Maurice Green (virologist)
Maurice Green was an American virologist whose research career spanned more than six decades. He is regarded as a pioneer in the study of animal viruses, in particular their role in cancer. Green founded the at St. Louis University School of Medicine in the late 1950s, and later served as its chairman.
Early life
Green was born on May 5, 1926, in New York, New York, to Jewish parents, David Green, an emigrant from Russia, and Bessie Lipschitz, an emigrant from Lithuania. Green is the oldest of four children.Following graduation from high school in 1944, Green served in the U.S. Navy, after which he earned a B.S. degree in chemistry from the University of Michigan, Ann Arbor in 1949, and then M.S. and Ph.D. degrees in biochemistry and chemistry from the University of Wisconsin, Madison. He then pursued postdoctoral research training at the University of Pennsylvania School of Medicine, serving as an instructor of biochemistry from 1955 to 1956.
Career
Green joined the faculty of St. Louis University School of Medicine as an assistant professor in the Department of Microbiology in 1956, being promoted to associate professor in 1960 and then professor in 1963. In 1964, he became professor of molecular virology and founding chairman of the ; he has since held this title and position.Green was a well-known tumor virologist, with a research career that spanned over 60 years. He played a critical role in developing adenovirus as an experimental system and made many important contributions in virology and molecular biology, leading to over 300 authored/co-authored publications and one U.S. patent. He first coined the term molecular virology . Many of his graduate students and postdoctoral fellows have gone on to successful research careers, making significant contributions to the fields of virology, molecular virology, and tumor biology.
in signing the National Cancer Act of 1971. This pen was given to Green at the White House bill-signing ceremony. |295x295px
Green's research in the 1960s and early 1970s was highly regarded because of the insights it provided into the role of viruses in cancer. It is thus notable that in December 1971, Green was invited by U.S. President Richard Nixon to attend the signing of the National Cancer Act of 1971 at the White House, an event that is generally viewed as the beginning of the ‘War on Cancer.’ At that bill signing, he was given one of the pens used by President Nixon to sign the legislation.
Educational and professional honors given to Green have included: multiple honorary societies ; an NIH lifetime Research Career Award ; the ; the 1976 ; the 1990 American Cancer Society John Krey III Memorial Award; the 2002 ; and the 2002 Academy of Science of St. Louis .
Green married Marilyn Glick on August 20, 1950. They had three children: , Wendy A. Green Lee, M.D. ; and Eric D. Green, M.D., Ph.D. currently director of the , National Institutes of Health. Green has three granddaughters and two grandsons.
Research
Green was one of the founding scientists in the field of tumor virology, an area of biomedical research investigating the role that viruses play in cancer. His early studies were major contributions to the general armamentarium of techniques and concepts used in experimental virology today.In the late 1950s and early 1960s, Green was among the first scientists in the world to study biochemical features of virus replication in cell culture and to develop and apply the emerging concepts of molecular biology. His major focus of investigation was human adenoviruses. He and his colleagues worked out the basic parameters for working with these viruses – for example, how to grow them in culture, to purify the virions, to extract and characterize the viral DNA, and to study gene expression at the RNA and protein levels. This work established the kinetics of infection, and showed that the infection was divided into two major stages of gene expression.
In 1962, scientists at the discovered that certain serotypes of human adenoviruses can induce tumors in newborn hamsters. This finding was not only of scientific interest, but it also raised concerns because the military was using live adenoviruses as vaccines against adenovirus-induced acute respiratory disease. Green was asked to learn as much as he could as quickly as possible about the 31 distinct viral serotypes known at that time. His studies included characterizing the viruses’ DNA, investigating the tumor-inducing properties of the viruses, and determining the molecular and kinetic parameters of adenovirus infection. He showed that adenoviruses could be divided into distinct groups based on these and other properties. These classic studies served to establish adenoviruses as a powerful model system that has since been used to address more global questions about virus replication, human cell molecular biology, infection and immunity, and neoplastic transformation. In subsequent years, the study of adenoviruses has provided key insights into tumor suppressors, cell proliferation, and the host immune response. They also emerged as a vehicle for human gene therapy
Also in the early 1960s, Green and others showed that human adenoviruses could transform rodent cells in culture into a malignant state. The mechanism behind this phenomenon was a mystery at that time. In 1966, Green published a paper in the Proceedings of the National Academy of Sciences showing for the first time that transformed cells express adenovirus-specific RNA that could be labeled in a fashion that would allow detection based on hybridization to adenovirus DNA immobilized on filters. This pioneering work helped establish the principle – applicable to all tumor viruses and relevant to tumor oncogenesis more broadly – that adenoviruses transform cells via continuous expression of their genes rather than by a ‘hit-and-run’ mechanism.
