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Cover Story

November 10, 2008
Volume 86, Number 45
pp. 13-20

The New Deal

Seeking closer ties, drug companies and universities shake up the model for research alliances

Lisa M. Jarvis

WHEN ALAN B. EZEKOWITZ was a trainee at Harvard Medical School, university labs received funding from drug companies with the message, "We'll check on you once a year." Now, as head of bone, muscle, immunology, respiratory, and endocrine R&D at Merck Research Laboratories, Ezekowitz isn't sure this traditional approach is fair. In practice, he says, it doesn't work out very well for the pharmaceutical industry.

More Access Scientists at Pfizer and Washington University in St. Louis can tap into resources at their nearby campuses. Washington U In St. Louis
More Access Scientists at Pfizer and Washington University in St. Louis can tap into resources at their nearby campuses.

Drug companies have long been a source of funding for academic laboratories, but the two entities typically stayed at arm's length. Pharma companies held the purse strings but were not involved in mapping out and executing the research goals. Some academic scientists argue that the distance existed for good reason: Research happening within university walls, they say, should be guided by the pursuit of knowledge, not profits.

Today, however, drugmakers are looking for more accountability and collaboration in their dealings with academia. Companies want to ensure the relationships are furthering their underlying goal of speeding up the validation and exploitation of drug targets. Academic institutions, meanwhile, are taking a more targeted approach to research. Academia is becoming amenable to opening its doors to drug firms—if it means access to new technology and the potential to diversify funding streams amid dwindling government grants.

The end result is a new breed of industry-academia alliance that closely connects researchers. In these collaborations, academic and industry scientists jointly come up with project proposals, divvy up the labwork, and patent and publish their results. The goal of this meeting of scientific minds—being pursued most prominently by Merck & Co., Pfizer, and AstraZeneca—is to accelerate the move from basic biology to drug targets and, ultimately, medicines.

"The approach 20 years ago was pharma gives a chunk of change, and then they have the rights to license any discoveries," says Laurie H. Glimcher, a professor at Harvard Medical School and a professor of immunology at Harvard School of Public Health. "I don't think that really works anymore. It has become apparent to many people in the private sector and the academic sector that closer ties between industry and academia are the wave of the future." Glimcher, who also sits on the board of Bristol-Myers Squibb, recently teamed up with Merck to work toward new treatments for osteoporosis.

"The approach 20 years ago was pharma gives a chunk of change, and then they have the rights to license any discoveries."

The advent of genomics and the development of high-throughput screening, rapid DNA sequencing, and advanced imaging means that scientists can quickly move from the discovery of a basic biologic concept—a pathway or potential disease target—to its analysis in humans. It's an R&D context rife with expensive equipment and extensive compound libraries that academic scientists would love to get their hands on.

"I think the time is right for a greater emphasis on bringing together both intellectual and physical tools in a coordinated way to solve ad hoc problems," says Rudolph L. Leibel, head of molecular genetics and codirector of the Naomi Berrie Diabetes Center at Columbia University Medical Center. Leibel helps steer a research collaboration between the medical center and AstraZeneca that is focused on metabolic diseases.

Leibel believes the move from the bench to the bedside can occur more quickly if researchers on either end of the spectrum—academics with expertise in establishing promising new targets and companies with compound libraries—would only work together.

IN PRACTICAL TERMS this means a shift away from the study of basic biological questions by individual researchers to a more holistic exploration of key medical problems. Under the new model, academic and industry scientists work together to design projects that might uncover answers to those broader questions. Such collaborations are a major shift from "the mostly atomized approach, which is historically the way a lot of biomedical research has been done," Leibel notes.

In September 2007, Merck became the first drug company to establish a broader R&D alliance with an academic institution when it announced an agreement to conduct research into oncology topics and central nervous system disorders with Harvard Medical School. The initial deal provided six Harvard labs with funding. And because Merck's Boston R&D site is within walking distance of Harvard, researchers from both sides have ready access to one another's labs.

More than ideas Columbia University's Leibel will host an AstraZeneca researcher in the coming months. Matt Porter
More than ideas Columbia University's Leibel will host an AstraZeneca researcher in the coming months.

This spring, the drug firm signed another agreement with Harvard, this time to fund osteoporosis research with Glimcher, whose lab discovered a pathway important in controlling the balance between building up and breaking down bone. The deal has trappings of typical sponsored-funding agreements: Merck hands over money and has the right to license molecules that come out of Glimcher's research. Not so typical, however, is that scientists from Merck and Harvard are working together to discover new signaling pathways and explore the function of a protein that mediates bone growth.

