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December 07, 2010

Interview of Gene Sequencing expert William Andregg of Halcyon Molecular by Sander Olson

Here is the William Andregg interview by Sander Olson. Mr. Andregg is the CEO and founder of Halcyon Molecular. Along with his brother, Michael, William invented the core polymer placement technology which allows rapid and inexpensive sequencing of DNA. Mr. Andregg is confident that by 2015 complete human genomes will be sequenced for only $1,000. He believes that DNA sequencing will eventually become sufficiently sophisticated, automated, and inexpensive that scientists will be able to sequence every tree in a forest, and may lead to advanced nanotechnology.

In a recent episode of TechCrunch TV’s “Speaking Of..”, Halcyon Molecular CEO William Andregg spoke about his dream to extend human lifespans long enough to travel to other star systems. William explains how his early focus on astronomy and physics eventually gave way to intense study of biology for that reason. In the video, he says how he is fascinated by long-living creatures like the Gal├ípagos tortoise and bowhead whale, and expresses optimism about how advanced biotechnology could determine their longevity-relevant molecular differences and use that knowledge to develop life-extension therapies for humans.

Question: How much does it currently cost to sequence ones genome?

Answer: Depends on what you mean by “sequence ones genome”. If you want a truly complete sequence, you can’t get that now. You could spend millions of dollars and you still wouldn’t have even a single truly complete human genome. There are much cheaper options to get something far less accurate and useful- getting down to about $10,000 currently. But we’re hoping that in five years when people talk about “sequencing ones genome”, they really mean it- really sequencing the whole thing, not just seeing part of it.




Question: How much of the entire human genome have we currently sequenced?

Answer: The most comprehensive reference assembly for the human genome still contains hundreds of gaps as of 2010, with millions and millions of missing bases.

Question: Current gene sequencing techniques employ short reads. What is the limitation with this approach?

Answer: Think of jigsaw puzzles. If a jigsaw puzzle has just a few big pieces like the ones they make for three year olds, it’s trivial to solve. But if it has tens of thousands of pieces like some expert-level jigsaw puzzles do, then it’s going to be a huge pain. That’s current sequencing technology. Short reads are the tiny jigsaw puzzle pieces. We want to solve the puzzle of the genome using the biggest pieces possible.

Question: So does that also help make the sequencing faster as well?

Answer: Yes, it makes putting the whole genome together less computationally intensive and thereby faster. It also improves the overall accuracy because with longer reads you can be more confident in the ordering of repetitive regions.

Question: You claim that DNA sequencing has the potential to "turn medicine into an information science". What exactly do you mean by that?

Answer: Taking the guesswork out of it, making it a precise, predictive science and less an art. In ten years you’ll have orders of magnitude more information about your own body and biology, and the sequencing revolution will be a big part of that. Biomedical researchers will also have orders of magnitude more information in general about how life works, and how health turns to illness.


Question: How do your views on longevity and life extension compare with those of Aubrey de Grey and Ray Kurzweil?

Answer: Parts of SENS urgently should be funded and tested. That being said, I work on sequencing and not on SENS, because our approach to curing aging is first to turn biology into an information science- actually getting to untangling the morass of metabolism that SENS does an end run around. I believe we can get to a complete mechanistic understanding of human biology in only a few decades, which is a timeline more like Kurzweil’s. On the other hand, if SENS were being vigorously pursued today, it might save millions of lives before the total understanding approach avails us. It is good to have multiple bets.

As for Kurzweil, maybe this isn’t fair, and I’d like to hear his thoughts on it, but I’m afraid his books demotivate people who would otherwise contribute to the cause, maybe by giving the impression to some that the Singularity is not only coming, but actually inevitable. Eat right, exercise, take these pills, and don’t worry- those smart hardworking scientists over there will solve everything for you. In contrast, a great thing about Aubrey as a leader is that he harangues people to actually get off their asses and make a contribution.

We might not survive the next twenty years. We may never cure aging. There is nothing inevitable about our success. Everyone who is talented enough to make a contribution should be trying to help, on all fronts, by any ethical means, like it’s life and death- because it is.

And the very most talented ones should send their resumes immediately to Halcyon.

Question: How will high-throughput DNA sequencing directly benefit longevity research?

Answer: We’ll sequence the genomes of every centenarian and every supercentenarian, and find out which genes directly relate to longevity and to early morbidity and mortality. We’ll sequence long-lived organisms, like the Galapagos tortoise, the bowhead whale, the bristlecone pine. We’ll sequence all species of Rockfish, a whole genus where there’s almost an order of magnitude difference in maximum lifespans between evolutionary close cousins. And all of that just scrapes the iceberg- that’s not even the imaginative or ambitious answer.

The grand design is to read, write, program DNA. The better and faster and cheaper you do that, the sooner we’ll hack biology and be free from disease. Billions of individual human genomes, and billions of genomes of domesticated animals, is only the beginning. The amount of genomic information on this planet that might help us hack biology is orders of magnitude vaster than that. You have quadrillions of unique genomes in your body, counting the metagenome of all your individual genomically different cells and the metagenome of all the stuff living in and on you. Someone will probably want to sequence every tree in a forest, or every leaf on a tree, or every bacterium in a speck of seawater. Someone will definitely sequence every ear of corn in a cornfield. We’ll probably sequence all the charismatic megafauna we can find on the planet, and all the trillions of less glamorous animals as well. But even that is only the beginning. People will do forward genetics studies where they sequence trillions of individual cells or model organisms. And there may be just as much or more sequencing of artificial genomes or genetic constructs in the course of solving synthetic biology- the writing and programming part of the grand design. Tangentially, synthetic biology might be the least insanely difficult way to robust nanotechnology, making anything you want from spoons to space elevators, just like your cells build things with atomic precision all the time, using a billion year old programming language that we aim to completely understand. And so sequencing might turn out to be upstream of a lot more than merely freeing humanity from all disease.

Question: Is Halcyon Molecular expanding? Are there any plans for an IPO?

Answer: Expanding carefully, with an extremely high bar. We only want the best of the best, of the best of the best of the best- iterating that to somewhere way above the 99th percentile. And the team we’ve built so far is like that, just unbelievably good. I think the level of talent in the Halcyon project might be every bit as elite as it was in the teams that worked on the Manhattan or Apollo projects. And given what we’re trying to do, that’s exactly how it should be.
As for the IPO question, if doing an IPO is consistent with the mission, we’ll do it. Halcyon is a mission with a company, not the other way around. Right now only people who care first and foremost about the mission have significant stock in the company. We’d have to think long and hard about letting that change.

Question: Who is funding Halcyon?

Answer: Elon Musk, Peter Thiel, Founders Fund, and several angels. We’ve also won about three million dollars in grants from NIH and other government agencies.

Question: How long will it take before sequencing the human genome falls to $1,000?

Answer: Well, right now it has infinity to fall from, because you can’t buy a complete human genome yet at any price. But as soon as that’s available- I think 2012 is a good guess- then we’ll see a thousand dollar complete genome in 2013.

Question: How much progress in this field can be expected by 2020?

Answer: Probably depends on how many of your most brilliant readers send me their CV’s today. Individual choices are what really matter to the arc of history.


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