KAREN WATKINS,C&EN NORTHEAST NEWS BUREAU

The high-technology market may have melted down this year, but the biotechnology market has been spared, for the most part. That's good news for chemical professionals seeking employment in the biotech industry. The opportunities are also good for chemists interested in working with biologists at more traditional pharmaceutical companies.

"This is a very exciting time to be in the industry," says Bob Jacobs, associate director of chemistry for pharmaceutical giant AstraZeneca. "The time has never been better for a creative person to make an impact. The challenge that faces us as chemists and as biologists is to be able to use genome information from the Human Genome Project efficiently and in a way that helps us to move forward."

The Human Genome Project has uncovered an increasing number of drug targets, which chemists address by developing small molecules that act on the targets. Consequently, as start-up biotech companies shift from a wholly biological emphasis to a small-molecule drug focus, they will need increasing numbers of chemists, says F. Raymond Salemme, founder, president, and chief scientific officer of 3-Dimensional Pharmaceuticals, a drug discovery company that employs a high proportion of chemists--85 out of a total of 190 employees.

This shift to small-molecule development is also occurring in other facets of the biotechnology industry, including applications in the chemical and agriculture markets, says Mark Burk, a chemist who is vice president of chemical products at San Diego-based biotech company Diversa.

According to Burk, there is a growing realization that, because the application of molecular biology leads to products in the chemical and pharmaceutical worlds, biotech companies will eventually be dealing with chemicals. Consequently, biotech firms are waking up to the need for chemists in their organizations to synthesize new molecules, develop analyses, and work on customer applications, he says. "The more you deal with chemicals, the more you need chemists to handle them. So there is a significant emphasis on the increase of chemists," he states.

Diversa employs approximately 20 individuals with chemistry backgrounds, out of a total of 275 employees, 195 of whom are in R&D, says Dan Robertson, a biochemist who is senior director in enzyme technology. To beef up its efforts in analytical chemistry and biocatalysis, Diversa intends to expand by 40 to 50 individuals, many of whom will be chemists, in the next year.

Another relatively small biotech company, Boulder, Colo.-based Array Biopharma, has a much larger complement of chemists: approximately 115 synthetic chemists and 15 analytical chemists, out of a total of 200 employees. Last year, Array doubled its scientific staff by adding 73 scientists, most of whom were chemists. The company plans to hire 40 to 60 more scientists, mostly chemists, over the next three years.

Array's chemists are engaged in small-molecule drug discovery, including high-throughput screening, predictive cheminformatics, parallel synthesis, analytical chemistry, medicinal chemistry, drug metabolism, and process R&D, says Tricia Haugeto, Array communications manager.

BIGGER BIOTECH and life sciences companies also have large numbers of chemists on their staffs.

AstraZeneca, for one, employs about 250 to 300 chemists in North America in the traditional chemist roles--bench research, identification of new chemical entities, and development of analyses for these chemical entities--as well as manufacturing, quality assurance, and regulatory affairs, says Mary Grigas, director of R&D human resources.

Though AstraZeneca's Wilmington, Del., facility is mature, opportunities in synthetic organic chemistry, computational chemistry, and molecular modeling are continual. A wide variety of positions are also open as the firm expands its R&D facility in Waltham, Mass.

San Francisco-based Gilead Sciences, a biopharmaceutical firm, employs about 120 chemists in chemistry-related positions; its total workforce numbers 1,040. "There is a strong demand at Gilead for chemists," says William A. Lee, senior vice president of research and product development. At the moment, there are four openings for chemists in discovery and 12 openings in development.

San Diego-based Aurora Biosciences currently employs about 15 chemists, primarily synthetic organic chemists, out of a total of more than 300 employees. During the next year, it plans to hire about 20 more synthetic medicinal chemists, says Associate Director of Chemistry Lewis Makings.

Vinh Dang uses a gas chromatograph at Gilead Sciences. GILEAD SCIENCES PHOTO

Aurora is looking for individuals with a deep background in synthetic chemistry and experience in doing multistep synthesis or combinatorial chemistry to support its drug discovery efforts. The company is planning to build up its medicinal chemistry, combinatorial chemistry, and analytical efforts.

The six-year-old agricultural biotech firm AgraQuest, based in Davis, Calif., employs 10 chemists in natural product chemistry, analytical chemistry, and formulations; six chemical engineers develop fermentation processes. President and Chief Executive Officer Pamela G. Marrone says the company plans to hire three or four more people next year in chemistry and chemical engineering.

