Programmable Life

Synthetic biology opens new doors on what life can be, and do. How will we utilize the awesome new tools at our disposal? In this video, Andrew Hessel of Autodesk moderates a discussion with Ellen Jorgensen of Genspace and Ryan Phelan of Revive & Restore.
Hessel: So this session is titled Programmable Life, which is certainly up my alley. I’ve been interested in how we program things with genetics for a long time. Both of you have your hands in various aspects of programming life. It’s hard to not have your hand into it in some way if you’re into genetics at all. But, first of all, let me just introduce you to the audience.
Ellen Jorgensen is the founder of Genspace in Brooklyn, which is one of the first community bio labs in the country, a very strong open science advocate, and an educator and mentor to iGEM teams, to Genspace members, etcetera. Really, if I was to define what you do in the programming life world, I would say you’re leading people who may not have made genetics or biology as a first choice in their life in training—you’re kind of the gateway to life science, would you say?
Jorgensen: You can use the word enabler, facilitator.
Hessel: And just for people that aren’t familiar with Genspace, give a little bit of an outline to the organization, the type of member, really how long it’s been going.
Jorgensen: Okay. Well, you’ve also heard from the members of BioCurious, which is your local hacker space here, in Sunnyvale. And I think the formats are similar, because we were all kind of dragged into structure kicking and screaming, and certain things just make sense. So, for example, we’re incorporated as not-for-profits. We have a certain amount of core equipment and facilities that are open to members to use. There is a very low barrier to entry. I don’t know what your price point is right now. Ours is $100 a month. And it gives you access to equipment and certain shared supplies, like gloves, pipet tips—but critical supplies. And also access to people that have some knowledge and can give training to people that come into this essentially with big ideas but don’t really know how to actualize them.
Hessel: So you weren’t a businesswoman before?
Jorgensen: Oh God, no. And in some ways, that’s part of the problem, because I think a lot of these places were started by people that were idealists, that were technical experts, but none of us had ever run a nonprofit, and, at least at Genspace, none of us had ever run a business at all. So I think it’s a miracle that we managed to produce something that’s been sustainable so far, and probably will go to the next step relatively soon, where we become more like a traditional nonprofit and get funding, either from foundations or the government or some other consortium of funders.
Phelan: Don’t get too traditional.
Jorgensen: Is that your advice?
Phelan: Yes, absolutely.
Hessel: Well, let’s introduce the audience to you, Ryan. Ryan Phelan has been a friend for many years, a colleague. We’ve bumped up against each other for a long time now. You do describe yourself as a serial entrepreneur.
Phelan: I do.
Hessel: Perhaps you can give us a little taste of your background in business.
Phelan: Sure. About 30 years of it has been spent in healthcare, in the field that I would call personalized medicine, primarily. And two different companies, Direct Medical Knowledge, started here in San Francisco, and also, most recently, DNA Direct, which was sold in 2012.
Hessel: And I think we’re in your space now.
Phelan: Yes. Autodesk is now in the warehouse where I started DNA Direct.
Hessel: And your present business is fascinating. Tell—
Phelan: Well, it’s not a business.
Hessel: It’s not? Oh, it’s a project, or…?
Phelan: Well, Revive & Restore—which, thank you, Steve, for the shout out—was started just two years ago by my husband, Stewart Brand, and myself as a project of the Long Now Foundation, which I hope many of you know about. And the big idea was to use Revive & Restore as a catalyst to help bring back extinct species. It has now merged into other areas, including working with endangered species, but we’re primarily known for our work with the passenger pigeon and with George Church, now with the woolly mammoth project to revive them both.
Hessel: Wow. So in the world of computers, you’re doing backups and restores of essentially crashed disks, or extinct species.
Phelan: Well, I guess you can imagine that these museum specimens that have DNA, in some ways, it is your crashed disk. I think more than just bringing back old data, old DNA from ancient museum specimens—that would be a feat in and of itself, if we could do that, to restore life. But in some cases, we’re actually—the real bleeding edge is thinking about can you improve life. And I can talk about that in more detail if you’d like.
Hessel: So these are very different, really, vectors. It’s difficult for me to see them immediately into direct programming right now—and very different stages in your career paths, in some ways, and goals. Ellen, what’s next for you? Like you started this, you’ve grown it. How many members have been through Genspace now?
Jorgensen: I don’t know. I mean we’ve taught hundreds of people to do genetic engineering.
Phelan: That’s so great.
