Finally, progress depends on personal human drive, vision, and the belief in being right, irrespective of distracting, even fatal, setbacks. The best example of sheer stubbornness is the work of Robert Edwards and Patrick Steptoe, who were the first to deliver a “test-tube” baby in 1978. Le Fanu believes that Edwards faced early and “bitter disappointment that would have convinced any lesser person to give up in despair.” A request for research funding to study in-vitro fertilization was rejected on grounds of distasteful ethics and lack of proven success in animals. When Steptoe and Edwards finally did get the official go-ahead, their first twenty or so attempts over two years ended in dispiriting failure. The will to go on in the face of such unequivocal defeat showed, Le Fanu perceives with hindsight, great “moral courage.”
After this, Le Fanu examines the development of new disciplines that grew up around these discoveries. For instance, the new science of pharmacology fostered extensive commercial programs of therapeutic drug development. These drugs were not made after working out the details of how a cell or tissue functioned. Le Fanu presses his argument that heavily financed chemistry “blindly and randomly” produced “remedies that had eluded doctors for centuries.” In sum, “the dynamics of the therapeutic revolution owed more to a synergy between the creative forces of capitalism and chemistry than to the science of medicine and biology.”
The business of medicine also legitimized technology as a means to solve specific problems. Renal failure (dialysis), intestinal disorders (endoscopy), deafness (the cochlea implant), heart rhythm disturbances (pacemakers), and failures of vital body systems (intensive care), together with new means to look at parts of the body that previously only revealed themselves in the autopsy room—all helped to make doctors feel that their calling was being transformed into something quite miraculous. And here, according to Le Fanu, was the seed of subsequent decline. For doctors “came to believe their intellectual contribution to be greater than it really was, and that they understood more than they really did.”
The peak of their achievement came in the 1970s. But by the end of that decade, Le Fanu asks, “where were the new ideas?” He sees this “pivotal moment” as one that “has until now hardly been commented on.”
Drug innovation waned once the limiting effects of burdensome government regulation kicked in after the thalidomide tragedy. A more rational and less random approach to drug discovery was “much less fruitful than was hoped.” Chance allowed for the unexpected; science did not. Diagnostic techniques came to dominate clinical care. Patients were commonly overinvestigated by batteries of tests, “downgrading the importance of wisdom and experience in favor of spurious objectivity.” But Le Fanu’s target is not the machinery of medicine:
The culprit is not technology itself, but the intellectual and emotional immaturity of the medical profession, which seemed unable to exert the necessary self-control over its new-found powers.
As doctors misunderstood and misused the tools available to them, they passed the responsibility for research to a new professional cadre of medical scientists. The “fall” was by now irreversible. Failures stacked up in all spheres of medicine, laboratory and clinical.
Basic science came to be dominated by molecular genetics. The discovery of DNA spawned new technologies that led to research into genetic engineering, genetic screening, and gene therapy. Naive investors, often ignorant about the wafer-thin credibility of the research they were paying for, poured millions into biotechnology companies. The result, according to Le Fanu, has been that “the impression of progress has not been vindicated by anything resembling the practical benefits originally anticipated.”
Worse, gene therapy has largely turned out to be “not only expensive but useless.” Why has the new genetics so far failed medicine? Le Fanu answers that “genetics is not a particularly significant factor in human disease.” And, in any case, genes are “complex,” “unpredictable,” and “perverse.” They are not amenable to easy understanding. Their involvement in disease is largely “incomprehensible.”
And what of the clinic? Le Fanu believes the huge error that doctors made was to be “seduced” by “the Social Theory,” an approach to the study of disease by which exposure to environmental hazards or to dangerous forms of human behavior are sought as the possible causes of diseases. These epidemiological inquiries suggested ways of preventing illness by altering the exposure or modifying a behavior.
Smoking is an obvious example. Le Fanu has no doubts about the link between smoking and lung cancer; but he believes the success of Richard Doll’s early work has rendered doctors and the public prey to the foolish view that many diseases are caused by unhealthy lifestyles. Le Fanu’s key exhibit for the prosecution is the dietary hypothesis of heart disease—namely, that what one eats will determine one’s risk of a heart attack. This idea, according to Le Fanu, is “the great cholesterol deception.” Accepting the mechanistic link between cholesterol and heart disease, he vehemently denies that diet can be counted on to cure it. He applies the same skepticism to similar claims about diet and cancer (“quackery”). Without any qualification, Le Fanu concludes that the Social Theory “is in error in its entirety” (his italics). He accuses epidemiologists of “deceit,” “idealist utopianism,” and “lack of insight.” The consequence is that the epidemiological perspective
has wasted hundreds of millions of pounds in futile research and health-education programmes while justifying the imposition of costly regulations to reduce yet further the minuscule levels of pollution in air and water. And to cap it all, it does not work. The promise of the prevention of thousands of deaths a year has not been fulfilled.
The fall of medicine was complete.
