The Networker

Molecular biologist Brian Clark works tirelessly to discover and develop connections among Europe's biogerontologists.

Sit down for a chat with British-born molecular biologist Brian Clark (pictured left), and it doesn't take long before the names start dropping: Francis Crick, co-discoverer of DNA's double helix; Sydney Brenner, pioneer in studying roundworm cell differentiation; Marshall Nirenberg, genetic code-breaker. Clark spent the early years of his career, in the '60s and '70s, working with these--and other--Nobel Prize winners. His first job after his postdoctoral training was in Crick and Brenner's cell biology division at the Medical Research Council (MRC) in Cambridge, U.K., where he dove into the heady work of unraveling the basic biochemistry of protein synthesis. More recently, Clark has funneled the same enthusiasm toward promoting the field of biogerontology. Drawing upon his old connections at Cambridge and beyond, Clark is one of a cadre of European scientists who've been fostering international research collaborations on the biology of aging.

Clark directs the Danish Centre for Molecular Gerontology at the University of Aarhus. As president of the International Union of Biochemistry and Molecular Biology, which represents 70,000 scientists in 71 countries, he's currently putting together a section on the biochemistry of aging at the organization's upcoming annual meeting in Toronto. He chairs a task force of the European Federation of Biotechnology that's establishing research ties with China, which he hopes will bear the fruit of scientific synergies in biogerontology, as well as other disciplines. And he advises several biotech companies. Given the many hats he wears as a scientist and an administrator, it isn't unheard of for Clark to be jetting to places as far afield as Los Angeles, New York City, Prague, and London in the course of a single week.

Clark, a short 66-year-old with a white head of hair, bright blue eyes, and gray, triangular eyebrows, is a people person who thrives on making connections. "He's very much a 'meeting man,' " says Anders Olsen, a Ph.D. candidate in genetics at the Buck Institute for Age Research in Novato, California, who did his master's degree research with Clark at Aarhus. According to biogerontologist Suresh Rattan, a research professor in Clark's group at Aarhus, when it comes to "creating new collaborations or bringing in people and asking them to join together and write [grant] applications, he is very enthusiastic."

Clark decided in the 1980s to rally scientists and resources around the cause of biogerontology research. He recognized that the study of aging had lacked robust scientific inquiry, and he conjectured that molecular biology tools could fuel real progress in the field--a forward-looking viewpoint that few others espoused at the time, says immunologist Claudio Franceschi, director of the Italian National Research Center on Aging in Ancona. "For me, he is a reference point," says Franceschi, "because [early on] it was not easy to have clear ideas about the direction that aging studies should take." Clark has an intuitive radar for identifying hot areas of future research, sometimes years in advance of his peers, adds Rattan. "He got convinced very early on that [it was] the right time to support this subject."

Opening Doors Into Protein Biochemistry

Clark, a native of Milford Haven, Wales, U.K., aspired from childhood to be a professor. He started school early--at age 2 and a half--and by high school had gravitated toward the sciences, particularly chemistry. "I was good at learning chemistry. ... It was orderly and precise, like following a cookbook." He had a knack for storing obscure information in his head. For instance, he recalls, he loved buses and memorized the license plates of all the ones that came through his neighborhood. He also liked learning to spell unusual words, such as "cteniform," which means "comb-shaped." Clark was an athlete as well. He developed an addiction to playing soccer in high school and became a big fan of Liverpool's professional team.

He went on to earn a bachelor's degree in chemistry and a Ph.D. in organic chemistry from Cambridge University, U.K., finishing his doctorate in 1961. With his wife, Margaret, Clark then moved to Boston, where he had secured a 3-year postdoc with Jack Buchanan, a biochemist at the nearby Massachusetts Institute of Technology (MIT) who was investigating the synthesis of nucleic-acid building blocks called purines and of proteins. A few months after Clark arrived at MIT, he took advantage of an unexpected opportunity. Biochemist Nirenberg of the National Institutes of Health gave a seminar describing a groundbreaking experiment in which he and a colleague had discovered how the cell interprets messenger RNA--by reading one triplet, or codon, of nucleotide bases at a time--to line up the amino acids that form proteins. "It was a very exciting talk," Clark recalls. It just so happened that an MIT researcher named Dan Levin, who lived next door to him on Newbury Street in Boston, had done a postdoc with Nirenberg; through this and other contacts, Clark learned that Nirenberg was looking to hire more people, and with Buchanan's blessing, he switched labs in 1962.

