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Can academia bridge the gap between bench and bedside?

Xconomy National — 

A few weeks ago I heard a pharmaceutical executive say at an industry meeting that academia shouldn’t be trying to develop drugs. They don’t know how to do it, his message was.

Now, he didn’t specify what he meant: Was it that academics do not know how to discover and optimize promising drug candidates, or that they can’t efficiently carry out the subsequent phases of drug development as a compound moves into clinical trials? But in a way, his comment was telling precisely because of its generalized nature. It represents a blanket view that is not uncommon in the industry (i.e., academia can’t make drugs) which is both right and wrong—and which stands as a barrier to bridging the infamous bench-to-bedside gap.

This gap is wide. The making of a drug usually starts with an interesting observation made by a bench scientist, and ends with an FDA-approved product. In between there are years of painstaking and costly work. Once a promising drug target has been identified it must be validated, any candidate compounds must be optimized and refined through specialized chemistry work, and those compounds must then be put through many animal studies to look at pharmacokinetics and toxicity. Then, paperwork must be filled to get permission from the FDA to study the compound in humans, and of course clinical trials must be designed and carried out at great expense.

This process must integrate two cultures—academia and industry–which often don’t know how to talk to each other. Academics, perched in their ivory tower, look down on the industry folks as uncreative and bureaucratic. People in industry resent the arrogance of academia and shake their heads at academia’s unfocused approach. More than once I have heard the comment that, when it comes to drug development, academics “just don’t know what they don’t know.”

From my own days in the lab, I know there’s some truth to the latter charge. Basic scientists are simply not trained to design their experiments in a way that will make it easier to move towards a clinical path. I worked with a set of proteins that had medical applications for bone regeneration. I knew everything about the proteins—all the downstream pathways possibly linked to them—and I knew the kinds of effects these molecules had on bone growth in mice and chickens. But never in my four years as a bench scientist did I think to design my experiments to help address a medical need. I wouldn’t have known how to, actually. And honestly, I didn’t really care. My pursuit was that of knowledge, not medicines.

Yet now, more than ever, those who pursue knowledge and those who pursue medicines must learn to coexist and cooperate with each other. The traditional model for drug development—in which academia’s role was largely restricted to basic research and industry took over as soon as basic discoveries were patented—is breaking down. Pharma’s massive multi-billion dollar investment in R&D over the last few decades has not yielded as many drugs as once hoped for. With investors losing confidence that early-stage biotechs are the sole answer to filling this pipeline void, attention is turning over to academia as the place to possibly carry discoveries a bit farther down the path to approval. So more and more, the ivory tower is poised to encroach into areas that have tended to be the exclusive turf of industry.

Take, for example, the translational medicine program at Massachusetts General Hospital. It is led by Mason Freeman, a physician who has inhabited both cultures: From 2005 to 2007 Freeman left academia to do a sabbatical as head of translational medicine for cardiovascular, diabetes, and metabolic diseases at the Novartis Institutes for Biomedical Research in Cambridge, MA. He then came back to MGH to run the translational medicine program.

Freeman’s group picked a lead compound in late 2007, performed all the studies needed to gain FDA permission to begin clinical testing, designed the clinical studies, and is now more than halfway through a phase II clinical trial in diabetics. The work was done for a biotechnology company that wanted to outsource it, and Freeman says his group took it on as a proof-of-concept program, partly to show to industry that such work can be done in academia.

Another example is the Broad Institute of MIT and Harvard in Cambridge, MA. Stuart Schreiber, director of the Broad’s Chemical Biology Program, says the institute has a “highly novel chemical substance” that looks like a promising candidate to treat cancer. The compound was discovered at the Broad in 2007, and since then Broad researchers have done all the optimization chemistry, as well as the animal pharmacokinetics and toxicity studies, so the compound is ready to go into the clinic. Schreiber adds that over a dozen clinical trials have also been launched by the Broad focusing on existing drugs that could be repurposed for other indications—the kind of work that usually done in biotech and pharma instead of academia.

Both Freeman and Schreiber said pharma’s prejudice about academics is partly justified. “For the most part, the typical academic health center and academic scientist doesn’t know very much about the rigors of drug development,” Freeman says. Schreiber adds that “overall, there has not been a long and outstanding record” of successful drug development programs in academia, “so industry has a good reason to be cautious in their enthusiasm about what academia can deliver.”

