Ready or Not: Here Comes the Post-Genomic Era

“These studies are not so much about the individual, in the sense of some brave new world where we’ll be able to predict what diseases they will develop and when,” says Professor Rory Collins, principal investigator of UK Biobank, a multi-million pound UK project to outline how genes, lifestyle and the environment form the architecture of many common diseases. “I think that’s just science fiction,” he remarks.

Nevertheless with the benchmark price tag of US$1000 for your personal genome sequence looming ever closer, there is one important question that demands urgent attention: Is society ready for this? In a pioneering effort to answer such questions, ClinSeq, the latest genome-sequencing study from the US National Institutes of Health, will sequence the genomes of 1000 individuals aged 45-65 and ranging from healthy people to those with a family history of coronary heard disease.

“How are patients going to make sense of all this information?” asks Flavia Facio Genetic Counsellor and lead associate investigator of ClinSeq. “We will be interacting with study participants from many walks of life to learn what types of information is useful to them and how we can return these results in a meaningful way,” she says.

“One of the main differences between ClinSeq and other DNA banking studies is that we are actually planning on returning individual genotype results to these participants,” notes Facio. “What will be interesting is: how are people going to react to different types of results?”

“If they find out they have a predisposition to a condition for which there is something they can do, say a variant in a Low Density Lipoprotein (LDL) receptor gene [leading to elevated cholesterol levels], they can maybe change their diet or medication,” she explains. “But if you find a variant in a gene that predisposes them to a condition for which there is not much we can do at the moment, what will they choose to do then?”

Knowing your genome - ethical considerations

The decision to feedback genetic information is a controversial one and some experts worry about the potential risks to participants. “I can tell you personally that I wouldn’t take part in such a study, because it would make it impossible to get insurance,” asserts Professor Collins referring to ClinSeq. “If a genetic test is done, and you’re fed back information, then you may be required to advise your insurer of that result,” claims Professor Collins. “Whereas if the genetic test is done but there is no feedback [as in UK Biobank], then there’s no requirement to advise insurers.”

The issue of whether insurance companies should be allowed to ask for genetic information has remains a topic of international debate. In April, the US Congress took steps towards a resolution when its House of Representatives passed the US Genetic Information Non-discrimination Act of 2007, which explicitly prevents discrimination by insurers or employers on the basis of genetic differences. “[The legislation] still needs to be voted on by the US Senate and signed by the president before it will become a law of the land,” highlighted a spokesperson from the US National Institutes of Health. “Progress on this legislation is being tracked with great anticipation, but as yet it is not finalised,” he commented.

The UK exists in a similar state of limbo. There, a voluntary agreement between the Department of Health and the British Association of Insurers is all that presently prevents insurers from setting their premiums on the basis of genetic tests. When this moratorium expires in 2011, no one yet knows what the situation will be.

But perhaps it won’t be all doom and gloom. Imagine a world where insurers set premiums based on the genetic risk factors present in a population, rather than on the individual. That’s just one possibility, but in any case it sounds like we’ve got a long wait ahead of us. “You’ll have to reach a certain critical mass of sequenced genomes in each population before you really learn anything,” says O’Halloran. “Only then can you begin to predict the medical costs of a population, and even then environmental factors will make this a rough guess.”

In 2001, the human genome project showed us that humans are 99.9% similar to each other. Soon the ability to sequence thousands, even millions, of human genomes could tell us what the human genome project could not; how the remaining 0.01% of the genome makes us different. For mankind, the consequences of this knowledge are likely to transform medicine, offering the opportunity to stop disease even before it strikes. For society, the consequences are still unknown; hence studies like ClinSeq may prove crucial in helping to prepare us for the ethical and political mine fields awaiting us in the post-genomic era.

X-Prize Foundation - Archon X-Prize for Genomics
http://www.xprize.org/xprizes/genomics_x_prize.html

Wellcome Trust - Ethics in Genetics
http://genome.wellcome.ac.uk/node30060.html