Hessel: So what’s next? Where does this go?
Jorgensen: That’s the thing that’s—I mean I came from a very traditional background. I mean I probably have a more traditional background in science than most of the people here. And if you’d asked me six or seven years ago that I would be running a bio-hacker space in Brooklyn, and friends with everybody from Quantified Self people to the FBI, I mean I [laughs]—so I can see kind of this huge gap between the general public and scientists. And I find myself more and more drawn to bridging that gap in some way, because there are incredible things coming down the pike, sitting on that can of miracles, as one person just put it. And the general public is really not ready for that, just because, I don’t think—and it may be generational, because if you think of what kids are learning in AP Biology now, they’re transforming bacteria in high school. So maybe it’s just a question of eventually it will become more commonplace, but I really feel myself drawn towards the enabling the communication, the whole aspect of putting the technology into the hands of people that’ve never had it before and seeing what they can do with it.
Hessel: And this is really hands-on technology. This is—
Jorgensen: Oh yes, we don’t teach anything that’s not a hands-on class in Genspace.
Phelan: So I have a project for you.
Jorgensen: Excellent.
Phelan: I’m so excited to actually get to meet you. One of the letters that I’ve gotten over the years of throwing out this idea of de-extinction really surprised me, and it came from the U.S. Fish and Wildlife. And they said, “Look, we’re listening to all this, you know, reading about de-extinction and these technologies of genome editing, and we’re wondering, could it actually be used to help endangered species?” And that perked us up really fast. And they said, “We’ve got a challenge with the black-footed ferret”—and I don’t know how many of you have ever heard of the black-footed ferret or seen it, but it is literally one of the most endangered mammals in America. It used to be completely widely spread across the Great Plains in great abundance, and sometime in the, I think the 1950s or ‘60s, it was presumed to be extinct—not once, but twice. And the second time, they found a small population in Meeteetse, Wyoming, and it turns out, now, 30 years later—at that time, in 1981, U.S. Fish and Wildlife said, “We’ve got to take this remaining group of ferrets and put them into a captive breeding program to try to help them get a head start.” Well, 30 years later, they’re still in a captive breeding program—they’ll probably still be in a captive breeding program now for another 50 years—and they’ve successfully bred over 8,000 ferrets. But now they’re starting to see signs of inbreeding—potentially. And what they know is that all these ferrets are basically related to seven cousins.
Now, this is not unique just to ferrets. It turns out there are other species that are going through species bottlenecks, and the question is, what can science do? So my project for you, Ellen, and for everybody else here—Revive & Restore has just recently funded, through a company called Cofactor Genomics, to fast-track doing whole genome sequencing on four ferrets, that would span the 30 years of the lives of these ferrets, from taking crowd-preserved specimens from 1981 to present-day specimens, plus some in between that are the result of breeding through artificial insemination. And the goal will be—and starting July 15, we’re going to put all the sequencing data out there for the public—to really crowdsource the bioinformatics and to see if we can engage scientists, citizen scientists and scientists—I’ve already tried to get David Haussler to commit some UCSC students to it, and I think the pressure’s on. And I think that what we’re going to find is going to be fascinating. So we’re madly putting together webpages that try to use most common lay language to describe, what’s the challenge? How do you describe lost alleles and all of this?
Hessel: And that’s my first question on this: Do you think this is going to be something that will be possible by someone walking up to Genspace, maybe having no previous background in this type of—
Jorgensen: Well, look at something like Foldit.
Phelan: Yes. Good example.
Jorgensen: I mean you really don’t—for those of you who don’t know, it was a structural problem in biology that was solved through gaming. And some of the people that were most successful at the structural solution were gamers, and not biologists.
So in this case, about a third of the people that come to Genspace are from a computer science-technology-engineering background. And the whole thing is, you know, coding life. That’s sort of the next frontier for them and that’s what turns them on, and a lot of them want to do something right away. And until they learn molecular biology techniques, there’s nothing that they can do physically in the lab. And they’re always saying, “Well, do you have any big data for me to work on?”
Phelan: Oh, this is great.
Jorgensen: And I’m always saying no. I don’t have big data right now. We don’t have any massive projects.
Phelan: July 15.
Jorgensen: Okay.
Phelan: I’m going to hand it to you.
Jorgensen: Definitely. So that’s one place where—
Hessel: So you’ve got data, you’ve got people…
Jorgensen: Yes, I mean that’s one obvious place where you can get people involved is in this data crunching.
