American Type Culture Collection Seeks To Expand Research Effort

Director Robert Stevenson takes its mission beyond keeper of the country's microbes to attract key researchers and funding ROCKVILLE, MD. - Like a headmaster looking after a huge dormitory of slumbering schoolboys, Robert Stevenson watches over 50,000 microbes suspended in a sleep of absolute biochemical inactivity. As director of the American Type Culture Collection, the 64-year-old bacteriologist provides scientists with clean, well characterized cultures of yeasts and fungi, monoclonal antibodies, and tumor cells. For the past decade Stevenson has worked hard to convince his most important patron, the National Institutes of Health in nearby Bethesda, that the collection, created one year before he was born, is still carrying out its original four functions: to acquire, preserve, authenticate, and distribute microbial cultures. Robert L. Stevenson does not look the part of a fastidious librarian of bacterial and cell cultures. His shirt is rumpled; his suede shoes, scuffed. With his relaxed demeanor and open smile, Stevenson would fit in well with the Saturday shoppers that roam the malls near his laboratories in Rockville, Md. But Stevenson thinks that he's exactly the right man for the task that lies ahead. "It seems like I've spent my entire career preparing for this job," he says. That career has taken him from academia to government to industry before depositing him at ATCC. He earned his doctorate in 1954 studying human pathogens at Ohio State University. A stint as a virologist at the U.S. Public Health Service in Cincinnati soon led to the directorship of the tissue culture collection at the U.S. Naval Medical School in Bethesda. Scientists there were doing the country's first bone marrow transplants, and Stevenson learned to handle human tissues for transplant. In 1960 he took over the cell culture and tissue collection at NIH's National Cancer Institute. In 1967 he left the government to direct biological research at Union Carbide Corp. in New York. That job, he says, taught him the importance of marketing. In 1980 he returned to Washington, becoming director of ATCC. But Stevenson also wants to move his operation into the 21st century. To that end, he's taking the ATCC in a new direction to try to attract young scientists as well as new clients. By allowing scientists in his labs to conduct more experimental research than ever before, he hopes to satisfy their intellectual thirst for knowledge. And by teaching them new techniques, he believes he can make the collection more attractive to industry and university scientists. Stevenson runs a $11 million operation overseen by a 31-member board of directors drawn from 21 scientific organizations. These scientists are carrying on a tradition started in 1925, when the National Research Council and the Society of American Bacteriologists established the ATCC as a repository for bacteria and fungi. That curatorial function is still the collection's bread and butter. The scientists, breadmakers, and pharmaceutical firms across the country who depend on Stevenson's cultures are also his ultimate masters. Their dollars, spent to buy microbes for research and product development, make up 70 percent of the collection's income. Many researchers can get such bacteria or cell samples free from their cohorts. But their samples may not be pure. During the 1960s and 1970s, for example, cultures in laboratories across the country were commandeered by a renegade cell line called HeLa cells. Many cancer researchers lost dozens of years of work owing to sloppy lab practices. That's where Stevenson's team steps in. For $45 - industry scientists pay $65 -- they send an investigator a clean culture. If scientists grouse about the price, Stevenson reminds them that they have "an obligation to invest their money wisely. If they use unclean materials, then it's all a waste." Stevenson is not above poking fun at himself. Standing in a pristine room of blue cinder blocks in the basement of the ATCC, Stevenson lifts the metal cover of a super-cold freezer to show a visitor samples of viruses and cell cultures buried inside. In an effort to keep the lid off the floor, he balances it on his head. It is a striking bit of buffoonery: a short, round scientist crowned by an enormous, pie-shaped hat. But Stevenson doesn't clown around when he ponders the future of the collection. The new science of molecular biology has created the biotechnology industry, opening the way to conquering such killers as cancer, heart disease, and AIDS. Increasingly, Stevenson's clients at pharmaceutical companies and research institutes are using this new technology. And Stevenson envisions his team of scientists joining these clients on the frontiers of modern biomedical science. To attract talented microbiologists, geneticists, and cell biologists, he