Human Genome Project


Eric Green on the Future of the NHGRI

Dr. Eric Green has been the Director of the National Human Genome Research Institute (NHGRI) at the National Institutes of Health (NIH) since 2009. Two years ago, he and his colleagues at the Institute came up with a strategic plan for the next ten years. Today we discuss the plan with the director and get his outlook on the future of human genomics.

Dr. Green says human genomics can be roughly divided into four chapters.

"Each chapter has come out of similar strategic planning processes. The first chapter was the human genome project, a very valuable start for the field of genomics. In 2003, we asked what next and we published a plan which was about the first use of this information that was provided by this first genome. Now we had to understand what the 3 billion letters of the genome meant. It was a new era for genomics and it was wide open. That was chapter 2 from 2003 to 2011, and it put us on a solid trajectory to get to the $1,000 genome. We sequenced a lot of people and a lot of animals. Then published in 2011 was the strategic plan for chapter three which would bring us into the clinic where all of a sudden we could see how genomics could be used in a powerful way to understand human disease but also other applications in genomics that would become part of medicine. And right now we are writing the story of chapter four of human genomics."

Though he is hesitant to name the fourth and current chapter ("you never like to write your headline until you've lived it out"), we do tease this out of him: "Making genomics mainstream and equitable in medicine."

Now that we have high accuracy long reads, would Dr. Green like to see larger population studies done with better quality? Where is the NIH at with the All of Us project? And how does the director see his mandate when it comes to balancing between basic and translational research?

On that last question, Dr. Green says being a physician, he may have pushed the translational side heavily, but overall he tries to keep a very diverse portfolio.

"We do not have the best technology for sequencing DNA. They need to be better. We don't want a $1,000 genome, we want a $100 genome, and maybe eventually get a $10 genome. So we want to continue to develop new technologies. And then on top of it, I need to study things in the clinic to see how they work. And the hard part will always be that balancing act. There's never quite enough money. You're just trying to figure out where am I going to get the biggest bang for my buck. And keeping your eye on the landscape because it's not all about NIH. Lots of people are doing genomics research, and what can we do better than others and what should we cede to others to do."

We finish with some personal questions about Dr. Genome, his name among colleagues.

Setting Better Expectations for Genomic Medicine: Geoff Ginsburg, Duke University

Guest:

Geoffrey Ginsburg, Director, Duke Center for Applied Genomics and Precision Medicine Bio and Contact Info

Listen (6:58) Genomic medicine occuring across the lifespan

Listen (2:40) What have been the key events since the Human Genome Project?

Listen (7:12) What do you make of opt-out databases?

Listen (9:57) What role will EMRs play in genomics?

Listen (3:07) What drives your optimism?

Genomic medicine is now being adopted across human lifespan, says Geoff Ginsburg in today’s interview.

Geoff is the director for Duke’s Center for Applied Genomics and Precision Medicine and joins us for the next installment in our series, Genomic Medicine Today: Where Are We?

Geoff starts by listing the various applications of genomics in medicine from prenatal screening to oncology to pharmacogenetics. He says that too much was promised too early with the first Human Genome Project, but he is optimistic that we are now setting better expectations and healthcare is seeing the benefits of genomics.

“We’re certainly not at the full realization of genomic medicine, but there are clear sign posts that it’s being applied to clinical medicine,” he says.

What role will electronic medical records play in taking genomics into mainstream clinical practice, we ask Geoff, and how are we doing with the consent issue?

Podcast brought to you by: Omicia - Offering end-to-end genome interpretation and reporting solutions to help diagnostic labs and research institutions unlock the potential of individualized medicine.

UCSC Up To More than Bioinformatics

UC Santa Cruz is well know in our field for their part in the Human Genome Project.  Led by David Haussler, the bioinformatics group there released the first working draft of the human genome sequence on the web, leading shortly to the UCSC Genome Browser, an essential open resource for biomedical science.  This was followed up last year by the launch of the  Cancer Genomics Hub (CGHub), a large-scale data repository for the National Cancer Institute. 

Is Big Science Worth It? Debating the Brain Activity Mappping Project

The bad boy columnist for the life sciences is at it again. Bill Frezza is an unabashed libertarian venture capitalist based in Boston who pens a regular column over at Bio-IT World called the Skeptical Outsider. Though he’s invested in our industry, he’s undeterred from disparaging things the industry holds sacred, such as the War on Cancer or the Human Genome Project. He is emboldened by two major influences. First, he had some success in the IT industry and sees important lessons there for the life sciences.

SEQUENCING: Hunkapiller Chips Away at PacBio's 'Perception Issue'

Podcast brought to you by: Ingenuity Variant Analysis - Identify causal variants from human sequencing data in just hours.

. . . and by Biotix - makers of A BETTER TIP(TM) for Next Gen Sequencing

Guest:

Mike Hunkapiller, PhD, CEO, Pacific Biosciences Bio and Contact Info

Chapters: (Advance the marker)

0:53 How does PacBio fit into the overall sequencing picture at the beginning of 2013?

5:45 Limitations of 2nd generation technology

14:18 What has been your goal as CEO?

20:11 Are there plans for a less expensive technology?

26:25 How would you characterize yourself?

30:31 Has PacBio already spent their reputation?

35:30 Thoughts on Ion Torrent, Oxford Nanopore, and Illumina

Is PacBio a solid company that has been victim of an over-hyped industry?

Sequencing has become a high stakes, treacherous business. No other technology in the life science industry has seen the same hype. For many years, including those when the human genome was first sequenced, Sanger type or first generation automated sequencing remained relatively unchanged. Applied BioSystems was the leader, providing their 3700 Automated Sequencer to both groups which worked on the first human genome. Then Illumina bought Solexa in 2006 and everything changed. This was next generation sequencing, and since then the pace of development has gone on a steep improvement curve that everyone is familiar with. Slides showing this curve sit in most industry leaders' slide decks.

Where is the technology in 2013? Last year began with the announcement from the two major players, Life Tech and Illumina, that they'd be sequencing a human genome in a day. But according to Shawn Baker, CSO at BlueSEQ and regular guest at Mendelspod, neither delivered. Baker maintains a neutral database on the various sequencing technologies over at www.blueseq.com.

"They haven't quite reached the 'genome in a day' goal. Illumina is closer with a 36 hour run from the HiSeq 2500 generating enough material. Life will have to wait until the PII chip, slated to launch sometime in the first half of 2013, is able to generate at least 50Gb per run," he said in an email. (Stay tuned for an upcoming overview with Shawn.)

At the beginning of 2012 Roche made a move on Illumina, showing how important the technology has become to drug development. In our 2012 series on sequencing, we featured some of the promising newcomers touting 3rd generation technology. PacBio had just launched their RS system. And we heard from some of the nanotechnology companies promising disruption soon, Genia and Nabsys.

Yet this year so far, we have heard none of the hype we have come to expect. Is the news this year that there is no news? Has the technology reached a more stable zone? To explore this question and find out what's happening in this exciting sub-industry, we'll be featuring another series on sequencing. And we launch it today with PacBio, and their new CEO, Mike Hunkapiller.

Mike has had an incredible view of the sequencing business. He was president of Applied Bio during their heyday with the 3700. He recruited Craig Venter and helped found Celera, the private enterprise which co-announced the sequencing of the human genome. He's been a partner at Alloy Ventures, the VC firm which funded Applied Bio and PacBio. He has seen and heard the hype that surrounded PacBio as they secured funding of $370 million, went public with a market valuation of $800 million and promised a 15 minute genome for $1,000 by 2013. And he saw them launch their system, burn through $500 million, and see their stock devalue quarter after quarter. So it's 2013 and where is the technology?

Mike's experience and steady, methodical approach shines through in this interview. He has a way of cutting through the hype as he talks about the limits of 2nd generation, or what he calls 'short read' technology and establishes an important place for PacBio and their success with long reads. I've heard several times this last year that PacBio had serious problems, among them accuracy. And this for a machine that cost more than any of the other technologies. Industry experts have wondered aloud if PacBio would suffer the fate of a meteor burning out.

I came away from the interview with much less skepticism. Hunkapiller says that PacBio has suffered from some "perception issues," and this year they've proved that their "accuracy is actually extremely good." His approach has been to focus on their existing customers and make sure they had success with the technology. The company has upgraded their software and their chemistry. Last month their stock shot up 46% on news that UC Davis would use the RS for the 100K Genome Project. What about Oxford Nanopore and their new technology? What about Illumina's recent investment in longer read technology? Hunkapiller answers these questions with great aplomb and is quite convincing that PacBio is certainly not out of the picture.

Note: The following correction has been made to this article. Originally it was stated that Illumina and Life Tech had both delivered on their claim to be able to sequence a human genome in one day, if not at the price they predicted. In fact, neither has delivered on the promise.



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