George Hirst

George Keble Hirst, M.D. (March 2, 1909 – January 22, 1994) was an American virologist and science administrator who was among the first to study the molecular biology and genetics of animal viruses, especially influenza virus. He directed the Public Health Research Institute in New York City (1956–1981), and was also the founding editor-in-chief of Virology, the first English-language journal to focus on viruses. He is particularly known for inventing the hemagglutination assay, a simple method for quantifying viruses, and adapting it into the hemagglutination inhibition assay, which measures virus-specific antibodies in serum. He was the first to discover that viruses can contain enzymes, and the first to propose that virus genomes can consist of discontinuous segments. The New York Times described him as "a pioneer in molecular virology." He worked at the Rockefeller Institute for Medical Research in New York City in 1936–1940, under the supervision of Homer Swift and Rebecca Lancefield, and then moved to the Rockefeller Foundation's International Health Division laboratories in 1940.

After the Second World War, Hirst joined the Public Health Research Institute in New York City, which had been established in 1942, where he remained until his retirement in 1983. He became head of the Infectious Diseases and Virology Divisions, and in 1956 succeeded L. Whittington Gorham as director of the institute, a position he held for nearly 25 years until 1981. During his tenure, he superintended its expansion and move to a new location on 26th Street and First Avenue. He also held a teaching position at the New York University School of Medicine.

Research

Hirst's earliest research, in the 1930s, was on bacteria, including pneumococci and streptococci, in collaboration with Lancefield and others. In 1940, at the Rockefeller Foundation, he started to work on influenza viruses – enveloped RNA viruses infecting humans, birds and other vertebrates – which were the focus of much of his subsequent research. Later, Hirst also studied other vertebrate RNA viruses, including poliovirus, mumps and Newcastle disease virus. Although viruses had been shown to infect animals in 1898, research on animal viruses was much less advanced in the 1940s and 1950s than that on plant viruses and bacteriophages, which were easier to handle experimentally.

Hemagglutination inhibition and vaccination

He soon realised that the hemagglutination assay could easily be adapted to measure the levels of antibody specific to the virus strain in human serum: any antibodies present bind to the influenza virus particles, prevent them from crosslinking red blood cells and so inhibit hemagglutination.

HIA is "a powerful epidemiological tool," according to virologist Vincent Racaniello,

Neuraminidase and the virus receptor

Hirst noticed that hemagglutination tended to wear off over time, and in 1942, he discovered that influenza virus has an intrinsic enzymatic activity that can release the virus from its attachment to red blood cells. Hirst demonstrated that red blood cells once de-agglutinated could not be re-agglutinated, and correctly deduced that the enzyme destroys a receptor for the virus on the red blood cells. This enzyme, then referred to as the "receptor-destroying enzyme" was later shown to be the influenza neuraminidase, another viral envelope glycoprotein, which acts as a sialidase. Like hemagglutinin, neuraminidase is essential for the influenza life cycle, being required for the progeny virus to leave the host cell.

Hirst subsequently found that influenza virus interacts with a similar receptor on its target cell during infection, providing a model for the initiation of viral infection that turned out to apply to all viruses.

Segmented influenza genome Starting in the late 1940s, Hirst carried out pioneering research into the genetics of animal viruses. Segmented genomes are also found in many other viruses.

Character and personal life His colleague Edwin Kilbourne described Hirst as "a scientist's scientist—a virologist's virologist" with an "incredible" variety of expertise and an "insatiable curiosity," who pursued the underlying explanation for his experimental findings with tenacity. According to Kilbourne, he was very private person who did not seek publicity. His non-scientific pursuits included music – he was both a musician and a musicologist – gardening, and the appreciation of nature.

Hirst married Charlotte Hart in 1937, and the couple had four sons and a daughter. In retirement he moved to Palo Alto, California. His wife predeceased him in 1990.

Key papers