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Eric D. Green is the director of the National Human Genome Research Institute. (Maggie Bartlett, NHGRI)

The Work Is Only Beginning on Understanding the Human Genome

Ten years ago, scientists released a map of our genetic blueprint. But, as Eric D. Green explains, there are many more mysteries left to unravel

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A decade ago, an international research team completed an ambitious effort to read the 3 billion letters of genetic information found in every human cell. The program, known as the Human Genome Project, provided the blueprint for human life, an achievement that has been compared to landing a man on the moon.

Dr. Eric D. Green was involved from the very beginning, refining some of the key technologies used in the project. At that time, he was a postdoctoral fellow and a resident in pathology at Washington University in St. Louis. He carved out his 5 percent of the genome, focusing on the mapping of the DNA of chromosome 7. Today, Green is the director of the National Human Genome Research Institute, which advances the understanding of the human genome through genomics research.

Let’s go back to the mid to late 1980s, when the idea for the Human Genome Project was first conceived. What was the motivation at the time?

It depends who you ask. Different people had different motivations. Keep in mind that the ’70s and early ’80s were the molecular biology revolution era. There were significant advances in methods that allowed us to isolate and study DNA in the laboratory.

In the U.S., for example, the Department of Energy got very interested in the notion of studying the genome because of interest in mutation, and the mutation process associated with some forms of energy, such as nuclear energy.

If you go to places like the National Institutes of Health, or you look at biomedical researchers and health-related researchers, they were very interested in being able to elucidate the genetic basis of disease. Among the many genetic diseases that were being considered, of course, was cancer.

A lot of other people across the biomedical research spectrum—even those working on model organisms, like flies and worms and yeast—recognized that if we could figure out how to comprehensively look at complex genomes, starting with flies and worms and yeast but then working our way up to humans, it would provide foundational information for understanding how the genome worked.

There was a coalescence of lots of different ideas that, with a backdrop of having incremental but important technological advances, made it seem that, while daunting, the problem of sequencing the human genome and determining the order of 3 billion letters was feasible.

Where did the material for the genome project come from? Whose genome was it?

When the genome project started, it was still pretty piecemeal. Different people were making different collections and DNA fragments called libraries, which are just pieces of DNA cloned. They would do it from anybody: Sometimes it would be the lab head, sometimes it would be the postdoctoral fellow or the grad student. They would just grab DNA back then when there were really no implications of that.

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