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.
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.