How Human Genome Sequencing Went From $1 Billion A Pop To Under $1,000 - Forbes

^In October 1990, a group of international researchers set a bold goal: to create a map of the DNA code that makes up the human genome. Each person has two sets of 3 billion bases, represented by the letters A, T, G and C, which are the unique set of instructions that guide their cells throughout life. "Without a doubt, this is the most important, most wondrous map ever produced by humankind," former President Bill Clinton proclaimed in a speech about the Human Genome Project. The final map and sequence was completed in 2003.

"The first genome cost us about a billion dollars," says Dr. Eric Green, who worked on the project since its inception and has been the director of the National Human Genome Research Institute for more than a decade. "Now when we sequence a person's genome, it's less than $1000, so that's a million-fold reduction." (The entire project came in around $2.7 billion, but that included sequencing different organisms, additional research and technology development.) 

"We said bring us your crazy ideas, bring us your really crazy ideas and bring us your almost insane ideas."

On Wednesday, Green and colleagues from the Institute published its strategic vision for the next 10 years of genomics and the potential for improving human health in the journal Nature. Green shared his thoughts with Forbes on how far we've come and what the future holds.

The following transcript has been edited and condensed for length and clarity.

The falling cost of sequencing a human genome over two decades.

National Human Genome Research Institute

On how the first success stoked innovation

The day the Human Genome Project ended, everybody was like, "We finished our marathon." We all collapsed after crossing the finish line. And everybody looked around and we said, "Oh, my gosh, we did it, we sequenced the first human genome, holy cow, we've got to come up with a better way to do this!" 

Our institute put out the headline as part of our 2003 strategic vision that we needed the "thousand dollar genome." We as a funder took on the responsibility of saying we need to stimulate technology development in this area. We said bring us your crazy ideas, bring us your really crazy ideas and bring us your almost insane ideas.

On how public-private partnerships accelerated development

While the federal government funded the Human Genome Project, there was a parallel effort in the private sector led by Craig Venter at Celera Genomics, followed by a proliferation of new sequencing companies, including Solexa, later acquired by Illumina, Pacific Biosciences and Oxford Nanopore Technologies. 

There was huge amounts of investment in the private sector and good investment in the academic centers. And that ecosystem of academia developing things, licensing out those advances to these private companies, the private companies developing things, then one private company buys another private company. It just keeps going. Now we fast forward 17 years later, we have all sorts of new technologies.

On sequencing the coronavirus

The human genome is 6 billion letters. The darn little coronavirus is 30,000 letters. From a technological point of view, it's very easy to sequence its genome and scientists did it in about three days. Now going and doing it at high throughput for diagnostic testing purposes is actually difficult because it's so small. You have to come up with ways in order to make it cost effective. That's why they're pooling samples and doing all these things.

On future research targets in healthcare

If you gave me a cheek swab, I could get your 6 billion letters mostly sequenced within a few days. I could put that information on a computer, and it will spit out a list of about 3 to 5 million places that your genome sequence is different compared to some reference. But there's probably only a few hundred of those 3 to 5 million differences that I can confidently say are medically relevant. In other words, we're still early on interpreting the human genome and interpreting how spelling differences in the genome are relevant for health and disease.

On the rise of genetic ancestry testing companies like Ancestry.com and 23andMe

I actually think that those direct-to-consumer companies have done a lot to make people more aware of genomics. And if they use ancestry as a tool to get people thinking about DNA and genomic analysis, I think that's great. 

The concerning side is getting a little too far ahead of the scientific evidence for the role of certain genomic variants in health and disease. I always worry a little bit about the overinterpretation of the health information. But the horse is out of the barn, you're not going to stop it. My attitude is we just need the scientific community to catch up. The more we get that validity associated with the role of genomic variants to disease, the more that we don't have to worry about people being misled. I think of this as a short-term problem.