Venter, Collins grace the Time cover, July 3, 2000

“It is fair to say that the Human Genome Project has not yet directly affected the health care of most individuals.” – Francis Collins, April 2010, Nature.

What’s in a genome?  Ten years ago, the completion of the Human Genome Project promised to usher in a whole new era of heath care.  Revolutionary gene therapies would soon conquer everything from cancer and heart disease to diabetes and autoimmunity.  A roll-call of our genes would unlock the causes (and the solutions) to death and disease.  But a decade on, most of these hopes have failed to materialize, and most of our lives haven’t changed.  So where’s the revolution?

A recent retrospective in Nature includes some sobering reviews by such genetic gurus as Craig Venter and Francis Collins.  Sure, there have been some significant gains.  In vitro genetic screening has greatly reduced the risk of many common genetic diseases at the pre-birth stage.  Risk factors for a range of adult diseases (including cancer) are coming into focus, and a host of new drugs have been developed.  But as scientists expected to find common genetic determinants underlying common diseases, they quickly discovered that the genome was anything but straightforward.  Instead, the genes behind disease have been shown to be highly complex and individually variable, even for widespread disorders.  There isn’t a SNP for cancer.

The problem is that currently, the field of genomics is data-rich and application-poor.  Thanks to companies like Complete Genomics, there is a flood of new genetic data and even more on the way – but we still don’t know how it works.  So far, the primary focus of interest (and funding) has been the most easily quantifiable advances, such as sequencing speed and costs.  Accomplishments in this arena have been impressive, but a complementary push for clinical applications is needed to sort through all of this genomic data that we still don’t understand.

The fate of commercial genetics hangs in the balance.  Companies like deCODE and 23andMe were born on the hope that laypeople might be willing to pay for a glimpse at their own DNA.  The bankruptcy of deCODE and troubling rumors about 23andMe raise the question of whether personal genomics is an industry born premature.  So far, their products feed a curiosity niche, not a utilitarian one.  When a genome points to little more than SNP-based correlations, few people can justify spending their recession-hit income on what remains a biotech novelty.

As Collins, Venter and others have suggested, a health care revolution requires bridging the gap between genomic data and its clinical utility.  Any disappointments of the past decade point to the directions of the next.  We’re learning that so-called “junk DNA” isn’t really junk, but can regulate the expression of other, coding sequences of the genome.  Untangling the various networks of gene regulation will illuminate the pathways which result in a given phenotype, pathological or not.  The roles of epigenetic processes are also undoubtedly complicating factors which will need to be better understood.

Most approaches over the past decade have used SNP chip analysis to identify mutations associated with particular phenotypes.  This type of analysis only looks at small parts of the genome, and has largely failed to identify the genetic determinants of most diseases.  The SNP chip approach will be phased out as whole-genome scans become faster and more affordable (costs should drop below $1000 within the next three years).  Complete Genomics aims to sequence 1 million human genomes within the next five years, and that’s a lot of data to crunch. Venter is calling for two ways of making better sense of this flood of whole-genome scans: more detailed phenotype analyses, and the development of computational tools that can link them to their genetic counterparts.

It’s interesting to note the parallel between difficulties encountered in genomics and neuroscience. Recent years have seen an increasing shift in brain science from localization (areas of the brain that “do” things) towards neural-network approaches.  Just as we’ll unlikely find a single gene that causes cancer, we’re not going to find the “irony zone” of the brain anytime soon.  Reconceptualizing both genomics and the brain as complex, interactive networks remains a necessary step to significant advances in either field (e.g. a health care revolution or AI, respectively). And despite these setbacks, we can expect big things on the way.

Genetics has already revolutionized our health care in certain respects. Preimplantation genetic diagnosis (PGD) has already made huge progress towards eradicating genetic disease before birth, a significant but often overlooked accomplishment. But more lies ahead. Coming decades will see the creation of genetic therapies based around the specific molecular details of a given disorder. Diseases such as pediatric cancer are already the target of multi-year genomic research, and more diseases will benefit from genomic research as costs come down. And as the genetic underpinnings of disease come into focus, personal genetics will also undoubtedly enjoy a second life – regardless of whether today’s companies survive to see it.

We’ve scanned the genome; what remains to be seen is what we can do with it.

Here is a short summary video from Reuters that may be of interest: