Lost without translation?BMJ 2010; 341 doi: http://dx.doi.org/10.1136/bmj.c4363 (Published 18 August 2010) Cite this as: BMJ 2010;341:c4363
- Geoff Watts, freelance journalist, London
Translational research—the term is everywhere. The Cooksey report on research funding emphasised the need for more of it.1 So do the Medical Research Council (MRC),2 the Academy of Medical Sciences, and the Office for Strategic Co-ordination of Health Research—the government body set up to coordinate health research.3 Several universities now have departments of it. You can do an MSc in it. There will be more attention to it in the European Commission’s 7th framework programme.4 The planned UK Centre for Medical Research and Innovation5 trumpets an intention to feature lots of it, and promises to grant it the prestige usually accorded to discovery research. There are several journals devoted to it. In 2007, fearful perhaps of falling out of fashion, the long established Journal of Laboratory and Clinical Medicine restyled itself Translational Research, with its original name downgraded to a subtitle. In short, translation has shot up the agenda, has become the indispensible ingredient. Which is, on reflection, rather odd.
The term “translational medical research” has generated a stack of definitions with different emphases (see box). Some definitions stress the laboratory end of the process of turning a scientific finding into something clinically usable; some stress the clinical end. Some draw attention to the two way traffic of insights and questions. Some read like a first year sociology essay. But all enshrine the same core intention: that scientific research findings should be exploited for the benefit of people with diseases. And herein lies the oddity; isn’t the whole point of medical research to do just that? In which case why the need to single out one element of the process, give it a special name, and start behaving as if it’s a novelty? What is going on?
Definitions of translational research
Just three of the many definitions to chose from…
“Translational research involves moving knowledge and discovery gained from the basic sciences to its application in clinical and community settings. This concept is often summarized by the phrases “bench-to-bedside” and “bedside-to-community” research.”—US Institute of Translational Health Sciences (www.iths.org/about/translational)
“It’s the bridge from discovery to delivery. It has a clinical goal or target in mind, which isn’t the case for basic research.”—Eric Rose, dean for translational research at Columbia University Medical Center6
“Research going from bench to bedside, where theories emerging from pre-clinical experimentation are tested on patients with a variety of disease conditions, and from bedside to bench where information obtained from preliminary human experimentation can be used to refine our understanding of the biological principles underpinning the heterogeneity of human disease.”—Institute of Applied Health Sciences, University of Aberdeen (www.abdn.ac.uk/ims/translational/)
In a word, embarrassment. For several decades, and largely unnoticed outside the biomedical research community, our runaway success at understanding human biology has outstripped our capacity—or in some cases, regrettably, our inclination—to apply what we already know. Shelf loads of potentially valuable insights go unexploited.
Disinterest and uncertainty
A little over a decade ago I had cause to talk to some of the scientists working in a large research organisation specialising in the cell and molecular biology that underpins most attempts to tackle cancer. From time to time I thought I would display my grasp of the researchers’ aims by leaping ahead in the strategy I imagined they were about to outline. “Yes,” I would say, once I’d heard about their progress in unravelling the detail of some intracellular signalling system or whatever. “I see where you’re going. If you can sort out the steps in this chemical pathway, you can identify new targets for drug therapy.” Far from responding, “Exactly. You’ve got it,” some appeared almost surprised by my conclusion. “Yes, I suppose you’re right,” was a not untypical response. Although employed in an organisation devoted to curing cancer, the horizons of at least some of the (mostly non-clinical) researchers were so focused on their delight in understanding the systems they were studying that they seemed to have forgotten why they had been hired to do the work. What counted was the search for understanding; exploitation was, for them, a secondary consideration.
The problem now seems more often to be one of uncertainty than of indifference. Lee Nadler, professor of medicine at Harvard Medical School, is a leading champion of translational medicine. He recalls a meeting at which a Harvard neurobiologist remarked that his department was discovering new molecules and new pathways all the time but that he and his colleagues didn’t know how to relate what they had found to human illness.
Professor Nadler can remember hearing people speak about “translating things from the lab to the human” when he joined the US National Institutes of Health (NIH) back in the mid-1970s. And long before that, translation (the concept rather than the word itself) was what motivated the late 19th century creation of the Johns Hopkins Hospital in association with Johns Hopkins University. However, it’s really only since the beginning of this century that the phrase translational research has been ubiquitous. Stephen O’Rahilly of the Cambridge Institute of Metabolic Science at Addenbrooke’s Hospital chairs the MRC’s Translational Research Group. “One driver of the current enthusiasm,” he says, “has been the relative failure over the past 10 years of the pharmaceutical and biotech industry to come up with new products.” This shortfall fostered a nervousness that the hitherto successful way of doing things had run out of steam. There needed to be a new way of combining the strengths of industry and academia.
