The distinguished Clark, Professor Emeritus at UCLA, (Sex and the Origins of Death, etc.,) attempts to explain to nonscientists the biology underlying molecular medicine. This is no small undertaking, and Clark is only partly successful. For the layperson, his work requires careful reading of dense text, mastery of a mysterious new vocabulary - "recombinant plasmids," "antisense RNA," - and the study of complex diagrams. After these demanding biochemistry lessons, Clark turns to a fascinating discussion of what it all means in terms of human health. He details the current state of gene therapy in discussing cystic fibrosis and severe combined immunodeficiency disease (the Bubble Boy disorder), in which copies of normal genes are being successfully introduced into the living cells of individuals with defective genes. In cancer, the ultimate goal of gene therapy is to alter and kill every tumor cell, and in AIDS to neutralize the effects of HIV. Clark, who is optimistic about reaching these goals, then devotes a chapter each to the profound effects on public health that DNA vaccination (injecting a gene from a pathogen, which would be more effective than today's vaccines) will bring in the next century, and to the significance of the Human Genome Project, due to be completed shortly after the turn of the century. He clearly sees an educated public as the best defense against misuse of genetic information, for instance, altering a fetus's genetic makeup with the best of medical intentions but without knowing all the consequences of doing so.

Although Clark insists that if one is to understand molecular medicine one must first understand molecular biology, those who find his biology lectures too academic for comfort can still savor the well-wrought medical and ethical discussions.

Booklist, October 15, 1997. Reviewed by William Beatty.
There are some 4,000 known genetic diseases in humans, and others will be discovered. Molecular medicine, which discovers them, is, however, relatively new, and genetics did not become a separate field until 1906. Helped by illustrations that genuinely illustrate, Clark leads us through the fundamental work of Avery, Nirenberg, and other pioneers. In the light of what molecular medicine has done, and some of its possibilities for the future, he thoroughly examines cystic fibrosis, severe combined immunodeficiency disease, cancer and AIDS. His accounts of the thinking and procedures that led to the isolation, cloning and transfer of genes are lucid and intriguing. Although his subjects have been treated reputably by others, Clark distinguishes himself by dealing with them as though they were topics to be studied for practical purposes. He concludes with expositions of the Human Genome Project and major ethical problems. Molecular medicine is hard to comprehend. Clark explains it clearly and logically, communicating some of the excitement of the researchers who study and use it.

The lack of clinical success in the field of gene therapy has not been for a want of an enormous amount of research, directed at cultured cells, animals and humans. By the end of 1997, 175 clinical trials involving different gene therapy protocols had been completed or were underway, and over 2,000 patients had been treated without any real evidence of success. The field had attracted two new journals and numerous books and, even more remarkably, at least two histories had been written. This must be the only new form of medical treatment that has attracted a historical review before it has cured a patient.

Concerned about the costs of the increasing numbers of apparently unsuccessful clinical trials involving gene therapy, the National Institutes of Health recently set up a working party to assess progress. In essence, its conclusions were that the field had tried to run before it could walk, that fewer clinical studies should be funded and that priority should be given to studies that set out to tackle some of the basic biological problems that are inhibiting progress.

In retrospect, it is easy to understand why this potentially productive endeavor has not moved as quickly as was hoped. The regulation of mammalian genes has turned out to be extremely complex. It has proved difficult to find the appropriate vehicles with which to transfer genes into cells, and in the case of many diseases, the target cells themselves have been equally elusive. But genuine progress has been made and there is no doubt that this approach has enormous promise. And it has a wide therapeutic scope for, as we as correcting disorders due to a single defective gene, it has potential for the management of cancer, infectious disease, vascular disease and many of the major killers of western society. But it may still be a long haul before some of the daunting technical problems are overcome.

William Clark sets out a well-balanced account of the complexities of this controversial field of medical research. He offers a clear description of how genes work, and of the attempts that are being made to isolate and transfer them to new homes; highlights some of the early attempts at gene therapy, and ends with a short discussion of some of the ethical and pastoral issues that arise from human genetic manipulation. Many other books of this kind have appeared over recent years; this one holds it own against most of the competition and its discussion of the technical aspects of gene transfer is better than most.

In The New Healers, William Clark takes on gene therapy with the same verve and clarity that made his previous books on the immune system and the biology of the cell such a pleasure. The main message is that gene therapy works. The first trials were on children suffering from a rare immune disorder called adenosine deaminase (ADA) deficiency. Blood tests show that the healthy ADA gene transferred to their cells functions normally, restoring the immune system to full capacity.

But gene therapy can do more than supply a healthy gene to repair a single-gene defect. More than half the trials underway are to treat cancer and AIDS, and several novel strategies are being developed. For instance, so-called adaptive immunotherapy involves stimulating the body's natural defenses against cancer by delivering genes for immune system molecules to cancer cells.

Besides gene therapy, we may soon have DNA vaccines, delivered into the body by a miniature "gene gun." These new vaccines deliver a more effective immune response, and are being developed against hepatitis, TB and even cancer. The human genome project is likely to provide researchers with even more ideas for improving our health.

But Clark sounds a warning note: we must insure that genetic information is used wisely by informing ourselves about the ethical issues involved. Otherwise we could see a backlash that might deny us the far-reaching benefits of gene-based medicine.