Phelan: Yes. Yes. Well, I think the beauty of it—and you’ve been doing this now for years, Ellen, and it sounds like a beautiful job of it, of really engaging people in this cutting-edge technology, using these tools and understanding it. And I think that more projects like this are just going to enhance the ability for new fields to actually utilize it. So for me, going from personalized medicine into now what I’m calling precision conservation, where conservationists and wild biologists can now start to take data like this and better target therapeutic treatments for these endangered species—and in some cases, it may involve cloning using genomic engineering, some day down the road. I don’t know if Fish and Wildlife is ready for that. I’m sure taxpayers are not ready to fork over money to have it be spent that way yet. But it’ll certainly help them where they’re doing captive breeding to make smarter choices on who you breed with. I mean they’re doing it based on purely what they call phenotype, just on how these animals look, and records of pedigrees. Well, think about using genetic analysis to do that. I mean it’s going to be great.
Hessel: I’m wondering if in the next 20 years, we might be having to do this with small populations of woolly mammoths.
Phelan: Well, we’re introducing the genetic variation at the get-go. But God knows, we’ll be doing other stuff with woolly mammoths—I hope.
Hessel: Ellen, I touched on this just before we got onstage, but Eri mentioned that she was kind of young and naïve in thinking she could do a hacker space for $35,000. What have you learned in this process here? What might you do differently, or recommend for the next person to come along that wants to create a hacker space?
Jorgensen: Well one thing I realize is how lucky we were in New York to have enough of a community to support a space like this. So the first thing I would say is make sure you send out enough feelers, start a meetup group or whatever, and make sure that your area is a place where you’re going to have enough of a consistent population of people that are interested enough to keep the space running. Because right now, I don’t know if anyone has come up with a really good sustainable model that includes the salary for a lab manager. And I think that’s probably one of the biggest hurdles is, unlike a biotech incubator space, where the small company, even though it’s a small company, they’re paying—I think the cheapest I’ve ever seen is $1,000 a month for half a bench space and a desk, and that’s the Harlem Incubator in Manhattan.
And you do need a certain amount of infrastructure that has to be paid for. Otherwise you—you can do little things, and certainly you can have a great educational space that’s only open when volunteers want to come. But if you really want to jumpstart innovation, I think you need just a little bit more—not much.
Hessel: Terrific. Now, we have about nine minutes left. I’d actually, because there’s been a lot of talking, I’d love for you guys to, if you have questions for Ellen or Ryan, I’d love to hear them.
Right over here?
James Temple: Hey, I’m James Temple with Re/code. I had a question for Ryan. I’m curious how you’re going about collecting the data related to the animal you’re hoping to help with the preservation of, and what exactly are you hoping people will do with it? Is it just a matter of identifying animals to breed that aren’t closely related, or does it go beyond that, potentially?
Phelan: Great. To start with, the DNA sequencing is being done by this company, Cofactor Genomics, and they’re actually assembling the genome, and they’re going to put that information on their software—it’s called ActiveSite. So it’ll allow citizen scientists—I hope—as well as professionals to actually crunch those genes very, very quickly and accurately. So as they say, it can take hundreds of thousands of genes and within seconds bring down that number to your most refined number of candidate genes.
Now, what are they going to do, as citizen scientists, to take specific questions that we’re asking regarding the relationship of these four different specimens spanning 30 years, to look for areas where they have lost heterozygosity? And what we’re looking for with those lost alleles potentially will be to compare it with the phenotypic changes that may have resulted in their loss of fertility, low sperm count and things like that. So we have very specific things we’re going to look for or ask crowdsourcing to help with. But the idea is ultimately to help find out what areas of the genome have been compromised over this time, through this population bottleneck, and potentially reverse it through genomic engineering.
Kristine Enea: Hi, my name’s Kristine Enea. I’m a recovering attorney, making her career change into science. And I’m curious, on the spectrum from M.D. and Ph.D. and citizen scientist, what is there in the middle?
Jorgensen: I’m sorry, I don’t understand the question.
Enea: Career paths.
Jorgensen: Oh, the career path between citizen scientist or Ph.D. There’s actually a lot in the middle. I mean there are people that may have only a bachelor’s or a master’s, but they may have a good idea. There are people from other fields that may be very highly educated in a different field and might want to come in and co-opt that technology for some problem that’s in their field.
It’s a space that’s just being explored now. I think I was less enthusiastic about that space in the beginning, but I’ve been won over. I have the typical prejudice of someone who came up through the Ph.D. system. It’s an apprenticeship, and if that apprenticeship can happen somewhere besides the university, then I think it could be pretty interesting.
