Sooner than we think we may be able to create everything we know synthetically. Bio-engineering is on the cusp of creating an era of inventions that will radically change our perceptions of the possible. What will life be like when we can create it ourselves?
Read the full transcript below. (Transcript by Realtime Transcriptions.)
Hessel: So Life 2.0. We’re still getting the hang of life 1.0, in many ways. Finally figuring out somehow how it works, I think, yeah. Just we’re still trying to figure out how to—we might be getting some peeks under the hood, but still trying to figure out how to apply it in the real world. We heard a lot about health and really some of the challenges that we’re dealing with right now.
Now, you two are friends, and you both come from very different perspectives in life. You’ve had a long life touching on many different technologies, still involved in genetics, more and more.
Eri, I met you in a hacker lab in Sunnyvale, one of the first garage labs I ever saw up and running, and really starting to bring a whole new generation into the world of life science. So let’s start by just the question Life 2.0, what is it to you? What do you see it as?
Brand: For me, it’s Life 1.1 in the sense that the main thing I’m focused on these days is trying to bring back extinguished species, starting with the wooly mammoth, passenger pigeons, moving to species we might welcome back.
I do this as a conservationist in the sense that our organization is called Revive and Restore. We want to bring back the woolly mammoth, not just to have it in the zoos, but to have it back in the hundreds of thousands in the north terrain tundra back into mammoth step grasslands, the way it did before; and likewise, the passenger pigeon please darken the sun again. Used to be 5 billion of them. We should get at least 1 billion back.
Hessel: And there are people taking this seriously.
Brand: People taking it seriously are people who have looked at the technology and realized that there’s a lot of very difficult stages, but there are instances of each one of the difficult stages that have already played out. So animals, where you have fossils less than about 200,000 years old, there’s recoverable—what’s called ancient DNA in there, and it’s also in the museum specimens. And thanks to shotgun sequencing, you can take that very fragmented, very contaminated DNA and having to do pretty high computer muscle, much harder than working with living DNA.
Nevertheless, you can rebuild the entire genome of this extinct species. And then the idea using George Church’s technique, and techniques like CRISPR, which is a genome editing technique, take the closest living relative of the woolly mammoth, the Asian elephant, and basically swap the woolly mammoth genes into the Asian elephant genome, implant that egg in a surprised mother Asian elephant; and out of that, hopefully get woolly mammoths who make more woolly mammoths. Simple.
Hessel: Absolutely simple. Straightforward. I can see it happening in bedrooms already. The biggest bottleneck, what do you see it being?
Brand: The biggest block will be—
Brand: Well, there’s funding, but I think that most people catch on—I mean, pretty soon—we hear people say well, if we can land a man on the moon, we can do so-and-so. If we can bring back the woolly mammoth, we can do so-and-so. And I think some folks are going to see what fraction of getting a man on the moon, one thousandth, $5 million, something like that. If you have woolly mammoths back on the planet, someone’s going to say I want that to happen. And then you’re off and running, and people ask how much does it cost.
And George Church, whose book I recommend, by the way, his flip version is to get the woolly mammoth back in three years, $5 million. In five years, $5 million, because the technology is moving so rapidly, as people, he was saying four to six times faster than Moore’s law, this is—the cost sophistication goes up. The capabilities move from impossible to expensive to routine in just a couple years.
And I expect that bringing back extinct species seems kind of radical now. In a few years, it will seem like a real conservative thing to be doing, which is exactly what we want.
Hessel: Eri, you have been a big part of really a wave of democratization in life science. From this garage lab that I saw you—met you in a number of years ago, you went on to found BioCurious, one of the first community laboratories in life science. Can you share a little about what you learned with BioCurious, what you are still learning perhaps?
Gentry: Sure. And I think it serves us to talk about why we were in a garage. So it’s nothing about being in a garage in Silicon Valley, although that can always work to your benefit. It was because we couldn’t afford lab space anywhere else, and that’s a huge problem in the life sciences.
As Stewart said, things are getting incredibly cheap, accessible, and people are more and more interested in being an active participant in their own health or even in manipulating cells. And that’s what we had noticed, because we were those same people. And I was working with people who were sick of academia, sick of not being able to take a risk because the system wouldn’t allow for it.
You are dependent on your PI, your principal investigator or where the money is to even try an idea. So the low-hanging fruit is people who think outside the box, what is low-hanging fruit, what’s cheap, what is doable. And basically, what can we do without anybody else.