"Merck is using their enormous resources to help us assemble huge expression arrays and integrate the signaling pathways in samples we give them," Glimcher says. In particular, Merck will use its proteomics and mass spectrometry capabilities to help elucidate substrates and other molecular participants in the bone-growth mediation pathway.

The two lead Harvard scientists on the project interact with Merck almost daily, Glimcher says. The team gets together once a month, and all participants have access to a virtual meeting room where they can post data. "We feel like it really is a research collaboration," Glimcher adds.

A slew of innovative R&D pacts have been unveiled in the year since Merck and Harvard joined forces. Yet although the shift toward a more collaborative approach between big pharma and academia is clear, the agreements follow no set pattern.

AstraZeneca, for example, has taken myriad approaches to broader pacts, even within the same institution. The British company has signed two separate agreements with Columbia that call for different levels of involvement.

Under the first deal, signed in June, the drug company and the university will collaborate to develop new drugs for diabetes and obesity. According to Håkan Wennbo, AstraZeneca's global project director for cardiovascular and gastrointestinal diseases, the pact has three broad goals: to elucidate the biology and find promising drug targets in diabetes and obesity, to establish clinical protocols that provide guidance about whether a drug is actually working, and to understand specific drug mechanisms in more detail.

To achieve those goals, a Columbia scientist makes a proposal and then is teamed with an AstraZeneca scientist. Together, they develop a line of inquiry that includes crafting a research plan, assigning responsibilities to each partner's lab, and determining methods of communication. For some projects, the research begins at Columbia and later shifts to AstraZeneca. For others, activities start jointly and can include deeper contact: In the coming months, for example, an AstraZeneca scientist will temporarily join Leibel's labs.

In AstraZeneca's second Columbia deal, which is centered on neurology, a similar joint research committee oversees the collaboration. However, the scientists are unlikely to work together as they do in the obesity pact. Rather, Columbia will continue to advance its understanding of neurogenesis, looking for new avenues to treat depression, whereas AstraZeneca will be responsible for providing molecules that can help test the pathways that Columbia discovers.

"What we're good at is making compounds—biological tools, if you like," says Alan Cross, AstraZeneca's executive director for early psychiatry and neurology. The idea is to supply Columbia researchers with reagents and other pharmacological tools to test pathways. AstraZeneca will then apply its in-house expertise in target validation.

Pfizer, meanwhile, is evolving an existing relationship with Washington University in St. Louis. The two organizations established ties more than 20 years ago, says Karen Seibert, vice president of Pfizer's research labs in St. Louis. The nature of that relationship has changed as the direction of Pfizer's research has changed, but in January, the partners announced a seismic shift in their pact. "It's an evolution away from the traditional funding paradigm toward what I view as a truly collaborative agreement," Seibert says.

Under the new approach, Washington University scientists across a range of disciplines make short research proposals related to immunology and inflammation. The proposals are reviewed by a joint steering committee cochaired by Seibert and Jeff Gordon, director of Washington University's Center for Genome Sciences. The academic researchers are then paired with Pfizer scientists to write a full proposal. "There is complete openness—no walls, no barriers," Seibert says. "The ideas develop collaboratively, and the focus often changes when our scientists come together to the table."

After considering the full proposals, the steering committee chooses some to fund. Scientists from industry and academia then work as a team to complete the projects, with free access to the resources at their respective organizations. In fact, Seibert notes, these projects become goals and deliverables for the scientists' annual employee performance reviews at Pfizer.

Obesity research Columbia University graduate student Yann Ravussin contributes to metabolic research in an alliance with AstraZeneca. Matt Porter
Obesity research Columbia University graduate student Yann Ravussin contributes to metabolic research in an alliance with AstraZeneca.

Since Pfizer and Washington University adopted the new approach early this year, progress has been significant. The first round of short proposals was submitted in April, with more than 80 investigators representing myriad departments applying—typically as interdisciplinary groups, Gordon says. Four of these short proposals from Washington University scientists were selected so that full proposals could be crafted together with Pfizer scientists. Those proposals were ready for review by the steering committee in September, and final funding decisions will be determined shortly.

Pfizer and AstraZeneca have similar broad collaborations with other institutions. For example, Pfizer has ties with the University of California, San Diego, and AstraZeneca has pacts related to Alzheimer's disease with Washington University and the Banner Alzheimer's Institute, based in Phoenix. GlaxoSmithKline, meanwhile, has inked a major deal with the Immune Disease Institute, in Boston.