Arif Shaikh : My name’s Arif, biochemist, cell bio. And the question I had was, you were saying originally like the population were cousins, right? Like of the ferret? So I know cousins would have similar genes, so there’d be some mutation, and how would you combat that genetic mutation to give the animal the strongest gene possible to survive on its own, considering it’s an extinct species?
Phelan: I think the one part that I may have left out as well is a new variable, which would be looking back, through museum specimens, for DNA prior to what may have been a bottleneck. So if all those seven founders are closely related, they are going to continue to compromise the health of that species over time. So you’re absolutely right on that, and one hope would be to actually look back in time at lost alleles.
Rob Reed: My name is Rob Reed. I’m a science fiction author, so I guess my corporation is Random House. I know it’s impossible to know this precisely, but I would love to know the approximate ship date for the passenger pigeon.
Phelan: Oh, I like the ship date. [laughter] So I believe he’s referring to when will we see a flock of passenger pigeons. And I’m betting on 2025. But individual passenger pigeons will be delivered along the way, probably in the next five years, I hope. We don’t consider a one-off a success. We consider the restoration of the species a success, so we want to see flocks in the wild.
Roger Erickson: Roger Erickson—ITBS I’m representing today. You mentioned this whole premise—everything you said is premised upon reviving and restoring dying species. But that’s the first bottleneck. Others will come very quickly after: reviving and restoring a habitat for them to live in, and then of course reviving and restoring whatever allowed that habitat to be prolonged. That quickly gets you into fighting industry interests, and very quickly into politics. So does Revive & Restore have plans for moving into those spaces?
Phelan: To move into habitat?
Erickson: And not just there, beyond.
Phelan: I think what Revive & Restore is trying to—as I said, is really serving as a catalyst to help organizations, conservationists actually think about replacing the species that have gone away, extinct species, actually replacing them back in their native habitat. And with that obviously includes a whole host of questions and concerns regarding getting rid of invasives that potentially are damaging. The heath hen is a really good example of a species that we’re talking about bringing back to Martha’s Vineyard—if Martha’s Vineyard wants a heath hen back, by the way. The species went extinct in 1930, and that island now has feral cats it didn’t have in the 1930s. It was an incredibly abundant bird. But unless they actually change their relationship to feral cats, and raccoons and skunks, that species can’t really return to that area. But there are people who would like to see that happen.
Yes, and I guess what I’m saying is there are already people in place—it’s a little bit like regulation. There’s regulation in place to introduce a species, the same way there are organizations that are working on ensuring that they’ve got the proper ecological habitat. We have to join forces with anyone like that. It’s not necessarily a space that we have to take on by ourselves, and couldn’t. But, absolutely, the integration of habitat is essential.
Jorgensen: Well, like us, you’re a platform. You’re a platform to make it possible. You don’t have to be everything to everybody.
Phelan: Yes. I think there’s one other area that I think might intrigue this group, which is this whole role of wildlife diseases. And it turns out that whether it’s the black-footed ferret, with sylvatic plague being a concern, with amphibians worldwide with chytrid fungus, with bats with white-nose syndrome, these are invasive diseases that are affecting populations all over the world, and I think there’s a huge role for synthetic biology, for genomically engineering and creating a better environment for our endangered species, and I think that is going to be a very interesting space that we’re looking forward to helping instigate change.
Hessel: We’ve got time for one last question and a short answer.
John Storella: Hi, I’m John Storella and I’m an attorney who has not yet recovered. [laughter] This is for Ellen—Do you think that bio-hacking is too subversive for traditional types of financing like venture capital?
Jorgensen: I can only tell you that whenever I’ve given a talk at a meeting where there were VCs around, they always look me up. The problem is they lose interest when they find out that Genspace doesn’t own the IP of the people that work there. But they’re very interested in learning what is going on in those spaces, because they identify them with things like the MakerBot coming out a makerspace, or these things that have become products or technologies. And even Apple Computer of course is the classic example. But we’re constantly being compared to that. So, yes, VCs are asking, but it really is on a case-by-case basis.
Phelan: It’s a good trend.
Jorgensen: Yes.
Hessel: Yes. We’re out of time, but please do follow up with Ellen or Ryan at the reception if you have more questions.
Jorgensen: Especially if you’re a VC.
Hessel: Yes, especially if you’re a VC. Thank you very much.