Albert Lasker Award
for Special Achievement in Medical Science

For a lifetime career that combines penetrating discovery in molecular biology with creative leadership in the public policy of chemical and biological weapons.

The 2004 Albert Lasker Award for Special Achievement in Medical Science honors a researcher who has made world-class contributions to two different aspects of the scientific enterprise: molecular biology and public policy. Matthew Meselson has deciphered fundamental biological problems and has helped to prevent the manufacture and spread of biological and chemical weapons.

In 1958, Meselson (then a graduate student of Linus Pauling at the California Institute of Technology in Pasadena) and Franklin Stahl showed that DNA duplication produces two identical daughter molecules, each containing one parental and one newly formed strand. This work provided compelling support for Watson and Crick's proposed mechanism of DNA replication and for their double-stranded helical model of DNA. To perform this experiment, Meselson and Stahl first grew bacteria in broth that contained heavy nitrogen and then switched the microbes to broth that contained light nitrogen. Because the cells incorporate nitrogen into DNA, this scheme allowed the scientists to distinguish between old (heavy) and new (light) strands. To analyze the DNA generated during the experiment, Meselson invented a technique called equilibrium density gradient centrifugation, which allowed him to distinguish between DNA molecules that differed slightly in density. In this way, he and Stahl showed that a parental helix made of two heavy strands duplicates to give two molecules, each composed of one heavy and one light strand.

This powerful method has also resolved other key issues in molecular biology. For example, in 1961 Sydney Brenner and Francois Jacob, working with Meselson at the California Institute of Technology, used this procedure to establish the existence of messenger RNA, the genetic intermediary between genes and proteins. That same year, Meselson used the density gradient method to learn how two DNA molecules produce new ones that contain a mixture of the parents—a process known as genetic recombination. In this experiment, he infected cells with distinct viruses, one labeled with heavy nitrogen and heavy carbon and the other unlabeled. By showing that recombinant molecules contained discrete segments from both parents, Meselson established in this and additional experiments that the recombinant molecules result from the breaking and joining of the two parent DNA molecules. Density gradient centrifugation has since been used by scores of scientists to answer a variety of biological questions.

Later, Meselson (by then on the faculty at Harvard University) turned his attention to another scientific issue. Researchers knew that bacteria destroy DNA from foreign strains by chopping it up. He found the first known protein to perform this feat—called a "restriction enzyme" because of its ability to restrict, or reject, DNA. A related group of enzymes turned out to be invaluable for manipulating DNA because they cut at defined sequences. The discoverer of that class of restriction enzymes, Hamilton Smith, credited Meselson's influence on his work in his 1978 Nobel Prize lecture. In other pioneering studies, Meselson correctly predicted the existence of methyl-directed mismatch repair, a process by which cells correct mistakes in their DNA.

In the past several years, Meselson has been tackling another central question: How does sexual reproduction contribute to evolution? Mixing two parents' characteristics produces offspring with new combinations of traits, and prevailing theory asserts that asexual animals and plants are doomed to extinction. Meselson and his colleagues have provided strong evidence that rotifers of the Class Bdelloidea, a group of tiny aquatic invertebrates, have evolved for tens of millions of years without sex—a conclusion that challenges current evolutionary thinking.

Alongside his work in molecular biology, Meselson has devoted much effort toward preventing the production and use of biological and chemical weapons. In 1963, he was invited to work at the Arms Control and Disarmament Agency in Washington, where he began exploring the U.S. biological weapons program. He reasoned that the United States had no need for such weapons and that pioneering them would only stimulate other countries and groups to acquire them. This rationale propelled him to persuade the government to abandon biological and chemical weapons, in part by writing papers for Henry Kissinger when Kissinger was Richard Nixon's national security advisor. Nixon unilaterally ended the biological weapons program in 1969 and subsequently extended the ban to weapons based on toxins, poisonous chemicals produced by living creatures.

Meselson helped to resolve other issues of military and strategic importance. During the Vietnam War, he led an expedition to Vietnam at the request of the American Association for the Advancement of Science. His group showed that the United States was mistaking civilian rice fields for enemy soldiers' crops. Meselson's findings prompted President Nixon to end U.S. herbicide operations in Vietnam.

Meselson's scientific fieldwork also helped solve two contentious puzzles of the Cold War. He investigated the "yellow rain" in Southeast Asia during the 1980s, purportedly a poison that the Laotians and Vietnamese, with Soviet assistance, were spraying on anti-government tribespeople. Meselson traveled to Southeast Asia, where he and his colleagues identified this substance as bee droppings—pollen eaten by the insects, which they then excreted in massive showers.

Another international controversy brought Meselson to Russia. In 1979, an anthrax epidemic killed more than 60 people in Sverdlovsk, U.S.S.R. The Soviets blamed tainted meat, whereas U.S. intelligence agencies suspected an airborne leak from a biological weapons facility. Meselson stated in Congressional testimony that the Soviet explanation was plausible, but that an on-site inquiry was needed. He repeatedly attempted to bring independent investigators to Sverdlovsk. Finally, in 1992, the Russian government allowed him and his wife, medical anthropologist Jeanne Guillemin, to bring a team to Sverdlovsk and probe the cause of the epidemic. The group examined preserved tissue samples, talked to city officials to learn how they responded to the outbreak, and initiated interviews with family members of those who died. The next year, Guillemin and Meselson returned to Sverdlovsk to conduct additional interviews. The victims lived in scattered locations, but the discussions revealed that their workplaces fell within a long narrow zone, with one end at the suspicious facility. Because bad meat doesn't travel in straight lines but wind often does, the researchers concluded that an airborne leak had caused the outbreak. Using local meteorological records, Meselson was able to pinpoint the day the germs had escaped.

With Julian Perry Robinson of the University of Sussex, Meselson directs The Harvard Sussex Program, which aims to increase the contribution of scholarship to the formation of public policy on issues involving biological and chemical weapons. Aided by experts in international law, Meselson and Robinson drafted a treaty in the late 1990s that would prohibit biological and chemical weapons under international criminal law. This pact would give courts of participating countries jurisdiction over any individual who orders the use of these weapons—much like the existing international agreements that govern airline hijacking, torture, and hostage-taking. The organization is trying to persuade governments to adopt the treaty, which would make purveyors of biological and chemical weapons international criminals.

While engaged in these policy-related activities, Meselson has maintained an active laboratory. His graduate and postdoctoral students include numerous scientific stars: Mark Ptashne (Lasker Basic Research Award, 1997), Susan Lindquist (Director of the Whitehead Institute), Steven Henikoff (Investigator of the Howard Hughes Medical Institute), and Sidney Altman (Nobel Prize in Chemistry, 1989). The contributions of these investigators highlight Meselson's mentorship talents.

Meselson is widely respected for his penetrating intellect and innovative insights. Among his scientific peers, he stands out as one whose talents and contributions have spanned molecular and international events alike.

By Evelyn Strauss, Ph.D.