Jack W. Szostak

• Born: November 9, 1952

• CANADIAN AMERICAN BIOLOGIST

Biologist Jack W. Szostak has led many groundbreaking investigations into the origins of life and genetic solutions to disease. His scientific contributions have earned him many honors, including the Nobel Prize in Physiology or Medicine in 2009.

• PRIMARY FIELD: Biology
• SPECIALTIES: Genetics; biochemistry; molecular biology

Early Life

Jack William Szostak is the son of Bill and Vi Szostak. His father, an aeronautical engineer with the Royal Canadian Air Force, was studying at Imperial College when Jack was born in London, England. He was still an infant when his parents returned to Canada. Jack and his two sisters grew up in Germany and Canada as their father was transferred to different posts during a twenty-year career. Eventually, the family settled in Canada near Montreal, Quebec.

An excellent student, Szostak became interested in science at an early age, particularly chemistry and biology. As a boy, he had a basement lab, stocked with substances his mother brought home from the chemical company where she worked, and produced several spectacular explosions. In high school, he built a hydroponic garden. One summer, he worked at his mother’s chemical-testing laboratory.

At the age of fifteen, Szostak graduated from Riverdale High School in the Pierrefonds-Roxboro section of Montreal. In 1968, he entered McGill University to begin his undergraduate education in cellular biology. Two years later, he joined the summer program at the Jackson Laboratory, a biomedical research institution in Bar Harbor, Maine. As part of the laboratory’s mission to investigate genetics in order to prevent, treat, and cure human diseases, Szostak worked with mice, dissecting thyroid glands to analyze mutant hormones.

Upon returning to McGill, Szostak concentrated on plant biology with a focus on algae and published his first paper on peptide hormones. He graduated with a bachelor of science degree in 1972, then used a fellowship to enter Cornell University to study the DNA sequencing of genomes of yeasts, microscopic single-celled fungi. He earned his PhD in biochemistry in 1977 and stayed at Cornell for two additional years to conduct further genetic research.

Life’s Work

In 1979, Szostak was appointed as a teacher of biological chemistry at Harvard Medical School and simultaneously became an independent researcher at the Dana-Farber Cancer Institute in Boston, Massachusetts. He continued to explore genetics, particularly the process of recombination, in which double-stranded DNA is broken and then repaired by combining it with other genetic material.

The following year, while attending a conference on nucleic acids, Szostak met Elizabeth Blackburn. A biological researcher at the University of California, San Francisco, Blackburn was conducting genetic experiments with freshwater protozoa that were similar in nature to Szostak’s studies of yeasts. In subsequent discussions, Blackburn and Szostak focused on the function of telomeres, regions at the ends of DNA molecules that protect chromosomes from degrading. The two scientists decided to collaborate to test whether Blackburn’s protozoa’s telomeres would work with Szostak’s yeasts.

Blackburn soon added former postdoctorate student Carol Greider, later a professor of molecular biology and genetics at Johns Hopkins University School of Medicine, to the collaborative team. In 1983, Szostak successfully became the first scientist to clone yeast telomeres. Meanwhile, Blackburn and Greider, applying the results of Szostak’s research, were able to isolate and identify telomerase, the enzyme that creates telomeres in DNA.

The recombination and telomere breakthroughs attracted many postgraduate students to Szostak’s lab and resulted in new opportunities. In 1984, when Szostak began teaching genetics at Harvard Medical School, he also accepted an appointment to the Department of Molecular Biology at Massachusetts General Hospital. By the late 1980s, when Szostak became a full professor of genetics at Harvard Medical School, his research team and Blackburn’s had expanded knowledge of telomere genetics. Szostak’s group produced mutated yeast cells that shortened telomeres and prematurely aged the cells; Blackburn’s group experienced similar results in mutating protozoan telomerase RNA.

Having exhausted the possibilities of yeasts, Szostak began to gravitate toward the study of ribozymes, which are ribonucleic acid (RNA) molecules that were discovered during the 1980s. Ribozymes catalyze chemical reactions and are key components in the study of how life originated billions of years ago, as well as potential agents in the creation of genetic therapies to combat diseases.

In the early 1990s, Szostak’s lab concentrated mainly on RNA. He developed a method of in vitro selection of biological molecules that would allow individual molecules to be screened for specific functions. Essentially an adaptation of the forces of natural selection, the test-tube technique allowed Szostak and his colleagues to evolve RNA aptamers (a term he coined), engineered acid-based molecules that bind to particular molecular targets like cells or tissues. Aptamers show great promise in their ability to zero in on specific diseases; in the early twenty-first century, the US Food and Drug Administration approved an aptamer-based drug for the treatment of age-related macular degeneration, a major cause of visual impairment.

