Also, the mechanisms for sharing credit are poorly defined and there are few mechanisms available for scientists to share grants and funding with their clinical colleagues, according to Dr. Cronstein. "Does a clinician become an author of a high-profile science paper for supplying one patient’s samples? Two? Twenty?" And although the National Institutes of Health has recently defined the coinvestigator mechanism, "even that tends to slight the noncorresponding author." Although the importance of bringing clinical and scientific colleagues together is generally understood to be critical, "finding the appropriate venues to do so is very difficult to accomplish in practice," he said.
In an ideal world, the science/clinical collaboration would be more fluid than fixed, whereby the clinical investigator studying a pathologic state "would interact with several different scientists who offer their appropriate expertise to tease out different components and different pathways," said Dr. McInnes. "One of the difficulties is that we often don’t know where the starting point is in the pathological journey. We are informed by the circumstances of where we are looking." In rheumatoid arthritis, for example, "a lot of our thinking [behind recent developments] was provoked by what the joint looks like after 5-10 years of disease. Maybe the next advance will be provoked by what the joint looks like after just a couple of days of arthritis, if we could get to that window," he said. Out of circumstance, then, the divide between basic and clinical research is process driven because there are many different processes at work at different phases even in one disease."
Each discipline also has its own distinct obstacles that can preclude fluid cooperation. "At the moment, the challenges of successfully translating a bit of science into an understanding of pathogenesis are gargantuan. There’s the ethics of looking at human tissue, the willingness of patient populations to participate, and just the pragmatics of whereabouts in the patient you can look," said Dr. McInnes. "If the disease is a disease of the lymph node or bone marrow, before it becomes a disease of the joint, it’s not impossible but it is quite difficult to get bits of lymph node and bone marrow from human beings, although that’s some of the real interesting science that underpins what the disease may be." Unlike cancer, in which biopsies are part of routine care and as such can more readily be used for scientific investigation, "it’s not routine to biopsy joint tissue or synovial lining in rheumatoid arthritis patients, even if it’s something you would like to do, and it’s absolutely not routine practice to biopsy lymph nodes or bone marrow. The ethics are marginal."
Finally, there are simply not enough properly trained clinician scientists, in medicine in general and rheumatology specifically, Dr. McInnes said. "When they do exist, they are often hard-pressed to meet the demands of both the scientific and clinical communities." Efforts to chip away at this particular barrier are underway, thanks to innovative collaborations, within and between universities and medical schools, often supported by government and/or pharmaceutical company funding. The university-wide Clinical and Translational Science Institute at NYU, for example, in partnership with the New York City Health and Hospitals Corporation and with funding support from the NIH, is one of more than 45 such centers nationwide charged with the task of training clinician scientists and accelerating advances from the lab to the clinic.
Similarly, Dr. McInnes is deputy director of a novel translational medicine consortium comprising the Scottish universities of Aberdeen, Dundee, Edinburgh, and Glasgow, funded by the Wellcome Trust, a global charitable foundation, and Pfizer. Called the Scottish Translational Medicine and Therapeutics Initiative (STMTI), its mandate is to create a "new cadre" of academic clinicians with expertise in translational medicine and treatment by offering doctoral fellowship training programs for clinicians. "The goal is to meet the ongoing need for appropriately trained clinical investigators who have the basic science understanding who are backed by basic science training and expertise," he said. "Such individuals can act de facto as investigators, but also as catalysts. They can drive motivation within the basic science community and also engage the clinical community."
Importantly, however, translational activity cannot be forced, Dr. McInnes stressed. There are many ways to achieve collaboration, but, in my opinion, they all require one thing: curiosity," he said. "If a scientist and clinical investigator share an interest in getting an answer to questions that are either identical or sufficiently close to each other, that is a fruitful platform for a successful translational partnership." For example, if a scientist can demonstrate that a pathway is present in the disease state of interest to the clinician, both the scientist and the clinician will be curious to understand how it operates within that disease state and that will drive their work."