must make the ATCC laboratories an exciting place to work. That means offering them opportunities to do research as well as sorting and cataloging (see accompanying story). Armed with such skills, the collection will be better able to attract financial support. "By getting a little more involved in research the [ATCC] will get more visibility and acceptance by the scientific world and even more funding," says Jennie Hunter-Cevera, an ATCC board member and director of a private culture collection at Cetus Corp. "I like to [tease Stevenson that he's] prostituting ATCC, but Stevenson says, no, it's called marketing." And there's the rub. Stevenson's vision is making some people worried, if not downright angry. Performing research is costly, and doing it would place the collection in competition for scarce funds with hundreds of university labs and other nonprofit institutions. As a first step toward expanding the ATCC, Stevenson is trying to raise $12 million for new labs and scientists, equipment, and storage space. The campaign disturbs people both inside and outside the collection, who fear that new facilities will make it possible for ATCC scientists to do work unrelated to the collection's role as curator of the nation's cultures. Amy Rossman, a mycologist at the U.S. Department of Agriculture in Beltsville, Md., is one scientist who has such concerns. "I don't think [the collection] should do research," says Rossman, an ATCC board member. "I see them hustling for money to do work just to get money. It uses up more of their [custodial] resources than they gain in money contracts. At every meeting there is this struggle, but Stevenson just won't hear it." "When I read about a new species of bacteria in a journal, I immediately go to the ATCC to get samples to compare with my own isolates." Lillian Moore at Virginia Polytechnic Institute has been doing that for the past 35 years. The 67-year-old bacteriologist uses the ATCC because it's where most of the new organisms discovered each year are studied and stored. When Cetus microbiologist Jennie Hunter-Cevera was at what is now Bristol-Myers Squibb, she phoned the ATCC every week. It was particularly helpful when, one day, while hiking in New Jersey's Pine Barrens, she came across an unusual organism that seemed to produce the compound she needed in her search for a new antibiotic. "It acted against a good range of organisms," she says. "But we wanted to know if it was unique. So we ordered a whole bunch of reference strains from ATCC, and that told us nature had produced a unique organism." For a Squibb scientist, that news was an important discovery. "It put us in a good proprietary position," she explains. Although some two-thirds of all requests for cultures come from academic scientists, individuals from industry are more likely to use the collection than would their counterpart on a university campus. The reason lies in the differing nature of research done at each site. In an academic lab the same culture may be studied for many years. On the other hand, a chemical company developing, for example, a bathroom disinfectant may call several times in one year to get an array of samples. Biologists find the ATCC to be a reliable source of clean, meticulously described yeasts and fungi, monoclonal antibodies, and tumor cells. Last year the privately owned, nonprofit collection shipped out 118,413 cultures, and each day 150 scientists phone Stevenson's staff of 210 to ask for help with sickly cell cultures and misbehaving bacteria. Thousands of others send in samples of their cultures, to be warehoused for posterity, offered to colleagues who wish to compare work, or preserved as part of an application for a patent. Samples are not accepted over the transom. The collection process starts when ATCC researchers notice an interesting organism in the scientific literature and ask the scientist for a sample. Twenty-four such specimens arrive at the ATCC each week, where they undergo a battery of tests. Scientists study each one before it is stored. They make sure a bacterial culture is not contaminated with a similar strain, and that a viral culture is free of any of a number of micoplasma. They test, for example, whether a specimen ferments sucrose or glucose. Researchers count the number of chromosomes in the nuclei of cell lines. Other researchers, meanwhile, conduct background checks, following a paper trail of journal citations. Finally, the clean, meticulously documented culture is frozen for storage. There it awaits a request from someone like Moore. On the other hand, his deputies heartily endorse such an effort. "My personal opinion is that we have to do research, such as the manipulation of DNA, that has little to do with collection activities, to keep us part of the [research] community," says William Nierman, head of the ATCC's molecular and plasmid biology