For the next 2 years, he worked at NIH to decipher the genetic code until another networking encounter opened an important door for Clark, when Brenner visited the Nirenberg lab. "He found out I was British," Clark recalls, "so he said if I was interested in a job in Europe I should contact him." Soon afterward, Crick wrote to Clark offering him a position at MRC in Cambridge, U.K. "I jumped at it," Clark recalls. Working with Danish molecular biologist Kjeld Marcker, Clark identified the codon that instructs the cell where to begin translating a strand of messenger RNA into protein. With their colleagues they were the first to obtain pure crystals of transfer RNA (tRNA)--a molecule that reads codons and delivers the correct amino acids during protein synthesis--and take rudimentary x-ray photographs of it in 1968. That work triggered a close race between the Cambridge University group and a rival team at MIT in deciphering tRNA's 3D structure at atomic resolution with x-ray crystallography, with the two labs publishing results within 2 weeks of each other.

Forging Ties in Biogerontology

In 1970, Marcker took a professorial position in the molecular biology department at the University of Aarhus, and 4 years later he used his influence to help bring Clark to the university. Clark arrived to start a department of biostructural chemistry and establish a protein crystallography research group.

Let them eat cake. Clark, who founded the department of biostructural chemistry at the University of Aarhus in Denmark, celebrates its fifth anniversary in 1979. The unit was later absorbed by the department of molecular biology. [Credit: Courtesy of Brian Clark]

By the early '80s, Clark was eager to branch out into unplowed territory, and aging caught his eye. "I just thought it would be nice to work on something that nobody knew anything about," he recalls. "I thought that with the development of molecular biological techniques, we could ask and answer important questions in the biology of aging, which researchers couldn't [answer] up to that time." Funding for such research was virtually impossible to secure in those days, but Clark networked his way to a solution. At a meeting in Australia, he got to talking with an American biotech entrepreneur. Recent studies of rats by other scientists had revealed a general decrease in protein production with age. The entrepreneur proposed that Clark join him in forming a company to develop compounds that would make up for losses in protein synthesis or in enzyme activity, thereby--potentially--delaying the aging process. The company, Senetek, was born in 1983.

With funding from Senetek, Clark began studies of how aging influences protein biology and set out to hire a postdoc. He talked with geneticist Robin Holliday, then at MRC's National Institute for Medical Research in London, who recommended a former grad student of his, biogerontologist Rattan. Rattan joined the Clark group in 1984 and started exploring what happens when skin, bone, and connective tissue cells grow old and enter a state of limbo--called senescence--in which they neither divide nor die (see "More Than a Sum of Our Cells").

In those days, Clark says, aging-related research held "very poor scientific standing," with many of his peers viewing it as "a scam." But Rattan says that Clark was able to enlist support for their studies from the then-dean of natural sciences at Aarhus, Karl Pedersen. "I really used to feel very isolated," Rattan recalls. "There were people who wouldn't let us use their facilities. They would just laugh at us--'Oh, aging is just hocus pocus.' But Brian had confidence in me, and the dean had confidence in Brian, so we carried on." Today, Aarhus University is one of the few places in Europe that offers a full-semester course on the biology of aging, which Rattan teaches. "None of these things could have been possible if people like Brian [had] not led the way," Rattan says.