Professor O’Rahilly identifies a second issue. “The Human Genome Project over-promised what it could deliver in terms of health gains. It was a fabulous piece of science, but there was too much hype. Politicians and paymasters are now asking, ‘Where’s the beef?’ Turning the promise into new therapies hasn’t happened with the speed that some of these initiatives suggested.” Which is why another “translator,” Roland Wolf, speaks of “the increasing emphasis by government on the commercial and medical exploitation of government-funded research.” As the scientific director of the Biomedical Research Institute at Ninewells Hospital and Medical School in Dundee, Professor Wolf helped to forge the Scottish Translational Medicine Research Collaboration and the link to its commercial partner Wyeth Pharmaceuticals. Back on the further margin of the Atlantic, but thinking about both sides of it, Nadler talks of accountability. “The MRC, the NIH, and other bodies in the world have funded people who do basic science, and the issue is one of return on investment. Is it benefiting our patients?”
But how is translational research supposed to “bridge the gap” or “unblock the pipeline” between bench and bedside? “Science and medicine are becoming more and more specialised,” says Professor Wolf. “To expect a clinical oncologist to develop the biomarkers that may reflect patient responses to a new drug is just not realistic.” Which means what, in practice? According to Professor Nadler, ensuring that a large slice of the funding goes to groups who not only do basic science but also want to tackle the clinical questions. “Translational science requires not an individual but a team to look at a problem.” And how do you assemble such teams? With difficulty, he admits. They need to be multidisciplinary. They also need the right incentives—and that doesn’t mean just money. Team science is harder, takes longer, and doesn’t earn the same recognition as discovery research. Indeed, the ultimate exemplar of scientific recognition, the Nobel Prize, offers a singularly unhelpful model. Far from recognising teams, it limits the number of winners to three.
Through what they call their Harvard Catalyst project,7 Professor Nadler and his colleagues have already secured substantial investment in translation: $75m (£48m; €57m) from the university and its collaborators together with a five year $117.5m grant from the National Institutes of Health. Their conviction is that the university and its associates already possess the key ingredients for successful translation: the brain power, the technology, and the clinical expertise. “What is missing is a systematic way for investigators from disparate disciplines and institutions to find each other and form teams, to gain open access to tools and technologies, and to obtain seed funding to embark upon new areas of investigation.” This is what Harvard Catalyst can provide.
On its more modest scale, how effective is the MRC strategy for boosting translational research? Professor O’Rahilly thinks that it can make a difference to the movement of ideas and findings along the pipeline to clinical application. “Imagine you have scientists beavering away in the lab and finding that molecule X prevents immune cells sticking to one another. Then they find a simpler smaller molecule that can do the same thing, that might be good for treating rheumatoid arthritis, and might be taken through into human trials.” The aim would be to encourage those scientists not to stop work when they have elucidated the lymphocyte biology but to play a part in furthering it. Fine. But is the strategy paying off? “The time from the inception of an idea through to a trial is often a decade,” says Professor O’Rahilly. “So it’s still too soon to know.”
Paradoxes remain. “Britain’s place in the forefront of biomedical research has come from its commitment to basic science,” Professor Wolf points out. And Professor O’Rahilly adds that staff at the celebrated Laboratory of Molecular Biology in Cambridge have never been required to keep practical applications at the forefront of their thinking—which has not prevented their work from having a big effect on clinical medicine. Hence the fears (which Professor O’Rahilly well understands) that “too much concentration on seeing findings through into the clinic could lead to a diminution in the number of basic insights being brought to light in the first place.”
Insofar as scientific discoveries have been finding their way into clinical practice for two centuries, and will continue to do so, it’s self evident that translation (by whatever name) happens, and will go on happening. The point now at issue is how far the biomedical research community can take firmer control of the process. How far it can be speeded up and given direction. How far it will be possible, years from now, to be certain that without all the current effort, this drug or that diagnostic would still be a mere speculation in Nature or Science—lost without translation.
Cite this as: BMJ 2010;341:c4363
Competing interests: The author has completed the unified competing interest form at www.icmje.org/coi_disclosure.pdf and declares no support from any organisation for the submitted work; no financial relationships with any organisation that might have an interest in the submitted work in the previous three years; and no other relationships or activities that could appear to have influenced the submitted work.
Provenance and peer review: Commissioned; not externally peer reviewed.