Am. I. Trop. Med. Hyg., 30(3), 1981, pp. 509—515 Copyright ©1981 by The American Society of Tropical Medicine and Hygiene OPPORTUNITIES AND RESPONSIBILITIES OF THE REFERENCE CENTER* ROBERT E. SHOPE Yale Arbovirus Research Unit, Department of Epidemiology and Public Health, Yale School of Medicine, Box 3333, New Haven, Connecticut 06510 The title of this talk must seem forbidding to Let me sketch the background of the Arbovirus many of you. A reference center is a service or Reference Center at Yale, then I shall share with ganization which on the surface, and especially to you my personal biases about the responsibilities the uninitiated younger scientists, connotes a mu and opportunities which a reference center a.f seum with doddering curators. I hope today to fords. counter that image and to impart a philosophy Reference centers do not begin as reference cen which has been successful in the hands of those ters. They begin as collections of scientists with with whom I have been fortunate enough to col a common research interest, and recognition that laborate over the past 15 years, and which will be protoplasm in the form of type species must be essential in the future if reference centers are to conserved. They require a physical and financial continue to be effective. resource sufficient to characterize and maintain As you may guess, I shall draw heavily from type species, and a spirit to cooperate and share my own experience with the World Reference freely with others. I cannot emphasize too much Center for Arboviruses at the Yale School of Med that a reference center cannot succeed without icine. The same philosophy with principles and cooperation and sharing. corollaries extends to a wide variety of similar The center at Yale was an outgrowth of The programs which most of you either operate or in Rockefeller Foundation's program on arthropod teract with. I have in mind for instance the World borne viruses. The Foundation in 1953 set up a Health Organization Centres for Research and world-wide network of laboratories' to study the Reference, the American Type Culture Collection, distribution, epidemiology, and disease potential the Pan American Health Organization designat of viruses biologically transmitted by mosquitoes, ed dengue reference center at the Walter Reed ticks, and other biting arthropods. A base labo Army Institute of Research, the Research Refer ratory was also established in New York City, ence Reagents Program of the Research Resources directed by the late Max Theiler. The New York Branch of the National Institute of Allergy and City laboratory trained personnel in serologic Infectious Diseases, the developing National In identification techniques, many of which were ac stitutes of Health programs for cryopreservation tually developed there. It also produced reference of filarids such as Wucheraria bancrofti, the re reagents and received viruses for identification. A pository for Aedes mosquitoes at Notre Dame concept was adhered to in the Rockefeller Foun University, the Center for Disease Control region dation field laboratories—no exotic viruses were al center for arboviruses at Fort Collins, Colo to be introduced. This dictum insured that the rado, the National Institute of Allergy and Infec agents sent to the reference center were isolated tious Diseases tick collection at the Rocky in the field and also originated there; the new vi Mountain Laboratory, and the U.S. Department ruses could not be laboratory contaminants. of Agriculture facilities in Ames, Denver, and At about the same time as The Rockefeller Plum Island. In fact, each of you who maintains Foundation program started, other organizations a cell culture, an animal, an insect, or a micro including the U.S. Army, the U.S. Navy, the U.S. organism in your research program is in reality a Public Health Service, and several universities reference center. and foreign governments embarked on similar field programs. In many cases, viruses were re ferred from these programs to the New York Lab * Presidential Address given before the 29th Annual oratory for identification, and a serological clas Meeting of the American Society of Tropical Medicine sification of arboviruses was refined. and Hygiene, Atlanta, Georgia, 6 November 1980. In 1965 the New York Laboratory was moved 509 510 ROBERT E. SHOPE to the Yale School of Medicine under the direction Fort Detrick; Allen had supplied 40 ml of Rift of Wilbur Downs and was designated formally by Valley fever sheep antiserum which had passed the World Health Organization as the Interna safety tests and was received with U.S. Depart tional Arbovirus Reference Centre. ment of Agriculture permission. It had been vir The Yale laboratory today maintains a collec tually unused (but not forgotten) stored in the tion of over 400 distinct serotypes of arboviruses freezer for 10 years. When I asked Wil Downs and other zoonotic viruses including the arenavi why he requested it, he answered “Iknew we ruses. Virtually all described arboviruses and would need it,―and indeed we did. many other zoonotic viruses are maintained ex Working in vertical laminar flow biosafety cab cept for those prohibited by the U.S. Department inets, we inoculated the virus into baby mice and of Agriculture—Rift Valley fever, African swine BHK-2 1 cells. The complement-fixation test of fever, African horsesickness, exotic bluetongue Jim Meegan and Jordi Casals, using mouse anti types, and Nairobi sheep disease—and those gen, was positive for Rift Valley fever almost si zoonotic viruses so hazardous that they can be multaneously with the hemagglutination-inhibi worked with only in maximum security facili tion test using mouse serum antigen and with ties—Machupo, Lassa, Ebola, and Marburg. electron microscopy by Owen Wood which I would like, now, to give you several examples showed bunyavirus particles in the BHK-2 1 cells. of the opportunities presented by reference center The diagnosis was transmitted simultaneously to material, each of which illustrates a principle or the World Health Organization, Geneva; through a significance factor which enriched the reference the U.S. Navy to Egyptian authorities; and to the center experience. foreign quarantine authorities of the U.S. De The first principle is: interaction among many partment of Agriculture and the U.S. Public scientific organizations is essential to exploit the Health Service. The agriculture inspector was at full wealth of a reference center. In October 1977 Yale by 8 o'clock the next morning to supervise I received a phone call from Jack Schmidt of the disinfection of the hoods in which the work was Navy Research and Development Command. done. The Rift Valley fever strain was shipped to Jack said that one of their virologists at NAM Plum Island and to Fort Detrick; the remaining RU-3 in Cairo, James Meegan, working with materials at Yale were autoclaved. No fewer than acute phase sera supplied by Imam Zaghloul seven organizations helped in the identification. Imam of the Egyptian Ministry of Health, had Within 3 days the diagnosis was secure, but it isolated a virus from fever cases from Sharquia could not have been made without a tremendous and Qalyubia Governorates northeast of Cairo. reference resource built on cooperation of many Could Yale help identify the virus? We receive organizations and years of preparation. dozens of such requests each year but what made The second principle is: cooperation between this different was the magnitude and seriousness veterinary and medical professions is essential to of the problem. As we were to find out, about progress. This is not an original concept, but one 200,000 persons were ill and by official count, 600 which we tend to forget. I shall continue the Rift had died or were to die.2 My notes of the phone Valley fever story. The Egyptian health authori conversation indicate that we discussed the dif ties rapidly determined that huge numbers of cat ferential diagnoses: dengue and yellow fever, un tie, sheep, and camels had aborted or died of the likely in the absence of Aedes aegypti in lower disease, and its spread to Egypt stimulated work Egypt; Lassa and Marburg viruses, unlikely to ers at Plum Island to test U.S. Army-produced kill mice in the pattern observed; Bunyamwera vaccines in sheep and cattle both for altruistic rea and Semliki Forest viruses, do not usually kill sons vis a vis world needs, and for U.S. readiness persons; and Rift Valley fever, fits most of the should the disease be introduced to our soil. We observations, but what would it be doing in Egypt at Yale retained a vicarious interest in Rift Valley where it had never before occurred? fever. While waiting for Jim Meegan's arrival from But opportunities arise under the strangest cir Egypt, I tried to locate a Rift Valley fever anti cumstances. Jerry Callis and Jerry Walker of the serum. The virus and its antiserum are not readily U.S.D.A. Plum Island Animal Disease Center available in the U.S. Fortunately, with tremen phoned during late July last year. There had been dous foresight, Wilbur Downs in 1967 had con an airline strike affecting J. F. Kennedy airport. tacted W. P. Allen, then with the U.S. Army at Some Nile rats from the Sudan had come through PRESIDENTIAL ADDRESS 511 U.S.D.A. quarantine inspection there, but were microbiologist starts an experiment with an infec delayed, then finally shipped on to Denver where tious agent. It may seem simplistic to state that they were to be used in rat control experiments. the agent should be identified before the experi On arrival in Denver, some rats were dead and ment and even during and after the experiment.