More than a decade ago, when genetic scientists completed sequencing the first human genome as part of the Human Genome Project, optimism for its value to medical science was unbounded. Researchers heralded an era of pinpoint diagnostics, medicines tailored to an individual’s distinct gene map and breakthrough cures for everything from rare genetic disorders to common chronic conditions.
Decoding the human genome took ten years and an investment of US$3 billion. Today, the cost of mapping an individual’s genetic code has dropped to about US$1,000 and can be accomplished in a few days. Still, decoding the meaning of 6 billion base pairs for more than 20,000 genes in an individual’s DNA is far from imminent.
“If we’ve learned anything since the completion of the Human Genome Project, it is that the relationship between genes and human traits is far more complex than we ever imagined,” said Timothy Caulfield, Canadian Research Chair in Health Law & Policy at the University of Alberta, writing in a December 2012 editorial for Globe and Mail, a nationwide Canadian newspaper.
To usher in an era of personalized medicine, genetic scientists will need a database of millions of individuals’ genomes to help them understand the variation in genome sequence data and its role in specific diseases. Building this database will require participation from individuals willing to share both their genomic data and their comprehensive medical information. Only then, scientists agree, can they decipher the relationships between individuals’ genetics and the influence of environmental factors on their health.
Efforts like the Canadian Personal Genome project, a massive research initiative to sequence as many Canadians as possible, are pushing the science in the right direction, experts say. But these efforts will take time and raise significant ethical issues around how such inherently personal data should be used and protected.
The risks of disclosure are numerous. From hiring and health insurance to obtaining loans or even adopting a child, public disclosure of an individual’s genetic map could put them at risk of being stigmatized based on their predisposition to disease. And while the risks are great, the benefit to any one person’s health of participating in such large-scale sequencing projects will be small, especially in the short term.
Just a few years ago, only about 100 genetic tests were available; today, more than 1,000 are empowering physicians to better diagnose, counsel and treat patients.
“Genomic medicine holds tremendous promise,” Cheryl Shuman, director of genetic counseling for the Hospital for Sick Children in Canada, wrote on a Globe and Mail forum. “But we have a long way to go in understanding and contextualizing all findings – and experience to date indicates that not all findings reflect an underlying disorder.”
STATE OF THE ART
Perhaps the greatest benefit thus far comes from using sequenced genomes for diagnosing disease, predicting disease risk, and pinpointing which drugs to use and at what dose (pharmacogenomics), said Ghia Euskirchen, director of the DNA sequencing program in the Center for Genomics and Personalized Medicine at the Stanford University School of Medicine (USA).
Just a few years ago, only about 100 genetic tests were available; today, more than 1,000 are empowering physicians to better diagnose, counsel and treat patients for certain well- characterized disease states. Pharmacogenomic applications are already used to determine optimal drug treatments for breast, lung, colorectal and skin cancer, as well as treatments for childhood leukemia. Experts estimate that at least one-third of the 900 cancer drugs currently in clinical trials will come to market with a DNA or molecular test attached.
But only a small number of genetic variants have been studied extensively enough to substantiate a connection to disease, Euskirchen said. Often, common chronic conditions like heart disease, diabetes and depression involve multiple genes and a complex host of environmental factors. For example, more than 60 gene variants have been associated with diabetes, but only 70%-80% of the disease’s occurrence can be attributed to genetic factors versus environmental influences, according to Dr. Ronald Ma, professor in the Department of Medicine and Therapeutics at the Chinese University of Hong Kong.
THROUGH THE LOOKING GLASS
Such complexity means the personal health value of genomic information in the short term, particularly for common diseases, remains questionable. “We don’t understand about 99.9% of what the genome is telling us,” Dr. Lynda Chin, who heads the department of genomic medicine at the MD Anderson Cancer Center in Texas, recently told The Wall Street Journal. “The predictive value is less until we do.”
Clearly, a lot of complex puzzle- solving remains to be done. “Partnerships are forming between pharmaceutical and DNA testing companies like 23andMe and Illumina to begin to combine individual genomic maps into the ‘master blueprint’ that will allow science to answer these questions,” Euskirchen said. “But the road to personalized medicine – unfortunately – is still a long and winding one.”