Genomics and Proteomics

Armed with the complete sequence of the human genome, pharmaceutical researchers are making great strides in the emerging fields of genomics and proteomics.

In their quest to develop medicines tailored to individual patients, these scientists are focused on genomics, which involves surveying an organism's entire genome, including the sequencing of individual genes and studying their expression. They are also looking at proteomics, which involves examining all of the proteins produced by a particular cell type or tissue and the variations produced by disease.

Researchers are increasingly deploying these technologies to conquer a broadening range of complex biological challenges throughout the drug development process.

Initially, genomic and proteomic R&D "was focused on yielding a plethora of potential new drug targets," says Mark S. Boguski, vice president and global head of Genome & Proteome Sciences at Novartis Institutes for BioMedical Research, in Cambridge, Mass. "But what we found, delightfully, is that these approaches, these technologies, these ways of thinking complement every stage of the pharma R&D process very nicely," he adds. Boguski leads a division that integrates genomics, proteomics, and bioinformatics technologies to advance drug and biomarker discovery and development. These disciplines can play a role in almost every phase down the line-from target discovery to investigative toxicology to the analysis of clinical data sets, he says.

Not surprisingly, these efforts are spawning new career opportunities within a range of companies???from pharmaceutical giants to the smaller firms that serve them. Proteomics and genomics are "becoming part of normal activity within pharmaceutical companies, and so we need talented people, especially people who are acquiring some specific new analytical and technical skills," says Brian Spear, director of Genomic & Proteomic Technologies at Abbott. He says some positions are open for people who are trained in these areas but cautions that, at present, "it's not a huge growth area."

Overall, the genomics market in the U.S. is probably growing at about 3 to 5% per year, according to Jonathan Witonsky, an industry analyst with Frost & Sullivan, a global consulting company. He is currently writing a report on the genomics business and estimates that the annual U.S. market for goods and services supporting this field totals approximately $4 billion to $5 billion.

The annual U.S. proteomics market, Witonsky estimates, is less than half the size of the genomics market, about $1 billion to $2 billion. But the proteomics market is likely growing a little faster than the genomics market-at about 4 to 5% per year, spurred by "a lot of pretty exciting technological advances that have been made in this area in the past three years or so," he says.

As researchers continue to develop the fields of genomics and proteomics, companies are likely to ramp up the number of people needed to support these efforts. But for now, demand for people in these fields will continue "to grow at a rate that is slightly more than the overall rate of hiring within pharmaceutical R&D," Spear predicts. "And I expect that we will be adding some people here at Abbott," primarily biostatisticians, bioinformaticists, and protein analytical chemists, he notes.

To be sure, genomics and proteomics may open the door to new opportunities for chemists with biochemical experience. At Novartis, for example, chemists play a big role, particularly "protein biochemists and, increasingly, synthetic chemists with oligonucleotide experience," Boguski says. He sees a "great resurgence of interest in chemists who deal with nucleic acids and oligonucleotides." A whole new interface between biology and chemistry is coming about as a result of this, he adds.

"But at this point, the people who are in the greatest demand at Novartis are master's degree-level scientists who are equally comfortable with biological and biochemical approaches to R&D and informatics," Boguski says.

In proteomics in particular, Boguski says, the current demand is for people with strengths in certain technologies like mass spectrometry and methods development. "It's still a maturing field. There is very significant room for improvement in sensitivity, throughput, and new experimental strategies around these tools," he adds.

Boguski notes that scientists who have this specialized knowledge coupled with an informatics background really have an edge. "The informatics of proteomics, which differ significantly from genome informatics, are really an emerging gap now in the field," he says.

To meet demand for people with this kind of training and experience, "we are not only hiring, we're giving internal courses to kind of retool current staff so that they can participate in this new technology," he says. Reasoning that employees already know how research is done in a pharmaceutical company environment, "it is just a matter of using our internal education programs to update and increase their knowledge of the latest technology approaches," he adds.

Schering-Plough is another company that is focused on building a workforce to fit its increasing application of genomics and proteomics. The company's research in these areas is focused on discovery-based approaches to support early clinical development, says Catherine Strader, chief scientific officer of Schering-Plough and executive vice president of the Schering-Plough Research Institute.

To that end, the work at Schering-Plough is aimed at the identification and validation of biomarkers that can predict clinical efficacy. "In addition, we are focused on genomic approaches to identify patients, for example, in oncology, who might respond especially well to our drugs. This area of science spans preclinical and clinical research, so there is a lot of feed-forward and feedback of data from preclinical and clinical studies," she adds.