For drug companies these deeper collaborations with academia are part of an effort to inject more certainty into the drug discovery and development process. With the cost of developing a new drug soaring beyond $800 million and new drug approvals in 2007 falling to their lowest level in more than two decades, companies recognize the need to improve their methods. And they believe academic labs can help.

"Before we can get to finding drug candidates, we have to satisfy ourselves that we are working on the very best targets and that we have the very best tools to understand the deep biology of complex pathways," Seibert says. And although Pfizer explores biological pathways and targets on its own, agreements like the one with Washington University bring alternative approaches, she adds.

ALTHOUGH BIG PHARMA offers research tools that academicians can only dream of, universities with medical schools???specifically teaching hospitals???can immediately try out hypotheses that would be difficult to test in a corporate setting. In other words, "the university brings access to the patients we are trying to serve," Seibert explains. Academic physicians have access to tissues and samples that can be used to sort out complex diseases, and they potentially have the ability to study broader disease trends in patients.

"If you have a strategic collaboration, you can much more quickly define and establish actual work."

For instance, obesity, the target of the first pact between Columbia and AstraZeneca, is a disease of both environment and biology—it encompasses genes, as well as what people eat, when they eat it, and how much energy they use in the process. Studying patients at Columbia University Medical Center can help pinpoint the factors that contribute to weight gain, notes AstraZeneca's Wennbo. The information can be used first to design new molecules to treat disease and later to design clinical trials to test them.

For AstraZeneca, a close alliance with a leading academic institution promises to help science happen faster than under the simpler relationships of the past. "If you have a strategic collaboration, you can much more quickly define and establish actual work," Wennbo says. "Negotiations can take a long time. Here, you can very quickly start research activities."

Some outside observers see that openness as the most attractive part of these collaborations. In the old days, a scientist in academia with an interesting compound could call up an industry friend and ask him or her to evaluate it, says E. J. Corey, a Harvard University chemistry professor and Nobel Laureate. "Now, lawyers have to write these complicated transfer agreements," he says. "It's cumbersome, and I think in the long run it may discourage innovation." Corey sees merit in finding new ways to facilitate collaboration.

Another advantage, participants in such collaborations say, is that these arrangements often bring together academic and industry scientists in one lab. The ability to easily exchange ideas and gain the perspective of another scientist can drive research forward—sometimes in unexpected and promising directions. "You might end up with new solutions, experiments, and models that you might not end up with if you only talk to excellent scientists who only work in a certain way," Wennbo says.

Ezekowitz Merck Research Laboratories
Seibert Pfizer
Gordon Washington U In St. Louis

Although a close working relationship between academia and industry has many benefits, some academicians are concerned about blurring the lines that have traditionally separated the organizations. Despite the advantages of these partnerships, Corey, for example, worries that such deals will in the long term loosen a critical tension between the profit motive of industry and the educational focus of academia.

Hector F. DeLuca, a biochemistry professor at the University of Wisconsin, Madison, also has concerns. "I am always hesitant to form an alliance like that because there's a difference in goals," he says. Although companies profess openness, he says, they sometimes don't want work published for intellectual property reasons or because they fear regulatory repercussions down the road. "There are a lot of restrictions with industry that I don't like to see in the academic world," DeLuca says.

The new collaborators say they have done their best to create agreements that take into consideration the different needs and constraints of both sides. For one, they maintain that academic scientists will enjoy complete freedom to publish, an issue that has hindered such collaborations in the past. The Harvard-Merck deal, for example, has to adhere to Harvard's guidelines that dictate only a brief period for the pharma partner to review a manuscript and file patents before a paper is submitted. "The decision to publish is with me—Harvard is very strict about that," Glimcher notes.

Merck's Ezekowitz, the former Harvard student, agrees. "With this agreement, there is no restriction on publication or on students and postdocs reporting information in any way if they're working on this collaboration," he says. "Having come from Harvard, I understand that as a tenet one should not violate."

And academic scientists involved in such collaborations see many benefits. At the forefront is the ability to advance science quickly and comprehensively. "We typically don't have the capacity in a university setting to mount the sort of very complex drug discovery programs that biotech and big pharma are able to do," Washington University's Gordon says.

At the same time, it's critical to establish and validate targets so that researchers understand "to the greatest degree possible how these molecules that we're targeting operate in the context of human biology," Gordon says. "Deep knowledge of human physiology—that's what we can bring to the table, and that's what is needed to make the process of drug discovery more economical with lower attrition."

