Celling cancer

One of the most remarkable features of the world of publishing over the last three decades has been the boom in the market for books that aim to explain the complexities of modern science to the man in the street. This success story is all the more surprising because some of the bestsellers of this genre deal with topics of great complexity in a way that moves even those who boast some knowledge of the field to admit, if not freely at least when pressed, that they have not the foggiest idea what the book is all about.

While some of the more accessible works of this kind have an irritatingly gratuitous or forced "reader-friendly" feel about them, and in their attempt to clarify may paint an inaccurate or over-stated picture, others offer excellent guides, even to the most arcane concepts or technologies of present-day science. The latter seem to come in two different varieties. First, there are those that are written with such gusto and raciness of style, and with a genuine knack on the part of the author for conveying the excitement of their work, that even those of complete scientific illiteracy are swept along by the tale. One of the earliest, The Double Helix by James Watson, is as popular today as it was when it first appeared in 1968. At the other end of the spectrum there are collections of beautifully written essays, or longer accounts, which as well as clarifying a particular field, are genuine works of literature in their own right. Peter Medawar, Stephen Jay Gould or Lewis Thomas would surely hold their own with any essayist of recent times.

Two new books that set out to help the general reader to understand how the tools of molecular and cell biology have been used to unravel the mysteries of the cancer cell offer excellent examples of the best of each of these varieties of popular science writing.

Watson's "warts and all" approach to conveying the excitement of a rapidly moving research field is used with great effect by the leading cancer specialist Robert Weinberg in his extremely lively account of how, in just a few years, cancer ceased to be a mysterious disease. This is undoubtedly one of the most remarkable stories of biomedical research of the last part of the 20th century, a period of scientific activity during which the totally unexpected and unpredicted seem to have become commonplace. The tale is even more surprising because, as Weinberg points out, cancer research was in the doldrums until as recently as the early 1970s. While it was clear that a few forms of cancer in some species other than man might be transmitted by viruses, and that others might result from the action of chemical carcinogens or other environmental toxins, nobody had the faintest idea where to turn next in the search for the fundamental cause of cancerous changes in cells. Yet, largely as the result of the remarkable technical developments of the DNA era, all this changed overnight.

Recombinant DNA technology - that is the ability to manipulate and transfer genes, and to dissect them at the molecular level - allowed virologists to work out how certain tumour viruses can enter cells and copy their genetic material so that it becomes inserted into the host's chromosomes. Furthermore, the cancer-producing properties of these viruses seemed to reside in one or more genes, which, therefore, became known as viral oncogenes. Quite remarkably, it was then found that all living organisms, including human beings, have genes that are very similar to viral oncogenes. It turned out that these homologues, later called cellular oncogenes, are part of our cells' normal genetic machinery, and are responsible for the control of their proliferation, specialisation and social behaviour with one another.

It appeared, therefore, that at some time during their evolutionary history, tumour viruses had acquired these genes and that they had changed their properties in their new home so that they were able to cause cancer under appropriate conditions. This bizarre story was not, of course, telling us that human tumours are caused by viruses. Rather, it was the discovery that viral oncogenes have their counterparts in the cells of all living things that led to the discovery of a family of genes that are responsible for a wide variety of normal cellular functions, but which, if they behave abnormally, can cause a cell to change its behaviour and become cancerous.

By this remarkably roundabout route, therefore, the notion evolved that many tumours may be caused by alterations in cellular oncogenes. But more surprises were to follow. It was soon discovered that a change of just one nucleotide building block of the many thousands that constitute these genes is enough to change their activities and to result in cancerous transformation. It is now clear that our cells contain many different genes which, if their structure is altered by mutations of this kind, or in other ways, can generate different forms of cancer. In many cases the malignant transformation requires more than one gene to be changed - in the case of common bowel cancers probably up to six or more. Rarely, we may be born with a defective gene that makes us more likely to contract cancer, but most cancers probably result from the acquisition of genetic alterations during our lifetime.

At last the biology of cancer started to make sense. In short, the disease appeared to be the result of subtle damage to our DNA, possibly as the result of years of exposure to noxious environmental agents or toxic by-products of the chemical reactions which underlie all normal living processes, defective genes that we might be unfortunate enough to inherit, and, above all, the ill luck to have the right combination of mutations in a particular cell population at the same time.

Weinberg tells this story with great pace and gusto, and pulls no punches along the way. It is a tale of remarkably talented scientists, false starts, major set-backs, quacks and frauds, laboratory fridges stocked with champagne waiting for the call from Stockholm which never comes, an embarrassing gaffe by the Nobel committee, jealousies, and major personality clashes. His drive and enthusiasm is reflected on every page, and his book, which reads like a good detective story, is extremely difficult to put down. While readers who know a little of the field may be mildly irritated by a few ungenerous descriptions of their colleagues, the sceptical view of clinical scientists, and the occasional lapse into insularity, I suspect that they too will devour what he has to offer at a single sitting.

John Cairns's approach to popular science writing is quite different. Here we have a collection of beautifully written, reflective essays covering the history of mortality, how molecular biology was spurred by the application of physics and chemistry to living processes and later applied to the cancer field, and a particularly original account of some aspects of the development of epidemiology and its importance to the study of cancer. His final essay deals with questions of overpopulation and what to him clearly is more important - that is the damage that we are causing to our environment. Cairns's writing is a fine example of how science can be presented to the general reader in an extremely scholarly way, and why writing of this kind can be of equal interest to fellow scientists, reflecting as it does a remarkable imagination and intellect.

If either of these books has a weakness it is in their accounts of the potential clinical applications of these extraordinary advances in the cancer field. While epidemiology has played a major role in teaching us how at least some forms of cancer can be prevented, the truth is that the discoveries at the molecular level have not made much impact in the clinic and probably will not do so for some time to come. This is not surprising - it was many years before the equally remarkable findings in microbiology and immunology of the turn of this century were translated into the control and treatment of infectious disease. The cancer field will undoubtedly evolve in the same way, though, I suspect, more rapidly.

Like so many of the most exciting periods of scientific advance, the sudden acceleration of pace described in these books reflects the chance coming together of information from many apparently disparate fields, each happening to reach a critical phase of development at more or less the same time. None of this could be planned or foreseen by the scientists involved, let alone by a government committee or research funding body. In truth, much of the success of the cancer field has come from curiosity-driven research on such diverse organisms as yeast, clams, amphibians and fruit flies, and cultured mammalian cells.

A well-known London surgeon once remarked that the answer to cancer would not come from men in white coats in laboratories, but as a sudden flash of inspiration to somebody observing workmen digging a hole in the road. He was wrong of course, but not completely off the mark. The answer to the basic nature of cancer has come from laboratories, but many of the key observations stem from work which was totally unrelated to the cancer field and which was pursued by those who simply wanted to understand some of the fundamental mechanisms whereby genes and cells function. In a climate in which governments and those that fund science are pressuring scientists more and more towards short-term practical goals, it is sobering to reflect on the way in which the cancer field has evolved over the last 15 years. Although it is the kind of story that has recurred time and again in the field of medical advance, it is one which never seems to have been appreciated by science policy makers.

Anybody who wants to understand the remarkable successes of cancer research over recent years should buy both books. Young people, particularly those interested in a career in science, should read Weinberg first and should then take their time and relish John Cairns's more reflective and thoughtful account, together with all the other wise things he has to say. And those who wish to "save British science" should consider clubbing together to purchase copies for holders of the purse strings for the support of basic biological research. Without a doubt, these works reflect all that is best at the two poles of popular science writing.

Sir David Weatherall is regius professor of medicine, University of Oxford.