[Senate Hearing 117-555]
[From the U.S. Government Publishing Office]


                                                        S. Hrg. 117-555

                 REVISITING GAIN OF FUNCTION RESEARCH:
                  WHAT THE PANDEMIC TAUGHT US AND WHERE 
                         DO WE GO FROM HERE

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

                                HEARING

                               BEFORE THE

                            SUBCOMMITTEE ON
                EMERGING THREATS AND SPENDING OVERSIGHT

                                 OF THE
                                 
                              COMMITTEE ON
               HOMELAND SECURITY AND GOVERNMENTAL AFFAIRS
                          UNITED STATES SENATE

                    ONE HUNDRED SEVENTEENTH CONGRESS


                             SECOND SESSION

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                             AUGUST 3, 2022

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          Available via the World Wide Web: http://govinfo.gov

                       Printed for the use of the
        Committee on Homeland Security and Governmental Affairs
        
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                               __________

                                
                    U.S. GOVERNMENT PUBLISHING OFFICE                    
48-703                        WASHINGTON : 2023                    
          
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        COMMITTEE ON HOMELAND SECURITY AND GOVERNMENTAL AFFAIRS

                   GARY C. PETERS, Michigan, Chairman
THOMAS R. CARPER, Delaware           ROB PORTMAN, Ohio
MAGGIE HASSAN, New Hampshire         RON JOHNSON, Wisconsin
KYRSTEN SINEMA, Arizona              RAND PAUL, Kentucky
JACKY ROSEN, Nevada                  JAMES LANKFORD, Oklahoma
ALEX PADILLA, California             MITT ROMNEY, Utah
JON OSSOFF, Georgia                  RICK SCOTT, Florida
                                     JOSH HAWLEY, Missouri

                   David M. Weinberg, Staff Director
                    Zachary I. Schram, Chief Counsel
                Pamela Thiessen, Minority Staff Director
    Andrew Dockham, Minority Chief Counsel and Deputy Staff Director
                     Laura W. Kilbride, Chief Clerk
                     Thomas J. Spino, Hearing Clerk


        SUBCOMMITTEE ON EMERGING THREATS AND SPENDING OVERSIGHT

                 MAGGIE HASSAN, New Hampshire, Chairman
KYRSTEN SINEMA, Arizona              RAND PAUL, Kentucky
JACKY ROSEN, Nevada                  MITT ROMNEY, Utah
JON OSSOFF, Georgia                  RICK SCOTT, Florida
                                     JOSH HAWLEY, Missouri

                     Jason Yanussi, Staff Director
                  Peter Su, Professional Staff Member
                  Adam Salmon, Minority Staff Director
                      Kate Kielceski, Chief Clerk
                            
                            C O N T E N T S

                                 ------                                
Opening statements:
                                                                   Page
    Senator Paul.................................................     1
    Senator Scott................................................    11
    Senator Johnson..............................................    14
    Senator Marshall.............................................    16
    Senator Hawley...............................................    19
Prepared statements:
    Senator Paul.................................................    35
    Senator Peters...............................................    37

                               WITNESSES
                       Wednesday, August 3, 2022

Richard H. Ebright, Ph.D., Laboratory Director, Waksman Institute 
  of Microbiology, Rutgers University............................     3
Steven Quay, MD, Ph.D., Chief Executive Officer, Atossa 
  Therapeutics, Inc..............................................     6
Kevin M. Esvelt, Ph.D., Assistant Professor of Media Arts and 
  Sciences, MIT Media Lab........................................     9

                     Alphabetical List of Witnesses

Ebright, Richard H., Ph.D.:
    Testimony....................................................     3
    Prepared statement...........................................    38
Esvelkt, Kevin M., Ph.D.:
    Testimony....................................................     9
    Prepared statement...........................................    73
Quay, Steven, MD, Ph.D.:
    Testimony....................................................     6
    Prepared statement...........................................    66

                                APPENDIX

Senator Peters documents submitted for the Record................    92
Senator Marshall documents submitted for the Record..............  1443

 
 REVISITING GAIN OF FUNCTION RESEARCH: WHAT THE PANDEMIC TAUGHT US AND
                        WHERE DO WE GO FROM HERE

                              ----------                              


                       WEDNESDAY, AUGUST 3, 2022

                                     U.S. Senate,  
                       Subcommittee on Emerging Threats and
                                        Spending Oversight,
                    of the Committee on Homeland Security  
                                  and Governmental Affairs,
                                                    Washington, DC.
                                                    
    The Subcommittee met, pursuant to notice, at 2:30 p.m., via 
Webex and in room 342, Dirksen Senate Office Building, Hon. 
Rand Paul, presiding.
    Present: Senators Ossoff, Paul, Scott, Hawley, and Johnson.
    Also present: Senator Marshall.

              OPENING STATEMENT OF SENATOR PAUL\1\

    Senator Paul. I call this meeting of the Senate Homeland 
Security and Governmental Affairs Subcommittee on Emerging 
Threats and Spending Oversight (ETSO) to order. I want to thank 
Senator Hassan for allowing this hearing to occur.
    Welcome to each of our panelists. Thank you for joining us.
---------------------------------------------------------------------------
    \1\ The prepared statement of Senator Paul appears in the Appendix 
on page 35.
---------------------------------------------------------------------------
    The purpose of this hearing by the Subcommittee on Emerging 
Threats and Spending Oversight is to discuss, as our name 
implies, the emerging threat posed by gain-of-function 
research. We will hear from a panel of three witnesses, all of 
whom are extraordinarily accomplished experts in the scientific 
community. We are grateful for their work and we are grateful 
to each of you for taking the time to appear with us this 
afternoon.
    Gain-of-function (GOF) research is a controversial 
scientific research method involving the manipulation of 
pathogens to give them a new aspect or ability, such as making 
viruses more transmissible or dangerous to humans. Despite all 
we have learned about the potential risks of this particular 
method of research, this is the first congressional hearing on 
this subject since the pandemic began.
    Today we will discuss what gain-of-function research 
entails, how gain-of-function research is defined, and whether 
the definition of gain-of-function research is applied 
consistently by the Department of Health and Human Services 
(HHS) Potential Pandemic Pathogens (P3CO) Review Committee. 
This is a committee that was set up to study potential pandemic 
pathogens.
    We will discuss the responsibility for how we determine the 
risks and benefits. We will also discuss how this committee 
operates, how this committee approves or denies projects from 
receiving Federal funding based on whether the pathogen is 
considered to be a credible source of potential future human 
pandemic, and if the potential risks, as compared to the 
potential benefits to society, are justified. In other words, a 
project is not gain-of-function if the review committee is 
unsure if a recombinant virus will create a future pandemic.
    There is a question of whether or not there is a reasonable 
expectation that it might be or whether or not it has been in 
the past, or what viruses should be and should not be 
experimented upon. This broad criterion gives one sole 
committee, which is comprised of an unknown group of 
bureaucrats--I believe the names are not released of who is on 
the committee so there is not necessarily any oversight of the 
oversight--the power to spend millions of taxpayer dollars on a 
single, preemptive guess, with potentially devastating 
consequences.
    Today we will also consider whether gain-of-function 
research was performed at the Wuhan Institute of Virology 
(WIV). First, no one, not myself or anyone I am aware of, 
argues that a recombinant super-virus that has been published 
in scientific journals is Coronavirus Disease 2019 (COVID-19) 
or a close relative. If--and I underline ``if''--COVID-19 
leaked from the Wuhan lab, it would be a laboratory-created 
virus that the Wuhan scientists have not yet, and are unlikely 
ever to reveal.
    I maintain that the techniques that the National Institutes 
of Health (NIH) funded in Wuhan to create enhanced pathogens 
may have or could have been used to create COVID-19. The 
American people deserve to know how this pandemic started and 
to know if the NIH funded research that may have caused this 
pandemic.
    Gain-of-function research has the potential to unleash a 
global pandemic that threatens the lives of millions. Yet this 
is the first time the issue has been discussed in a 
congressional committee.
    I am sure each Member of this Committee, as well as the 
full Senate, can agree that we need stronger government 
oversight of how our tax dollars are being used to finance 
experimenting with possibly fatal diseases.
    Again, I thank each of our distinguished witnesses for 
being here today and I thank Chair Hassan for working with me 
to convene this meeting.
    Before we begin I would like to note that I have invited 
Senators who are not on the Subcommittee to also attend today. 
Therefore, I ask unanimous consent (UC) to allow Senator 
Marshall and Senator Johnson to fully participate in the 
hearing, provided that any Members of the Subcommittee be given 
deference in the order of recognition. Without objection.
    Next I would like to remind witnesses that any written 
testimony they have, anything that they have submitted, will be 
included in the record, and to please keep your opening remarks 
to around 7 minutes.
    With that I am going to introduce the witnesses, and we 
will hear their remarks after the introduction, which is 
slightly different than we do sometimes, and then I will 
introduce the next witnesses.
    The first witness will be with via WebEx. It is Dr. Richard 
Ebright. Dr. Richard Ebright is the Board of Governors 
Professor of Chemistry and Chemical Biology and the Director of 
the Waksman Institute of Microbiology at Rutgers University. 
Dr. Ebright completed his undergraduate degree from Harvard 
University in biology, where he earned summa cum laude honors. 
He later received a PhD in microbiology and molecular genetics, 
also from Harvard.
    Dr. Ebright's research has led to over 175 publications as 
well as over 40 issued and pending patents. He has received 
numerous awards for research and is currently a member of the 
American Academy of Arts and Sciences as well as the 
Institutional Biosafety Committee at Rutgers University. He is 
a Fellow of the Infectious Disease Society of America, the 
American Academy of Microbiology, American Association for 
Advancement of Science. He was the editor of Molecular Biology 
for 16 years.
    Dr. Ebright currently serves as the project leader of three 
current NIH research grants, has provided testimony to the 
House Committee on Energy and Commerce on the 2014 anthrax 
incident, and was a founding member of the Cambridge Working 
Group, whose cautionary statement on gain-of-function research 
involving potential pandemic pathogens remains as relevant as 
the day it was released in July 2014.
    Dr. Ebright.