So we were trying one of those concepts in our garage lab. It was simply to quantify the cancer-killing ability of certain cells, and we ended up being able to do that as a two-person operation, and me having no background in bio except trying to bring people who knew more and more than I did around me.
And what we would do is have some kind of scientist, like Rob Carlson, like you—I remember asking you several times if you would come and speak. And people would show up. We completely basically broke the walls on our house because people demanded it, and we ended up needing bigger and bigger space just to convene.
People would drive for literally two hours from Sacramento, just to hear a scientist talk and then to hang out with other people who were interested in the same topic as them, but outside of the walls of academia or institutions.
Brand: What kind of background were the people? Were they coming from biology or genetic—
Gentry: Sometimes. And it didn’t always matter to them. We have a lot of artists and a lot of musicians. It’s no surprise. So there’s a DIY bio.org mailing list, which has done a tremendous job at getting people involved. They have thousands of people across the world who share pretty high-level talks about biotech and how you can do it from home to community lab.
And at one point two years ago, cofounder Jason Bobe said 50% were artists, and that—it’s very interesting when the people who are shaping a revolution are artists. They look at the world in a different way, and some of these artists are turning into biologists. They’re getting the skills that they need in order to do the work that they think needs to be done.
And it is possible in a garage and in community labs. And with all the people coming, realized we just needed something more. This isn’t a two-person operation. This is dozens around us, thousands of people across the country, and it’s growing. It’s grown tremendously since those few years ago.
Hessel: How many members does BioCurious have now?
Gentry: At our lab at any given time, we’ll have from 10 to 40 people. We can’t fit much more, and that’s unfortunate. That’s because it was six friends who started BioCurious as a lab. So now it’s a separate lab that anyone can be a member of in Sunnyvale.
And we went on KickStarter as one of the first projects, thinking that we’re going to try to raise $30,000, and we’re never going to get it. Today, it’s a world of difference with funding. We ended up raising $35,000, which is a ridiculously low amount that we thought was a lot. And that’s the sort of naivety that helped us get the job done. We just didn’t give up until it was created. And we see the same phenomenon, like the person who started our bioluminescent project, which has some seeds in the glowing plant project, which just raised $500,000 on KickStarter, started by an artist.
Hessel: So for those that don’t know this, another KickStarter, this time to make a glowing plant, raised about $500,000 in about four or five weeks and has become one of the real lightning rods, so to speak, in this next generation of biotechnology, because they actually intend to send out the seeds for glowing plants. As I understand, they are moving along very well in progressing.
Stewart, how are you funding your work with de-extinction? How are you attracting scientists and community members to this project?
Brand: The conservation guys don’t want us to take any money from conservation sources, and so—
Hessel: Threatening their—
Brand: And they needn’t worry, because who’s showing up, we have these founding funders putting in $10,000 a piece. There are 15 of them so far, probably more to come. They tend to be VCs and people from digital tech and folks who I think want to have a foot in what they see as the next platform, plus just being part of something wild and crazy and charismatic and yet actually potentially quite practical; bringing back extinct species.
It feels like they know it’s going to be a century-long story. That’s one of the reasons we are doing it within The Long Now Foundation. Wooly mammoths, you get a baby girl woolly mammoth. She won’t have a baby girl woolly mammoth for 20 years, unless we develop artificial uteruses, which maybe that will occur, but probably not. Or maybe it will.
So you are engaging the nature I care about, which is conservation, which is biodiversity, richness of the natural biology at its time frame and at its level, sort of an evolutionary frame, and that’s what I studied at Stanford back in the ’50s was ecology and evolution.
What I love about this and what I think some of our funders are enjoying is that this is a way to catch up on what’s going on with molecular biology. So the stuff you guys are already engaged in, I’m still learning what this CRISPR means. Everybody can know this new genome editing technique refers to clustered regularly interspaced short palindromic repeats, and you are using an enzyme called Cas9.
This is getting seriously sophisticated out there, folks. And I think one of the things to understand is the digital code is pretty difficult and complicated. It is so easy and Minecrafty compared to genetic code, which is 3.8 billion years of spaghetti code with no engineering involved at any stage. So reverse engineering it is out of the question. This is very interesting code to work with.
Hessel: But you make a great point, like a lot of—many people are speaking about biotechnology of DNA code as really the next IT industry, the next programming industry. Is this fair, particularly you were just at the Homebrew Computer Club meeting on Monday.
Brand: Which I missed.
Hessel: Which Stewart messed. We know some of the history around this, the professional enthusiast coming into the field, just with interest, enough of an infrastructure foundation to really support those—the first creators and builders in the field and, of course, world-changing results. Do you see, with your recent experience, your long experience analogies here? Is this fair?