Late in the 1990s, in addition to his other duties, Szostak joined the Howard Hughes Medical Institute, a private nonprofit organization headquartered in Chevy Chase, Maryland, that funds biological and medical research. Between 2000 and 2007, Szostak was also associated with the National Aeronautic and Space Administration (NASA) and was an active participant in the Astrobiology Institute in California. A principal investigator of NASA’s exobiology and evolutionary biology program, he contributed his expertise to studies of the origin, evolution, and distribution of life in the universe.

In the 2000s, Szostak’s laboratory research began to center on the creation of protocells, which are replications of ancient inorganic matter that, as a result of chemical processes organized into biological life, established a metabolism, became self-reproducing, and evolved into higher forms. He and his team continued to work on the protocells, including testing to see if RNA would be able to replicate and how to sustain cell membranes. Though he had to retract a 2016 paper published in Nature Chemistry when the team was unable to replicate the results regarding the peptide explored in the initial study, he continued to work toward progress. In working to unravel the question of how life began, Szostak hopes ultimately to produce genetically generated and chemically based treatments of diseases to help preserve and prolong human life. Szostak joined the faculty of the University of Chicago in 2022.

Impact

Since the early 1970s, Szostak has worked in tandem with his colleagues in attempting to understand the intricacies of genetics. His research in a number of related areas of molecular biology has far-ranging implications across several disciplines.

Szostak’s collaboration with Elizabeth Blackburn and Carol Greider, which resulted in the discovery of the telomere-creating enzyme telomerase and earned the trio the 2009 Nobel Prize in Physiology or Medicine, offers tremendous promise for combating aging and degenerative diseases. Szostak’s technique to develop aptamers has considerably shortened the evolutionary period of RNA molecules and simplified the screening process, opening the door for the genetic targeting of particular diseases. His contributions to NASA programs may pay dividends in the future, if humans ever explore other planets and strange new worlds beyond the solar system, and his investigations into the origins of life ultimately may reveal one of nature’s longest-held secrets and could pave the way toward human immortality.

Szostak’s recognitions for his innovative research include memberships in the National Science Foundation, the National Institutes of Health, the National Research Council, and the American Academy of Arts and Sciences. He was elected to the National Academy of Sciences in 1998 and to the New York Academy of Sciences in 1999. In addition to the Nobel Prize, he shared the 2006 Lasker Award with Elizabeth Blackburn and Carol Greider for their joint discovery of telomerase. Szostak has also been honored with the National Academy of Sciences Award in Molecular Biology (1984), the Genetics Society of America Medal (2000), the Heineken Prize for Medicine (2008), and the Oparin Medal (2011).

Bibliography

Atkins, John F., et al., editors. RNA Worlds: From Life’s Origins to Diversity in Gene Regulation. Cold Spring Harbor Lab, 2010.

Dharmapalan, Biji. From Telomere to Evolution, in Conversation with Nobel Laureate Jack W. Szostak." Science Reporter, Nov. 2022, pp. 25-28, nopr.niscpr.res.in/bitstream/123456789/60781/1/SR%2059%2811%29%2025-28.pdf. Accessed 15 Oct. 2024.

"Jack W. Szostak—Facts". Nobelprize.org, 2014, www.nobelprize.org/nobel‗prizes/medicine/laureates/2009/szostak-facts.html. Accessed 15 Oct. 2024.

Kauffman, Stuart. Investigations. Oxford UP, 2000.

Lerner, Louise. "Pioneering Scholar of Genetics Appointed University Professor in the Department of Chemistry and the College." UChicago News, news.uchicago.edu/story/nobel-prize-winning-biochemist-jack-szostak-join-university-chicago-faculty. Accessed 15 Oct. 2024.

Marcus, Adam. "On Second Thought: A Welcome Correction." The Boston Globe, 15 Dec. 2017, www.bostonglobe.com/ideas/2017/12/15/second-thought-welcome-correction/zHu3gz6jgONa7fFhU0ieEI/story.html. Accessed 15 Oct. 2024.

Szostak, Jack. "From Telomeres to the Origins of Life." Interview by Claudia Dreifus. The New York Times, 17 Oct. 2011, www.nytimes.com/2011/10/18/science/18conversation.html. Accessed 15 Oct. 2024.

Szostak, Jack W. The Origins of Life. Cold Spring Harbor Lab, 2010.