TESTIMONY OF RICHARD H. EBRIGHT, PH.D.,\1\ LABORATORY DIRECTOR, 
     WAKSMAN INSTITUTE OF MICROBIOLOGY, RUTGERS UNIVERSITY

    Mr. Ebright. Thank you. Chair Hassan and Members of the 
Committee, thank you for inviting me to discuss gain-of-
function research and its oversight. I am Board of Governors 
Professor of Chemistry and Chemical Biology at Rutgers, the 
State University of New Jersey, and Laboratory Director at the 
Waksman Institute of Microbiology. In my oral statement I will 
discuss the definition of gain-of-function research of concern, 
risks and benefits of the research, U.S. oversight of the 
research, and steps to strengthen U.S. oversight of the 
research.
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    \1\ The prepared statement of Dr. Ebright appears in the Appendix 
on page 38.
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    What is gain-of-function research of concern? Gain-of-
function research of concern is defined as research activities 
reasonably anticipated to increase a potential pandemic 
pathogen's transmissibility, pathogenicity, ability to overcome 
immune response, or ability to overcome a vaccine or drug.
    Gain-of-function research of concern involves the creation 
of new health threats, health threats that did not exist 
previously and that might not come to exist by natural means 
for tens, hundreds, or thousands of years.
    Gain-of-function research of concern is a small part of 
biomedical research. It constitutes less than one-tenth of 1 
percent of biomedical research and less than 1 percent of 
virology. However, because gain-of-function research of concern 
can cause pandemics, this small part is highly consequential 
and requires effective oversight.
    What are the risks? Gain-of-function research of concern 
poses high, potentially existential, risks. Gain-of-function 
research of concern poses material risks by creating new 
potential pandemic pathogens. If a resulting new potential 
pandemic pathogen is released into humans, either by accident 
or deliberately, this can cause a pandemic.
    Gain-of-function research of concern also poses information 
risks, by providing information on the construction and 
properties of new potential pandemic pathogens. Publication of 
the research provides instructions, step-by-step recipes that 
can enable a rogue nation, organization, or individual to 
construct a new pathogen and cause a pandemic.
    What are the benefits? Gain-of-function research of concern 
provides limited benefits. Gain-of-function research of concern 
can advance scientific understanding, but gain-of-function 
research of concern has no civilian practical applications. In 
particular, gain-of-function research of concern is not needed 
for, and does not contribute to, the development of vaccines 
and drugs. Companies develop vaccines and drugs against 
pathogens that exist and circulate in humans, not against 
pathogens that do not yet exist and do not circulate in humans.
    What should oversight entail? Because gain-of-function 
research of concern poses high, potentially existential risks 
and provides limited benefits, the risk-benefit ratio for the 
research almost always is unfavorable and in many cases is 
extremely unfavorable. Therefore, it is imperative that gain-
of-function research of concern be subject to national or 
international level oversight to ensure before the research is 
started that risk-benefit ratios are acceptable and risks are 
mitigated.
    Effective oversight includes three components. First, 
research proposals that include gain-of-function research of 
concern must be identified and flagged. Second, a risk-benefit 
assessment must be performed. This entails enumerating risks 
and benefits, weighing risks and benefits, and reaching a 
decision, either to proceed as proposed or to proceed with 
additional risk mitigation, or not to proceed.
    Third, compliance with the decision from the risk-benefit 
assessment must be mandated, monitored, and enforced.
    I turn now to U.S. oversight of gain-of-function research 
of concern.
    Before 2014, there was no national-level U.S. oversight of 
gain-of-function research of concern. In 2014 to 2017, the 
government put in place a moratorium on Federal funding for 
``selected gain-of-function research,'' defined as research 
activities reasonably anticipated to increase the 
transmissibility or pathogenicity of influenza, severe acute 
respiratory syndrome (SARS), or Middle East respiratory 
syndrome (MERS) viruses. The policy was referred to as the 
Pause.
    Under the Pause, 18 projects were paused. However, at least 
7 of the 18 projects that were paused were allowed to resume 
almost immediately. More important, other projects that met the 
definition for coverage, including a project on SARS-related 
coronaviruses by EcoHealth Alliance and its Wuhan-based 
partners, were not paused, due to the failure of the NIH to 
identify and flag all covered projects.
    At the end of 2017, the Pause was lifted and was replaced 
by an HHS policy that requires risk-benefit assessment before 
awarding HHS funding for ``research involving enhanced 
potential pandemic pathogens,'' defined as research activities 
reasonably anticipated to increase the transmissibility or 
pathogenicity of a potential pandemic pathogen. The policy is 
referred to as the P3CO Framework.
    Under the P3CO Framework, covered projects must be 
identified and flagged by the funding agency, the NIH, and 
covered projects must be reviewed by an HHS Secretary-level 
committee, the P3CO Committee.
    The P3CO Framework assesses the reasonably anticipated 
results of the proposed research. The reasonably anticipated 
standard employed by the policy is equivalent, in all respects, 
to the reasonable person standard employed in U.S. 
administrative law and U.S. civil law.
    In principle the P3CO Framework ensures risk-benefit 
assessment of gain-of-function research of concern. However, in 
practice, the P3CO Framework has existed primarily on paper. In 
the 4\1/2\ years since the policy was announced, only three 
projects have been reviewed. Most covered projects, including 
the project by EcoHealth Alliance and its Wuhan partners, were 
not reviewed, due to a failure by the NIH to identify and flag 
covered projects.
    In addition, the P3CO Committee has been non-transparent 
and unaccountable. The names and agency affiliations of its 
members have not been disclosed, its proceedings have not been 
disclosed, and even its decisions have not been disclosed.
    Current U.S. oversight of gain-of-function research of 
concern thus has serious shortcomings. Moving forward, any 
effective system of U.S. oversight of gain-of-function research 
of concern must address these shortcomings. My recommendations 
are as follows:
    First, responsibility for U.S. oversight of gain-of-
function research of concern should be assigned to a single, 
independent Federal agency that does not perform research and 
does not fund research.
    Second, U.S. oversight of gain-of-function research of 
concern should cover all U.S. and U.S.-funded research, 
irrespective of funding source, classification status, and 
research location.
    Third, U.S. oversight of gain-of-function research of 
concern should be codified in regulations with force of law and 
should be mandated, monitored, and enforced.
    Fourth, U.S. oversight of gain-of-function research of 
concern should be transparent and accountable.
    Thank you for your attention, and I would be pleased to 
address questions.
    Senator Paul. Thank you, Dr. Ebright.
    Next we will have Dr. Steven Quay. Dr. Steven Quay is the 
Founder and Chairman of the Seattle-Based Atossa Therapeutics. 
Atossa Therapeutics is a clinical-stage biopharmaceutical 
company that develops novel therapeutics and delivery methods 
for breast cancer and other breast conditions, with the goal of 
preventing the two million yearly breast cancer cases 
worldwide.
    Earlier in his career, Dr. Quay received his MD and PhD 
from the University of Michigan, trained as a postdoctoral 
fellow at Massachusetts Institute of Technology (MIT), and 
served on the faculty of Stanford University's School of 
Medicine.
    Dr. Quay's published contributions to the world of medicine 
have been cited extensively, and he is a medical entrepreneur. 
He has founded six startups, invented seven Food and Drug 
Administration (FDA)-approved pharmaceuticals, and is the 
holder of 87 patents and over 130 pending U.S. and foreign 
patent applications.
    He is also an author. Notably, during the pandemic, Dr. 
Quay published his No. 1 Amazon best seller, Stay Safe: A 
Physician's Guide to Survive Coronavirus.
    Finally, Dr. Quay recently presented testimony to lawmakers 
as part of an expert forum convened by the House Select 
Committee on Coronavirus, titled ``Led by Science: The COVID-19 
Origin Story.''
    Dr. Quay.

    TESTIMONY OF STEVEN QUAY, MD, PH.D.,\1\ CHIEF EXECUTIVE 
               OFFICER, ATOSSA THERAPEUTICS, INC.

    Dr. Quay. I am honored to participate with my esteemed 
colleagues, Doctors Ebright and Esvelt, in this forum entitled 
``Revisiting Gain-of-Function Research: What the Pandemic 
Taught Us and Where Do We Go From Here.''
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    \1\ The prepared statement of Dr. Quay appears in the Appendix on 
page 66.
---------------------------------------------------------------------------
    I offer six statements in opening. One, there is no 
dispositive evidence the pandemic began as a spillover of a 
natural virus in a market. All evidence is consistent with a 
laboratory-acquired infection. I do understand this conclusion 
is not widely held, I can spend an entire hearing painstakingly 
going through the scientific evidence for this conclusion, but 
that is not the purpose of today's meeting.
    I am happy to discuss the evidence contained in my written 
remarks during questioning. I am also willing to publicly 
debate any virologist on this question, at any time or place. 
Only one infectious disease doctor was willing to debate this 
question with me last year in a formal debate format, and he 
lost.
    I am also willing to testify under oath, if requested.
    No. 2, all evidence is consistent with an accidental and 
not a deliberate release.
    No. 3, SARS2 has features consistent with synthetic biology 
gain-of-function research. Two features involve acceptable 
academic gain-of-function research, the receptor binding domain 
optimization and the furin cleavage site. These two features 
have never been found in nature and related viruses that could 
have reasonably started the pandemic because of the closeness 
of these viruses to Wuhan.
    These two features are, on the other hand, routinely 
engineered into viruses. In 2018, United States and WIV 
scientists proposed inserting ``human-specific furin cleavage 
sites in a bat virus backbone.'' Two years later, SARS2 
appeared on the WIV's doorstep. SAR2 is a bat-derived virus 
with a human-specific furin cleavage site.
    One region of SARS2, called open reading frames (ORF8), has 
features of forbidden gain-of-function research, asymptomatic 
transmission and immune system evasion. The WIV was engineering 
a protein related to ORF8 to have these two forbidden 
properties before 2019, as shown in two master's degree theses 
available only in Chinese.
    COVID exhibits 40 percent asymptomatic transmission, 
unheard of for a new respiratory virus. Patients infected with 
an acquired deletion of ORF8 have a milder infection. Could the 
reduced efficacy of vaccines and natural immunity be an 
engineered feature? It appears likely.
    Six, in December 2019, the Wuhan Institute of Virology was 
conducted synthetic biology research on the Nipah virus, which 
is 60 percent lethal in low-containment, biosafety level 2 
(BSL-2), 3 facilities. The Nipah virus was in an infectious 
clone format. Nipah is a BSL-4 level pathogen and a Centers for 
Disease Control and Prevention (CDC)-designated bioterrorism 
agent. This is the most dangerous gain-of-function research I 
have ever encountered. We should assume this research continues 
to this day at the WIV.
    I will close with five recommendations for future gain-of-
function research.
    Where did the pandemic begin? The competing hypotheses are 
a natural spillover at the Hunan Seafood Market in Wuhan and a 
laboratory-acquired infection. Two recent papers purport to 
claim the pandemic began at the Hunan Market in December 2019. 
There are at least six serious problems with these papers.
    The most important are that in the early months no animal 
has ever been found to be infected with COVID-19 anywhere, 
including the market, and the molecular clock of SARS2 places 
the first human infection in the fall of 2019, long before the 
December market cases. All infections in the market in human 
were what is called Lineage B, and not the most ancestral 
lineage, Lineage A. I, like many other scientists, believe the 
market cases were a superspreader event, on this first chart 
here.
    The earliest cluster of hospitalized patients with both the 
Lineage A and B virus was at the People's Liberation Army (PLA) 
Hospital in Wuhan. This hospital is about six kilometers from 
the WIV, and on Line 2 of the Wuhan subway system, as shown in 
this chart. All early cases are in hospitals adjacent to Line 
2, and the probably that this was a chance occurrence is 1 in 
68,000.
    The Line 2 Covid Conduit, as I called it, includes the PLA 
Hospital, the WIV, the market, and the international airport. 
You can literally walk down into the subway system from the WIV 
in China and next exit outside in London, Paris, Dubai, Los 
Angeles, or New York, all before having any symptoms. Modeling 
by others suggests that the pandemic could not have occurred 
without the international spreading impact of Line 2.
    Has gain-of-function research been useful to the COVID 
response or any other public health infectious disease 
emergency? I have found no evidence that gain-of-function 
research helped in either the COVID pandemic or other smaller 
epidemics.
    We now know that an Messenger Ribonucleic acid (mRNA) 
vaccine can be designed within literally days of a new outbreak 
once the pathogen is sequenced, and large-scale manufacturing 
can begin soon thereafter. This capability has now been fully 
road-tested and provides, in my opinion, the best defensive 
capability against future microbes.
    It is also important to point out that gain-of-function 
research is a tiny sliver of all research funded by NIH. 
Specifically, there were over 36,000 Research Project (RO1) 
grants funded by NIH in 2020, the latest year with statistics. 
Of these, the self-described gain-of-function on potential 
pathogens research grants numbered only 21 in the latest 
funding year. Even expanding this by tenfold with a less 
stringent definition of gain-of-function would mean we are 
talking about less than 1 percent of all NIH research funding. 
I cannot imagine a scenario where but for this tiny research 
effort a new pandemic occurs.
    What reforms should be considered in order to assure that 
such research is conducted in a safe and transparent manner? 
While I found no actual benefit of gain-of-function research, I 
believe efforts to ban it, given the vested interests of 
literally the entire virology community, is a hill too steep to 
climb. A proposal that I believe is achievable is the placement 
of all select agent research within the existing institutional 
review board structure used for human clinical trials. I 
believe this effort would put guardrails around the most 
dangerous aspects of this research, and has the added benefit 
of international acceptance, including in China.
    My second reform would be to separate government oversight 
from the funding agency, and the model would be the Atomic 
Energy Commission.
    My third suggestion is to place Western biotechnology 
equipment under export controls and monitoring. There are ways 
to build into these systems a forensic and law enforcement 
capability that could, for example, with probable cause and a 
court-ordered search warrant allow the work of any lab in the 
world to be scrutinized remotely.
    My fourth recommendation is simple: do not put dangerous 
infectious disease laboratories near subways, like Line 2, 
where every major city in the world is accessible with the 
incubation period of an infection.
    Finally, I am including what I call gain-of-opportunity 
research, going into caves where humans are seldom found, 
taking a bat fecal sample containing thousands of viruses, 
bringing those viruses back to a laboratory, and culturing the 
specimens where a virus might be controlled in a diverse 
natural environment, is now able to grow unrestricted in pure 
culture, provides an immense increased potential risk, a gain 
of opportunity for the virus.
    This is the goal of the Global Virome Project, a Gates 
Foundation-funded, Eco-Health Alliance-associated effort. Their 
stated goal: collect the estimated 500,000 unknown viruses that 
are capable of infecting humans and bringing them back to a 
laboratory near you. What could go wrong?
    Could I have the last slide here.
    What happens if we have these hearings and nothing happens? 
In December 2019, we performed a remote audit, forensic 
examination of the Wuhan Institute of Virology and found 
synthetic biology experiments with the Nipah virus. As the 
chart shows, they had created a cloning vector with a virus the 
U.S. CDC defines as a bioterrorism agent. Nipah virus is one of 
the deadliest on the planet, with a greater than 60 percent 
lethality.
    Why were they conducting this experiment? I do not know. 
But laboratory-acquired infection with this virus, if it became 
airborne, would make COVID-19 look like a walk in the park.
    The work of this Committee is critical to protecting the 
American people as well as the people of all countries from 
future pandemics, manmade or natural. If we now fail to act 
with the knowledge we have, history will judge us poorly.
    Thank you for the opportunity to speak.
    Senator Paul. Thank you, Dr. Quay. Our final witness is Dr. 
Kevin Esvelt. He is currently an Assistant Professor at the MIT 
Media Lab group, where he leads the Sculpting Evolution Group.
    Dr. Esvelt received his BA in chemistry and biology from 
Harvey Mudd College and would later complete his PhD in 
biochemistry at Harvard University, as a Hertz Fellow.
    While working in the laboratory of David Liu at Harvard 
University, Dr. Esvelt invented phage-assisted continuous 
evolution (PACE), which is a synthetic microbial ecosystem for 
rapidly evolving biomolecules. Later, during his time as a Wyss 
Technology Fellow, Esvelt's focus centered around the 
development of gene drive technology. Many of Esvelt's 
contributions related to the bioethics and biosafety of such 
gene drivers, and he is credited as the first to describe how 
Clustered Regularly Interspaced Short Palindromic Repeats 
(CRISPR) gene drives could be used to alter the traits of wild 
populations in an evolutionary stable manner.
    In his recent work at the Sculpting Evolution Group, Dr. 
Esvelt and his colleagues invented the new technology known as 
``daisy drives,'' which would let communities aiming to prevent 
disease alter wild organisms in local ecosystems.
    Throughout his career, Dr. Esvelt has been a champion of 
universal safeguards, transparency, raising scientific 
awareness of developing early warning systems to reliably 
detect any catastrophic biological threat, and advising 
policymakers on how to best mitigate global catastrophic 
biorisks.
    Dr. Esvelt.