Le Fanu’s criticism of wildly exaggerated claims and expectations for the new genetics is shared by many of those who are leaders in the field. David Weatherall, who runs the Institute of Molecular Medicine at the University of Oxford, pointed out only last year that
the remarkable complexity of the genotype-phenotype relationship has undoubtedly been underestimated during the early period of the revolution in the biomedical sciences that followed the DNA era. It has led to many statements being made about the imminence of accurate predictive genetics that are simply not true…. It is far from certain that we will ever reach a stage in which we can accurately predict the occurrence of some of the common disorders of Western society at any particular stage in an individual’s life.8
Research tends to support Le Fanu’s view that genes are mostly a minor determinant of human disease. Studies of twins enable investigators to explore the genetic and environmental contributions to disease (although they tell us nothing about important interactions between the two). In one recent report, for example, evidence from twins showed “that the overwhelming contributor to the causation of cancer” was not genetic. If genes play an important part, then the risk of cancer should be substantially greater in identical twins than in nonidentical twins, and this was not the case.9 For breast cancer, only 27 percent of all causes can be traced to genetic factors. Prostate cancer was the disease in which genes had the most important part to play (42 percent of risk was explained by genes).
Genetic fatalism about disease is a myth that needs to be exposed once and for all. It is very unlikely that a simple and directly causal link between genes and most common diseases will ever be found. This message is not one that many scientists want the public to hear; continued political support for funding genetic research depends on persistent public credulity.
The prevailing if rather private realism among some scientists about the contribution of genetics to our understanding of human disease makes the recent hoopla about a reported first draft of the human genome all the more difficult to accept. An editorial writer for The Times of London, under the nonsensical headline “Secrets of Creation,” concluded with hundreds of other journalists that
this is a breathtaking moment for genetic science, for human health, even for philosophy…. The greatest scientific journey of this century starts here, with this directory; as its alphabet is decoded, the prediction, treatment and understanding of disease should be revolutionised…. It could, in particular, revolutionise the treatment of cancer, which is caused by malfunctioning genes.10
Not so. The fact is that progress in exploiting the genome will be painfully slow. Its importance lies not in the existence of a working draft of the genome—by itself, this tells us very little—but rather in its opening up the possibility for sequencing multiple copies of the human genome to discover variations among individuals in health and in disease. Even knowing this variation—a precondition for practical application—is of limited value, since the chief task of research must now be to study how variations in gene sequences interact with different environmental exposures, and gradations of each exposure, so as to alter the conditions of risk. I doubt that we will get far along this path during my lifetime (I am thirty-eight).
Having emphasized the importance of humility in the face of unfettered journalistic hyperbole, I should also mention the isolated signs of small steps forward. Le Fanu mocks the lack of progress in gene therapy since the first report of successful treatment for a type of inherited severe combined immunodeficiency disorder (SCID) in 1990. The recipient of this intervention, Ashanti de Silva, is now thirteen years old. She received eleven infusions of gene-corrected cells ten years ago and she has, in the words of her doctor, “thrived” ever since.11 Moreover, during the past decade, the techniques for giving new genes to patients with SCID have improved. In a recent report, the delivery of normal genes to two infants with SCID corrected their abnormal immune function. Ten months later, both children were living at home, growing and developing normally without any side effects. A third child has also been treated and was at home, fit and well, four months later.12 While it is far too early to draw firm conclusions, technical improvements in gene delivery do seem to translate into clinical benefit. One should still be cautious here: SCID is a rare condition amenable to correction with a single gene. Most common diseases will not be so easy to deal with.
Le Fanu’s opposition to the social theory of disease is, if anything, even greater than his skepticism of genetics. His vehement condemnation of the social theory is a regular subject in the columns he writes for the London Sunday Telegraph.13 Epidemiological studies produce, he claims, “spurious statistical associations whose contribution to useful knowledge is zero.” How has this “nonsense” come to be so ingrained in medicine? Le Fanu explains:
First, this type of study is easy to do: it takes no special expertise to switch on a computer, trawl through the social habits of a large group of people and come up with a “new” finding. Second, they have the veneer of scientific objectivity, with lots of figures and statistics whose publication in a journal is visible evidence of the researcher’s productivity.
David Weatherall, "From Genotype to Phenotype: Genetics and Medical Practice in the New Millennium," Philosophical Transactions of the Royal Society of London, Vol. 354, B (1999), p. 2008.↩
See Paul Lichtenstein et al., "Environmental and Heritable Factors in the Causation of Cancer," The New England Journal of Medicine, July 13, 2000, pp. 78-85.↩
The Times of London, June 23, 2000.↩
See W. French Anderson, "The Best of Times, the Worst of Times," Science, April 28, 2000, pp. 627-629.↩
See Marina Cavazzana-Calvo et al., "Gene Therapy of Human Severe Combined Immunodeficiency (SCID)- X1 Disease," Science, April 28, 2000, pp. 669-672.↩
See, for example, James Le Fanu, "Scientists Who Should Carry a Health Warning," Sunday Telegraph, July 9, 2000, p. 2.↩
David Weatherall, “From Genotype to Phenotype: Genetics and Medical Practice in the New Millennium,” Philosophical Transactions of the Royal Society of London, Vol. 354, B (1999), p. 2008.↩
See Paul Lichtenstein et al., “Environmental and Heritable Factors in the Causation of Cancer,” The New England Journal of Medicine, July 13, 2000, pp. 78-85.↩
The Times of London, June 23, 2000.↩
See W. French Anderson, “The Best of Times, the Worst of Times,” Science, April 28, 2000, pp. 627-629.↩
See Marina Cavazzana-Calvo et al., “Gene Therapy of Human Severe Combined Immunodeficiency (SCID)- X1 Disease,” Science, April 28, 2000, pp. 669-672.↩
See, for example, James Le Fanu, “Scientists Who Should Carry a Health Warning,” Sunday Telegraph, July 9, 2000, p. 2.↩