Several different chemical specialties are used by the life sciences industry. AgraQuest, for one, is looking for chemists with experience with biological organisms, according to Marrone. "Natural product chemists are particularly valuable," she says.

Trained synthetic organic chemists are especially desired. "All of our chemists come in with a strong synthetic organic chemistry background," says Eric Sjogren, vice president of chemistry for the inflammatory and viral disease unit at Palo Alto, Calif.-based Roche Bioscience, one of Roche's five research centers.

Analytical chemists are needed to support all these synthetic chemists, of course. "We've seen a greater demand for trained analytical chemists as companies push drug metabolism studies earlier and earlier in the drug discovery process," Sjogren says. "We work aggressively to find and attract such candidates." Roche needs specialists in nuclear magnetic resonance spectroscopy, chromatography, mass spectrometry, solid-state characterization, and spectroscopy in general, adds Mike Maddox, senior scientist in Roche's central R&D.

At Roche, analytical chemists do physical and chemical characterization of new chemical entities, as well as development of analytical methods for both new compounds and formulations, Maddox says. "In central R&D, most of the effort is providing service to the synthetic chemists. In the business units, the work is more project oriented."

 PROCESS CHEMISTS--synthetic organic chemists who scale up processes--are in continual demand. "New drugs have to be made under increasing cost pressure," says Hans Maag, vice president of medicinal chemistry in Roche's neurobiology business unit. "Long gone are the days when scale-up was a grunt activity, when you simply scaled up a process without changing it," he adds. "Processes have to be devised and improved to fit the requirements of the pharmaceutical industry in the current climate."

This evolution has gone unnoticed in the academic world, says Colin Beard, vice president for central R&D chemical services at Roche Bioscience, leading to something of a staffing problem. "To be honest, there is a lack of recognition at the universities that this is an honorable and worthwhile career. Most of the young people we interview have not heard of process chemistry, and very few have thought about it as a career for themselves."

There is a large unmet opportunity, then, for chemists who wish to work in a group that sits between the research and pilot-plant stages. The challenge of this area is in taking a product developed by medicinal chemists, who have the luxury of using whatever reagents and process conditions are convenient and quick, and finding the best way to make it in a very restricted setting to meet economic, environmental, and regulatory demands.

 IN ADDITION to these more general chemical specialties, there is a need for individuals with very specialized knowledge--bioinformatics and cheminformatics, for example. Roche Bioscience has a bioinformatics unit and also employs computational chemists who interact with the company's medicinal chemists and X-ray crystallographers, Sjogren says.

Aurora is also hiring cheminformatics experts. Since its merger with Vertex, Aurora's focus has changed from biology-oriented assay development to drug discovery. It plans to leverage Vertex's expertise in cheminformatics by hiring people who are "interested in and tech-savvy in regard to computational methods as applied to drug discovery and medicinal chemistry," Makings says.

Bioinformatics and cheminformatics have become integral parts of the drug discovery process. "A small but important component of our organization is computational chemists doing modeling, calculation of physicochemical properties, and other types of cheminformatics roles," says AstraZeneca's Jacobs. "This area is clearly expanding in our industry. It is extremely competitive in terms of our ability to hire very highly qualified people."

Chemical engineers are also in demand in biotech companies, mainly for manufacturing and for scaling up synthesis routes that process chemists have developed. "We need chemical engineers especially if they have experience in biological areas like the use of enzymes," Diversa's Burk says. "Such experience, on top of chemical engineering training and background, fits well in the industry."

Biogen, a Cambridge, Mass.-based biopharmaceutical firm, uses chemical engineers--typically at the bachelor's degree level--in process improvement, process design, and process development, says Keith Hall, the firm's head of employment. Chemical engineers are also needed in the design of new processes as the company expands its facilities in Research Triangle Park, N.C., and builds new ones in Europe.

THE GIANT pharmaceutical firm Eli Lilly & Co. employs "quite a few" chemical engineers, says Jim Kassebaum, Ph.D. chemistry recruiter, because of its need to ramp up processes for new compounds and to get these compounds registered with the Food & Drug Administration. Because of their knowledge of the ins and outs of manufacturing processes, engineers play a useful role in process development, manufacturing, quality control, quality assurance, and government relations.

At AstraZeneca, chemical engineers are involved primarily in operations and supervisory roles. They also work in process engineering, quality assurance, product certification, packaging, and manufacturing technology, Grigas says. "Our vice president for manufacturing is a chemical engineer," she notes. "This highlights the sort of opportunity there is in an environment like ours."