department. "If we are not perceived as technically capable, scientists are unlikely to give us materials." In addition to persuading his critics that the ATCC's mission has not changed, Stevenson also spends a lot of time these days worrying about where he'll house his growing collection. Squeezed into the cinder-block room in the basement of the ATCC are 46 stainless steel containers, each 3 feet around. Inside each container, called a pod, are 40,000 ampules of biological material suspended at -160°C. Stevenson's specimens are housed in three small brick buildings. Each year he adds four pods. But there's only so much room. It is not clear where he will place next year's additions. That's why he's looking for $12 million to move the expanding collection and staff to new buildings a few miles away. He is counting on $6 million to be donated by food processing and pharmaceutical companies - industries that use microbes - to build more laboratories and buy new equipment. In addition, he would like to establish a $6 million endowment to hire more scientists. With expanded facilities, the ATCC could actually do more work in molecular biology. But an increased emphasis on molecular biology might mean that less attention will be paid to collecting, storing, and distributing cultures, say the USDA's Rossman and other users of the collection. This kind of talk can make NIH administrators nervous. Thirty percent of the ATCC's revenues come from NIH and the National Science Foundation, primarily as contracts. NIH, especially the cancer institute, depends on the ATCC to supply and warehouse cultures essential for research. "We want to make sure all [outside] investigators have access to pure authenticated cultures," says Marjorie Tingle, project officer for the ATCC's general support contract at NIH. "This is their [the collection's] main function, and that's the bottom line." That attitude is shared by Bernard Fields, a member of the advisory council for the National Institute of Allergy and Infectious Diseases, which Stevenson says "called me out on the carpet" during its May meeting. "ATCC, like everyone in this field, is moving into molecular biology," says Fields, the chairman of the department of microbiology and molecular genetics at the Harvard Medical School. "And that usually means research. I don't have any problem with them doing research." But the ATCC's top priority, he says, must always remain "its service function. We don't want the scientists who use the collection to get shortchanged." Stevenson denies he plans to plunge into molecular biology. "People are always willing to take potshots at you if you have high visibility," he says sharply. "Being a research institute is not our role." But Stevenson knows that he must combat the image of his staff as unskilled drones. Many scientists tend to belittle the painstaking, but often unexciting, work that ATCC scientists do. "People don't realize the skills they have," says Hunter-Cevera. "I have to fight the same sort of attitude at Cetus. `We can do research,' I tell them. `We are not just a service group.' We have very low status." The status of the ATCC is changing as it does more molecular biology. The collection is already working with NIH's National Institute for Child Health and Human Development on a project to map human DNA. "It's easier to get support for our kind of research than for systematics and taxonomy," says Nierman. "The genome project and human genetics will deliver health-related materials to the public, so it's easier to get funded." Hunter-Cevera believes that expanding the ATCC's scientific outlook is as much a matter of good science as good public relations. "Stevenson has the vision that for ATCC to stay on top it has to get into the new school of molecular biology," she says. "The cheapest way to enter the 21st century is to get these skills by taking on extra research grants. "You also have to realize that, to get good people, you have to let them do contract work," she adds. "They want to learn new skills, because the other work is tedious and boring." She suggests that employees could use their time profitably by investigating how immune system substances work, by studying genes to come up with a new, molecular-level definition of what makes a species, and by experimenting with recombinant DNA products. Stevenson dismisses those who believe that his strategy is taking the ATCC off on inappropriate tangents. In an age of increasing scientific specialization, Stevenson sees himself and his crew as essential generalists. He says, "We are the ones who have to put together the information and analyze and put it into perspective for everyone else." Its experimental mission, he insists, is part of ATCC's original mandate.

American Type Culture Collection Seeks To Expand Research Effort

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