The Race to the $1000 Genome: Sprinting Toward the Finish Line

Industry Insider

The question of when it will be possible to sequence a human genome is being replaced by concerns whether the average consumer will choose to have his or her genome sequenced.

Patrice M. Milos, PhD, Vice President and Chief Scientific Officer, Helicos BioSciences Corporation

The scientific community has moved beyond the question of when it will be possible to sequence a human genome as the reality of high throughput sequencing continues to rapidly take shape. Now, the true question is whether the average consumer will choose to have his or her genome sequenced. Many factors will contribute to this decision, most of which will remain largely personal. Perhaps the single key factor that merits examination is whether a genome sequence will provide information that will have consequences on lifestyle, family decisions, and available healthcare and treatment options.

As consumer use of the technology increases, the life science industry needs to enact a regulatory framework to ensure effective monitoring of accurate genome sequence data generation and separately, its interpretation. We must also guarantee that genome discoveries can be harnessed rapidly to benefit patients. A key issue for pharmaceutical and biotechnology companies is the role that each should play in supporting consumer acceptance and confidence while educating the public regarding how this information can benefit patients and physicians. A proactive approach to both the regulatory framework discussions and the research being driven in pharmaceutical and biotech labs will benefit everyone.

In my former role as a pharmaceutical executive responsible for integrating genomic knowledge into the drug discovery and development pipeline, I often described a hypothetical scenario in which a patient’s genome sequence would be integrated into the pivotal, decision-making Phase III clinical trial to allow subsequent analysis of genomic information and trial endpoints. A mere vision at the time, of course, but at this juncture, we must harness that potential and strive to make it a reality in order to enhance the benefit of medicines for patients. In fact, this potential is now more vital than ever because of the ongoing struggle pharmaceutical companies face in the wake of increasing scrutiny surrounding the risk/benefit ratio for new medicines. The pace of scientific research continues unbridled, and the future of the marriage of technology, scientific discoveries, and knowledge of diseases appears brighter each day. With that, the race is on to bring the scenario to fruition.

So, where are scientists in the race to the $1000 genome—a theoretical benchmark that can be considered a potential game-changing approach to integrating with Phase III clinical trials and personalized medicine? This concept was developed by the National Human Genome Research Institute of the National Institutes of Health (NIH) to suggest that if a technology inflection could be achieved in the availability and affordability of this science, then people would have the option to have their genome sequenced. In 2006, Helicos BioSciences, along with many other immensely talented technologists all with a vision of making DNA sequencing increasingly cost-effective, was awarded a $1000 genome grant from NIH. Clearly, the race is heating up—in only two years, new short-read sequencing technologies have reinvigorated what many would have once thought a predictable, methodical science: de novo sequencing and re-sequencing of a multitude of organisms. New experimentation is now within reach, and new questions can finally be asked of genomes that will enable the scientific community to better understand, diagnosis and treat disease.

To win the race to the $1000 genome, scientists must first overcome the challenging hurdle of maximizing knowledge gleaned from individual genomes in order to make discoveries that allow for the creation of new medicines and enhance the ultimate delivery of health care that can be personalized. While many question the value of possessing individual genome sequences, one only has to look a few short years back to the time when there was doubt surrounding the concept of sequencing a single genome. Would we trade the knowledge gained from the Human Genome Project? What might now happen to our collective knowledge if we are to look at the genome information on a population of over 1,000 individuals as we have embarked on in the $1000 genome project?

Where many once questioned the ability of genome-wide association studies (GWAS) that interrogate a limited set of common genetic variants to identify the relationship of genetic variation and common disease, the past 18 months has set aside this question with hundreds of genes now associated with common disease in such studies. Statistical methods to analyze GWAS projects, while limited only two years ago, are now emerging as scientists deposit GWAS data openly into the public domain to develop and enhance the methodologies required to translate genetic variation into new disease discoveries. Can extrapolation from the current one million single nucleotide variants to a potential of three billion nucleotides (or six billion, in fact) and accompanying structural variations be that much more challenging? I would suggest not; statisticians, computational biologists and mathematicians seem ready for the challenge.

Fundamental to the elucidation of the relationship between genome data and associations relevant to health and wellness are the depth of studies designed to inform the validity of the data. Population-based studies examining gene associations are underway to examine the significance of disease associations emerging from the GWAS studies. These studies will shed light on the relationships between genotypes and phenotypes. But will the validity of genotype/phenotype relationships hinder individuals from going a step further and gaining access to their genome sequence? Again, I would suggest not. The scientific community must provide a mechanism that allows individuals to obtain their genome sequence with the rigor of quality and accuracy to accompany this data that is independent of this validity.

In addition to personal whims, many outside factors will impact an individual’s decision to have his or her genome sequenced and the ultimate acceptance of this technology in the context of drug discovery and development. One factor, which in the past might have been considered a potential hindrance to the advancement of this research, has been eliminated with the passage of the Genetic Information Nondiscrimination Act (GINA) earlier this year in the 110th Congress. This law is an important step toward ensuring that individuals who have their genome sequenced will not face discrimination in the workplace or have limited options for health insurance. The life science industry must continue policy framework discussions that seek to ensure the accuracy of sequence information obtained and utilized by patients and physicians. We must also make scientific contributions within the pharmaceutical and biotech industries to achieve a vision that will ultimately translate into a better and brighter future for patients.

About the Author
Milos, who joined Helicos BioSciences in June 2007, serves on the National Advisory Council for Human Genome Research and was pivotal in the establishment and oversight of key strategic investments in the genomics area.