Transplanting Autoimmune Research

What's the difference between testing a typical small molecule drug, and testing a novel cell therapy strategy? And where might the latter raise ethical challenges that the former doesn't? These questions are extensively discussed in my book, and given human drama in a recent story by Jennifer Couzin-Frankel in the Feb 12, 2010 issue of Science ("Replacing an Immune System Gone Haywire").

Couzin-Frankel describes the numerous difficulties that researchers have faced in attempting to validate autologous bone marrow transplantation for the treatment of (often nonlethal but highly debilitating) autoimmune disorders like type 1 diabetes, Crohn's disease, and multiple sclerosis. The idea of this procedure is to "reset" the immune system by purging patients of their bone marrow cells, and then returning healthy bone marrow to them. The approach has shown some promise for certain autoimmune disorders. However, response is highly variable and unpredictable, and validating and applying bone marrow transplantation for autoimmune disorders is beset by numerous ethical and logistical difficulties.

A major one is the risk-benefit balance: bone marrow transplantation requires exposing patients to the dangers of the transplantation procedure (6.6% mortality in one report of lupus patients). And yet, the procedures appear to work better in patients whose disease is not yet advanced. Testing the procedure therefore requires recruiting more or less healthy, at risk patients (sometimes children) into studies that expose them to serious risk of mortality. Clinicians understandably balk at referring their patients to such studies, making recruitment very difficult.

A second challenge is funding: many of these approaches involve using the patient's own bone marrow cells. There is nothing to patent-- and hence, little commercial interest in bone marrow transplantation for autoimmune disorders. This deprives this promising line of research needed resources.

And all this creates the perfect storm for a series of ethical challenges not directly addressed in this article (but covered in my book and articles): the siting of such studies in low and middle-income settings. Prohibitive costs, plus extreme difficulty recruiting patients who are otherwise eligible for somewhat effective and extremely expensive monoclonal antibody therapies, makes the siting of such trials in economically disadvantaged settings very attractive. This gives rise to what I have elsewhere called "expedient" justification for recruitment. Not surprisingly, then, one of the first trials of the procedure was performed in Brazil, and the article closes by mentioning that ongoing trials involving high-income country researchers are recruiting from São Paulo, Prague, China, and Argentina. This is good news if people in those settings have a reasonable prospect of having widespread and affordable access to bone marrow transplantation once it becomes validated. But it is troubling indeed if people in these countries will be bearing considerable burdens for the sake of knowledge benefits that will primarily (or most expeditiously) accrue to patients in high-income settings. (photo credit: Wellcome Images, Compact Bone, 2009)