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PHRI: A Seven Decade Legacy of Excellence

PHRI was established in New York City seven decades ago as a freestanding research institute that emphasized the application of basic science knowledge to address major health issues. In 1942, Fiorello LaGuardia, Mayor of New York City, established the Public Health Research Institute with Dr. Ralph Muckenfuss, director of the Bureau of Laboratories, as the first director of the Public Health Research Institute. It was a unique structure being the only basic medical research organization at the time receiving municipal support. The original payment from the City was $100,000 per year.

Through the decades, PHRI scientists have made seminal discoveries in the fields of biocehmistry, genetics, micro-biology, virology, immun-ology, cancer, neurobiology, and infectious diseases. These researchers, many of whom are household names in science and medicine, forged a culture of discovery that earned them numerous awards including membership in the National Academy of Sciences and subsequently a Nobel* prize while at PHRI or after their departure to other institutions. (*Eric Kandel received his Nobel award at Columbia in 2000.)







A Subjective History of the Public Health Research Institute

By Leonard Mindich

Five ocean liners from Hamburg were sitting at anchor in New York harbor in 1892. A cholera epidemic was raging in Germany and a number of passengers on the ships showed signs of the disease. New York City had large areas of poor sanitation and squalor. The outbreak of a cholera epidemic in New York was a real threat. Yet, there was no mechanism for determining which of the passengers were infected. This was the state of affairs when the antecedent organization of the Public Health Research Institute was created.

The state of biomedical research in the this country is different today from what it was at the turn of the century and even from what it was in 1942 when the Public Health Research Institute was established. We know so much more about the genetics and chemistry of living systems. We are in the midst of an incredible revolution in the increase in biological knowledge. The nucleotide sequences of human genomes have been determined. We can transfer genes from one animal to another, from bacteria to animals and from animals or humans to bacteria. Yet, we are back where we started.

Geneticists of the early twentieth century would probably be amazed to see the progress that has taken place in their field. The same is true for cell biologists, neurobiologists, immunologists and biochemists. However, early microbiologists would find a sobering and challenging situation. Although many of the bacterial diseases that were the scourges of mankind for millennia have been conquered through the development of antibiotics and prophylactic immunization, we are still subject to a large number of infectious diseases. Many of these diseases are as devastating as plagues. In the United States and in some African countries, AIDS has raised the specter of uncontrollable massive infection of populations.

The situation was similar at the beginning of the past century. The diseases were different, but the fear was the same. Pneumococcal pneumonia, diphtheria, whooping cough, small pox, polio, flu, tuberculosis, and scarlet fever were only some of the maladies that society faced. The then recent advances in bacteriology offered the hope that a concerted attack on these diseases would yield relief. Institutes were set up in many parts of the world to sponsor research aimed at the eradication of infectious diseases. Some of these institutes have grown into universities; others have remained as institutions devoted primarily to basic research of relevance to medical or infectious disease problems. The Pasteur Institute in Paris is probably the most famous example that has retained its original mission and much of its original form.

In 1892, at about the same time that these great institutions were being created, the City of New York established an emergency diagnostic laboratory to deal with an outbreak of cholera. Dr. Hermann M. Biggs, who had lobbied for its establishment was named as the head of this laboratory. He soon recruited Dr. William Hallock Park, one of the few trained bacteriologists of the time. Dr. Park was to become the leading force in the development of a highly professional and innovative service of the Department of Health. During the 43 years that Dr. Park was active in the Department of Health, a number of diseases were confronted and the Department was responsible for both diagnostic work as well as development of treatments and production of therapeutic or prophylactic materials. Much of the work done there served as models for public health research and activity for the rest of the country and world.

In 1910 this enterprise was established as the Division of Laboratories and in 1913 the name was changed to the Bureau of Laboratories, which ultimately had a Research Laboratory and a Diagnostic Laboratory. The research program of the Bureau of Laboratories was facilitated by the appointment of Dr. Park as Professor of Bacteriology at New York University in 1898. The university appointment served as a bridge for the infusion of academic talent and philanthropic funds into the Bureau. Some of the Bureau staff had joint appointments in the department of Bacteriology.

Dr. Park retired in 1936, and with his departure the connection with New York University was broken. It became apparent that a mechanism was needed to enable the research program of the Bureau of Laboratories to accept funding from sources other than the municipality and to be able to function outside the restrictions of municipal programs. During the mayoralty of Fiorello LaGuardia, it was decided to set up the Health Research, Inc, which would be a mechanism for the support of research in the Bureau of Laboratories, allowing for greater efficiency than possible within a municipal organization and free from political influence. The Health Research, Inc. became the Health Research Fund, Inc. The Fund was self supporting through its accepting of research funds and its association with the Manhattan Convalescent Serum Laboratory which was developing and selling sera from convalescent patients as therapeutic agents. Although the Fund was operating successfully, it was felt that a reorganization was necessary to facilitate the research program. Mr. David M. Heyman and Dr. Thomas M. Rivers, both members of the Board of Health became interested in this problem and ultimately formed a committee that recommended that an organization with a long term contractual arrangement with the city was needed. In 1942 the Public Health Research Institute was established. Dr. Ralph Muckenfuss, who was the director of the Bureau of Laboratories, was designated as the first director of the Public Health Research Institute.

It was unique in being the only basic medical research organization receiving substantial municipal support. The original payment from the City was $100,000 per year. Thirty years later this had reached $350,000 per year with the State contributing the same amount. This arrangement continued until the financial crisis of 1977 forced the City to suspend payments. The ability of the PHRI to weather a reduction in funding of $700,000 per year was a testimony to the initiative of the staff, its ability to garner additional funding and the high regard that PHRI had with the National Institutes of Health.