TESTIMONY OF KEVIN M. ESVELT, PH.D.,\1\ ASSISTANT PROFESSOR OF 
             MEDIA ARTS AND SCIENCES, MIT MEDIA LAB

    Mr. Esvelt. Chair Hassan, Ranking Member Paul, Senators, 
thank you for the kind invitation. I have to say that I have no 
special insights regarding the origins of COVID. In fact, I 
kind of doubt that there is sufficient evidence to be 
conclusive in one way or the other. But our models suggest that 
knowing where it came from would not actually help us defend 
against future pandemics.
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    \1\ The prepared statement of Mr. Esvelt appears in the Appendix on 
page 73.
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    I agreed to speak to a bipartisan hearing today because 
this is the Emerging Threats Subcommittee, and I am 
increasingly concerned by our continuing failure to recognize 
an increasingly dire technological threat.
    Leo Szilard who invented the nuclear chain reaction and 
launched the modern nonproliferation movement, is a scientific 
hero of mine, and he wrote, ``The most important step in 
getting a job done is the recognition of the problem.''
    The problem is not our inability to agree on what does or 
does not constitute gain-of-function research or even whether 
the putative benefits of this research outweigh the risks of 
accidents. Rather, the problem is that we are so used to 
thinking of pandemics as a health and safety issue that we have 
missed the national security implications of identifying 
viruses that could be deliberately unleashed to kill millions 
of people.
    Let me illustrate. When the genome of SARS2 was first 
posted online, scientists did not have to wait for physical 
samples of the virus to become available to begin studying it 
and working on countermeasures. That is because we could order 
synthetic deoxyribonucleic acid (DNA) corresponding to the 
genome of the pathogen and assemble infectious samples using 
freely available, step-by-step protocols.
    From a biomedical perspective, that is a triumph, 
particularly because it only costs a few thousand dollars, and 
the price is plummeting. But from a security perspective, that 
means that thousands of researchers could gain access to a 
novel pandemic agent, as soon as it was identified as such.
    Thankfully, we still do not know of any particularly 
concerning examples, that is, agents that would likely cause a 
pandemic if they were to be released, even at multiple sites. 
If we did know, then the modern-day equivalent of a terrorist, 
like Seiichi Endo, who is a graduate-trained virologist and 
doomsday cultist, who sought samples of Ebola and used chemical 
weapons to commit mass murder, might have well assembled them 
and released them in airports by now.
    But if you work in public health and infectious disease you 
naturally want to know what the next threat might be so that 
you can better prepare defenses. That makes sense. That is why 
both United States Agency for International Development (USAID) 
and NIH have funded research attempting to find or create novel 
pandemic-capable viruses in labs all over the world.
    Now we disagree on whether some of those experiments might 
fall into an arbitrarily defined category called gain-of-
function research. We biologists disagree over what a species 
is. Did you know that a tiger and a lion can interbreed? But 
what nobody disputes is that in the hope of preventing natural 
pandemics both agencies seek to identify viruses that could 
kill as many people as a nuclear weapon, to alert the entire 
world to what they find, and to publicly sharing the complete 
genome sequences of those viruses so that skilled scientists 
everywhere will be able to make infectious samples.
    The tragedy is that these are health experts, well-meaning 
health experts, who have dedicated their lives to fighting 
infectious disease, and they struggle to imagine anyone evil 
enough to deliberately cause one. They never considered that 
these advances in technology, which are continuing, plus a list 
of pandemic-capable viruses, would allow a single skilled 
terrorist to unleash more pandemics at once than would 
naturally occur in a century. No one warned them, perhaps 
because, as has been previously noted, they lack independent 
security oversight of their work.
    Now it is always possible that we could save more lives by 
helping to prevent natural pandemics than we would lose due to 
deliberate acts of terrorism. But according to our numerical 
cost-benefit model, it is not even close, even for the best-
case scenario. The reason is there are so many viruses in 
nature, most of which will never encounter a human. The lowest 
published estimate suggest that for every pandemic virus that 
does spill over in a century there are 100 that will never 
encounter a human.
    That means if you identify one at random, even if we could 
perfectly prevent it from spilling over and causing a pandemic, 
that one virus, then we have a 1-in-100 chance of actually 
preventing a pandemic. But if there is just a 1 percent chance 
of deliberate misuse per year, then in that same time period we 
can expect to cause a pandemic. In other words, pandemic virus 
identification, whether it is created in the lab or whether it 
is just identified in the wild, is expected to kill 100 times 
as many people as it would save.
    For 75 years, the United States successfully kept nuclear 
weapons out of the hands of terrorists. In the wake of a 
pandemic that has killed more people than could any 
thermonuclear explosion, it is time to start doing the same for 
pandemic viruses.
    For starters, Congress could study the issue and release a 
finding on whether pandemic virus identification endangers 
national security. It is just that simple. Then, if necessary, 
reform USAID and NIH research. It could require an oversight 
committee of experts from security agencies to review all 
requests for proposals in the life sciences. It could update 
the Federal Select Agent Program to automatically regulate 
viruses at the first sign of pandemic capability, because these 
are the most dangerous agents out there. It could require all 
DNA synthesis orders to be screened for hazards.
    Perhaps most important, Congress could legislate 
catastrophe liability, that is, liability for human-caused 
events that result in more than 1 million American casualties, 
as SARS2 has, and require general liability insurance to cover 
it. That would induce the market to price in the cost of 
negative externalities and cause professional insurance risk 
analysts to perform those cost-benefit analyses.
    Now I am optimistic about this issue because we just need 
to buy time. If we can keep pandemic-capable viruses out of the 
hands of terrorists for a decade then we can deploy new, 
general-purpose defensive technologies. These range from 
ubiquitous sequencing that can detect any emerging threat, to 
perfect protective equipment for our essential workers, to low-
wavelength germicidal lights, and these together could protect 
us from all pandemics, whether natural, accidental, or 
deliberate.
    Pandemic proliferation is a solvable national security 
problem, but only if we recognize it as one. Thank you.
    Senator Paul. Thank you, Dr. Esvelt. We will start with 
Senator Scott from Florida.