Monsanto is hiring chemical engineers in St. Louis; Luling, La.; and other sites throughout the U.S. These engineers work on scale-up for new formulations and process engineering for existing projects, says Becky Prevost, staffing lead for Monsanto's technology business.

Though biotech and pharmaceutical companies hire chemical engineers mostly at the bachelor's level, they need chemists at all levels--bachelor's, master's, and Ph.D. These companies try to strike a balance between the number of Ph.D. holders and the number of B.S./M.S. individuals in their employ. Roche Bioscience, for instance, has about two B.S. employees for every Ph.D., Sjogren says. The ratio is reversed at Array Biosciences, where about 70% of scientists have a doctorate, Haugeto says.

Lilly has one and a half to two B.S./M.S. employees per Ph.D. in the laboratory environment, Kassebaum says. And its development opportunities are not limited to Ph.D.s. People at the B.S./M.S. level can move up the technical or management ladder or even move outside the laboratory environment, he states.

At Monsanto, too, "there are plenty of opportunities for B.S./M.S. people," says Prevost. "Since we are a plant science company, we typically look for an individual with some experience in agriculture or plant sciences. The focus is more targeted for Ph.D.-level candidates. We have fewer needs for individuals with a Ph.D. background compared to B.S./M.S., though there are plenty of opportunities for a Ph.D. with strong analytical chemistry skills."

Bachelor's- and master's-level chemists are eagerly sought by biotech firms. "B.S. and M.S. people have always been an extraordinarily valuable commodity," says 3-Dimensional Pharmaceuticals' Sa-lemme. "We recruit aggressively for those. In the industry, they are highly regarded and well compensated." Gilead's Lee adds: "B.S./M.S. people are surprisingly difficult to hire in this area, especially synthetic organic chemists."

Apart from degree level, biotech and pharmaceutical firms look for varying amounts of industrial experience, depending on the position.

"For the most part, we like scientists with a minimum of three to five years of industry experience," says AgraQuest's Marrone. Other companies say recent chemistry graduates are also desired, particularly those who have been involved in an internship or research program. Array, for one, targets "scientists with three to eight years' experience in a major pharmaceutical company as well as recent graduates from prestigious organic chemistry programs," Haugeto says.

Individuals right out of school have good prospects for employment in the biotech and pharmaceutical industries even if their biology background is limited, provided that they have a strong chemistry background and, if they are Ph.D.'s, a record of publications, says Gilead's Lee.

However, a chemist coming from an unrelated chemical industry such as petrochemicals will have a tough time finding a job in life sciences R&D, Biogen's Hall says. Biogen will, however, look at nonpharmaceutical chemists and engineers early in their careers if they "have had good process or scale-up experience, say in resin manufacturing--experience in taking products from the lab and understanding how to apply them to a highly regulated manufacturing environment with very tight quality requirements," he says. "That's the type of experience that could transfer to us."

SECURING A POSITION is just the beginning of the challenge that the biotech and pharmaceutical industries offer the chemist. One issue faced by chemists who work in a biology-oriented company is that chemists and biologists are trained to use different terminologies and see the world differently, reflecting the types of jobs they are expected to do.

"For chemists and biochemists, the years of chemical training prior to biological training are very important, providing excellent analysis skills," says Robert Booth, senior vice president and head of Roche Bioscience's inflammatory and viral disease unit. "Biological training is useful in offering a systems approach to discovery. Both offer a different perspective."

Because so many fields come into play in biotechnology, a company like Diversa is very multidisciplinary, Burk says. "Chemists must necessarily speak the language of many different disciplines, mostly biological," he states.

Lilly's Kassebaum notes that almost every chemist plays a role on some kind of interdisciplinary team in which he or she has to deal with biologists in an iterative process to develop products. "It is a plus for a chemist to have some understanding of the life sciences field and how it works, so he or she can communicate with biologists," he says.

There is some diversity of opinion on the importance of a chemist's exposure to the biological sciences. One camp argues that it is not necessary for a chemist to have a strong biological background to work in the biotech industry. For companies like Biogen, the deciding factor between two individuals with similar backgrounds is not whether one had a few credits more in biology or a related life science but how the company estimates "soft skills" such as potential for immediate achievement.