Clark had always liked the idea of international cooperation; he had been active since 1969 in planning summer school courses about molecular biology on the Greek island of Spetses, which were funded by the Advanced Study Institutes program of NATO, the European Molecular Biology Organization, and the Federation of European Biochemical Societies. So he began plugging into the community of researchers on aging. At the European level, a nascent biogerontology movement had begun to coalesce (see "Europe Wakes Up to Aging") through the efforts of molecular gerontologist Dick Knook. In 1976, Knook, then director of the Institute for Experimental Gerontology in Rijswijk, the Netherlands, had started up Eurage--a 12-year transnational initiative funded by the European Economic Community. The initiative promoted networking and brainstorming among scientists who were investigating the diseases and biology of aging. Clark learned about Knook's project, and in 1984, he teamed up with geneticist Jan Vijg, then at the State University of Leiden in the Netherlands, to form a molecular biology section within Eurage.

Networking in the flesh. Since 1969, Clark (right) has periodically helped organize summer schools about protein biology on the Greek island of Spetses. Here, in 1980, he enjoys sun, sand, and science with Athanasios Evangelopoulos (left) of the National Hellenic Research Foundation and Kenneth Murray of the University of Edinburgh. [Credit: Courtesy of Brian Clark]

After the funding for Eurage expired, Clark, Knook, Franceschi, and other colleagues won a grant from the European Commission (E.C.)--the executive branch of the newly formed European Union--to support Molgeron, a network of 12 European research labs that were studying the molecular basis of aging. With Clark serving as coordinator, Molgeron paid for conferences and short-term exchanges of personnel from 1994 to 1998. It was a "very important" collaboration that made it possible for otherwise isolated research groups "to meet and talk and exchange experiences and techniques," says Franceschi. From 1999 to 2000, Clark ran another project called Genage, also funded by the E.C., which supported postdoc salaries, travel expenses, and bench research for four European labs studying genes involved in cell senescence.

Two Steps Forward, One Step Back

Meanwhile in Denmark, Clark, along with others including Danish geneticist Vilhelm Bohr, who worked at the U.S. National Institute on Aging but also promoted science in his home country, had been pushing to establish a national institute on aging. Their efforts were rewarded when the Danish Research Council backed the creation of the Danish Centre for Molecular Gerontology in 1996. Bohr, who also was and is an adjunct professor at Aarhus, served briefly as director before passing the baton to Clark. The center is a currently an institute "without walls" that has three core research groups, but Clark, Bohr, and their colleagues hope to secure more government money to build a unified headquarters.

However, the fight for European funding in biogerontology remains an uphill battle. Clark and other leaders in the field have for years informally lobbied E.C. bureaucrats to bolster financial support of research on the biology of aging. Their efforts seemed to pay off under the European Union's 1998-2002 research and technology budget, known as the Fifth Framework Programme (FP5), which identified aging as a scientific priority for the first time. But the current Framework agenda, FP6, has proved a big disappointment, providing "shockingly low" support for the biology of aging, Clark says. Many biogerontologists, Clark included, suspect that their field has been outmuscled by scientists and organizations lobbying for money on major diseases such as cancer.

That denouement has led Clark to conclude that biogerontologists need to muster their own lobbying forces. "One has to talk to people who are in a position to change [the funding priorities], and those are the politicians." Clark says he has begun to do that at the grassroots level, meeting with officials in Aarhus to advocate for support from local agencies.

In addition to feeding his passion for science, Clarke and his wife play tennis and badminton, and he still has a thing for public transit vehicles. "Sometimes I go and have coffee in a cafe window in the city, and watch the buses go by for an hour to check up on them," he says.

But above all else, he loves soccer. "He's crazy for football," says Franceschi, laughing. "He's capable of interrupting or leaving a scientific meeting for a half-hour because there is an important game." Clark's favorite team is still Liverpool, notes former master's student Olsen. Anytime Liverpool played a soccer match, "you would have to discuss it the next day at the coffee break. He would describe every shot, every goal," Olsen recalls. "It was a standing joke that if you had a favor to ask of him, you should wait until Liverpool had won a game."

* Ingfei Chen, a contributing editor for SAGE KE in Santa Cruz, California, doesn't mix science writing with sunbathing.

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