               OPENING STATEMENT OF SENATOR SCOTT

    Senator Scott. All right. Thank you, Chair.
    Dr. Esvelt, in your testimony you talk about USAID funding 
gain-of-function experiments through Discovery & Exploration of 
Emerging Pathogens--Viral Zoonoses (DEEP VZN), the program 
which specifically conducts experiments geared toward pandemics 
and virology and Strategies to Prevent (STOP) SPILLOVER, which 
as you know, research is spillover between animals and humans. 
Can you talk about what these programs specifically are and why 
they may be dangerous?
    Mr. Esvelt. DEEP VZN and STOP SPILLOVER are extensions of 
USAID's long-running PREDICT program, the goal of which was to 
predict pandemics, that is, to identify viruses in the wild 
that had a good chance of spilling over and causing a pandemic 
in humans. This is part of the laudable One Health program 
which seeks to identify essentially hotspots where viruses are 
likely to spill over into humans and cause a pandemic. The idea 
is if we find these hotspots, educate the community, teach them 
what to do in the event of an outbreak, then we might be able 
to stop it before it reaches our shores. That makes sense.
    But again, they do not seem to have thought of the security 
issues associated with publishing a list of pandemic-capable 
viruses, by threat order. Now we cannot necessarily know 
whether a given pandemic would take off until it is spreading 
in humans, but there is a narrow set of laboratory experiments 
that can tell us, does it look like a human endemic virus, in 
certain traits? These are a tiny subset of all experiments that 
really are not very useful for anything else. They do not help 
with therapeutic development.
    Part of PREDICT was to take samples of these viruses, bring 
them back to the lab, run these kinds of experiments, sequence 
the genomes, share them. They did not find anything 
particularly scary, but they found some candidates that looked 
fairly nasty, including at the Wuhan Institute of Virology. It 
is hard to know what USAID did and did not approve, but they 
are listed as an acknowledgement, as is NIH, on a paper that 
recombined those dangerous-looking but definitely not pandemic-
capable viruses, and then performed experiments to see, did 
they look like they could plausibly cause prescription drugs.
    Senator Scott. Do you think these programs are dangerous?
    Mr. Esvelt. I think any program attempting to identify an 
agent that would be widely accessible and could be deliberately 
released to kill millions of people is pretty much the 
definition of dangerous, yes.
    Senator Scott. Do you think that USAID, whose main job is 
to provide humanitarian aid globally, has the oversight for 
programs and experiments like STOP SPILLOVER and DEEP VZN, 
which are not humanitarian in nature?
    Mr. Esvelt. I think there is a very strong humanitarian 
case for preventing pandemics. I think that the absence of 
security oversight means that USAID was probably just not aware 
of the security consequences of their work, and it remains to 
be seen whether they will decide that it is inadvisable to 
maintain a ranked-order list of those most threatening viruses.
    Senator Scott. Do you think they have the oversight ability 
to handle this job?
    Mr. Esvelt. It is unclear exactly who they are seeking 
advice from. My understanding is that they are seeking advice 
from folks with greater security expertise, and the real 
question is what actions are going to come of that.
    Senator Scott. Would these programs go through a P3CO 
review?
    Mr. Esvelt. My understanding is that federally funded 
research does go through P3CO review. However, it is unclear 
whether the basic find-the-pathogens program, would go through 
such review because until you find it and at least run some 
characterization to determine whether or not it looks like a 
pandemic virus it would not necessary be regulated. As 
previously mentioned, due to the transparency issues with that 
committee it is very much unclear what their remit is and is 
not.
    Senator Scott. Do you know who is on the panel for P3CO?
    Mr. Esvelt. I do not.
    Senator Scott. Is it not public?
    Mr. Esvelt. My understanding is it is not public.
    Senator Scott. Why would it not be public?
    Mr. Esvelt. That is an excellent question.
    Senator Scott. Do any of the witnesses know why it would 
not be public?
    Mr. Esvelt. No.
    Dr. Quay. No. I know it is not public and I do not know why 
it is not public.
    Senator Scott. That is part of our Federal Government, 
right?
    Dr. Quay. Correct.
    Senator Scott. Do they think Americans are not smart enough 
to understand it?
    Dr. Quay. You will have to ask the people at the NIH.
    Senator Scott. Do you know how they made the decision not 
to make the names public?
    Dr. Quay. No.
    Senator Scott. OK. For each of you, do you think that the 
P3CO review is comprehensive enough on NIH grants or do you 
think gain-of-function grants have been approved without a P3CO 
review?
    Senator Paul. Let us go to Dr. Ebright. I do not want to 
leave him out. Then we will go to each of you. Dr. Ebright, 
would you like to respond to that?
    Mr. Ebright. Yes. As I mentioned in my summary statement, 
there have been only three P3CO reviews in the 4\1/2\ years 
that the P3CO Framework has been in effect. The majority of 
gain-of-function research of concern enhanced potential 
pandemic pathogen research supported by NIH has not undergone 
P3CO review. It has not undergone P3CO review for the simple 
reason that the NIH has not identified and flagged the 
proposals as subject to P3CO review and has not forwarded the 
proposals for P3CO review.
    Senator Paul. Let me ask the other two to respond as well.
    Dr. Quay. Yes. I think, just echoing Dr. Ebright, it has 
been a failure, I think, at this this point in time, and so we 
need to find an alternative, which is perhaps to take it out of 
the NIH, make the oversight outside of the agency that is 
funding.
    Mr. Esvelt. One major problem is that gain-of-function is a 
terrible term. It applies to most of biotechnology in the raw. 
You can try to add qualifiers as you want. But it also 
inherently does not catch efforts to identify perfectly natural 
but nevertheless highly lethal pandemic-capable viruses. It 
really does not matter where the thing comes from. What matters 
is do you know that there is a good chance that it causes a 
pandemic.
    Again, maybe you do not think we can ever be confident more 
than, say, 50 percent for a given virus, but if you get a list 
of eight viruses that you are 50 percent confident, it is 
possible to make all eight, let them go, and you have pretty 
good odds there.
    I am concerned by efforts to continue to focus on gain-of-
function because it is so ill-defined, and it seems more 
productive to narrow in on the classes of experiments that can 
substantially increase our confidence that a virus is pandemic 
capable, wherever it comes from. I certainly echo the calls for 
external security oversight.
    Senator Scott. Do you think there is appropriate oversight 
of existing research after it has been approved, to ensure 
continuous compliance?
    Mr. Ebright. I would say that there is not. Importantly, 
the P3CO Framework does not mandate compliance. If the P3CO 
committee makes a decision that the research may not proceed, 
that decision is only advisory to the funding agency. It is not 
mandated for the funding agency. The funding agency is free to 
accept or not accept the decision, and it is free to determine 
whether to monitor or not to monitor the progress of the work. 
This is a major shortcoming.
    Senator Scott. Thank you.
    Senator Paul. I want to interject on the definition, 
whether gain-of-function is good definition or not. That began 
with the NIH. They gave us the definition and we started with 
that. I do think Dr. Esvelt is making some good points that we 
ought to be concerned with viruses that are not created but 
that actually come from nature that could cause pandemics. I 
think part of this discussion is to try to figure out where we 
get to.
    Senator Johnson.

              OPENING STATEMENT OF SENATOR JOHNSON

    Senator Johnson. Thank you, Mr. Chairman. How long have we 
had gain-of-function capability? Is that with the CRISPR 
technology? Mr. Esvelt.
    Mr. Esvelt. I should probably defer to Dr. Ebright on that.
    Senator Johnson. Dr. Ebright, how long have we even had 
this capability?
    Mr. Ebright. The discussions have been underway since 2002 
and 2003. The first examples involved reconstruction of 
previously eradicated or extinct pathogens. Those presented a 
prototype for understanding experiments that would create new 
health threats and the need to address them. Again, we are 
talking a two-decade-long discussion.
    Senator Johnson. The technology emerged or they started 
discussing it and then developed the technology--which came 
first?
    Mr. Ebright. The discussions occurred as the technology 
emerged. It became possible to do this effectively, starting at 
the beginning of the millennium. The technologies have 
increased in sophistication and have increased in ease and 
decreased in cost over time.
    Senator Johnson. Talk about the ease and the cost because I 
have heard it is very accessible now and it is very cheap, and 
a knowledgeable individual can basically do this in their 
garage.
    Mr. Ebright. That is an exaggeration. But as Dr. Esvelt has 
pointed out, given the genome sequence of a virus it is 
typically possible to reconstruct infectious particles of the 
virus and to do so for costs well under $10,000 in one-person 
month or two-person months. For an equipped laboratory, the 
kind of laboratory that would be present in any State program, 
and that is present in many research laboratories at academic 
institutions, this is eminently possible.
    Senator Johnson. Reconstructing a virus is one thing, but 
my understanding of what, at least, the theory might be with 
severe acute respiratory syndrome coronavirus (SARS-CoV-2) is 
there is gene splicing that occurred here and some very unusual 
markers in this furin cleavage site and it would be beyond my 
comprehension exactly what that means. But talk to me a little 
bit about the whole gene-splicing aspect of this.
    Mr. Esvelt. There are two ways to edit a virus. Nowadays 
the easiest way is usually to assemble it from scratch using 
synthetic DNA. But if it large then in some cases it is better 
to create the altered piece that you wish to insert into the 
virus and then use a tool such as CRISPR to do the insertion 
into the backbone.
    With respect to the cost, the first virus with a chemically 
synthesized genome from synthetic DNA was made in 2002. Since 
then, the cost of gene synthesis has fallen by roughly 1,000-
fold. Today the cost of ordering the components of an 
infectious influenza virus, for example, the synthetic DNA 
costs less than $1,000, and that does not require any further 
editing. That requires following the reverse genetics protocol, 
transfecting it into the cells to get the infectious virus.
    I estimate that there are around 30,000 people who can do 
that, who have doctorates, and you can say 125 virology Ph.D.s 
per year are in the United States. That is roughly one-third in 
the world. There are probably four times as many people who 
have degrees in other disciplines, such as mine, who can do it. 
Assume a 20-year career, and that is 30,000 people, add a few 
technicians.
    Senator Johnson. Was there a specific incidence or 
something that concerned people that caused the Pause?
    Dr. Quay. Yes. There were experiments in influenza in the 
Netherlands and Wisconsin that took a virus that was 90 percent 
lethal but not airborne and created it and made it airborne 
through passage in the laboratory.
    Senator Johnson. That occurred when?
    Dr. Quay. In 2013, 2012.
    Senator Johnson. That caught the attention of who? I mean, 
who was alarmed by that and instituted the Pause? I know it had 
to have occurred under President Obama, but which member of our 
health agencies?
    Dr. Quay. I think Dr. Ebright would be the best to answer 
that.
    Senator Johnson. Dr. Ebright.
    Mr. Ebright. The proximal impetus for the Pause was a 
series of events, laboratory accidents at Federal laboratories 
that have access to and storage of potential pandemic 
pathogens. The accidents included an anthrax incident at the 
CDC, another anthrax incident at a U.S. Army facility at Dugway 
in Utah, and the finding of unsecured vials labeled ``smallpox 
virus'' in an FDA NIH freezer in Maryland. Those three 
incidents, occurring in close succession, resulted in a hearing 
in the House Energy and Commerce Committee and then action by 
the Office of Science, Technology, and Policy. The Pause was 
driven, ultimately, from the White House, from the Obama Office 
of Science, Technology, and Policy.
    Senator Johnson. Listening to your testimony I am assuming 
all three of you would agree with this statement that this 
research--and I would say even the mining of dangerous 
potential pathogens, crawl in a bat cave and try and pull these 
things out and bring them to a lab--there is surely no benefit 
that overrides the risk. We should not be doing this at all.
    Dr. Quay. Yes. I call it gain-of-function and gain-of-
opportunity, where you bring a virus back. As I said, my 
analysis is that it has not contributed to the response to this 
pandemic.
    Senator Johnson. We should not do it. I mean, we can talk 
about controls but the bottom line, we should not have controls 
so we should not even do it. Is that your position as well?
    Mr. Esvelt. For balancing the potential benefits of 
prevention against the risk of accidents it can go either way, 
depending on the numbers you use for those. You can reasonably 
come out with either answer. When you add the misuse case, that 
is what absolutely blows it out of the water.
    Senator Johnson. Dr. Ebright.
    Mr. Ebright. I believe a strong case can be made, or a case 
can be made that certain components of gain-of-function 
research of concern, particularly components involving 
pathogens that are currently in human populations, are 
categorically separate and more justifiable than other 
components of gain-of-function research of concern.
    For example, currently SARS-CoV-2, the virus responsible 
for COVID, is present in millions of humans and is generating 
variant after variant. Gain-of-function research of concern on 
SARS-CoV-2 involving the creation of new variants and analysis 
of the threat posed by them arguably can be justified because 
this is not creating new health threats that will not arise 
without intervention but is addressing a health threat that is 
in place currently.
    For that reason and for reasons like that, I believe 
enhancing the oversight of the research is more a more 
effective and more prudent strategy than simply banning it.
    Senator Johnson. I would say improved oversight but would 
you also agree dramatically limit it?
    Mr. Ebright. Absolutely.
    Senator Johnson. OK. Thank you, Mr. Chairman.
    Senator Paul. Senator Marshall.

             OPENING STATEMENT OF SENATOR MARSHALL

    Senator Marshall. Thank you, Mr. Chairman, and I hope 
America is listening today. To our witnesses let me say 
welcome, and I regret that none of you were able to get into 
the Kansas State University biochemistry program, but I 
certainly appreciate your credentials that are all here today.
    I think it is important to not only identify the true 
problem but also talk about where we have been, and you all can 
help us fill in some of the pieces here when we talk about 
gain-of-function research.
    It was late in 2011, when the National Science Advisory 
Board on Biosecurity (NSABB), which is the NIH's advisory 
board, stopped two scientists from publishing an influenza 
gain-of-function study that I believe Dr. Ebright was referring 
to. They stopped it because they were afraid it could afraid 
bioterrorists. This is 2011. Over a decade ago, scientists had 
figured out how to make H5N1, which is highly pathogenic avian 
influenza, more contagious.
    In 2012, those 2 scientists and 39 others implemented a 
voluntary gain-of-function research pause on influenza 
experiments. In early 2012, Dr. Fauci encouraged all influenza 
scientists to pause gain-of-function, and said, and I am 
quoting Dr. Fauci, 2012, ``It is essential we respect the 
concern of the public, domestically or globally, and not ask 
them to take the word of the influenza scientists.'' It is 
interesting to me that Dr. Fauci was focused on the messaging 
but he still wanted to continue the gain-of-function research.
    Again, in 2012, Dr. Fauci also said, almost prophetically, 
that he worried about unregulated laboratories, perhaps outside 
the United States, doing work sloppily and leading to an 
inadvertent pandemic. He went on to say the accidental release 
is what the world is really worried about.
    I go forward to 2014 now, after biosecurity accidents in 
United States research labs, which our witnesses have talked 
about, the Obama White House implemented the second gain-of-
function moratorium on influenza plus MERS and SARS because of 
the potential risk of lab accidents and inherent gain-of-
function danger. But gain-of-function still continued at the 
University of North Carolina, research later that we shared 
with Dr. Shi, the Bat Lady.
    Nevertheless, clearly the U.S. Government and Dr. Fauci 
knew that the viral gain-of-function research was very 
concerning. Almost counterintuitively, while Dr. Fauci 
encouraged United States scientists to pause their GOF studies, 
Dr. Fauci offshored the paused research to China, not once but 
twice. In 2012, Dr. Fauci gave a new grant to Peter Daszak's 
EcoHealth Alliance for influenza research in China, and then 
again in 2014, Dr. Fauci gave another grant to Daszak for SARS 
research in China. Daszak partnered with who? The Wuhan 
Institute of Virology.
    In late 2017, NIH announced a lift on the gain-of-function 
moratorium, what became known as the P3CO Framework, that we 
referred to, apparently without consultation from a Senate-
confirmed State Department head or national security 
leadership. Also significant, there was no Office of Science 
and Technology Policy (OSTP) director in place and only an 
acting HHS Secretary at the helm.
    What was the result of this? NIH essentially lifts the 
moratorium on their own by slipping it in-between 
administrations and self-policing. Today we cannot see the 
research record for Dr. Fauci's offshore projects because the 
Chinese Communist Party supposedly has EcoHealth's records, and 
NIH resists sharing theirs.
    I will get to my question now. Dr. Ebright, could EcoHealth 
research in China have led to the COVID-19 pandemic and Dr. 
Fauci's worst fears that a lab accident in a foreign lab became 
reality?
    Mr. Ebright. Yes. Lapses in U.S. oversight of gain-of-
function research of concern may have caused the current 
pandemic, and could cause future pandemics. The U.S. Government 
funded high-risk gain-of-function research and high-risk 
enhanced potential pandemic pathogens research at the Wuhan 
Institute of Virology in 2016 to 2019. The research overlapped 
the pause that was in effect in 2014 to 2017, and met the 
criteria to be paused, but was not paused.
    The research also overlapped the subsequent policy, the 
P3CO Framework, that has been in effect from 2018 to the 
present, and met the criteria for Federal risk benefit review 
under the P3CO Framework, but did not undergo Federal risk 
benefit review under the P3CO Framework.
    Senator Marshall. Thank you so much. I have to stop and 
point out, too, that USAID, who is knee-deep in this type of 
research, is part of the State Department, where they can get 
the security advice that they should have asked for before they 
cleared this with P3CO.
    Certainly I believe that this virus came from Wuhan, China, 
and that it is a product of gain-of-function research. This is 
a bipartisan national security issue, like several of our 
witnesses have testified, that this viral gain-of-function 
could become, and has become a weapon of mass destruction, that 
this model--this is a 3-D model of what the COVID virus looks 
like, and this is the gain-of-function. This is the protein 
spike, the two units that allows this key to fit into the door 
perfectly and the cleavage site and all that. This became a 
nuclear hand grenade, is what happened.
    Dr. Quay then Dr. Esvelt, considering the extreme risk of 
this research and the incredulous obstruction by the NIH, 
USAID, EcoHealth, and China, should Congress immediately pause 
this dangerous research?
    Dr. Quay. I think that is an appropriate step for Congress 
to take.
    Senator Marshall. OK. Dr. Esvelt.
    Mr. Esvelt. I think it would be somewhat dangerous to 
attempt to pause gain-of-function research when it is evident 
that that term is so malleable as to be evaded at will, and 
also could plausibly do damage by applying to science that is 
not specifically directed at potential pandemic pathogens.
    Senator Marshall. Are there any countries that you would 
say we should not be doing this type of research with?
    Mr. Esvelt. When it comes to identifying pandemic-capable 
viruses that could kill millions of people and will necessarily 
be shared with scientists worldwide who will be able to access 
them, I do not think that we should be doing it. I do not think 
that China should be doing it. I do not think that anyone 
should be doing it, because it is expected to kill 100 times as 
many people as it might save, even if we could perfectly 
prevent an identified natural virus from spilling over.
    Senator Marshall. Thank you, Mr. Chairman. I have some more 
questions if we have time for later, but I yield the floor 
back. Thank you.
    Senator Paul. Senator Hawley.

