Antibiotic Treatments Over The Past Century
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.…
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 American's 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, 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.