The Institute was comprised of three departments at its inception. These were Infectious Disease, Applied Immunology and Nutrition, which became Biochemistry. Though small in size and housed in simple quarters at 16th Street and the East River, the quality of work and the recognition of the staff of the Institute were great. Among the early members of the staff were Drs. Freund, Lowry, Colowick, Kalckar, Stetten, Racker, Ratner and Hirst. Dr. George Hirst was ultimately to become director of the Institute for 25 years. During this time the Institute grew in size and eventually moved to a new building at 26th Street and First Avenue. The site of the building is across the street from the original Carnegie Laboratory of New York University where much of the early work by Park and his associates was done at the turn of the century.

The accomplishments of the Bureau of Laboratories under Dr. Park include the development of testing for diphtheria, the inoculation of the population of New York against this disease, the testing of tuberculosis vaccines, the testing of the population for tuberculosis, the pasteurization and grading of milk as a means of combating both tuberculosis and summer diarrhea which was a major killer of children. The famous case of "Typhoid Mary" was dealt with along with the general problem of dealing with disease carriers. The Bureau was a leader in the analysis of pneumococcal pneumonia and in the preparation of therapeutic sera.

The Public Health Research Institute extended and deepened the research activities of the Bureau. The Institute became world renowned for the pioneering work of Dr. Jules Freund on the stimulation of the immune response. The viral hemagglutination test was developed at PHRI by Dr. George Hirst. It was here that the complexity of the influenza genome was first understood. The nature of cell receptors for virus infection was first clarified at PHRI. In biochemistry, major advances in the understanding of metabolic processes were made. The structure responsible for the transduction of nutritional energy into ATP, the molecular currency of bioenergetics was isolated in Dr. Ephraim Racker's laboratory at PHRI. More recently, important steps in the understanding of memory were taken in Dr. Eric Kandel's laboratory and some of the earliest experiments on oncogenes were done here in Dr. Hidesaburo Hanafusa's laboratory. In addition, the gene for the toxic shock syndrome was cloned at PHRI.

The original mission of the Institute was to conduct research in areas related to the public health problems of New York City. Over the years, the research program has included a rich assortment of projects involving basic biomedical research. Major advances have been made in virology, biochemistry, bacterial infectious diseases, neurobiology, genetics and immunology. The association of the Institute staff with New York University continued. Most of the staff had appointments as faculty in the School of Medicine and many graduate students at New York University pursued their doctoral research at the Institute. The Public Health Research Institute joined with the Bureau of Laboratories and New York University to create a research facility for the study of the etiologic agent of AIDS. This became the Aaron Diamond Aids Research Center, which now plays a major role in the search for treatments of HIV infections.

In the year 2002, the staff of PHRI moved to a new state of the art facility in Newark, New Jersey. The building was shared with the department of Microbiology and Molecular Genetics of the University of Medicine and Dentistry of New Jersey and the National TB Center. The staff became associated with UMDNJ and participated in the graduate student training program. PHRI operated independently until 2006 when it merged with UMDNJ and was established as a research center of the University. The PHRI staff has faculty positions in the departments of medicine, biochemistry and microbiology and molecular genetics. Dr. David Perlin, who had been the Scientific Director of PHRI since 1993, was appointed the director of PHRI in 2005. He has led the expansion of the Institute’s infectious disease mission for a number of years and has been instrumental in developing a further enrichment of the University’s activity in infectious disease research. We now have a regional biocontainment facility connected to our laboratory building, facilitating work on pathogenic organisms that require extraordinary care.

It is also sobering, that after so many years of startling medical progress, we should find that society is still prey to infectious diseases and that we are only at the beginning of learning how to combat these new challenges. The major emphasis of the research programs at PHRI at the present time is on infectious diseases. A number of groups are working on tuberculosis with approaches ranging from molecular and structural studies to evaluation of therapeutic strategies in third-world communities. Other groups are pursuing investigations of staphylococcal infections, fungal infections and HIV. The PHRI faculty is also involved in studies of immunology, virus structure, mechanisms of genetic exchange and gene expression. PHRI scientists are taking advantage and contributing to the advances in the localization and movement of specific protein and nucleic acid molecules in cells. PHRI has developed programs that have operated in other counties. A program of Directly Observed Therapy was conducted in Siberian prison camps through the Soros Foundation. Furthermore, a program dealing with community based tuberculosis is operating in South Africa, and currently we are developing important links with laboratories in China and Europe.





Directors:

Ralph S. Muckenfuss, M.D. 1941-1942
Otto A. Bessey, Ph.D. 1942-1945
Ralph S. Muckenfuss, M.D. 1946-1947
Walter W. Palmer, M.D. 1947-1950
L. Whittington Gorham, M.D. 1951-1956
George K. Hirst, M.D. 1956-1981
Richard P. Novick, M.D. 1981-1992
Lewis Weinstein 1992-2005
David S. Perlin, Ph.D. 2005-present





References:

Morris Schaeffer.
William H. Park (1863-1939): His laboratory and his legacy. AJPH 75, pp 1296-1302

Anon.
1963. History of the Bureau of Laboratories. pp 18
Microbiology in New York City
The New York City Branch
The American Society for Microbiology, 1975
Merrill W. Chase, Editor

Paul S. May.
New York's Commitment to Public Health. pp 12-18 in MNYC
Marion E. Wilson. The Gateway: Bacteriology Comes to America. pp 1-11 in MNYC

George Hirst.
The New York City Public Health Research Institute. pp 59-60
The Tenth Anniversary of the Public Health Research Institute of the City of New York. April 21, 1952. Reprinted from the Bulletin of the New York Academy of Medicine. December 1952, second series, vol. 28, no. 12, pp 827-841. A symposium with an address by the Surgeon General. Includes a history of PHRI by L. Whittington Gorham.



 
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