Brand: So you saw the personal computer guys from that many years ago cackling together and reminiscing. Do you think your crowd is going to be cackling together and reminiscing like that as many years from now?
Gentry: I was trying to think about it. I think if that’s what we wanted, then we could create that, and—straight answer, I don’t know; but Daniel Kottke, who calls himself Apple employee number one in the garage said in 30 years, you’re going to be having one of these. And my instant reaction was since we were in the computer history museum, which was founded by members of the computer history—Homebrew Computer Club, we’re going to need some sort of biological history museum. We’re going to need to understand that in context.
Brand: Starting out right away, before there’s much history to put in it.
Gentry: Isn’t there?
Bradley: There you go. Add that to your repertoire.
Hessel: And even in this recent wave, what I look at as the modern edge of biotechnology, where it’s going digital, really starting with the sequencing projects and the Human Genome Project, now with being able to 3D print the DNA molecule, we actually have almost a 25-year history just in digital biology. So maybe it is time to start considering that.
Brand: And it’s well to remember Homebrew Computer Club came after a whole lot of competition. You had the longhaired programmers, the hackers of the ’70s basically, and then the narrow-tied programmer engineers who had been working 25 years at that point and had already done mainframes, had done mini-computers. And along came personal computers and they were sort of risible to the narrow-tie crowd, why would you waste your time with these toys.
And the answer was because we can do whatever we want with them. And it turned out that, I think, smaller and smaller, then smart phones, whatever’s next. So this shrinking down of the empowering of amateurs basically is the stage we’re looking at here, but it’s still the case that for us to bring back extinct species, we’re not going to do at BioCurious. We’re going to probably do it at the Wyss Institute at Harvard with George Church’s multiplex automated genome engineering machine, which is this robot that replaces squadrons of post-docs with pipettes and generates a—writes genes, then generates them into now microbial, including the ones we’re interested in, generates multiple genes at once in there, which obviously we need to do, if we need to move dozen scores, hundreds of genes from one species to another.
So that’s all pretty industrial-level stuff, but the costs are coming down, and there’s going to be glowing plants and stuff like that out there, drawing fire away from us. Thank you very much. All those nice people that are doing a nice thing like bringing back woolly mammoths and saber tooth tigers, don’t worry about them. It’s the growing plant people we have to worry about.
Gentry: That’s not true.
Hessel: What are your thoughts on that? Are these DIY researchers, are these the younger generation coming in, are they the ones that are going to be doing the projects that catch people’s attention more than something as big as being able to bring back extinct species?
Gentry: Stewart mentioned he’d be working in George Church’s lab. I thought as soon as people see a video of this, they’re going to think about hmm, well, how can I recreate George Church’s machine, and what can I do with that and how can I make it open source and hackable and for the people and not for George Church’s lab.
Brand: There’s a lot of transparency. George is in academia. He started in business, whole approach is transparency. Our whole approach is transparency, and there’s an open source aspect to a lot of this end of what is possible with genomics. And so ideally, you will get some of the benefits of open source, and there will be lots of people who patent something and make a lot of money with it.
Hessel: So you think we’ll see a generation of bio entrepreneurs coming into the space as we saw with computing? I’m hesitant to use the word killer app, but is there a low-hanging—
Hessel: —low-hanging fruit in this space that you see that you might think—what would you buy? What would you make or buy in this space to start turning it into—
Brand: Presumably everybody is watching you to tell where the new business break-throughs are, right? So what do you see?
Gentry: Sure. Next year research is going to be around man and machine. So where are we headed with the future being human and what does that mean. There’s a big issue of identity there, when we’re realizing what we’re made of—made up of microbially, ratio of 10 to 1, non-human cells to human cells. And we’re just now able to afford to sequence what’s living inside and on our bodies.
Hessel: Just to interject, a company called uBiome, just another crowd-funded project, just launched—started shipping their kits a few weeks ago to be able to assay microbes anywhere you want to explore them, prep on your body for about $79 per test.
Gentry: I bought a couple.
Hessel: Really quite impressive. So again, waking people up to the idea that there’s a lot of life around them, that they’re not paying attention to today.
Brand: Did you know there are amateurs out there doing experimental fecal transplants?
Hessel: Experimental fecal transplants. Fecal transplants, by the way is people have gastrointestinal disease is usually because you have a population of microbes in your gut that just for whatever reason don’t work for you and fecal transplants have produced some miracle cure, be I didn’t know there was starting to be amateur work done in the space, but then—
Brand: There is. It is the simplest medical procedure you can think of, bend over. I mean, where—where do you report the results? Amongst probably a small and interests cadre of people.
