On April 25, 1953, Francis Crick and James Watson published a one-page paper that many believed would revolutionise biological research. Building on the work of Rosalind Franklin and Maurice Wilkins, they had discovered DNA’s double-helix structure, providing the first glimpse into how organisms inherit and store biological information. But, 60 years later, has their discovery really had the transformative impact that the world expected?
The media marked the publication’s 60th anniversary with much fanfare, hailing the breakthrough that “ushered in the age of genetics”, and calling it “one of the most important scientific discoveries of all time”. The British newspaper The Guardian featured the headline, “Happy Birthday, DNA! The golden moment that changed us all”.
To some extent, they are right. The finding forms the basis of genetics and has opened up promising new research areas, such as synthetic biology, in which biological systems are created or modified to perform specific functions. Likewise, it has facilitated important innovations, such as pharmacogenetic cancer treatment, in which drugs target specific genetic defects within cancer cells.
Moreover, DNA has acquired a certain mystique in popular culture. According to Dorothy Nelkin and Susan Lindee, it has become a sacred entity - the modern equivalent of the Christian soul, an individual’s essence. While some forms of biological determinism, such as the belief that race or gender dictates a person’s destiny, have been widely rejected, the idea that a person can be genetically predisposed, say, to get into debt, become a ruthless dictator, or vote regularly in elections remains socially acceptable.
But, almost from the beginning - and most intensely since 1971, when Time magazine published a special section entitled, “The New Genetics: Man into Superman” - science and society alike have tended to overestimate the impact of genetics. When the Human Genome Project published the first draft of the fully sequenced human genome in 2000, Henry Gee, an editor of the journal Nature, predicted that scientists would be able “to alter entire organisms out of all recognition to suit our needs and tastes” by 2099. “We will have extra limbs, if we want them,” he asserted, “maybe even wings to fly.”
Thirteen years later, Gee’s prediction looks increasingly unlikely, with the Human Genome Project so far having failed to meet expectations. Indeed, in 2010, the science writer Nicholas Wade lamented that, a decade after the project was launched, geneticists were “almost back to square one in knowing where to look for the roots of common disease”.
For example, a 12-year studyof 19,000 white American women found that 101 genetic markers that had been statistically linked to heart disease had no predictive value. Self-reported family histories, by contrast, proved very accurate in predicting the disease.
In fact, most diseases are not caused by single genes. As a result, after a few early successes with atypical single-gene disorders such as Huntington’s disease, progress has stalled. Common variants typically explain a small fraction of genetic risk.
Genetics has been a source of particularly high hopes when it comes to cancer treatment. Between 1962 and 1985, cancer-related deaths in the US rose by 8.7 percent, despite the use of aggressive chemotherapy drugs and radiation therapy, highlighting the dangers of a one-size-fits-all approach to treatment. An understanding of the genetic determinants of patients’ therapeutic response, it was believed, would enable doctors to develop individualised treatment programmes, sparing more responsive patients from harmful overtreatment.
But patients are not the only variable. Cancer, too, is heterogeneous, even in patients with the same diagnosis. After sequencing the entire genomes of 50 patients’ breast cancer tumors, researchers found that only 10 percent of the tumours had more than three mutations in common. According to a recent study mapping genetic mutations in 2,000 tumours, breast cancer can actually be divided into ten subgroups.
Similarly, a genome-wide analysis of malignant cells from four kidney-cancer patients showed that, while they were related, they had mutated in many different directions. Two-thirds of the genetic faults identified were not repeated in the same tumour, let alone in any other metastasized tumours in the body. Given that a pharmacogenetic drug targets one mutation in the tumour, it will not necessarily work on the other mutations. In addition, as the cancer adjusts to the drug, further mutations are likely to occur, diminishing the drug’s efficacy.
To be sure, pharmacogenetics has made a profound difference for some patients. Barbara Bradfield, one of the original subjects in research trials for the pharmacogenetic cancer drug Herceptin, has now been stable on the drug for more than 20 years. But such success stories are far too rare to constitute a “golden age” of genetics.
The high price of such drugs is limiting their impact as well. Herceptin can cost up to $40,000 annually, and newer cancer drugs cost even more, making them prohibitively expensive for most patients.
The US Supreme Court is currently faced with the question of whether genes can be patented. If the court upholds the biotechnology company Myriad Genetics’ patents on two genes which, in some variants, are linked to higher risk for breast and ovarian cancer, the company will retain exclusive rights to use the genes in research, diagnosis and treatment for two decades, preventing rivals from developing cheaper alternatives. Women have already been denied access to a diagnostic test, because insurers refuse to pay the company’s high prices.
Manufacturers claim that gene patents, which now cover 25-40 percent of the human genome, are vital to recouping their investments. But such patents mar DNA’s “birthday” celebrations for the patients who stand to benefit from the fruits of genetic research - if only they could afford them.
Donna Dickenson, Emeritus Professor of Medical Ethics and Humanities at the University of London, was the 2006 winner of the International Spinoza Lens Award for contributions to public debate on ethics. She is the author of the forthcoming book Me Medicine vs We Medicine.
A version of this article first appeared on Project Syndicate.
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