"We are also working hard to leverage these newer technologies for our existing commercial products," Strader says. "For example, with our anticancer therapy Temodar [temozolomide], we are evaluating whether a genomic approach can help us identify additional patient groups for whom this drug may be particularly effective."

Within Schering-Plough, the jobs in genomics and proteomics "are in pharmacogenomics, which extends from preclinical to clinical research, and in genomic and proteomic approaches to the identification of biomarkers," Strader says. The skill sets are integrated within therapeutic areas, for example, oncology or cardiovascular research, where researchers apply genomic approaches to programs.

Schering-Plough plans to expand its workforce in several areas in 2007. "In the areas of genomics and proteomics, we have a strong need for scientists with backgrounds in biochemistry, genomics, and molecular imaging," Strader says. "And we will continue to build our development capability in using biomarkers and imaging techniques."

Like these larger pharmaceutical firms, some genomics and proteomics companies forecast the kind of business growth that would support modest hiring in the coming year and beyond.

"For the most part, the bleeding-edge areas of technology have been moving to proteomics, and in genomics, applications are still coming on-line and products are still being introduced, as we respond to the needs of our customers," says Rodney Moses, vice president for global talent acquisition at Carlsbad, Calif.-based Invitrogen. "So we'll still need great genomics specialists in applications development, technical service, sales, and marketing. The proteomics field is developing quickly, and clearly, we'll continue to bring on board great talent as we expand our product portfolio."

Chemists play an important role at Invitrogen, particularly with labeling and detection technologies, Moses says. "While most of the chemists we have brought in recently are organic chemists, the convergence of science in all areas, such as biology, chemistry, and even physics, indicates that there will be opportunities for qualified people from all scientific disciplines."

In addition to needing great scientists, Invitrogen is also seeking people with strong skills in areas such as finance, information technology, and operations, Moses says. "We're definitely more than a 'test tube shop'; we have to be on the lookout for people in both line and staff functions as well."

Hiring may be up slightly, too, at La Jolla, Calif.-based ActivX Biosciences, a small biotech firm that takes a chemical approach to proteomics, focusing on what it calls activity-based proteomics. "Basically, we apply chemical tools in a proteomic context to understand issues of drug selectivity and toxicities in real tissues in real time across species," says John W. Kozarich, the company's chairman and president. "And that kind of information gives the pharmaceutical scientist an understanding of the scope and limitations of his compound and some insight into the species comparison to understand the relevance of animal models to human disease."

ActivX has been "slowly adding people" to its payroll following a difficult period in 2003 in its drug discovery program. At that point, the company ran into a toxicity problem with a key clinical candidate and, consequently, lost its venture capital funding, Kozarich explains. Fortunately for ActivX, Tokyo-based Kyorin Pharmaceutical, with which it had been collaborating, stepped in to buy the company in a deal that was finalized in February 2005.

"By the time we were acquired, we were down to 29 people from a high headcount of 55," Kozarich says. Now, ActivX has 43 full-time employees, "and we will probably add at least a few people in 2007," he says. "If our collaboration business picks up based on our new platform—in which we have been able to assay more than 400 protein kinases in situ—we could add a significant number of employees."

Chemists will likely be part of the incoming mix of ActivX's new hires. The company employs about 10 chemists, who are currently focused on medicinal chemistry. In its recruiting efforts, the company favors candidates with strong synthetic chemistry backgrounds coupled with "some sort of biochemical, biological dimension—something they may have acquired during a postdoc experience," for example. On the basis of job applications he receives, he is "finding that more and more chemists have both types of skills, which is probably a reflection of the market."

Having a dual background in chemistry and biological systems may also be a boon for those wanting to work in the instrumentation field. At Thermo Fisher Scientific, for example, development of instrumentation for genomic and proteomic research is "the key growth area," according to Ian D. Jardine, the company's vice president of global research and development, who is located in Thermo Fisher's mass spectrometry facility in San Jose, Calif. "The importance of understanding genomics and proteomics—for every aspect of medicine and drug development—has never been clearer," Jardine says.

As scientists start to understand more about the incredible complexities of biological systems, "it is obvious that much more sensitive, vastly faster, and significantly more accurate and precise systems will be required for rapid diagnosis and subsequent therapeutic intervention," he adds. To deal with the staggering complexities of proteomics, "today's actually quite phenomenal tools will need to be superseded with even more sensitive, even higher throughput devices, while continuing to push capabilities such as accuracy and precision, but especially dynamic range, which is a significant problem in analyzing biological systems," he adds. Given the complexities of this area of research, "I cannot imagine that the intense effort in this entire area will diminish-ever."

Chemists of many specialties are a natural fit in the instrumentation business, Jardine says. "Apart from their ability to readily understand biological systems at the molecular level, most chemists are well-trained from their lab experience in handling, and sometimes building, instrumentation. And perhaps most important, they are usually thoroughly trained in the absolutely critical skill of problem solving."

To support R&D in genomics and proteomics in 2007 and beyond, Thermo Fisher Scientific anticipates that it will need to hire protein chemists as well as organic and analytical chemists, Jardine says. In addition, it will likely take on biologists, molecular biologists, electrical engineers, mechanical engineers, software scientists, and other specialists for instrument development, as well as data systems and postacquisition processing specialists in areas such as informatics, bioinformatics, and laboratory information management systems.

Any company involved in the highly sophisticated fields of genomics and proteomics will need to employ an array of scientists to drive its progress. Not surprisingly, some pharmaceutical firms are attacking their genomic and proteomic research with the same multidisciplinary team approach they are using throughout the drug discovery process. For example, Abbott's Spear says, a successful team might include someone who has very good analytical chemical skills in chromatography and mass spectrometry; someone else whose experience is in bioinformatics, algorithms, and information analysis; and a third person who might be a molecular biologist with a lot of experience in altering cell growth.

"In my area of Abbott, at least, we are looking for a wide range of diversity—not just in terms of educational training, but also in age, gender, race, national origin—in the people we hire," Spear says. "Therefore, when we are recruiting, we try to be more flexible in defining the qualities we are looking for. Diversity really does pay off," he adds. "When we put together a varied mix of people in a team, I've found that they have some of the most exciting discussions that often lead to some of the best ideas you can imagine."

Invitrogen seeks out candidates who will generate that same kind of creative energy. "As an organization, one of the common traits that drive our people is a passion for our quest to improve the human condition," Moses says. "There are many people with great skills in many different areas, but it's that passion and drive that really set our people apart."

Thermo Fisher Scientific also favors candidates who demonstrate both great enthusiasm and vivid imaginations. According to Jardine, "Dreamers who can't imagine why something won't work are an incredible asset."

Even though hiring in genomics and proteomics is modest, it is proving difficult to find candidates who possess the right mix of scientific expertise and character traits. "Often, we are looking for really good people who have skills in emerging areas of technology or science, and they make up a pretty thin layer. Candidates with experience in both molecular biology and biostatistics, for example, are few and far between," Spear says. "There isn't a regular source of them; it takes a lot of looking."

To be sure, companies are scouring every available talent source to find the cream-of-the crop candidates. "Our Talent Acquisition Team has been very successful in finding great people for the organization through direct recruiting, websites, and trade shows," Moses says. "We've also been very successful with our employee referral program, which we believe is a great way to find talent while simultaneously giving our employees a greater stake in the company's success."

In addition, Invitrogen has recently implemented a new iTalent Applicant Tracking System, which allows its recruiters to go back to people with strong qualifications who may have applied previously but were not hired simply because "the time was just not right," Moses says. "In some areas of the country, or for that matter, around the world, we might have to become more creative in acquiring talent, especially as the demographics of the global workforce continue to change."

In fact, Schering-Plough is already breaking down geographical barriers to find coveted candidates. For example, "we are importing talent from other countries," says Alex Desamour, director of global staffing at Schering-Plough Research Institute. At the same time, the company is working with outplacement firms to identify applicants from other companies. And "we are maximizing our campus recruitment," he says, noting that "university recruiting and hires from our industry have been our best sources." Companies cannot afford to leave any stone unturned, he says. "It's a very competitive environment."

As genomics and proteomics assimilate into the drug development process, Boguski predicts, the supply of the necessary scientists will rise to meet demand. For example, "in the genome era, initially, there was a critical gap of people who knew something about bioinformatics, but then, in the late 1990s, in response to that demand, many training programs at both the master's and Ph.D. levels sprang up. And those programs continue to thrive today." Following this same pattern, he believes, "master's-level and Ph.D.-level programs in protein chemistry and protein biochemistry will begin to evolve."

Scientists of all stripes cannot help but gravitate toward this exciting frontier, some say. Given their potential for broad application across nearly every aspect of pharmaceutical R&D, genomics and proteomics are clearly the way of the future. Reaching the goal of individualized medical treatment "will require a profound understanding of genetic differences, disease susceptibilities of individuals, and mutations as [evidenced] in cancer," Jardine points out.

Researchers are making great strides toward that end. "Breaking out of the anticlimactic period following the end of the high-profile Human Genome Project, we are now really starting to integrate what we've learned there," Boguski observes. "It's an exhilarating time for anyone involved in genomics and proteomics research."