Also arguing for a strong chemistry background, even at the expense of biology, is Roche's Maag, who says: "What we focus on in hiring is a strong synthetic background for synthetic chemists. Any education in biology is very much secondary." According to Sjogren, "The biology and other aspects of drug discovery, they learn on the job. We look primarily for strong synthetic chemistry skills backed with critical thinking and problem-solving ability."

THE OTHER CAMP argues that biological experience is truly important. According to this viewpoint, in day-to-day communications with biologists, chemists should show a general understanding of biological processes that are important to their projects. To ensure that its employees are capable of communicating with biologists, AstraZeneca looks for exposure to a variety of disciplines through course work and research work, says AstraZeneca's Jacobs.

Though a solid chemistry background is essential to both camps, those who argue for a biological background say chemists should have "a predisposition of interest, some background in understanding the fundamental concepts of biology, and an appreciation of how chemistry applies to biology," Jacobs says. "Individuals with very little interest in dealing with that interface screen themselves out quickly during the interviewing day."

In fact, says AstraZeneca's Grigas, biology will certainly find its way into the background of serious candidates for jobs in the life sciences. "Many of the folks who have chosen this track have had some significant biological training through course work and education," she says.

Gilead's Lee has observed that chemists in a biological setting are highly motivated to adapt to the biological environment and quickly learn what is required to operate and communicate within that setting. "My experience is that chemists really like working in the biological environment, being able to apply the skills and knowledge of their training to real-world problems that are easy to relate to," he says.

Biotechs are waking up to the need for chemists in their organizations to synthesize new molecules, develop analyses, and work on customer applications.

Biotech and pharmaceutical companies are fairly uniform in the types of personal characteristics they look for in prospective employees. Biogen's Hall says that, among candidates with similar academic records from good schools, "what distinguishes a candidate is a sense of achievement--people who seem to be successful and who drive others to be successful.

"We also look for good teachers and good students, people who are open and share and help coworkers learn," Hall adds. "We look for people with a fertile mind and a thirst for knowledge--people who are inquisitive."

Roche Bioscience seeks individuals with critical thinking skills "to look at and interpret data, and to determine the next steps to take," Sjogren says. A candidate should also have demonstrated problem-solving skills, decision-making ability, and an ability to understand fields outside of his or her project, he continues.

Obviously, a candidate must be flexible and must have the ability to interact in multidisciplinary teams with biologists, geneticists, formulation experts, and clinical workers, Roche's Booth says. "It is absolutely critical that members of our drug discovery teams have good communication skills and team skills," he emphasizes. "Everything's done in teams," adds AgraQuest's Marrone.

Initiative, says AstraZeneca's Jacobs, is one of the most important qualities sought in a candidate. "In particular, B.S. and M.S. candidates should demonstrate that they've been exposed to a research project where they've been asked to generate hypotheses and design experiments to address these hypotheses. This shows initiative, the ability to be creative, and expertise in analytical thinking and developing strategies."

ENTHUSIASM, the firms agree, is key to success. "We don't want to imply that we require a biology background in terms of demonstrated expertise," says AstraZeneca's Jacobs; "rather, there is an opportunity for a person with enthusiasm and curiosity to learn on the job and work at the chemistry/biology interface."

"Our focus in hiring people, be they chemists or biologists, is their excitement level and their commitment," Diversa's Robertson says. "The people we're getting as chemists are quite excited. Creativity, enthusiasm, and communication are what you need to strive for to be successful here."

As long as biotech and pharmaceutical companies are in business, there will be a strong demand for chemists. "The drugs of the future are to a large part going to be small molecules, and those small molecules must be created by chemists," Gilead's Lee says. He stresses that "chemists are not so easy to hire these days because there are so many more opportunities since medical science has blossomed in the past 10 years."

Indeed, people who hire at biotech and pharmaceutical companies say they must compete fiercely for qualified job-seekers. "There is a very strong demand for hiring chemists throughout the country," says Roche's Sjogren.

Although demand is strong, there are a lot of chemists seeking positions as well. "We have no problem finding qualified candidates," Monsanto's Prevost says.

As an indication of the supply of chemists seeking jobs in biotech, Aurora Biosciences interviewed 80 chemists at a recent American Chemical Society meeting and is now in the process of narrowing the group of candidates down and bringing the best ones to San Diego for more in-depth interviews. "The need for chemists is tremendous in San Diego," comments Makings.

For chemists who are hesitant about working in biotechnology, Lee advises: "Don't be put off by the biotech label." Biotech and pharmaceuticals encompass a broad set of technologies, "almost all of which involve chemists more as we go forward."

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