Correspondence

The Molecular Medicine Series

N Engl J Med 1995; 332:1240-1241May 4, 1995

Article

To the Editor:

As a physician and a molecular biologist, I am struck by the Journal's series on molecular medicine. To my ear, the series is marked by a kind of overexuberance that belongs in a sales pitch for biotechnology investors, not in a reasoned review for physicians. For example, an article on gene regulation (Oct. 6 issue)1 concludes, “Knowing the molecular details of these processes will ultimately allow us to rewrite the genetic language when it goes awry.” This is a remarkably optimistic view. The distance between understanding molecular details and developing a clinically useful intervention is vast and may never be bridged. The fact is that molecular biology, after 20 years of enthusiastic claims, has yet to contribute much to the day-to-day care of our patients. It has contributed tremendously to our understanding of the basis of health and disease, and I believe this has a value to society that is independent of practical applications. It seems a dangerous act of hubris, however, to insist that these advances in science will have clinical usefulness. If they do not work, how believable are we? It is sobering to look back to a time 30 years ago when it seemed certain that interferons would transform medicine. I believe that as physicians practicing in academic centers, we have a responsibility to make balanced assessments of the prospects for clinical application of scientific advances.

Mark Stoeckle, M.D.
Cornell University Medical College, New York, NY 10021

1 References

1. 1

   Rosenthal N. Regulation of gene expression. N Engl J Med 1994;331:931-933
   Full Text | Web of Science | Medline

Author/Editor Response

Drs. Rosenthal and Schwartz reply:

Dr. Stoeckle sees the molecular-biology glass as half empty. For us it is half full. We do not agree that it is “a dangerous act of hubris . . . to insist that these advances in science will have clinical usefulness.” Of course, not all scientific endeavors in biology have clinical utility. But most of the people we know in medical research laboratories work in the hope that their projects will find clinical applications. Indeed, we think it is not hubris to aspire to a clinically useful outcome of one's research.

Dr. Stoeckle disparages “20 years of enthusiastic claims” for molecular biology. It is true that the methods of genetic engineering were developed in the 1970s, but concerted efforts to apply molecular biology to clinical problems have been going on for about 10, not 20, years. It was only in the mid-1980s that private investors came up with the financing required to launch the biotechnology industry. In gauging the speed of medical progress it is instructive to recall that Kekulé envisioned the benzene ring in 1865, thereby making possible organic chemistry and a science-based pharmaceutical industry. But it was not until the late 1920s that the first clinically useful antibiotic was synthesized. Kl-730 (Prontosil), a benzene ring with a new kind of side chain — a sulfonamide group — was discovered 60 years after benzene itself.

Dr. Stoeckle points out that 30 years ago “it seemed certain that interferons would transform medicine.” Fortunately, some serious people did think of interferon as revolutionary, and encouraged the research that led to interferon alfa, a clinically useful treatment for hematologic cancers. But, more important, the development of interferon alfa opened the way to other natural polypeptides with growth-controlling properties, such as erythropoietin, granulocyte colony-stimulating factor and granulocyte–macrophage colony-stimulating factor — all of considerable medical importance.

We are sorry that Dr. Stoeckle thinks molecular biology “has yet to contribute much to the day-to-day care of our patients,” and we regret his view that we show too much enthusiasm in the Molecular Medicine series. However, the validity of his opinions depends on the kind of day-to-day care one gives. We would agree that orthopedics has not yet benefited much from molecular biology. But physicians in fields such as oncology, infectious diseases, clinical genetics, and pathology cannot afford to retreat from the path it has laid down.

Nadia Rosenthal, Ph.D.
Robert S. Schwartz, M.D.