              OPENING STATEMENT OF SENATOR HAWLEY

    Senator Hawley. Thank you, Mr. Chairman. Thanks to the 
witnesses for being here.
    Dr. Quay, if I could start with you. You said in your 
written testimony that the genome of COVID has some of the 
hallmarks of gain-of-function research, and in particular three 
genomic regions you say have the signature of synthetic 
biology. One region has features of the two types of forbidden 
gain-of-function research that are associated with bioweapons 
development. You said in your opening remarks that you believe 
COVID-19 was the product of gain-of-function research and was 
from a lab leak from the Wuhan Institute of Virology.
    My question, I guess, is, do you think China engaged in a 
coverup to prevent the world from knowing the true origins of 
this virus and a lab leak?
    Dr. Quay. I think there is abundant evidence that they have 
not shared all the information they had at the time. They 
continue to not share information. I could give you a laundry 
list of 20 things that they have done, starting with a website 
with 21,000 viruses. On September 12th at 2 a.m., someone was 
in the Wuhan Institute of Virology. That had been available to 
virologists for a decade. It was taken offline. It has not been 
returned. We have asked to see it, and no one, that I know of, 
has ever seen it. It goes on from there.
    Senator Hawley. Are you concerned with the continuation and 
expansion of Chinese gain-of-function research?
    Dr. Quay. I think I testified here that in December 2019, 
they were doing synthetic biology on a cloning vector of the 
Nipah virus, which is 60 percent lethal. We just experienced a 
1 percent lethal virus. My estimates would be that that could 
set us back a millennium. The black plague was a 20 percent 
lethal event and it was 250 years for civilization to return.
    Senator Hawley. Let me ask you this. How safe were the 
testing conditions at Wuhan, to your knowledge?
    Dr. Quay. I think that a lot of the Western virologists 
actually use the findings of that as a way to get around saying 
it was OK at the beginning. All of the work that I have 
described is being done at what is called BSL-2, 3 level, which 
is commonly spoken of as a dentist's laboratory level of 
biosafety. Maybe a little higher than that, but that is not a 
bad euphemism.
    Senator Hawley. You said, I think, in your testimony, that 
this is the most dangerous research that you have ever 
encountered. What makes this particular research so dangerous?
    Dr. Quay. If you doing experiments with a pathogen that is 
60 percent lethal but is not airborne, and you make it airborne 
in the laboratory and someone walks out with it--Nipah has a 
21-day incubation period. It is perfect for wide spread without 
being detected. We cannot afford 10 percent lethality.
    Senator Hawley. Yes. Dr. Ebright, let me ask you about the 
merits of gain-of-function research because I was struck by 
something you said in your written testimony. You said gain-of-
function research has no civilian practical applications. From 
a research perspective, then, why do it? I mean, what is the 
value, the real value of gain-of-function research?
    Mr. Ebright. Not a matter of value but incentives, 
particularly incentives within the academic research ecosystem. 
Gain-of-function research of concern is fast and easy, much 
faster and much easier than vaccine or drug development. Gain-
of-function research is publishable and gain-of-function 
research is fundable. With those four incentives in place--
fast, easy, fundable, and publishable--the research will be 
performed. Eliminate any one of those incentives and it will 
not be.
    Senator Hawley. Thinking about China for a second, what is 
China's interest in gain-of-function research?
    Mr. Ebright. They have witnessed the United States leading 
the way with gain-of-function research. Most gain-of-function 
research of concern performed to date has been performed either 
in the United States, with U.S. funding, or overseas with U.S. 
funding. China has wished to be part of that and has 
participated in gain-of-function research of concern in China 
with U.S. funding and has also supported gain-of-function 
research of concern in China entirely through Chinese programs.
    Senator Hawley. Let me ask you this. Gain-of-function 
research and bioweapons, what is the connection there? I mean, 
what role does gain-of-function research play?
    Mr. Ebright. As I mentioned, there are no civilian 
practical applications. There are immense bioweapons practical 
applications. As you have heard from Dr. Esvelt, the potential 
pandemic pathogens that can emerge from such studies are 
potential weapons of mass destruction--inexpensive, accessible, 
easily distributed weapons of mass destruction.
    Senator Hawley. Let me ask you about some of the things 
that you have commented on with regard to what NIH and Dr. 
Fauci have said, and frankly, the lies they have been caught in 
regarding the coronavirus. I want to highlight two of them.
    In response to a congressional inquiry from October 2021, 
just last year, the NIH attempted to walk back assertions by 
NIH Director Collins and Fauci that NIH had not funded gain-of-
function research in Wuhan. You commented at the time, saying, 
and I am going to quote you now, ``NIH, specifically Collins, 
Fauci, and Daszak lied to Congress, lied to the press, and lied 
to the public, knowingly, willfully, brazenly. On May 11th, Dr. 
Fauci said the NIH and National Institute of Allergy and 
Infectious Disease (NIAID) categorically has not funded gain-
of-function research to be conducted in the Wuhan Institute of 
Virology.'' You commented on that, saying the documents make it 
clear that assertions by the NIH Director, Francis Collins, and 
Fauci, that the NIH did not support gain-of-function research 
are untruthful.
    Expand on that if you would. What are the implications of 
Dr. Fauci's continued blatant dishonesty regarding NIH's 
funding of gain-of-function research in Wuhan?
    Mr. Ebright. I stand by my statement. The statements made 
on repeated occasions to the public, to the press, and to 
policymakers by the NAIAD Director, Dr. Fauci, have been 
untruthful. I do not understand why those statements are being 
made because they are demonstrably false.
    Senator Hawley. In my few remaining seconds here, let me 
ask you about an effort to shut down any kind of questioning of 
the origins of COVID. On February 19, 2020, a group of 
virologists and others published that famous letter, infamous 
letter, in The Lancet, which said, among other things, ``We 
stand together to strongly condemn conspiracy theories 
suggesting COVID-19 does not have a natural origin.''
    Of course, we later found out that The Lancet letter had 
been organized by Peter Daszak, president of EcoHealth 
Alliance, who we have discussed today operated a lab in Wuhan, 
with a $600,000, 5-year annual grant of taxpayer dollars from 
Fauci's NAIAD to study bat coronaviruses.
    That letter conveniently concluded by stating, ``We declare 
no competing interests.'' Many people designate this letter as 
the first effort to quash any kind of debate about the origins 
of COVID-19. Do you think that labeling the lab leak theory as 
a conspiracy theory so early on have the effect of slowing down 
investigations into the origins of the virus?
    Mr. Ebright. It certainly had that effect, but The Lancet 
letter that you described was only one of two efforts to impose 
the false narrative that science shows SARS-CoV-2 entered 
humans through natural spillover, and that that is the 
consensus view of scientists. One of the efforts was The Lancet 
letter you discussed. The other effort was coordinated and 
orchestrated through the National Institutes of Health, through 
the NAIAD Director, Dr. Fauci, and the NIH Director, Dr. 
Collins, and resulted in the publication of an opinion article 
entitled ``Proximal Origins of SARS-CoV-2,'' making the case, 
again, that SARS-CoV-2 could not have been a product of a 
research-related spillover.''
    Senator Hawley. Thank you very much. Thank you, Mr. 
Chairman.
    Senator Paul. Thank you. Had there not been a pandemic I 
think there would still be a need for this hearing. This 
discussion, Dr. Ebright got this started back as early as 2003, 
2004. Others have commented on the danger of being able to 
manipulate influenza viruses to be used as either weapons or by 
accidental release.
    But I think given that there was this pandemic, that a 
million Americans died, I lost friends, good friends, to the 
pandemic--I think we should be curious. I am perplexed by the 
lack of curiosity to know are there any precautions we can 
take, is there any kind of government oversight that we could 
do to try to prevent this from happening.
    Now some will say, we cannot prove it came from a lab. That 
is, in all possibility, true, that we cannot prove it. But 
there are arguments to be made and examination of facts to give 
us an idea of whether it might have come from a lab. Even if we 
did not, I think that this could have come from a person in a 
lab handling a virus, if it was a virus out of nature, and we 
have discussed that as well.
    I do think that we have to get to the truth of the matter 
of whether or not dangerous research was going on that should 
have been reviewable. We had a pause of gain-of-function 
research, but then we had research occurring during the pause 
that should have gone to this committee, this P3CO committee, 
and did not get to the committee.
    I think Dr. Ebright described it well. He says that in 
Wuhan, in the 2016 to 2018 period, they were constructing novel 
chimeric SARS-related coronaviruses that combined the spike 
gene of bat SARS coronavirus with the rest of the genetic 
information of a SARS1-related virus, one that was already 
known to have lethality, and they found that it could 
efficiently infect human airway cells and exhibited up to a 
10,000-fold increase in viral growth.
    But when we have asked before, is this gain-of-function, we 
get sort of arguments and protestations that this is not gain-
of-function as if this is no big deal and the experts looked at 
this. As we look farther into this we find that the experts 
never looked at this, that it is sort of a select-in kind of 
program to this committee. It does not go looking for dangerous 
research. It looks at it if you come to them and say, ``Hey, I 
think I have gain-of-function research. Do you all want to look 
at my research?'' And so there is this opting-in aspect to 
this.
    But I think it is important that we get to the truth. Was 
there research going on in Wuhan that was dangerous? Was it 
funded by the NIH, and should it have gone through this 
committee process?
    By the definition that they have given us, gain-of-
function--I think I agree with Dr. Esvelt--can be better 
defined, and particularly if we are going to have oversight on 
this we are going to have to figure out what our oversight is 
going to be. By all means moving forward we need to ask and 
include the scientists to get a precise definition of what we 
are talking about if we want to have more oversight.
    We have to look back before we look forward, not so much to 
assign blame but to figure out is it really necessary. Do we 
need to have hearings on this? Should we have follow-up 
hearings? Should we have legislation? If a million people died 
and there is a chance this came from a lab, I think without 
question we should. Both sides of the aisle should be looking 
at this.
    My question, and I think it is pretty clear but I would 
like to go through everybody, even though Dr. Ebright has said 
this was gain-of-function, to each of the three witnesses, was 
the research, where you take the backbone of a SARS1 virus that 
has known lethality, and you mix it together with an unknown 
bat virus, S protein genes to create a new virus, was this 
gain-of-function according to the NIH definition and should it 
have been reviewed and discussed by this committee that was 
supposed to prevent dangerous research from going on?
    We will start with Dr. Ebright.
    Mr. Ebright. As you mentioned, the Wuhan Institute of 
Virology constructed novel chimeric SARS-related coronaviruses 
that combined the spike gene of one coronavirus with the 
genetic information of another. They showed that the resulting 
viruses efficiently infected human airway cells and efficiently 
replicated in human airway cells, and they showed that the 
resulting viruses exhibited up to 10,000-fold enhancement of 
viral growth in lungs and up to 4-fold enhancement of lethality 
in mice engineered to display human receptors on airway cells.
    Based on those facts, and they are, indeed facts, the 
research was gain-of-function research of concern subject to 
the Pause, and was enhanced potential pandemic pathogen 
research subject to the P3CO Framework. Nevertheless, due to 
the failure of the NIH to forward the proposals for review, the 
work was not paused and there was no P3CO review.
    Senator Paul. Dr. Quay.
    Dr. Quay. The Wuhan Institute of Virology is unique in the 
entire world. Before 2019, 65 percent of all publications on 
coronaviruses came from that single institution. They are 
unique for two reasons. For almost a decade, they were going 
into bat caves throughout China and actually into Africa as 
well, 20 visits a year, and bringing these samples back to the 
laboratory.
    On the one hand they had the largest collection of raw 
material backbones from nature to then do gain-of-function 
research on. They trained in Galveston, Texas, and in North 
Carolina, and were doing experiments, published experiments 
between 2015 and 2019.
    I believe it is the confluence of those two activities, 
gain-of opportunity, bringing things back from bat caves, and 
gain-of-function research, that led to the pandemic.
    Senator Paul. Dr. Esvelt.
    Mr. Esvelt. On the list of experiments you would need to 
perform in order to learn whether a novel virus could 
potentially cause a pandemic you would need to test growth in 
human primary cells, such as human airway epithelial cells, and 
you would need to test transmission in a suitable animal model.
    The question is, if they were not intending to determine 
whether a novel recombinant event between these coronaviruses 
could lead to something that might kill millions of people then 
why were they doing it? If there was no chance that it would 
come up with a result that looked like it was more dangerous, 
what is the point? What is the scientific hypothesis?
    Again, whatever you call it, what they were trying to do 
was identify a biological agent that has a good chance of being 
able to kill millions of people if released. They shared the 
description of what they did and they shared the genome 
sequence, because they thought that this would make us safer, 
because they think that knowing which viruses in nature might 
cause pandemics makes us safer.
    They did not consider the security risks, and it is worth 
noting that both USAID and NIH funded those particular 
coronavirus chimeric studies. USAID, to my understanding, has 
since disavowed those chimeric recombination studies and 
announced that they will only focus on finding natural 
pandemic-capable viruses, which is at least a step in the right 
direction. But again, I would call that gain-of-function. 
Another reasonable scientist would say, no, that is not gain-
of-function, because the term is so ill-defined.
    Senator Paul. Even beyond the term, though, would it be 
qualified as dangerous research that actually should have gone 
before this committee, the P3CO committee, and been reviewed?
