Future of Genome Research: More Therapies, Scarcer Funding

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BETHESDA, MD—This past October saw the 20th anniversary of the start of the Human Genome Project; and this year marks the 10th anniversary of the publishing of the draft human genome sequence. To commemorate what it describes as the start of a new era for genomics, the National Human Genome Research Institute (NHGRI ) hosted a conference on the future of the science on the campuses of NIH last month.

NHGRI leaders also crafted a strategic vision for the next 20 years of genomic research, which was published in the February issue of Nature. That vision foresees continued growth in the field of genomic medicine and the creation of more gene-specific therapies. However, as private funding for experimental drugs becomes harder to come by, those therapies may need to have their start
at NIH.

Two Decades of Genome Research

“I can vividly remember the sense of purpose we all had [20 years ago],” said Eric Green, MD, PhD, NHGRI director, at the start of the conference. “And I can also remember the great sense of fear, since we did not know exactly how we were going to map and sequence the human genome.”

That fear gave way to hard work and the energy that drove the project forward at a break-neck pace for over a decade. The publication of a reference human genome sequence in 2003 put an end to the Human Genome Project, but kick-started an entire field of science that has touched on every area of human health. Genomics has provided new insights into cancer, into the molecular basis of inherited disease, and how gene variants affect disease—discoveries that have led to new therapies. There is also the nascent field of pharmacogenomics—testing patients prior to treatment to determine if certain medicines will be effective or not.

All of this has been made possible by the precipitous drop in the cost of gene sequencing due to new technology. “That is the key thing that has energized and propelled genomics forward,” Green said.

When the technology was first developed, the cost of sequencing an entire genome was somewhere around $20 million. Analysts currently predict the price of sequencing a human genome to drop below $1,000 in the next couple of years.This puts cutting-edge genomic
research well within reach of small companies and university researchers.

“It took all the sequencing capacity in the world about 13 years to produce the first human genome sequence,” said Mark Guyer, PhD, director of the NHGRI Division of Extramural Research, and co-author of the Nature article. “In 2003, around the time we completed the Human Genome Project, technology had improved to the point where 100 machines could sequence a human-sized genome in about three months. In 2011, one machine can produce a human-sized sequence in about five days.”

The Next Ten Years

The Human Genome Project laid the foundation for genomics. It allowed scientists to understand the basic structure of the genome. The last six years have been consumed with understanding the biology of the genome and the biology of disease. While great advances have been made, very little of this research has had a direct impact on patient health. According to NHGRI’s strategic plan, that is what the next decade will be about—understanding and advancing the science of genomic medicine. Only after researchers have a grasp on how genomic medicine can impact disease will advances begin cascading into the realm of patient care.

“There have been over 1,000 gene variants linked to disease,” said NIH Director Francis Collins, MD, PhD, who led NHGRI during the
Human Genome Project. “Most of these variants have only modest effects [on disease], but it is exciting. But we haven’t gotten to the point where most of this is actionable in encounters between physicians and patients. Are we in a position to take knowledge about diseases and take fundamental knowledge and move forward?”

NHGRI leaders expect the next decade will change the answer to that question from a “maybe” to a decisive “yes.” An expanding body of knowledge about gene and disease biology will likely identify the genetic basis of most single-gene disorders in the next 10 years, the NHGRI strategic plan states. Molecular pathways that are implicated in single-gene disorders may hold clues for the diagnosis and treatment of common disease.

Providing a Foundation for New Therapies

For the growth of the field to continue at the exponential rate it has seen during the last 10 years, researchers worldwide will need to continue close collaboration. NHGRI’s plan stresses the importance of rapid data release for immediate research applications. NIH will also need to act as a jump-starter for basic research that could eventually lead to therapies.

Collins said that NIH will need to invest time and money into taking basic discoveries in the direction of translating them into therapeutics. “This has been primarily thought of as an enterprise for the private sector, which has been putting huge amounts of dollars into this, but results are not as gratifying as we might have hoped. Success is declining despite increased investments.”

Pharmaceutical companies are pulling back investments in developing new therapeutics in certain
areas, especially in those involving the brain, Collins said. Small biotech companies are also struggling to find venture capital money, since investors are looking for quick returns instead of long-term investments.

Not only is drug development a long-term proposition, but also 95% of candidate compounds eventually prove ineffective. About 20% of new molecular entities with new applications over the last few years have come out of public sector research investments followed up by private sector development. “We’re not going to become a drug developing company,” Collins said. “But we could build upon experiences already successfully carried out by other NIH institutes to try to build a platform for genomic drug development.”

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