremendous movement of migratory 
birds. But it's also important to remember that birds move 
other than by flying. Sometimes they are traded as live 
animals, and we have restrictions on that in the United States 
but not all countries do. Sometimes birds are smuggled, and 
they can be smuggled for a variety of reasons, but some of the 
species of birds that are popular smuggling targets can harbor 
H5 viruses.
    So we've got to be concerned with the movement that people 
induce, and of course the worst case is that someone could do 
something like this intentionally, and that is also one of the 
things that we have to always keep in mind. So while we've got 
one system that has drastically improved in the last year, and 
we are certainly working aggressively at the borders for any 
importation, there are numerous ways of spreading and we have 
to be alert to all of them.
    Senator Harkin. Wasn't the 1918 virus, didn't they finally 
figure out, wasn't that also a bird virus?
    Dr. Gerberding. We have worked with our collaborators in 
the Department of Defense to characterize the 1918 virus, and 
it has the signatures that strongly indicate it was an avian 
origin. Where it merged from birds to humans, we don't know, 
and there is more work going on with more constructs of that 
virus that might give us additional clues.
    The last two pandemics were not avian viruses. They were 
caused by a reassorted virus, where a seasonal flu virus mixed, 
probably in a pig, with another flu virus and genes were 
exchanged, and that's where the H2 and the H3 emerged. So it 
can occur either by evolution from bird viruses or by mixing up 
human genes, and again we can't say which is the most likely.
    In an area of the world like Asia, where there is an 
intense mixture of pigs, poultry, and people--I guess I'm 
saying a lot of P's today--but poultry and people, you just 
have an incubator where the mixing and matching of these flu 
virus genes is at its best, and so there are certainly areas of 
the world where are differentially investing our resources for 
surveillance because we believe that would make sense. It's 
like putting your hurricane preparedness along the coast. There 
are areas where just biologically this could be more likely, 
and we want to make sure we have the strongest systems for 
detection and response in those areas.
    Senator Harkin. Before I close up, Dr. Treanor, do you have 
anything you want to add to enlighten us in our search for what 
we should be doing this year and what we need to be focusing 
on?
    Dr. Treanor. Everything has really already been covered. I 
will point out that it is critical to maintain, I think, the 
very excellent portfolio that Dr. Fauci has mentioned of 
investigator-initiated research through traditional granting 
mechanisms, to maintain that fundamental base of basic science 
that supports all of these activities, and I think that's 
important not to forget about as these funding decisions are 
made.
    Senator Harkin. Anything else, before we move on?
    Well, I guess I would just maybe try to sum it up by saying 
that the threat that made the headlines here within the last 
couple of years and got everyone alarmed, and now has subsided, 
the threat is still as real if not more real than it was then; 
that in the last year we have made some progress. We have begun 
funding the development of vaccines, and we're doing more 
research into the other methodologies of developing those 
vaccines.
    We are beginning to stockpile antivirals. Well, now, maybe 
I should have talked about that. Our goal was--what was it? 
Twenty-five percent. We had a goal of 25 percent, a stockpile 
of antivirals that would reach 25 percent of our population. I 
don't know where we are right now. Where are we on that?
    Dr. Parker. We're right on target. We're right on target 
with our plan, with the funding available, where we're at right 
now, and I've got the numbers in my testimony. But we're on 
target with the plan, and a lot of this is going to come to 
completion by fiscal year 2008.
    You know, another thing that is I think an important part 
to comment on, too, with the antivirals, some of the programs 
particularly with antivirals also stimulate the industry to 
move in a positive direction as well. The programs were 
successful in that regard in establishing a capability, an 
increased capacity to manufacture antivirals, so that has been 
I think a very positive, another positive aspect of these 
programs.
    Senator Harkin. So we're on target on the stockpile?
    Dr. Parker. As far as the planned, our plan to purchase, to 
date.
    Senator Harkin. Well, maybe we need to, again, take another 
look at that and see if that should be ramped up or what. I 
don't know. We'll have to take a look at that this year.
    Also I think it seems to me the one place where we are 
falling down or inadequate is in developing systems to get 
vaccinations out to people in a short amount of time and having 
the State, local governmental agencies, public health agencies, 
but also other entities structured in a way that we could 
respond to this.
    I mean, we can have all the antivirals we want. We can get 
great vaccinations ready, and the pandemic hits, and all of a 
sudden, who is out there to administer it? What's your 
structure? How do you deliver it? How do you inform people?
    It seems to me that's the one place, at least from my 
limited knowledge, where we're kind of falling down on this. It 
seems the research is moving ahead fine, the CDC is doing its 
job, our researchers. The drug companies are developing these, 
they're looking at them, but we're not developing that 
infrastructure.
    Dr. Gerberding. I agree with you, and I want to emphasize 
that one of the requirements for the States' money is to 
exercise a plan, and this year they were expected to exercise 
their vaccine delivery capability using seasonal flu vaccine. 
So we're practicing at the State and local level.
    In Iowa, 100 percent of the health districts in the State, 
the county health departments in the State, have plans. But now 
coming up we'll be asking for more formalized exercises to 
understand where the gaps really are, and if we believe there's 
a systems problem here, what is it and what else is necessary 
to fix it? So I think after these exercises develop, we could 
give you more information about what gaps appear to be present 
and what we think needs to be done to close them.
    Senator Harkin. That's encouraging. That's going on right 
now?
    Dr. Gerberding. Yes, it is.
    Senator Harkin. Nationwide, or just sort of----
    Dr. Gerberding. In every State, in 62 jurisdictions, the 
States, the territories, and in four cities in America that we 
fund.
    Senator Harkin. So you'll have some data on that, what, by 
this summer or something like that?
    Dr. Gerberding. Yes, we will.
    Senator Harkin. Well, that would be okay. That would be 
okay. We won't be done with our budget and our appropriations 
by then, will we? That would be very helpful, because I just 
sense that we've really got to focus more in that area.

                         CONCLUSION OF HEARING

    Well, if there's nothing else, I want to thank you all for 
not only being here this morning, but each one of you, thank 
you for your leadership in this area and so many other areas of 
biomedical research and surveillance and public health. Thank 
you all very much.
    [Whereupon, at 11:30 a.m., Wednesday, January 24, the 
hearing was concluded, and the subcommittee was recessed, to 
reconvene subject to the call of the Chair.]

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