[Congressional Record (Bound Edition), Volume 158 (2012), Part 13]
[Extensions of Remarks]
[Pages 18536-18537]
[From the U.S. Government Publishing Office, www.gpo.gov]




              ANTIBIOTIC TREATMENTS OVER THE PAST CENTURY

                                 ______
                                 

                         HON. BRIAN P. BILBRAY

                             of california

                    in the house of representatives

                       Monday, December 31, 2012

  Mr. BILBRAY. Mr. Speaker, I submit an essay by a San Diego innovator, 
Dr. Jeff Stein, President and CEO of Trius Therapeutics. Dr. Stein 
provides a fascinating account of the evolution in the discovery of 
antibiotic treatments over the past century.
  Dr. Stein's story is a vivid example as to why the private sector and 
public sector must work together to innovate as a means to save lives. 
Dr. Stein's company is one of many across the United States working to 
prevent infections and improve Americans' quality of life.

     Antibiotics Redux: Medicines That Change the Course of History


             Dateline: April 1945. Hill 913, northern Italy

       The 22-year old second lieutenant didn't know if it was the 
     machine gun, mortar round or artillery shell blast that got 
     him. Ordered to take out the machine gun nest hidden in a 
     mountaintop farmhouse all he recalled was that he was 
     dragging his platoon's wounded radio operator to safety when 
     he felt a searing pain in his upper back, then nothing. The 
     platoon medic took one look at the wounded lieutenant, 
     injected him with the maximum survivable dose of morphine, 
     indicating this by marking the letter ``M'' on his forehead 
     in his blood, then, assuming he would not survive his wounds, 
     left to treat other wounded platoon members. Although his 
     initial wounds, which included a damaged spine, an 
     obliterated kidney and a mangled right arm did not kill him 
     outright, the lieutenant was shipped home with little 
     expectation he'd survive. His parents were called to his 
     hospital bedside three separate times for a death vigil.


                     April 1945. Rutgers University

       Four-thousand miles west of Hill 913, 25-year-old graduate 
     student Albert Schatz,

[[Page 18537]]

     having recently submitted his patent application for his 
     discovery of the antibiotic Streptomycin, was trying to 
     figure out how to make enough of it for human testing. Tests 
     in guinea pigs showed that Streptomycin was safe and 
     effective in the treatment of infections caused by gram-
     negative bacteria and Mycobacterium tuberculosis. What 
     motivated Schatz was that in the first half of the century 
     bacterial infections--pneumonia, tuberculosis and blood 
     stream infections--were the top three causes of death in the 
     U.S. Wounded servicemen from World War II were especially 
     prone to infections from gram-negative bacteria and the only 
     other widely available antibiotic at the time, penicillin, 
     was largely ineffective against these pathogens. As a child 
     Schatz had experienced close friends dying of tuberculosis 
     and as a medical bacteriologist stationed in an Army hospital 
     in Florida during the early years of World War II, Private 
     Schatz sat helplessly by the bedside of dying solders whose 
     infections did not respond to penicillin or the experimental 
     antibiotics then available. He was passionate and highly 
     committed. Schatz produced Streptomycin from the soil 
     bacterium Streptomyces griseus growing in 1-liter 
     fermentation flasks running 24-hours a day in his basement 
     laboratory at Rutgers. By the end of 1945 he had produced 
     what he believed to be enough to treat one patient.


     March 1946. Percy Jones Army Hospital, Battle Creek, Michigan

       The attending doctors had virtually encased the 
     lieutenant's body in ice in a desperate attempt to lower his 
     body temperature. His weakened immune system made him 
     susceptible to infection and he had developed a severe lung 
     infection that subsequently spread to his blood with 
     resultant high fever. Massive doses of penicillin were 
     ineffective. He was dying. Word of his condition made its way 
     to Rutgers and Albert Schatz who subsequently rushed the 
     first experimental dose of Streptomycin to Percy Jones 
     Hospital to treat the lieutenant. The effects were nothing 
     short of miraculous. The lieutenant's fever broke within 24 
     hours and his lung infection cleared within a week. He would 
     survive. Later that year Streptomycin would go on to become 
     the world's first experimental medicine to be tested in a 
     double blind, placebo controlled clinical trial--the gold 
     standard in clinical research--where it was shown to be 
     effective and safe for the treatment of TB.
       The lieutenant's name? Bob Dole. Yes, that Bob Dole who 
     would go on to become Senate Majority Leader and, in 1996, 
     candidate for the Presidency of the United States.


                                 Today

       What is instructive about this true story of how an 
     antibiotic altered the course of history is that we are 
     presently on a retrograde course back to the early 20th 
     century with respect to the treatment of bacterial 
     infections. In the five-year period from 1983 to 1987 there 
     were 16 new antibiotics approved, whereas from 2008 to 2012 
     there were only two. At the same time, there is an explosive 
     emergence of multidrug resistant bacteria that are rendering 
     existing antibiotics largely ineffective. Combat veterans 
     returning from the Middle East have been diagnosed with drug 
     resistant strains of the gram-negative pathogen Acinetobacter 
     baumanii for which there are virtually no treatment options. 
     The multidrug resistant NDM-1 strain of Klebsiella 
     pneumoniae, which initially emerged from India, has spread 
     globally. One in three people in the world are infected with 
     a dormant version of Mycobacterium tuberculosis and a growing 
     number of these, reported in 60 countries, have emerged as 
     the highly virulent XDR-TB strain which is resistant to both 
     first- and second-line TB therapies and can only be treated 
     with a multiyear regimen of toxic drugs. Indeed, today's 
     situation would likely ignite the same sense of urgency in 
     Albert Schatz that he felt in 1945.
       Fortunately, we have passionate and committed contemporary 
     versions of Albert Schatz working to develop new antibiotics. 
     Because of the enormous capital requirements and complex 
     regulatory pathway for antibiotics, however, these 
     individuals are now largely found in small biotech companies 
     where the truly innovative antibiotics are currently being 
     developed. It is unclear which, if any, of these companies 
     will succeed in delivering critically needed medicines to the 
     market. As drug resistant bacterial pathogens continue to 
     proliferate, regulatory headwinds and market dynamics have 
     made antibiotic development extremely challenging. While it 
     is encouraging that this disconnect is receiving growing 
     recognition and action amongst regulatory authorities, these 
     small antibiotics companies, such as Trius Therapeutics where 
     I am CEO, wait to see whether these regulatory incentives, 
     such as the GAIN Act recently passed by Congress, can be 
     implemented in time to make the development of new 
     antibiotics clinically feasible and financially tractable. It 
     will certainly be a race in which the outcome could alter the 
     course of history and yes, save lives.

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