To comprehend genomes is to begin to unlock the mysteries of life. One of the aims of the Human Genome Project, an international research program launched in 1990, was to map and then sequence every bit of DNA in a composite human genome. The project was heralded as the first step toward personalized medicine, a new age in health care when prevention and treatment of illnesses would be guided by examining a person’s genome and genetic predispositions. Understandably, expectations for the Human Genome Project ran high, and in 1996 President Bill Clinton glowingly foretold a not-too-distant future in which parents, armed with a map of their newborn’s genetic structure, could identify the risks for illness. In his vision, the fruits of the project would help “organize the diet plan, the exercise plan, the medical treatment that would enable untold numbers of people to have far more full lives.”
When the HGP was completed in 2003, that vision was still out of reach. Thanks to technological advances, it’s now on the horizon. The expense of genomic sequencing is falling fast; in Canada today it costs $10,000 to sequence an individual genome. “Once a whole genome costs $1,000 or less, entire families will get their genomes sequenced,” says Michael Hayden, director of the Centre for Molecular Medicine and Therapeutics at the University of British Columbia. “But what will they do with that information?” Whole-genome sequencing generates enormous amounts of raw data that must be analyzed by highly qualified medical geneticists and genetic counsellors, both in short supply (Canada has about eighty medical geneticists and 230 genetic counsellors). “DNA Sequencing Caught in Deluge of Data,” ran one recent headline in the New York Times, reflecting a common view that modern medicine doesn’t yet have the expertise to tell us what this data means, much less how to act on it. (...)
As the demand for whole-genome sequencing grows, so will profits, but the big money in personalized medicine will come from the development of treatments. Progress to date has been slow and confined to monogenic diseases such as Huntington’s, whose origin lies in a mutation on a single gene inherited from one parent. Because monogenic diseases are relatively rare, sequencing the genomes of those affected generates a manageable amount of data. Yet only 10 percent of monogenic diseases have yielded to treatment. On the other hand, multigenic disorders, such as cancer, diabetes, or Alzheimer’s, result from a complex interplay of genetic mutations and environmental factors. A given mutation on a person’s genome may not necessarily express as a malignant disease, so identifying the probability of a multigenic disease is extremely challenging. Traditional indicators such as family history, diet, and lifestyle may still be far more predictive than genetic testing for individual risk.
Compounding the problem, the bodily pathway of a multigenic disorder is complex and difficult to trace, and each person’s metabolism responds in a highly idiosyncratic way to the conditions that cause disease. To discover how individuals’ systems respond to the genetic risk for a multigenic disease requires comparing data gathered from the genomes of thousands of test subjects, ideally involving research findings and tissue samples from bio-banks worldwide. And once potential treatments for these disorders are identified, they require long-term clinical trials.
Convincing governments and other funders to support these kinds of initiatives rather than searching for a magic bullet to cure a disease such as cancer presents a challenge. “Getting population cohort studies launched in Canada is very difficult,” says Tom Hudson, president and scientific director of the Ontario Institute for Cancer Research. “It’s less sexy than funding basic human genome research.” Hudson has made consulting with clinicians and assessing their requirements a high priority. “We need to turn the question around,” he says. “We have to identify the medical need and make sure our research programs create paths to address those clinical questions. It’s like starting a puzzle from the end.”
More problematic is the reality that the human genome is still a vast catalogue of the unknown and scarcely known. The Human Genome Project’s most startling finding was that human genes, as currently defined, make up less than 2 percent of all the DNA on the genome, and that the total number of genes is relatively small. Scientists had predicted there might be 80,000 to 140,000 human genes, but the current tally is fewer than 25,000 — as one scientific paper put it, somewhere between that of a chicken and a grape. The remaining 98 percent of our DNA, once dismissed as “junk DNA,” is now taken more seriously. Researchers have focused on introns, in the gaps between the coding segments of genes, which may play a crucial role in regulating gene expression, by switching them on and off in response to environmental stimuli.
by Mark Czarnecki, The Walrus | Read more:
Illustration by Alain Pilon