Money is also a clear motivator for academia. The funding environment for universities has been turbulent in recent years, to say the least; U.S. government funding, in constant dollars, has been declining since 2004. Furthermore, some academic researchers claim that the National Institutes of Health, the primary source of biomedical funds, has become conservative about the kinds of projects that receive grants.

Although industry funding represents just 5% of overall R&D money spent in academia in 2006, academic leaders acknowledge that schools need to look beyond government and to private sources for funding.

"In this day and age, it is very important for investigators to have access to many different funding streams," Gordon says. "One of the consequences of this constricted NIH budget is a conservatism. There are editorial decisions made by investigators about what seems to be the safest, most obvious ideas for peer review." To Gordon, risk-taking is essential to developing ideas that are both innovative and well grounded.

"I've seen a shift in my own sources of funding over the past couple of years," Harvard's Glimcher says. The majority of her funding used to come from NIH, whereas now, public and private sources are more balanced.

"Industry at the moment might benefit from getting something
into the market quickly, but it also might destroy the
free-ranging activity of the professor."

Thanks to the Merck collaboration, Glimcher has established an entire "bone team," complete with separate lab space in Harvard's School of Dental Medicine where the scientists can interact with other experts in the field. She points out that her background is in immunology, far from bone health. "I don't think we could have done that without the presence of Merck," she says. "We're bona fide members of the skeletal biology community now."

SKEPTICS of deep relationships between industry and academia concede that drug companies can be an important source of funding. "The problem is, we can't support the academic world anymore," says UW Madison's DeLuca, noting that he has received private funding in addition to government grants throughout his career. However, DeLuca thinks the better way to manage industry funding is with the traditional model: Industry pays for research, stands back, and then has first right of refusal on any discoveries that come out of that work.

DeLuca, whose research in vitamin D is at the root of eight commercial drugs and who has himself started a biotech firm, sees several reasons for maintaining distance between industry and academia. "Academics are allowed to drift around and investigate what they want; industry wants to harness that," DeLuca says. "Both are important, but we can't destroy the academic world because it will destroy the innovative new pathways being discovered. Sure, industry at the moment might benefit from getting something into the market quickly, but it also might destroy the free-ranging activity of the professor."

But academics involved in industry partnerships say they have incorporated measures to maintain that spirit of openness. In Columbia's collaboration with AstraZeneca, Leibel stresses, idea generation starts at the university, rather than being dictated by its big pharma partner. "Some people think we end up doing contract work for a pharmaceutical company, and that's not the case," he says. "In fact, the flow of impetus and the design of experiments have always come primarily from within the academic institution."

Furthermore, many think this new breed of alliance provides graduate students and postdocs with a glimpse inside big pharma—an invaluable experience when it comes time to decide on a career path. "It's incredibly valuable exposure," Glimcher says. Looking back on the many scientists she's trained during the past 25 years, Glimcher notes that their career trajectories have spanned academia and industry and that some have even returned to practicing medicine. "It's good to have a sense of what it is like to work in industry," she adds.

Leibel notes that in any relationship he's had with industry, he's made a point of bringing his students to meetings related to science. "It's been universally true that those students have found that interaction extremely interesting not only from the point of view of the science—some of that information is not yet in the public domain—but also because they get to see what the lifestyle is," he says.

In the case of Leibel's partnership with Merck, students are learning to write protocols that will be vetted by the company, a completely different process than writing a grant application for NIH.

It remains to be seen whether the new model will become the rule rather than the exception for how industry and academia collaborate. The alliances are relatively young, and it will be years before participants can look back and assess whether working together accelerates the search for new and better drugs and whether it leaves the freedoms and knowledge-driven focus of academia intact.

"We've done it the traditional way for a long time, and we continue that to a certain extent," Pfizer's Seibert says. But she sees value in tapping a new kind of synergy between academic and industry scientists, a synergy that seems to be emerging with ease. After all, Seibert points out, "we do share the same basic scientific interests."

Cover Story

  • The New Deal
  • Seeking closer ties, drug companies and universities shake up the model for research alliances
  • New Models For New Technologies
  • Enlight uses financial backing from three pharma firms to pull breakthrough technologies out of academia

Save/Share »

Chemical & Engineering News
ISSN 0009-2347
Copyright © 2009 American Chemical Society

Cover Story

  • The New Deal
  • Seeking closer ties, drug companies and universities shake up the model for research alliances
  • New Models For New Technologies
  • Enlight uses financial backing from three pharma firms to pull breakthrough technologies out of academia


Save/Share »



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