    Mr. Esvelt. Here is where you come back to the problem of 
thinking this is a health and safety issue rather than a 
national security issue. The question is why are we trying to 
identify readily accessible agents that could plausibly be used 
to kill millions, and will, as soon as identified, fall into 
the hands of all of our adversaries as well as, perhaps, 
individual terrorists who would want to use them?
    The fundamental principle behind even wanting to do these 
experiments in the first place is, I think, a fundamental 
threat to not just national security but international 
security. It is hard to see why you would ever want to do this, 
when you think about the misuse potential. I have not seen 
anyone else publish a numerical model of that.
    Senator Paul. People have said, well, the closest relative 
that we have found is only 96 percent identical to COVID-19. 
This could not have come from the lab. They have also 
mistakenly accused those who say it came from the lab saying, 
oh, it came from this particular variant. I think what people 
who are saying that this could have come from a lab are saying 
is that there could also be possibly other viruses that are 
closer that were manipulated or that the one that is 96 percent 
analogous to COVID-19 could have gone through serial cell 
culture and become COVID-19.
    I would like to ask the three of you whether or not the 
variant that is 96 percent analogous to COVID-19, could it, 
through serial passage, be transformed to COVID-19? Is it 
possible? Is it so far away that you cannot do it 
experimentally? Could you do it through gene splicing? Could it 
be done? Or is it something that argues that this could not 
have come from the lab?
    We will start with Dr. Ebright.
    Mr. Ebright. The closest relatives are more on the order of 
97 percent identical to SARS-CoV-2 genome than 96 percent. 
Viruses with that level of genetic difference cannot rapidly, 
in the time scale of weeks or months, move from their State 
into being a proximal progenitor of SARS-CoV-2. However, in the 
laboratory those viruses can be combined, at will.
    They can be combined, in particular, using a method that 
would be described as constructing a consensus genome virus. In 
a constructed consensus genome virus, one takes the sequences 
of several related viruses, identifies the most commonly 
observed nucleotides at each position in these sequences, and 
then synthesizes the nucleic acid corresponding to the average, 
if you will, the consensus genome for the group of viruses.
    This has been done successfully in coronaviruses. This has 
been done and published a decade ago in coronaviruses. That 
kind of research could have been done using viruses that are on 
the order of 96 to 97 percent identical in their genome 
sequences to SARS-CoV-2 and with two or three or more such 
virus genome sequences, one could develop a consensus.
    That is just 1 of a series of potential routes by which one 
of the known viruses with 96 to 97 percent identity could, 
through a laboratory, in a relatively short time, be 
transformed into a progenitor of SARS-CoV-2.
    Senator Paul. Dr. Quay.
    Dr. Quay. The three sets of viruses that are closest to 
SARS2 are one from southern China, RTG-13, and a series of 
BANAL from northern Laos. As indicated there are probably 1,200 
letters different in the whole 30,000-letter alphabet. In 
nature, that takes approximately 40 years, so the most common 
ancestor is about 40 years ago. But most of that can be done in 
a couple days in a laboratory.
    However, I do not believe we currently have the starting 
material, the backbone on which SARS2 was found. I think it is 
one of the other 21,000 viruses in the database that was taken 
down at 2 a.m., September 12, 2019.
    Senator Paul. A great deal of information was destroyed by 
the Chinese.
    Dr. Quay. It was taken offline and not available. I do not 
know if it was destroyed.
    Senator Paul. Dr. Esvelt.
    Dr. Esvelt. If a Ph.D. student proposed to take a 30,000-
base-paired viral genome and attempt to passage it in the 
laboratory to acquire 1,000 or so mutations, I would say that 
is not a Ph.D. project. Go do something else. I concur with Dr. 
Ebright that the only way that you could get something so 
divergent would be to computationally design it and synthesize 
it, which could certainly have been done, from what dataset, 
and again, why? Why would you do such a thing unless you want 
to know what the ancestral virus was like and whether the 
ancestral virus was dangerous. There are basic science reasons 
why you might want to know where they all came from, but at the 
end of the day the reason why this research is of interest to 
us is the risk of pandemics.
    Again, why would you run the tests to determine whether 
something was pandemic capable? They certainly ran those on all 
of the other coronaviruses that they found and thought might be 
dangerous. On the other hand, they never published anything 
like that, right, and presumably they would have. They 
published their data on the other stuff.
    This is why I do not think we have enough information to 
know, but it was definitely not passaged in a lab from 
something that was maybe 7 percent----
    Senator Paul. I agree, and one of the things that tips us 
off that they may have been trying was in 2018, they asked for 
money from Defense Advanced Research Projects Agency (DARPA), 
and in that money they wanted to insert the furin cleavage 
site, which makes it highly infectious in humans. If they had 
the idea of that and they are asking for money, they must have 
thought, wow, we can do this and this is going to be a great 
experiment. Even our government, finally, at that point, 
decided not to fund that.
    But what they are asking for, and this is why I think there 
was a ``holy cow'' moment when all of a sudden these scientists 
see the sequence of COVID-19, they say, ``Oh, my goodness. 
Didn't they ask us, in 2018, to put that furin cleavage site 
in?'' Lo and behold, it is there.
    What I am going to ask, and I am going to finish with this 
and then we will have another round if some people would like 
to ask some other questions, is, Dr. Quay, could you sort of 
lay out, in as simple a fashion as possible, two or three items 
about the virus that makes you think it came from--and I do not 
think anybody knows, with 100 percent, whether this came from a 
lab or whether it came from animals, but if there is some 
compelling evidence that suggests it could have come from the 
lab. Even if it was a 10 percent chance it came from a lab it 
is another reason for us to be concerned about having oversight 
on this kind of research.
    Can you give me two or three things that this virus has 
that makes you think it is from a lab versus some of the 
evidence for MERS and SARS that it came from animals?
    Dr. Quay. Yes. There are three regions--the receptor 
binding domain, the furin cleavage site, and this protein 8 
from a gene called ORF8. With respect to the receptor binding 
domain, if you look at what happened with SARS1, we have the 
virus sequenced when it first was in civet cats in the markets. 
It jumped into a few humans. We have the virus sequenced then. 
It started infecting more. Then we have the virus sequenced 
when human-to-human passage could occur and an epidemic 
occurred. You can see the progression of mutations as the virus 
adapted from being in civet cats and then being in humans. The 
first jump into humans it had only 15 percent of the mutations 
it needed to support an epidemic.
    OK. Let us look to SARS-CoV-2. When you look at the virus 
that first entered the human population, out of all of the 
changes in the receptor binding domain there are 200 amino 
acids, 4,000 possible changes. There were only 17 mutations 
that could make it a better virus. Its receptor binding 
optimization was 99.5 percent, and, in fact, one of the 17 
ended up being the Delta variant. That kind of optimization, 
juxtaposed by the fact that there were no patients in Wuhan, 
36,000 blood-backed specimens tested for antibodies, not a 
single patient was infected.
    Let us go back to SARS1. Twenty percent of all people in 
the markets were infected while the virus was practicing to set 
up an epidemic, 1 percent of the general population. We would 
have expected 360 in the general population in Wuhan, and we 
had zero.
    Furin cleavage site has obviously never occurred in this 
related virus, the sarbecoviruses, that split from their 
cousins, the MERS viruses, around the time of William crossing 
the Channel, 1060. That was when sarbecoviruses came. There has 
never been a furin cleavage site, and the genetic sequence of 
it uses a code that has never been used, the CGG-CGG dimers, it 
is called, which has never been used before.
    Finally, ORF8, this protein that goes into the bloodstream 
and suppresses interferon response so you are asymptomatic, and 
suppresses major histocompatibility complex (MHC) antigen 
presentation, so you cannot make good antibodies. This was the 
subject of two master's theses at the Wuhan Institute of 
Virology. I have found no Western scientists that worked on 
this location in the genome before 2019. The protein is not 
present in MERS. It has a 5 percent homology in SARS1. Between 
SARS1 and SARS2 there is a protein there but it is only 5 
percent homologous.
    But this master's thesis, the first one optimized its 
function in suppressing interferon, symptoms of fever and 
chills, and suppressed its antigen presentation. The second one 
was making synthetic biology tools so you could move it around 
inside genomes.
    Senator Paul. To reiterate, there have been no animals 
found that have COVID-19. When they did find that animals had 
the first SARS and MERS, they found it out within months. When 
they tested the animals in question, 90 percent of the animals 
had the SARS virus. We have not found any animals yet with 
COVID-19. Most viruses that come from animals first are not 
very infectious at first and they infect a few humans. You do 
not have a pandemic that does this. It smolders and then does 
this. During the smoldering phase you find background 
antibodies that people have had it, even if they do not know 
they had it.
    When they tested the background of people who were working 
with the animals that had COVID they found 20 percent of them 
hand antibodies to having had SARS.
    Dr. Quay. SARS1, yes. Correct.
    Senator Paul. But then if we test the people in the 
marketplace we are not finding that. If we look at the people 
in the Wuhan marketplace we are not finding significant numbers 
that were positive, and finding almost nobody positive from the 
previous year that had been ill.
    Dr. Quay. No. It is zero out of 36,000.
    Senator Paul. Thank you.
    Why do we not do a second round, and we will go in the same 
order. Senator Johnson.
    Senator Johnson. Dr. Quay, how did we find out about the 
Nipah virus?
    Dr. Quay. In December 2019, five patients at a Wuhan 
hospital had their specimens sent--a bronchial lavage, where 
they stick into the throat and get a specimen--to the Wuhan 
Institute of Virology for sequencing. The process is to amplify 
it with a polymerase chain reaction (PCR) process. You make a 
lot of copies of what is in the specimen and you usually, 
inadvertently, make copies of what is going on in the 
laboratory.
    The Wuhan Institute of Virology probably regrets, but they 
put a 55 million-letter database of the background information 
up in the gene bank, which is the NIH's database there, of 
everything going on. We found 20 strange things in these 
patient specimens--honeysuckle genes, horse viruses. Nineteen 
of the things we found were in publications from the laboratory 
over the previous 2 years. This clearly was a signal of what 
was going on in the lab around there.
    The one thing they did not publish on was the cloning 
vectors of the Nipah virus. It is in the patient specimens 
because it was in the laboratory at the time, not in the 
patients, and they have never published on that at this point 
in time.
    Senator Johnson. How do we know it is 60 percent lethal?
    Dr. Quay. The Nipah has had epidemics, sporadic epidemics 
in the belt around Africa and India, Bangladesh, and it is 
between 60 and 80 percent lethal in the pockets where it comes 
out. It is not very transmissible like Ebola so it kills 100 or 
200 people and then burns out. But if they made it airborne it 
would be different.
    Senator Johnson. OK. This is a virus that occurs in nature 
but you detected it in this database.
    Dr. Quay. I detected cloning vectors of it. They are 
manipulating it, which is not allowed by biological treaties.
    Senator Johnson. That is a pretty scary scenario right 
there, that the Wuhan lab that might have been the originator 
of the coronavirus is fooling around with something far more 
deadly.
    Dr. Quay. Yes.
    Senator Johnson. Obviously mum is the word.
    Dr. Ebright, I am a little confused. You talked about, if 
we were doing gain-of-function on the current coronavirus that 
would be OK. That is not the indication I am getting from Dr. 
Esvelt here. The thing that really concerns me is--and I am not 
saying that you are saying this is the justification. You are 
just saying the reality situation is we have research centers, 
we have scientists that are doing this gain-of-function 
research, I mean very dangerous gain-of-function research, for 
two completely unnecessary reasons, because it is fundable and 
it is publishable. You have a little greed involved and you 
have hubris. Is that what you are saying?
    Mr. Ebright. The research is performed because it is fast, 
easy, fundable, and publishable. In the academic research 
ecosystem those are determinants of what research gets pursued.
    Senator Johnson. I view that as a very corrupt research 
ecosystem. If that is what is driving research, and very 
dangerous research, it is so that you can get a funding grant 
just to do something for grins and then he can publish it and 
get the academic kudos for it. I am sorry. I just find that 
sick.
    Mr. Ebright. I would not use the term corrupt. I would not 
see any real difference between this than the activity of a 
hedge fund or the activity of a bank or a broker. The key point 
is that because of these incentives, self-regulation from 
within the community is insufficient. The scientific research 
community will follow the incentives. It will never effectively 
self-regulate on these issues.
    For this reason, we have regulations with force of law for 
vertebrate animals research and for human subjects research. We 
need regulations with force of law for gain-of-function 
research of concern.
    Senator Johnson. I think the difference, if it is a bank or 
hedge fund, they are doing things for an economic incentive, to 
produce something to fund a manufacturing site or fund some 
kind of business. I am not hearing the benefit of this 
research. I am seeing the risk. I am seeing the danger. I am 
not seeing the benefit, other than what you are saying, for the 
researcher itself to get money, to do something that is 
dangerous, and have the academic kudos for being published.
    I do not know. Maybe you do not like the word ``corrupt.'' 
It is completely useless. It has no benefit to society. It just 
has risk. It just has danger.
    Dr. Esvelt, do you disagree with that assessment?
    Mr. Esvelt. I think that all institutions follow their 
incentives, and I think that set of incentives--fast, easy, 
fundable, and publishable--insofar as fundable and publishable 
are ways of curing heart disease and cancer and forestalling 
