[This post was co-authored by Sean Harper, Amgen’s executive vice president of R&D.]
People in the tech industry often like to say that we overestimate the short-term impact of new technology and underestimate the longer-term value. The human genome project is a superb example of this truism.
Overpromise was indeed rampant during the interval around the 2001 publication of the first human DNA sequence, but it’s easy to understand the excessive expectations inspired by such a momentous achievement for society.
A Tortuous Route From The Human Genome Project to New Drug Discoveries
The unraveling of the genetic identity of our species ranks as one of the greatest accomplishments in the history of science.
However, the human genome sequence, in isolation, is not a readily interpreted blueprint or wiring diagram. It is more like a parts list. The physiological roles of the individual genes are the key to understanding disease relevance and discovering new medicines, but these roles are not apparent from a single individual’s sequence. Thoughtful experts knew this at the time, but the enthusiasm for the milestone led to exaggerated claims.
Over the past few years, we have seen the result of this hype: malaise that afflicts many who believed that public and private investment in the Human Genome Project would have an immediate, dazzling impact on healthcare. In fact, new medicines based exclusively on this information were not forthcoming, partly because it takes 10 to 15 years for a pharmaceutical enterprise to transform a basic discovery into a practical therapy. It is also evident that the route from the human genome sequence to new drugs is more tortuous than many had anticipated.
The cynics’ view about the long-term value to society was reinforced by another disappointment. The genome project, coupled with new technical capabilities, fueled a spate of genome-wide-association studies (GWAS), which aim to assess the impact of common human genetic variants on the risk of disease. Bear in mind that a human genome is a gargantuan storehouse of information with well over a billion letters of genetic code, called nucleotides, strung together. That’s equivalent to a book more than 10 million pages long!
The vast majority of these differences are common variants; they are shared among a significant portion of the population. GWAS allowed us to ask, do common variants influence disease risk? While the answer is yes—GWAS results have provided a windfall of hints about disease-relevant genes—they are nearly a bust in terms of delivering actionable information for drug discovery.
But we shouldn’t mistake the absence of revolutionary success for a lack of progress. Putting aside the long-term prospects for improvements in health, investment in genomics has brought significant incremental benefits to science and medicine. Since 2001, most activities in biomedical research have utilized sequence information in one way or another. The genome project provided valuable infrastructure—roads and bridges to facilitate and enhance the pace of discovery. For example, the first hunt for a disease gene, underlying the devastating Huntington’s disorder, required nearly a decade before success was achieved in 1993. After the genome project, the time to track down rare disease genes was cut by a factor of ten, and today, it takes only a few weeks in many cases to find such genes.
Mining for a Single Nucleotide And Unlocking the Promise of Human Genetic Variation Studies
The most promising technological breakthrough in terms of treating disease may be the emergent technique of ultra-high-throughput DNA sequencing. Through this technology, we can begin to mine
