In my spare time, I enjoy reading about the history of science, and since arriving at Cold Spring Harbor Laboratory last August, I have been particularly interested in the role of CSHL in the history of genetics and molecular biology.  I have been especially struck by the large number of prominent quantitative biologists who have been affiliated with the Laboratory, in one way or another, and I thought it would be useful to draft a short history focused on quantitative biology at CSHL.  Below is an initial attempt at this document.  I’d be interested in comments or corrections any history buffs out there might be able to offer.

Adam Siepel

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A Short History of Quantitative Biology at Cold Spring Harbor Laboratory

While quantitative biology was not considered a distinct area of focus at CSHL until recently, quantitative methods have long been important in research at the Laboratory. Charles Davenport, who introduced genetics to the Laboratory in 1898 and founded the Station for Experimental Evolution in 1904, arrived with a strong appreciation for quantitative methods. Early in his career, before his prominent and controversial role in the American eugenics movement, Davenport was an enthusiastic supporter of the “biometric” approach to the study of heredity, pioneered by Francis Galton and Karl Pearson in England and characterized by its heavy reliance on newly emerging statistical techniques. For a time, Davenport was a co-editor of Pearson’s influential journal, Biometrika. He later split from the biometricians and became a supporter of Mendelian models of inheritance but remained enthusiastic about mathematical modeling in genetics. (The major divide between the biometricians and Mendelians would eventually be reconciled by the great statistical geneticist, R.A. Fisher.)

In the early to mid 1900s, the summer program was central to research at the Laboratory. One summer visitor was a young Sewall Wright, who would later become one of the founders of theoretical population genetics, with Fisher and J.B.S. Haldane. Wright spent rewarding and formative summers at the Laboratory as a student in 1911 and 1912. He enjoyed his time at Cold Spring Harbor so much that he returned in the summer of 1920, while on leave from a position at the USDA. As it happened, he met his future wife, Louise Williams (also a biologist) at the Laboratory that summer.

Davenport’s son-in-law, Reginald Harris, became director of the Biological Laboratory at Cold Spring Harbor in 1924. In 1928, Harris introduced a program in biophysics that was critical in establishing the Biological Laboratory as a true year-round research institution. A few years later, in 1934, Harris launched the first Cold Spring Harbor Symposium in Quantitative Biology. The Symposium went on to become a hugely influential forum for the dissemination of research across many areas of biology, but particularly in quantitative biology. Harris’s successor, Eric Ponder, continued to promote quantitative biology, focusing the Symposium on topics in biophysics through 1940.

In the middle decades of the 20th century, biophysics gave way to genetics as the major focus of research at the Laboratory, but an undercurrent of quantitative thought remained. Perhaps the most influential CSHL-affiliated quantitative biologist of this time was Max Delbruck, a prominent physicist who had moved into biology in the late 1930s and became a key figure in the emergence of molecular biology. Delbruck was particularly important in stimulating interest in biology from other physical scientists, including Erwin Schrodinger, whose popular 1944 book “What is Life?” made an impression on both Watson and Crick, among many others. In 1945, Delbruck launched the Phage Course at Cold Spring Harbor Laboratory, which would continue until 1970 and was highly influential in training many pioneers in molecular biology (including a young Jim Watson), a number of whom were recruited from physics. A group led by Delbruck and two close associates who would later share the Nobel prize with him, Salvador Luria and Alfred Hershey, met regularly in the summer at Cold Spring Harbor Laboratory and became known as the Phage Group. Hershey moved his laboratory to CSHL in 1950, and soon afterward he and Martha Chase carried out the famous Hershey-Chase experiment, which helped establish that DNA was the molecule that carried genetic information.

While the best known research at the Laboratory during this era was focused on molecular genetics, there was one prominent evolutionist and population geneticist, Bruce Wallace, based at the Laboratory from 1947 through 1958. Among many other things, Wallace contributed to an influential CSHL Symposium on Population Genetics in 1955, which was attended by Wright, Dobzhansky, Kimura, Crow, and Mayr, among other luminaries of the field.

One interesting episode in this mid-century era concerned Claude Shannon, the father of Information Theory and one of the most influential applied mathematicians of the 20th century. It is a little known fact that Shannon’s Ph.D. thesis, submitted in 1940 to the Mathematics Department at MIT, was focused not on communication theory but on population genetics and was based in large part on work carried out at Cold Spring Harbor Laboratory. At the time, Shannon’s Ph.D. supervisor at MIT, the great inventor and engineer Vannevar Bush, was president of the Carnegie Institution of Washington, the parent institution of the Department of Genetics at Cold Spring Harbor, and he arranged for Shannon to visit the Laboratory to work with Barbara Burks, a highly respected behavioral geneticist with interests in mathematics and statistics. Shannon spent the summer of 1939 at the Laboratory and wrote a highly original thesis on an algebra that described genetic changes in an evolving Mendelian population. Sadly, he never published the work and it had little impact in genetics.

When the Biological Laboratory and Department of Genetics at Cold Spring Harbor finally merged in 1962, the new institution was formally called the “Cold Spring Harbor Laboratory of Quantitative Biology,” a name that lasted until 1970. The 1970s saw the introduction of computers to CSHL, led by Rich Roberts and Jim Garrels. Gradually, bioinformatics became increasingly developed to support growing efforts in DNA sequencing and genomics. In the 1990s and early 2000s, two computer specialists on the CSHL faculty, Lincoln Stein and Michael Zhang, became prominent in the bioinformatics community. Other investigators, such as Mike Wigler and Dick McCombie, made increasingly heavy use of computational tools and techniques in their research programs in genetics.

For a number of years, quantitative biology research continued in the absence of a designated unit, but in 2008, the Center for Quantitative Biology was created, with Mike Wigler as Director. The Center would later be rechristened the Simons Center for Quantitative Biology in recognition of generous donations from the Simons Foundation.

References

Crow, J. F. (2001). Shannon’s brief foray into genetics. Genetics (Vol. 159, pp. 915–917).

Provine, W. B. (1989). Sewall Wright and Evolutionary Biology. University of Chicago Press.

Provine, W. B. (2001). The Origins of Theoretical Population Genetics: With a New Afterword. University of Chicago Press.

Susman, M. (1995). The Cold Spring Harbor Phage Course (1945-1970): a 50th anniversary remembrance. Genetics, 139(3), 1101–1106.

70-Year Archive of Cold Spring Harbor Symposia on Quantitative Biology. http://symposium.cshlp.org/site/misc/index_archive.xhtml