aging, those are all certainly fundable and publishable, 
perhaps not as fundable as we would like. Certainly research 
into defenses against the next pandemic is right now somewhat 
fundable. I wish it could be more fundable. It is publishable, 
right? It depends on----
    Senator Johnson. What you are talking about fundable and 
publishable have a beneficial reason. What I am hearing from 
the three of you witnesses, there is just not a benefit to 
this.
    Mr. Esvelt. One clarification. You mentioned on endemic 
human viruses like SARS2, why do this. If you want to predict 
the next variant that is going to arise anyway, within a couple 
of months, one that already exists, then that is why 
researchers do things like deep mutational scanning of the 
spike protein to look and see which ones of them might have a 
bit of an edge in terms of maintaining infection while evading 
immunity a little bit, and is likely to maybe be the next 
variant. That then lets us design the next vaccine against the 
variant and guess correctly.
    We have to do this with flu every year. Flu vaccines are 
terrible, usually, because we often guess wrong. That kind of 
research can help improve our guess as to what is correct.
    But as soon as you make a change that would not occur in 
nature, then it becomes dangerous because that is something 
that a more pathogenic mutation could be inserted. That becomes 
a problem and there is no justification for doing that because 
nature is not going to come up with it.
    Senator Johnson. OK. Thank you, Mr. Chairman.
    Senator Paul. Senator Marshall.
    Senator Marshall. Thank you, Mr. Chairman, and thank you 
again to our witnesses for hanging in there with us.
    I want to start by going back to a comment that Dr. Esvelt 
made, that USAID paid for gain-of-function research in China. 
Most people do not realize that because USAID will not give us 
the records, and we have been trying for over a year to get 
those records, which is why we are holding up one of their 
nominees as well. Thank you for pointing that out, Dr. Esvelt.
    I am going to go to Dr. Ebright next and talk a little bit 
more about EcoHealth Alliance, about their record of 
noncompliance. They could not provide research records to NIH 
when NIH requested them. They did not have an adequate 
agreement with Wuhan Institute of Virology. They do not use 
appropriate rate of pay for researchers. There continues to be 
noncompliance with financial conflicts of interest policies.
    Dr. Ebright, based upon EcoHealth Alliance's record of 
noncompliance, should they continue to be eligible to receive 
Federal funds?
    Mr. Ebright. Their most important aspect of noncompliance 
was that they were informed by the NIH, in terms and conditions 
in the notice of award for their grant, that in the event they 
encounter viral growth in their engineered coronaviruses that 
exceeded the growth of the parent coronaviruses by more than a 
factor of 10, they must immediately inform NIH and immediately 
stop the research. They did not do this.
    That is not merely a financial violation. That is a serious 
hazard violation and a violation that may be connected to the 
origins of the current pandemic.
    With that being said, it is inexplicable that they were 
awarded subsequent Federal awards and that they remain eligible 
to receive Federal awards.
    Senator Marshall. I need to submit for the record--thank 
you for the answer--a couple of articles. The first, I quoted 
Dr. Fauci. This is an article from Science, July 2012. A 
handsome, young Dr. Fauci. I want to submit that for the 
record.\1\
---------------------------------------------------------------------------
    \1\ The document submitted by Senator Marshall appears in the 
Appendix on page 1443.
---------------------------------------------------------------------------
    My next two questions I want to submit something from The 
Wall Street Journal, a couple of articles as well regarding 
genome sequences.\2\
---------------------------------------------------------------------------
    \2\ The document submitted by Senator Marshall appears in the 
Appendix on page 1446.
---------------------------------------------------------------------------
    Senator Paul. Without objection.
    Senator Marshall. We will go to Dr. Quay next. You may be 
familiar with the genomic sequences in NIH's database--I think 
you spoke about them--that Chinese scientists asked to be 
removed and how they were, from early COVID Wuhan patients. Do 
you believe there could have been more data in NIH's database 
submitted by Chinese scientists that could hold a key to the 
COVID-19 origins?
    Dr. Quay. Yes. This was a really nice piece of work by 
Jesse Bloom at the University of Washington, who found not in 
the NIH database but on some Amazon web servers the actual 
sequences of viruses from very early patients that had been put 
on GenBank and then removed before they were published and made 
available.
    The remarkable thing is, again, going to another piece of 
good research, the virus that first came out, the first Wuhan 
virus, is three mutations away from what we now know is 
probably the first virus, but that is a computational method. 
It is kind of complicated. But anyway, there is a prediction. 
There are three mutations that have never been seen in humans 
before the first virus that we have in humans. The specimens 
Jesse found had some of those.
    We know that the Chinese have viral sequences that are 
ancestral to what we have, and the more of those we get, the 
more we will get to the bottom of this.
    I will point out that these sequences were from September 
and October 2019, 2 months before any person in the market was 
sick. Again, the timing of the market spillover does not 
coincide with the genetics of the virus.
    Senator Marshall. Dr. Esvelt, anything to add to that?
    Mr. Esvelt. No, other than Jesse is certainly one of the 
foremost experts in this field, and if you want probably some 
of the best answers that science can give then I would 
recommend that you request his input.
    Senator Marshall. Thank you. My last question. For 20 
years, NIH sponsored EcoHealth's partnership with scientists 
from the Wuhan Institute of Virology. The Chinese scientists 
have bragged that their virus sample database is the largest in 
the world.
    They took that database offline in September 2019. NIH 
asked EcoHealth for research records. EcoHealth told them that 
the records are in the custody of the Chinese government. Is it 
possible that the database taken offline by the Chinese 
government was data collected by EcoHealth and belongs to 
American taxpayers? Dr. Quay.
    Dr. Quay. Since the work has been funded, in part, by U.S. 
taxpayers, then by definition access to that would be 
important. I also think that we do not have to rely on the 
Wuhan Institute of Virology for releasing that. I believe 
within U.S. jurisdiction there will be copies of that database. 
It is too valuable not to have in your own possession if you 
are doing research on it.
    Senator Marshall. Do you think there is any way we can 
still get any of that data that is missing? I feel like, 
somewhere we are going to find the grandfather of COVID, or the 
cousin or something here in these data banks.
    Why did they take them down? What is the advantage of them 
taking them down? Do you think we can ever find what we are 
missing?
    Dr. Quay. It was taken down at 2 a.m. on September 12, 
2019, which is--I guess everyone works hard but that is a 
little suspicious to be doing it at that point in time.
    I believe it contains closer precursors, and my hypothesis 
is it contains the one that is 50 mutations or 100 mutations, 
not 1,200 away, and it was too obviously a smoking gun.
    But again, if you are collaborating on that and you are 
spending 10 years building a database inside the Wuhan 
Institute of Virology, you are going to mirror that database in 
your own facilities, which means that it has to be at EcoHealth 
Alliance somewhere.
    Senator Marshall. Thank you. Dr. Esvelt, anything to add?
    Mr. Esvelt. Just note that I agree with Dr. Ebright's 
assessment from earlier, to the extent that China is doing this 
research, because it is scientifically sexy and glamorous and 
is fast, easy, publishable, et cetera. Chinese scientists have 
the same incentives as Western scientists in this regard.
    In fact, it is very clear that this research is not in 
China's strategic interest. China has no more interest than we 
do in handing out the blueprints to agents that can kill 
millions of people, including their people. This is not in the 
interest of any established, powerful nation. The question is, 
can we show leadership and persuade them of that?
    Because as long as we are doing it, we are making it--we 
are contributing to the fact that this is seen as glamourous 
research. It gets published in our top-tier journals. Many 
Chinese scientists get bonuses for publishing in our top-tier 
journals. We are driving these incentives because we persist in 
seeing this, again, as a health and safety issue rather than a 
national security issue.
    I think it is in our power to change it, and I think this 
is one issue where our interests are actually aligned with 
those of China, and indeed, every other established nation. 
These are asymmetric tools of mass death.
    Senator Marshall. OK. Dr. Ebright, anything we did not ask 
you that we should have?
    Mr. Ebright. That I do not know, but I just wanted to agree 
completely with the last remark by Dr. Esvelt.
    Senator Marshall. Thank you, and I yield back.
    Senator Paul. I want to thank everybody for being part of 
this hearing. I do not see this as the end. I see this as the 
beginning of trying to understand what caused the pandemic and 
trying to come up with solutions.
    Each of your statements, which is longer than your 
testimony, will be available, for anybody who is interested.
    I want to point out one thing from Dr. Ebright's testimony, 
for those who say, well, lab leaks should be discounted. They 
do not ever happen.
    At one point Dr. Ebright writes, ``The second, third, 
fourth, and fifth entries of the SARS virus''--this was the 
first one--``into human populations occurred as a laboratory 
accident in Singapore in 2003, a laboratory accident in Taipei 
in 2003, and two separate laboratory accidents in Beijing in 
2004.''
    For people who say that it is a conspiracy theory that this 
could have come from the lab, they are discounting our history. 
The history has had these lab leaks. Whether or not we will 
ever know, with 100 percent certainty, whether this came from 
the lab, we have had lab leaks, and we have to realize the 
potential danger of these pathogens.
    We did not get a great deal of time into the answer. We got 
a little bit into the answer, but each of the scientists we 
asked today were asked to let us know how we could better 
supervise or oversee this kind of research.
    The interesting thing to me is I think they all worked 
independently but they came up with basically very similar 
solutions, an independent body outside of the funding 
organizations or those receiving the funding, to make the 
recommendations, something akin to an independent agency like a 
nuclear regulatory agency.
    In fact, I have already been using the analogy when people 
ask me and say, ``What is this like?'' It is essentially we do 
not let anybody sell centrifuges to Russia or centrifuges to 
Iran. There are rules on the export of things. I think Dr. 
Esvelt, in particular, has talked about the security aspect of 
this.
    What I would really like to come of this, and I mean this 
sincerely, is I would like to have a bipartisan bill that comes 
forward for better oversight. Maybe it is not oversight of 
gain-of-function but maybe it includes things that some people 
consider to be gain-of-function. Maybe it is more general, 
pandemic viruses. There are a lot of ways we can discuss it.
    But the bottom line is I do not think the people doing the 
research are able to adequately and objectively regulate 
themselves, and I think having a million people die, there 
should be bipartisan curiosity in this, that we should be able 
to move forward.
    My hope is that your suggestions, that you have taken the 
time to put in writing, you have taken the time out of your 
busy careers to come here, that these suggestions will become 
legislation. If we can get a bipartisan bill to come forward, 
what I would like is that our people who help us write the 
legislation can communicate with the three scientists here. We 
are willing to hear from a dozen more scientists, anybody who 
wants to. I want scientists to be involved in this.
    But I do think that ultimately the people making the 
judgment should not be from one small field of science. Some 
have said, ``Well, none of the three scientists there are 
virologists.'' I do not have a problem with virologists being 
part of this, but I do have a problem with them all being 
virologists, the same way I have a problem with behavioral 
science being approved for funding by all behavioral 
scientists. I think that there need to be people who understand 
science on this, but I think there also needs to be people on 
the committee, as Dr. Esvelt as mentioned, that understand 
bioterrorism and biosecurity.
    I think it should be a mixture. This is something we can 
talk to the scientific community about. I do not think an 
absolute ban is what we want. What we want is better oversight 
of this. But we cannot have something where three projects have 
been looked at in the last 7 years. That means they are not 
looking.
    The fact that they did not look at what went on in Wuhan, 
and then some of the folks I asked in committee about this were 
saying, ``Oh, our scientists looked at it and approved it,'' 
even that is not really true. They did not look at the 
research. They just ignored the research. It did not go before 
the committee. They have not been honest.
    If we want trust in public health, trust in government, 
trust in science, trust in research, trust in the NIH, and 
trust in the grants that we give our universities, billions of 
dollars, we need to have transparency and honesty. We cannot 
have a committee where the people are cloaked in secret. I 
mean, what is this? This is completely insane.
    I think we have made some progress. I want to move forward, 
and I, for one, am open to work with any Democrat in the Senate 
to make this a bipartisan bill, and to make it an evenly-keeled 
where all the voices are heard, that we do not rashly create 
any legislation that would hamper science, but we create 
something that would have oversight and might save lives.
    I truly think that a million people died in our country, 
six million people died, and I think it was from a lab leak. I 
think it is something that we need to have precautions against. 
I think it was accidental, by the way. But I think if we do not 
do anything, what if this gets in the hands of somebody who 
actually really wants to harm America or the world, or just 
some psychopath? What could happen?
    Right now we are doing nothing and have changed no 
behavior. We have had this pandemic and we have changed not one 
bit of behavior. I think it is about time that we do get 
together, that we are all curious, and that we do not make this 
about Republicans and Democrats but make this about how we, as 
a people, come together to try to make this world a better 
place.
    Thank you all for appearing.
    [Whereupon, at 4:13 p.m., the Subcommittee was adjourned.]

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