Elizabeth Beach Keller

American Biochemist Elizabeth Beach Keller (1918-1997) is best known for her discoveries regarding the formation of proteins, in particular the "cloverleaf" model of transfer RNA (ribo-nucleic acid). Keller's model illustrates how transfer RNA provides the directions for the genetic information within DNA to form proteins. A help to her fellow scientists, Keller's "cloverleaf" model was still used in textbooks into the twenty-first century.

The future biochemist was born Elizabeth Waterbury Beach on December 28, 1918, in Diongloh, in the Fujian Province of China. Keller's parents were congregational missionaries, and she was their youngest daughter. Returning to the United States as a child, Keller received her formal education there. After studying for several semesters at Oberlin College in Oberlin, Ohio, she received her bachelor of science degree from the University of Chicago in 1940. The following year she married Geoffrey Keller, but the marriage later ended in divorce. Five years after graduation, Keller earned her master's degree from George Washington University in Washington, D.C., and in 1948 she received her doctorate in biochemistry from Cornell University Medical College in New York City. After earning her Ph.D, Keller worked as an assistant professor at the Medical College from 1946 to 1948. From 1948 to 1949 she served as an Atomic Energy Commission fellow at the College of Medicine at Ohio State University in Columbus.

Took Posts at Educational Institutions

Following her fellowship at Ohio State, Keller devoted much of the next few decades to research and teaching. After teaching at the Huntington Memorial Laboratory of Massachusetts General Hospital from 1948 to 1950, she was a resident fellow at Harvard University from 1950 to 1952 and a research associate at the university from 1952 to 1958. From 1958 to 1960 Keller was both a resident fellow and a special fellow with the United States Public Health Service, and from 1960 to 1962 she served as a research associate at the Massachusetts Institute of Technology (MIT), located near Harvard in Cambridge. At both Harvard University and MIT, the focus of Keller's research was protein synthesis.

Worked with Holley at Cornell

In 1965, Keller was asked by future Nobel Prize-winning biochemist Robert W. Holley to join his biochemical research team at Cornell University in Ithaca, New York. As a member of Holley's team, she participated in a study of the structure of transfer RNA. Transfer RNA are small RNA molecules that contain 75 to 95 nucleotides. Individual cells contain many different transfer RNA molecules. Most of these molecules act as carriers of amino acids and take part in protein synthesis.

Holley, who obtained his Ph.D. in organic chemistry at Cornell University in 1948, began investigating various biochemical puzzle questions while still a student at the university. By 1960 he, together with other researchers, were able to demonstrate that transfer RNAs are involved in the assembly of amino acids into proteins. Holley and his research team devised techniques that could separate the different transfer RNAs from the cell's total molecular mixture. By 1965, he had determined the composition of the transfer RNA that incorporates the amino acid alanine into protein molecules. He did this by digesting the molecule with enzymes, identifying the pieces, then figuring out how they fit together. It was the first time that the sequence of nucleotides in a nucleic acid had been determined.

At Cornell, Keller helped Holley and his team build on previous research into the biochemistry of genetics. She investigated the structure of different nucleic acids and how these various structures affected the formation of proteins. During this period, as part of Holley's research team, she developed her well-known cloverleaf-shaped model of transfer RNA. Keller represented a very complex arrangement using the simplest of materials: paper, Velcro, and pipe cleaners. With these materials, she designed models of 77 subunits of a form of transfer RNA. According to some accounts, Keller enclosed a sketch of her cloverleaf model inside a Christmas card that she sent to Holley.

Keller believed that the cloverleaf-shaped was the best way to reveal how transfer RNA helps control the genetic information within DNA so that it is translated into protein synthesis. The specific function of transfer-RNA is to find and transport the appropriate amino acids that will be joined together to form proteins. Her model successfully described this, and it quickly became useful to other scientists in determining and illustrating how proteins are made inside of cells. As quoted by the New York Times, Cornell University colleague Joseph Calvo commented: "Her work was like taking the engine out of a car to see how it works. If it works outside the car, you know something."

Keller's contributions to Holley's team were an integral part of an enormous, ongoing effort to reveal the secrets of the genetic code. She provided information on which other scientists could build. However, because Keller tended to work behind the scenes, her name is not well known outside of her field. As Calvo remarked, "Anybody in the field would know that [cloverleaf] design today but would not know Betty. . . . [she] figured out a way to make proteins outside the cell so they could be studied."

The cloverleaf model was published by Holley as part of a larger work that detailed the genetic code of DNA. That extensive work would earn Holley the 1968 Nobel Prize in Physiology or Medicine, which he shared with Marshall Warren Nirenberg and Har Gobind Khorana. Taken together, these scientists' research helped explain how the genetic code controls the synthesis of proteins. In awarding the prize, the Swedish Academy of Sciences noted, as quoted on the Nobel Prize Web site: "The interpretation of the genetic code and the elucidation of its function are the highlights of the last 20 years' explosive evolution of molecular biology which has led to an understanding of the details of the mechanism of inheritance." In recognition of her contribution to his efforts, Holley shared some of his Nobel Prize money with Keller.

Later Career

Following her work with Holley, Keller focused on cancer-causing genes. After she retired in 1988, she was named emeritus professor of biochemistry and molecular and cell biology at Cornell University. She remained with the institution, conducting research in molecular biology, until shortly before her death at age 79 from acute leukemia on December 20, 1997. Keller was survived by her second husband, Dr. Leonard Spector, who she married in 1984, and by sisters Frances B. Bingham of New Haven, Connecticut, and Sandy Socolar, of New York City.

Books

American Men and Women of Science, 20th edition, R.R. Bowker, 1998.

Notable Women Scientists, Gale Group, 2000.

Periodicals

New York Times, December 28, 1997.

University of Chicago Magazine, April, 1998.

Online

"Nobel Prize in Physiology or Medicine," Nobel Prize Web site,http://nobelprize.org/medicine/laureates/1968/press.html (January 15, 2005).