The development of new drugs can be an extremely lengthy, costly, and frustrating process, with an estimated investment by pharmaceutical companies reaching as high as $2-4 billion over more than a decade to bring a drug to market, often with little guarantee of substantial return.
Against this backdrop sits the discipline of translational medicine, which builds on discoveries in basic biology by a broad range of researchers in industry and academia and moves them closer to the patient’s bedside. At the same time, translational medicine promises to enhance the understanding of many of the mechanisms underlying disease.
Garret FitzGerald, a leading translational medicine expert at the University of Pennsylvania, told a Capitol Hill briefing organized by AAAS that the current drug development system in the United States is flawed and in need of change. The number of new drugs getting to market has remained the same for decades, while costs have skyrocketed.
“This represents an unsustainable model,” he said, and to change it, “we need to unlock translational opportunities afforded by the science.”
FitzGerald defined translational medicine as a discipline devoted to translation of the promise of basic scientific discoveries to create novel therapeutics, diagnostics, and approaches to management that benefit public health.
To harvest its potential, he said, society needs to invest in a particular type of human capital in the biomedical workforce.
“A disturbing trend in the last 20 years is that we have lost aspects of the workforce due to a great demographic shift in biomedical science,” FitzGerald said, noting that there are fewer people with skills in basic science who also pursue clinical research into disease mechanisms. “They are increasingly rare birds,” he said, “and we pay a price for that in terms of drug development, regulatory processes, and clinical care.”
FitzGerald, the McNeil Professor of Translational Medicine and Therapeutics at the University of Pennsylvania and director of the Institute for Translational Medicine and Therapeutics at the Perelman School of Medicine, spoke 31 July to a group of congressional staffers, researchers, and industry representatives. His talk, “Translational Science: From Research to Practice,” was co-sponsored by AAAS and its journal, Science Translational Medicine.
In introducing FitzGerald, AAAS Chief Executive Officer Alan I. Leshner referred to the long, expensive, and frequently futile journey of taking promising research findings in the laboratory and developing them into a useful therapy for patients.
University of Pennsylvania researcher Garret FitzGerald discusses the promise of translational medicine at a July 2012 Capitol Hill briefing.| Video by Carla Schaffer/AAAS
The topic of the talk “reflects an attempt by the research and biomedical communities to bridge what has been termed the ‘Valley of Death’ between basic and clinical science or between clinical science and actual practice,” said Leshner, who also serves as executive publisher of Science. “In some sense, without it, there is no serious improvement in practice and no application of innovation in real-life settings. From a scientific and public health point of view, it is extremely important.”
Unlocking the Potential
FitzGerald agreed, calling for an improvement in biomedical and academic infrastructure to support interdisciplinary translational science efforts and collaborations and to help academia become a greater player in drug development and discovery. This has already begun, he said, noting the recent creation of the National Institutes of Health’s National Center for Advancing Translational Sciences, which supports the development of translational medicine centers around the country. In the majority of the developed world, he said, there is a similar and substantial investment in translational research infrastructure.
He pointed to two recent examples of the field’s success:
- A team of researchers led by Jean Bennett, professor of ophthalmology and cell and developmental biology at the Perelman School of Medicine at the University of Pennsylvania, cured a rare form of blindness in dogs. Despite this compelling proof of principle, the team found it hard to attract support either from the NIH or industry to advance their work to tackle the human disease. A translational therapeutics center at the Children’s Hospital of Philadelphia and the University of Pennsylvania’s Institute for Translational Medicine and Therapeutics provided crucial support to continue the work. Since then, the research has delivered dramatic clinical success and attracted substantial funding from NIH, industry, and philanthropic sources.
- Researchers led by Carl June, the Richard W. Vague Professor in Immunotherapy at the Perelman School of Medicine at the University of Pennsylvania, used genetically engineered immune system T cells to attack leukemia cells. Penn’s Abramson Cancer Center, where June directs the translational research unit, and the Institute for Translational Medicine and Therapeutics provided crucial funding to sustain the program before it attained the clinical success that has now attracted substantial support from the NIH and from industry.
“These results illustrate nicely the potential of translational medicine,” FitzGerald said after the briefing. “Their shared characteristics were an unremitting focus by dedicated and talented leadership over a prolonged period—more than a decade—and support from intramural centers and institutes to sustain the effort until it attracted, by its success, the substantial, sustained support from NIH, philanthropy, and industry to develop further and broaden its clinical applications.”
FitzGerald also highlighted the potential of translational medicine to support the repurposing of already approved drugs. Perhaps the most striking and cost-effective example of repurposing is the use of aspirin at low doses to protect the heart.
He and his colleagues are interested in exploiting the variability in how patients respond to the same dose of the same drug, specifically developing science-based paradigms for predicting a patient’s responses to pain-killer medicines and cardiovascular risk from non-steroidal anti-inflammatory drugs.
The National Heart, Lung and Blood Institute recently funded a large consortium, which FitzGerald directs, to integrate a variety of disciplines from genomics to imaging. The consortium will develop new hypotheses about how to predict safe and effective responses to drugs and then test these possibilities in clinical trials. He said the consortium’s efforts are “another example of translational medicine in this way applied to the increasing personalization of medicine.”
Newer technologies, particularly focusing on diagnostics, are also being developed by the translational efforts of bioengineers. He pointed to an implantable microchip developed at MIT that can be programmed to deliver small amounts of drug on a schedule while minimizing toxicity. He also described a bedside nuclear magnetic resonance device that could detect “with exquisite sensitivity” tumor biomarkers and help determine whether a tumor is benign or malignant.
New Models for Drug Development
FitzGerald was less generous with what he sees as “unrealistic expectations and outmoded structures around intellectual property” in both academia and industry.
But that’s beginning to change. The old model of the large, vertically integrated drug company that did everything from drug discovery to development to bringing the product to market—yet was shrouded in corporate secrecy—is slowly fading.
“We are witnessing the disintegration of large, vertically integrated companies and a move towards a more modular approach to drug development and collaboration,” he said, “where the investigators from academia, pharma, and biotech—often drawn from different countries—will collaborate.”
He also discussed how academia and industry might collaborate without the limitations of intellectual property issues and how both the U.S. Food and Drug Administration and NIH might encourage more collaborative behavior between industry and academia.
In the end, he noted, improving translational medicine capabilities is critically important to the United States’ continued ability to compete internationally in drug development.
6 September 2012