In subsequent years, Green made many other contributions to adenovirus molecular biology. He discovered two of the proteins required for adenoviruses to transform cells, and also other proteins that usurp the infected cell and convert it into a factory for virus replication. This later work played a key role in further establishing adenovirus as an experimental system, attracting other research groups and producing many important discoveries. For example, RNA splicing were discovered using the adenovirus system by researchers at the Cold Spring Harbor Laboratory and the Massachusetts Institute of Technology
In addition to determining many of the basic concepts of adenovirology, Green conducted seminal studies to determine the role that these viruses play in human cancer. He demonstrated that although these viruses are endemic in the human population and have oncogenic potential in rodents, they appear to play no detectable part in the formation of any of the major human cancers.
Green studied not only adenoviruses but also many other tumor viruses. At the time, it was commonly hypothesized that inasmuch as tumor viruses cause certain cancers in animal species, they might also cause cancers in humans. Green embarked on a large study to ask whether human cancers contain tumor virus genes. This study, funded by the National Institutes of Health via the Virus Cancer Program, was a major component of President Richard Nixon's ‘War on Cancer.’ Green collected over 2500 tumor samples and analyzed them for the presence of different DNA and RNA tumor viruses. Nearly all the samples were negative. These carefully controlled data, which were published in a series of papers, argued strongly against a viral etiology of human cancer. One exception was the detection of papillomavirus DNA in urogenital cancers; Green was probably the first to make this finding, although he was the second to publish it in the scientific literature.
Later, Green's research extended to the RNA tumor viruses. Before reverse transcriptase was discovered by , Green wrote a review predicting that the enzyme must exist in the virion of retroviruses. In the early 1970s, he and his co-workers conducted important studies on the biochemical features of reverse transcriptases of avian and murine RNA tumor viruses. These studies revealed the subunit structure of the enzyme and helped define the polymerase and Ribonuclease H activities inherent with that enzyme. He coupled this basic research to the effort to detect RNA tumor viruses in human cancer. Tremendous effort was directed to the ‘simultaneous detection’ assay in which proteins are extracted from tumor samples, separated by size, and then examined for reverse transcriptase activity. There was angst associated with those studies because of the importance of the research and because the workers could occasionally detect weak activity. As was later shown, this activity was not due to infection by RNA tumor viruses, but rather to endogenous reverse transcriptase activity. These studies were negative, again arguing against a viral etiology of cancer.
In recent years, Green has focused his studies on the multifunctional adenovirus oncoprotein E1A, which is necessary for cell transformation of adenovirus non-permissive cells. He was among the first to demonstrate that individual functional domains within E1A are independent, an observation that has since been exploited by other laboratories studying a number of regulatory proteins. Most recently, Green has been focused on the 80-amino-acid E1A N-terminal transcriptional repression domain in order to understand the mechanism of gene control and regulation by this potent transcriptional repressor he has also examined the potential application of repressing medically important genes by E1A's transcriptional repression function
In addition to his own research, Green is well known for founding, building, and leading the at the Saint Louis University School of Medicine. This internationally recognized institute and its research faculty was the site of numerous important studies on viruses, cancer, AIDS, and contemporary molecular biology.
In summary, Green's research contributed to – and, in fact, greatly stimulated – the fields of virology and molecular biology. His contributions continue to illuminate fundamental aspects of virus biology, transcriptional regulation, and mechanisms of oncogenesis.