Abstract
Dr H. Fred Clark, a colleague and friend, passed away on April 28, 2012. Drs Frederick Murphy, Stanley Plotkin, and Paul Offit, who knew Fred at different stages of his career, recall his life.
Frederick Murphy
Fred was a born naturalist; he might as well have shipped out with Joseph Banks on the HMS Endeavor or with Charles Darwin on the HMS Beagle. Even as a veterinary medical student at Cornell this was evident to his classmates. For example, he was captivated by the behavior of the large rattlesnake kept (behind glass) by an anatomy professor, and in his off time, working at Cornell's Baker Institute for Animal Health, he performed investigations on Western equine encephalitis virus and on a unique pathogenic mycoplasma that he isolated from a wild rabbit.
Fred spent two years at the Centers for Disease Control and Prevention (CDC) in Atlanta, working with the great Charles Shepard, a world authority on rickettsial diseases and the person who in 1960 cracked the age-old dilemma of working with the etiologic agent of leprosy, Mycobacterium leprae. Shepard did this by inventing the mouse footpad system to grow the bacterium. He then used the system for antibiotic sensitivity testing, the basis for all subsequent antibiotic treatment regimens. Since the success in cultivating M. leprae lay in the lower temperature of mouse footpads (~34°C), other similar sites were sought. I remember that for years Fred kept a very large black rat snake (Elaphe obsolete, the largest snake in the eastern US) in Shepard's unused large autoclave. Staff members from throughout the Division of Viral and Rickettsial Diseases came by regularly at feeding time. Alas, M. leprae did not grow in the snake, and it was not until 1970 that the nine-banded armadillo was used to grow the bacterium.
While at CDC, Fred also worked on mysterious viral isolates from salamanders, lizards, and snakes, obtained during heroic outings in the woods of north Georgia on weekends. Some of these isolates entered the rather obscure but intriguing literature of vertebrate mammology; others were lost in the mist of time, but all reflected Fred's bent as a naturalist. Fred visited CDC some years later and spent a day in those north Georgia woods with me and with my four sons. It was a fantastic, enchanting day, remembered well by the boys, as Fred caught salamanders under every rotten log and then proceeded to give lessons in their biology and natural history—an enchanted teacher who enchanted students.
Stanley Plotkin
I first met Fred when he came to the Wistar Institute in 1968 to work on rabies. I had come myself to Wistar in 1957 and among other things was involved in rabies vaccine development. It soon was apparent to me that he was a clever and talented worker in the laboratory, and also that he was an independent and strong character. So we became friends.
In the rabies lab Fred did fundamental studies on how rabies virus spreads from neuron to neuron, how growth in neuroblastoma cells increases its virulence, and how it could cause chronic disease. At a certain point in the early 1980s, funding for rabies gave out, and Fred looked around for another project to work on. By that time I also had a lab at The Children’s Hospital of Philadelphia, and had obtained funding to develop a vaccine against human rotaviruses, which cause diarrhea and vomiting in infants that can lead to dehydration and death. One estimate at the time was that 600,000 infants per year were dying of rotavirus disease.
When I realized that Fred was available I jumped at the chance to hire him. He immediately attacked the problem, which was not simple. As happens often in science, his first discoveries were only partly satisfactory, and later a serious safety issue, induction of intussusception, was identified in tests of a rotavirus vaccine developed at NIH. But Fred persisted with determination and made reassortants between bovine and human viruses that were both safe and effective.
Working with Paul Offit and me, Fred thus found a path that eventually led to a successful licensed vaccine, RotaTeq. This vaccine has already dramatically reduced rotavirus infection in the US and is saving thousands of infants’ lives in poorer countries.
But Fred was not only a talented laboratory scientist. He was deeply interested in helping human beings here and in developing countries, particularly Haiti, and unlike some of us his interest was an active part of his life, to which he devoted much energy. It is not surprising that his last effort before his fatal hospitalization was to attend a fundraiser for Fonkoze, an economic development agency in Haiti of which he was a founding member. His humanitarian instincts were part of the reason that he was so deeply invested in developing a rotavirus vaccine.
Thus, Fred was not only a talented scientist, but an excellent and committed human being, and by the way equipped with a droll sense of humor. I will certainly miss him as a scientist and as a friend. Perhaps his best epitaph was something written by himself: “An investigator seeking a natural progression of thoughts and experiences leading to a lucky success in developing a life saving vaccine would find only confusion. I was blessed by a plethora of experienced mentors who gifted me with useful insights and was equally blessed by those who abandoned me to feed upon my own ideas. It was a grand ride in a wilderness of unknowns. It may have led to a vaccine capable of controlling a source of terror to parents everywhere. It may even survive us. What more could one ask?”
Paul Offit
I first met Fred in 1980, when beginning a fellowship in infectious diseases at The Children’s Hospital of Philadelphia. While searching for a research project, I interviewed with Fred in his office. He was just beginning to study human rotaviruses with an interest in developing a vaccine (which would come 26 y later). Fred was calm and engaging, explaining the importance of a rotavirus vaccine for the world. While Fred was talking, I couldn’t stop looking at a picture just above his left shoulder. It took me a while to figure out who it was. Eventually, it hit me: Dag Hammarskjold, former Secretary General of the United Nations and one of only a handful of people to win a Nobel Prize posthumously. It was an odd picture for a scientist to have on his wall. But it told me something about Fred. Like Hammarskjold, Fred was dedicated to justice, fairness.
For 30 y, often interacting seven days a week, Fred taught me what I needed to know to be a scientist. He was a master of logic, invariably knowing exactly what the problem was as we struggled to develop a small animal model to study the disease. This allowed us to eventually determine several aspects of rotavirus pathogenesis and immunogenesis as well as the genetics of rotavirus virulence and neutralization phenotype. But in the midst of the science Fred never let me forget why we were doing what we were doing. One of the single happiest moments in my life was seeing the pictures of Fred taken during a trip to Nicaragua to celebrate the introduction of our vaccine. Surrounded by the Minister of Health and hundreds of adoring parents, the look on his face was beatific. He had done what he had set out to do. Who among us ever gets a chance to make that claim?
Submitted on behalf of the global infectious diseases community by Paul Offit, Stanley Plotkin, and Frederick Murphy