They both said, however, that there are a few groups in the country based out of universities and hospitals that, like their own, are beginning to take things much farther than academia traditionally has. Schreiber brought up Vanderbilt Medical Center in Nashville, TN, as a good example. There, researcher Jeffrey Conn leads a program in drug discovery. In a deal much more characteristic of what would happen in the biotech setting, Conn’s group recently signed a $10 million deal with Johnson & Johnson to develop treatments for schizophrenia.

“We believe academic organizations can perform these functions if they have the right people,” says Freeman of these kinds of drug development efforts. Finding people with industry expertise is crucial, they both said. At the Broad, salaries offered to scientists are on par with what they would earn in industry—a luxury that academic centers can’t usually afford. Schreiber says that at the Broad there are “maybe 60 scientists who’ve been in the pharma industry,” and many of them are among the institute’s senior leadership.

Of his own program, Freeman says: “We have specialized scientific and clinical expertise that can be extremely important to the early decisions about whether a therapeutic compound is going to work in a disease. We have imaging tools, trained human physiologists, laboratories of human investigation—and all of this can be tremendously powerful.”

Of course, as they say, the proof is ultimately in the pudding. Only when some of these promising compounds make it through phase III and into the market will the “new academia” model be validated. Until then, industry’s skepticism will be entirely justified.

Sylvia Pagán Westphal is Xconomy's life sciences columnist. You can reach her at swestphal@xconomy.com or you can follow her on Twitter at http://twitter.com/sylviawestphal. Visit http://www.xconomy.com/author/swestphal/ for Sylvia's full bio and disclosures. Follow @

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  • Observer

    Well it is a provocative subject, but isn’t the question really whether the very applied art of drug discovery / development for profit is an appropriate activity for an academic institution using federal funding? Once the personal profit motive comes in the supposedly altruistic mores of academia presumably go out the window.
    Re the initial comment, the art and science of drug design is obviously very difficult to accomplish and is full of pitfalls, the knowledge of which comes with long experience, or there would be more new drugs. Why would one assume that the professionals in pharma, typically recruited from the best schools, are less adept than inexperienced academics?
    So there will be some successes, but it does not seem to make sense a priori as a way to spend tax dollars.

  • Ted

    A more pertinent question would be “why are academic institutions developing drugs, anyways?”

    It creates a host of ethical dilemmas from top to bottom, with what is likely a very limited social payoff. The only advantage I can see is the opportunity to leverage still more cheap labor from graduate and post-doctoral students.

    There are more problems with pharmaceutical drug development than you can shake a beaker at, but transferring the process into the academic system has dim prospects.


  • Anthony Rodriguez

    I agree with the previous comments that full drug development from discovery to clinic in academia is both ethically dangerous and commercially inefficient. These drug development groups based in academic institutions that are seeing success share a common theme: hiring industry seasoned scientists and leaders. Experience is the name of the game here and why certain groups will be successful in academia. You also have to consider the ability for an academic to learn and absorb new knowledge to be just as important. Remember all scientists with PhDs started as academics at one point before they transitioned to industry. If an academic wants to be involved in drug development and has access to industry knowledge, they will become the experts themselves. The academics CAN learn, pharma just needs to be willing to work with them and vice versa.

    I think these academic drug development groups are going to be successful to a certain degree because they combine industry experience with willing academics in a setting that allows for hands on patient (or customer) interaction and non-diluted R&D funding.

    Let’s face it, big pharma does not produce new drug leads like they use to do. Today’s model is to acquire ones in development in an effort minimize the cost. What does it matter if that acquisition target is from academia or an industry savvy start-up?

    Taxes should not be a concern either. My money goes to academic funding agencies like the NIH so they can execute a mission to improve health care in this country. What good will my taxes be to me if the novel life science innovation they fund is left on the academics bench?

    There is plenty of room for a pharma business model that utilizes academic resources to bring lead products to a position ready for the large capital investment required for clinical trials. Such a model would be cheaper and more efficient to the company and potentially lead to lower cost of pharmaceuticals and potentially better healthcare today.