On challenging tradition to treat infection

02 Sep 2015

Written by Dr. Tachi Yamada

I can remember vividly when, as a young academic physician in the early 1980s, I experienced the terrible tragedy of seeing patients with AIDS lying our hospital beds waiting to die from their HIV infections because we had no treatment for them. The feeling of sadness, frustration and hopelessness was almost overwhelming. With the typical hubris of those of us who trained in medicine in the 1970s we had assumed that the problem of infectious diseases was one that was disappearing because of the discovery of so many classes of antibiotics which were being used liberally to treat patients with all manner of infections. The AIDS epidemic was a sobering taste of what it might have been like to be a physician in the early 20th century when no treatments were available for even the most common of infections. It is a singular triumph of the medical and pharmaceutical science communities that the first medicine to treat the condition, AZT, became available within just 6 years after the seminal report of 5 patients with AIDS to the US Center for Disease Control in 1981.

Yet, today we are faced with the harsh reality that the treatment of infectious diseases has not made quantum advances since the advent of antibiotics and antiretroviral therapies. Why? Because in the face of medicines that threaten their survival, microbes simply evolve to become resistant to them. We have learned many things about delaying this process such as using combinations of antimicrobial agents so that a single mutation would not be sufficient to confer resistance. Nevertheless, it is inevitable that the microbes will find a way to survive – it is only a matter of time. One problem is that after the first heady days of antibiotic discovery it has been extremely difficult to discover new classes of these compounds. Most of the newer antibiotics have been chemical iterations of existing ones in the same class.

A bigger challenge still is to change the paradigm of thinking about treating infections. Rather than small iterative evolutionary advancements in science, what is needed are bold unprecedented and even revolutionary approaches to managing infections. Instead of the traditional approach of treating people with medicines that kill microbes, are there ways to enhance the natural human defenses against infections, or is it possible that microbes could be directed to kill each other, or can we invent extracorporeal devices that might rid the body of infection without putting the host at risk? Traditional ways of thinking have not yielded solutions so it is obvious that we need an ecosystem that promotes the challenging of dogma and the taking of big risks with a tolerance for many failures in order to find that needle in the haystack that will lead to success.

The full impact of a virulent microbe that resists therapy can be understood best in the context of an infection for which there is no treatment. Witness the recent Ebola crisis which threatened the whole world, or the SARS crisis when the economies of nations as wealthy as Singapore and Canada were put at risk. The problem of resistant infections must be viewed through the lens of national and global security beyond health risk alone. The emergence of a highly lethal and rapidly spreading antimicrobial resistant infection surely will lead to untold numbers of deaths and unimaginable misery. But, in addition, it could result in walling off of communities, closure of national borders, complete restriction of travel, disintegration of health systems and, subsequently, collapse of economies. The real possibility of such an apocalypse argues that the problem of antimicrobial resistance is the most important challenge that humankind faces today and must be met with a completely effective solution.

For this reason I am delighted to be able to take part in this modern-day Longitude Prize project. It is directed at addressing the problem of antimicrobial resistance by challenging the world to come up with a way to diagnose infections in an inexpensive, accurate, rapid and easy to use manner. By permitting health workers to use the right antimicrobial agent at the right time the selective pressure on microbes to develop resistance will be greatly reduced. Like the original Longitude Prize, success in the endeavor will have lasting consequences to make human life better. The harsh reality is that we cannot afford to fail in this effort.

Dr. Tadataka (Tachi) Yamada is a Venture Partner with Frazier Healthcare.