The Medical Biochemistry of Poverty and Neglect
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Author(s)
Beginnings
One of the happiest memories from my early 20s was returning on the train from New York on a winter evening in 1980. Earlier that day, I had just met Professor Anthony Cerami, one of the youngest full professors at Rockefeller University and head of the Laboratory of Medical Biochemistry. I had just interviewed for the MD/PhD biomedical scientist training program at Rockefeller and Cornell Universities and was headed back to New Haven, Connecticut, where I was a Yale undergraduate senior major in molecular biophysics and biochemistry.
My life’s ambition was to explore the then emerging field of molecular biology and apply it to the study of medically important parasites. Earlier, a Yale professor I had met at a seminar and reception, the eminent protozoologist, Luigi Provasoli (1908–1992), had informed me that Rockefeller University was expanding its commitment to tropical pathogens and had begun studying them at the cellular, immunological, and molecular level. At that time, some of Rockefeller’s greatest and most important scientists—including the Nobel Laureate Christian DeDuve, Zanvil Cohen, William Traeger, and, of course, Tony Cerami—were creating a new field of molecular and immunological parasitology. During my interview, I was captivated by Tony’s philosophy of science, which (briefly stated) was to focus on the disease rather than a particular field of scientific inquiry and to use all tools then available to identify a disease target and develop new therapies. I knew shortly after meeting Tony at my MD/PhD interview that he was someone with whom I needed to work and from whom I could learn much. Today, in the little library of my office at Baylor College of Medicine, I still have in my possession the 1978–79 Rockefeller University catalog, which I remember devouring on that train ride back to New Haven. Under the section entitled “Laboratory of Medical Biochemistry,” it read: “The objective of the laboratory is to apply the knowledge of chemistry to understand the pathogenesis of diseases and to develop drugs to treat them." I knew even then that this would be my calling and place in the world.
Starting in the summer of 1980, and especially in the first years of the MD/PhD program, I remember how generous Tony was with his time, often meeting me for breakfast in the Rockefeller University cafeteria to kick around new ideas for a doctoral dissertation. Tony liked to push his graduate students to come up with new and innovative projects for their research. I always remember how proud he was of his MD/PhD students and their ability to break new ground and create game-changing paradigms.
My passion for studying human hookworm infection happened around this time and was written about in 2007 in a book by Dr. Gerald W Esch titled Parasites and Infectious Disease: Discovery by Serendipity and Otherwise. Briefly, while thinking about new projects in Tony’s lab, an epiphany came to me when I read a 1962 paper published in Experimental Parasitology by a Rockefeller parasitologist named Norman Stoll, who had since retired. The paper had the title “On Endemic Hookworm, Where Do We Stand Today?” In that paper, Stoll wrote: “As it was when I first saw it, so it is now, one of the most evil of infections. Not with dramatic pathology as are filariasis, or schistosomiasis, but with damage silent and insidious. Now that malaria is being pushed back, hookworm remains the great infection of mankind. In my view, it outranks all other worm infections of man combined . . . in its production, frequently unrealized of human misery, debility, and inefficiency in the tropics.”
Despite the fact that hookworm infection was generally acknowledged as a leading cause of global anemia, I can remember going to Index Medicus—the PubMed of its day—to discover that almost no molecular biology had been applied to hookworm during the 1970s and into 1980. I thought initiating molecular biology on hookworms could open some interesting doors in the field of molecular parasitology.
Moreover, working on hookworm for my dissertation was a great fit with the Rockefeller Foundation’s new Great Neglected Diseases of Mankind (GND) program, launched in 1977 by Dr. Kenneth Warren (1929–1996). Like Tony, Ken was also a scientific and medical visionary, who had the idea to fund world-class scientific units in the United States, including the Rockefeller’s Laboratory of Medical Biochemistry, and link them to leading overseas laboratories in Oxford, Cairo, Israel (Weizmann Institute), Stockholm, Mexico City and Bangkok to solve neglected disease problems. The emphasis was on parasitic infections that plagued people living in poverty. Ultimately, the activities of these molecular parasitology units would be integrated into a GND network that would meet regularly in Woods Hole or elsewhere. In addition to an extraordinary track record of scientific productivity and international scientific collaboration, the GND program and network trained an entire generation of scientists committed to tropical infections, many of whom remain close colleagues.
Tony and I took the approach to try to better understand the hookworm parasite and its relationship with the human host by identifying molecules that adult hookworms release as they feed on human blood. One of those, published in the Journal of Experimental Medicine, turned out to be a protease that had the ability to degrade host fibrinogen and other blood products. Working daily with Dr. Nguyen Le Trang, a senior research scientist at the Laboratory of Medical Biochemistry, we were able to isolate one of those proteases and even propose the idea that it might be possible to immunize people with such molecules as a potential vaccination strategy. Thus, in the true spirit of the Laboratory of Medical Biochemistry, we were able to take a global public health threat that today affects more than 400 million people—roughly one-third of the world’s people who live in extreme poverty—and identify a promising approach to preventing that disease.
Read the full article in Molecular Medicine.