Medicine is not different than other branches of science. The germ theory of disease, proposed in the 16th century, needed three centuries of additional discoveries before completely replacing the “bad air” or miasma theory. In modern times the pace of change has picked up from centuries to decades. The treatment of “germs” with antimicrobial agents was embraced and celebrated with three Nobel Prizes in Medicine between 1939 and 1952. In 1939 it went to Gerhard Domagk for the discovery of prontosil, a sulfa drug and the first commercially available antibiotic (although they were not called that until 1942). In 1945, Sir Alexander Fleming, Ernst Boris Chain and Sir Howard Walter Florey were awarded the Nobel "for the discovery of penicillin and its curative effect in various infectious diseases". Then in 1952, Selman Abraham Waksman won "for his discovery of streptomycin, the first antibiotic effective against tuberculosis".
From treating microbes, the next wave of Nobel discoveries involved recognizing that microorganisms caused more diseases than originally supposed. There it took only a decade from the publication in 1984 in The Lancet of Barry Marshall and J. Robin Warren’s demonstration that Heliobacter pylori caused gastric ulcers to the acceptance by the NIH in 1994 that evidence supported H. pylori as the cause of peptic ulcer disease. They were lauded with the 2005 Nobel Prize in Medicine. And in 2008, the Nobel Prize in Medicine went to Harald zur Hausen "for his discovery of human papilloma viruses causing cervical cancer” and Françoise Barré-Sinoussi and Luc Montagnier "for their discovery of human immunodeficiency virus".
But change is sometimes difficult in medicine and the status quo can stifle new innovation. Few know that anticipating Marshall and Warren by almost three decades, a Greek physician, John Lykoudis, successfully treated his own gastroenteritis with antibiotics in 1958 and received a Greek patent in 1960. His attempts to publish his findings in JAMA were rejected and he was fined in 1968 for treating his peptic ulcer disease patients with antibiotics, even though it cured them.
In considering opportunities to invest in companies with new ideas in medicine, separating those whose departure from conventional wisdom represents ignorance or inexperience from those whose departure represents a fundamental rethinking of a long standing problem is a challenge. But the big ideas will almost always seem radical and even ridiculous at first because they flaunt or ignore the conventional wisdom all physicians have been taught.
A recent example was the publication this month of a “Metabolic theory of septic shock” (J. Pravda, World J Crit Care Med. 2014 May 4; 3(2): 45-54.) which proposed a non-immune cause for the damage and mortality of sepsis. This contradicts the long-standing cytokine storm hypothesis, which remains the prevailing theory despite over 40 clinical trials that failed to provide clinical validation and often resulted in increased mortality in the treatment arms.
A new company, Therashock, was started by the theory’s author, a practicing physician. With colleagues, they tested patient plasma samples from a failed sepsis trial for the predicted toxic agent. They found it increased in all sepsis patients as their condition gets progressively worse and falls in all survivors during convalescence. Furthermore, they found an existing approved drug that neutralizes the toxic agent in vitro.
Is this a successor to the Nobel pace of change? If so, it will follow a new path. Like the Greek physician, John Lykoudis, Jay Pravda is not in an academic institution where testing would be supported. Instead, his startup company, Thereshock, is seeking funding for the initial clinical trials in sepsis patients of an approved drug candidate, which Dr. Pravda believes will fundamentally change the course of sepsis. This could be a rare opportunity to fund a real revolution in medicine; something which will move the needle, no pun intended, in the Intensive Care Unit where sepsis is the most costly and dangerous diagnosis.