Human Trials
Scientists, Investors, and Patients in the Quest for a Cure
SUSAN QUINN
Perseus Publishing, Cambridge, MA, 2001, 320 pp, $26 hardback
ISBN 0-7382-0182-0

Howard Weiner is not a typical physician, and the engaging story of his on-going attempts to bring relief to millions of sufferers from autoimmune diseases (such as multiple sclerosis and rheumatoid arthritis) is far from the norm in the field of drug development. For that reason, Susan Quinn’s tale of his efforts is both hopeful and enlightening: hopeful because his research, while not yet commercially viable, holds tremendous promise; enlightening because his dedicated and unyielding drive to cure his patients of their diseases is unusual.

In today’s world of drug discovery, major pharmaceutical companies, which use exhaustive combinatorial chemistry and high-throughput screening techniques, identify most new products. These companies are more often interested in discovering potentially profitable therapies that can be applied to a given disease than in starting with a disease and attempting to find its treatment. Many potentially viable drug candidates, for example, sit in laboratories untested because their utility is not widespread enough to balance the costs of development. (To be sure, numerous small biotech companies have emerged with a single-minded purpose, but even their determination seems more driven by bottom-line possibilities than patient-driven concerns.)

The process of drug development described by Quinn, however, begins not in an industrial laboratory but in a Harvard Medical School research group. Weiner, who specializes in autoimmune diseases, was one of the first to realize the possibility of treating these disorders with “oral tolerance”, and he and his team of scientists were principal in advancing this theory.

Autoimmune disease causes a patient’s immune system to destroy otherwise normal, healthy tissue; the attacks’ trigger mechanisms remain unclear, although scientists are beginning to develop promising theories. Recent studies using oral tolerance in rats have proved wildly successful: When rats with the equivalent of human multiple sclerosis are repeatedly fed the myelin proteins that their immune systems attack, they are cured of the disease.

To develop this research further, Weiner’s group formed a company called AutoImmune, which raised the venture capital necessary to test Myloral, an oral formulation of myelin meant to cure humans of multiple sclerosis, and Colloral, a collagen formulation intended for patients suffering from rheumatoid arthritis. His journey included hiring corporate managers, battling academic egos, placating nervous investors, planning human trials, and convincing a skeptical medical community of the validity of his work.

Quinn’s revealing tale of Weiner’s (and AutoImmune’s) efforts is filled with firsthand accounts punctuated by entries from Weiner’s diary. The result is an insider’s view of the excitement and disappointment inherent in all scientific advances. The interface between an academic research project and its corporate evolution, as seen through the originating scientists’ eyes, is interesting and instructive.

Unfortunately, the oral-tolerance-based drugs presented in the book were not successful, and AutoImmune failed. However, neither Myloral nor Colloral were ineffective treatments; rather, their tests simply proved them to be no more efficacious than placebos; in fairness, the placebo effect in these trials was greater than others previously recorded.

Probably the most important aspect of Quinn’s narrative is its demonstration that adequate study design is crucial to clinical research. In the case of Myloral, for example, choices to speed the testing process that were predicated on AutoImmune’s financial situation may have contributed to the outcome: Early dosing trials were all but omitted, resulting in the fact that the tested Myloral dosages may have been too low. Ultimately, though, the quest for a cure, as described in Human Trials, is a case study of the hopes, plans, missteps, serendipitous discoveries, and tremendous efforts that are inherent in drug development.