Hessel: Talking really low-hanging fruit here.
Gentry: Celebrity feces.
Hessel: So I’ve seen people take microbes, make cheese out of it, from different parts of the body. You see like Newman’s Own in different ways. There are food products?
Bradley: Naval cheese, wow. Can we sell mammoth hide and mammoth meat before you got mammoths? I suppose something might occur.
Gentry: And I was recently in China, and got to visit the Beijing Genomics Institute, where they showed me at this point, it was a dead and taxidermic pig that they had made to glow, so they had made several fetal pigs glow. So it’s like these glowing plants, but this is taking it a step further to mammals. And they lived, they were fine, normal pigs, but they glowed when you shined a black light on them. This would never be allowed in the U.S.
At least at one point, there were people who are creating glow-in-the-dark fish, and these are outlawed in the state of California. And it’s not that difficult, but our reaction is it’s just that. It’s very reactionary, because we don’t have the standards to allow or regulations that are aware of these new capabilities of science and genetics.
Hessel: I think some people aren’t aware that you can’t even use a 23 and me kit in every state, just to assay your own genome profiles.
Brand: On account of creativity issues or what?
Hessel: I’m not sure. They need a physician as an intermediate.
Brand: So we don’t have it in Arkansas. In China, were there amateur biotech people emerging? Because in a way, what we’re hoping for with GMOs, a lot of things is that bolder, less over regulated countries are going to be the places where a lot of the breakthroughs happen, and did you see at BGI a sense that they were going to be able to move faster and stranger than, say, we can?
Gentry: Yes, absolutely yes. They’re moving at an incredible pace, and their first feat was to just say that they were going to seek one half of one percent of the human genome and that was before they even had a facility or any funding, so retroactively, the Chinese government gave them money because this claim of theirs got written up into nature. That’s a really big deal.
And they have been doing things like that ever since, but because of the lowered price cost there and the ability to do things that just wouldn’t pass our regulations here, they are going to move beyond us, and they’ve already progressed so quickly. They are a major player, and when I was there, after showing me some of the new plants that they have grown, some new hybrids that are meant to be bigger, they grow more quickly and they’re more nutritious, they showed me also grouper fish that had their genes spliced, so they were bigger and more delicious.
They even make their own yogurt with bacteria, their own special brand of bacteria, and they said they want to be the new—bran brand probiotic bacteria that’s even more wonderful than our probiotic.
Gentry: Of course more wonderful.
Hessel: This is actually fascinating, because this is not a case of Chinese copying the U.S. In fact, they’re using the U.S. technologies, the Lumina machines, et cetera, and actually being able to move forward because of will, because of scientific training. When I was there, there were 4,000 bioinformatics scientists averaged age 22 working in the facility, which is remarkable, all trained in computers on the way in the door, and then perhaps being more fearless in the exploration of the space.
Brand: Is it mainly Carolina? To you see this in India, Philippines, Southeast Asia, other places or do we know?
Gentry: I don’t have a strong background or global knowledge of genetics, but I know I see BGI again and again, and it doesn’t strike me that any other country has capabilities that they do in this arena.
Hessel: That’s fantastic. I have one—maybe if you were invited to the White House tomorrow, what’s one thing you’d really want them to understand? And then we’ll open it up to some questions. What does our government need to pay attention to?
Brand: The White House has been wonderful on synthetic biology. Right after Craig Venter did a computer generated genome, implanted it into a different creature and it became the creature of the genome, the software created its own hardware, they had a gathering at the White House to basically hold forth about the regulatory environment and the way to think about synthetic biology and where it was headed, and basically, it was a pretty libertarian document they came up with.
This is an area which is moving quickly, it’s important that it move quickly. The government should not stand in the way. The government should be sure that there’s no bio-terrorism issues or things like that, which it turns out is in some ways easier to do than people first think, and that let the marketplace decide where the great usefulness is going to be here.
So I think that if Obama or any of his people were in the audience here, they would be nodding away with other people who are nodding and wondering what the people are not nodding are having a problem about.
Gentry: There’s radical shifts in the way that we are learning today. Some of us talk about how academia is broken and the university will not—no longer exist in the next 20 years, and I think we need to reflect all of the changes that come out of a changing way of learning and as it relates to biotech, people are leaning outside of academia. I didn’t realize I wanted to work in bio until after I graduated college having been so grateful that I was leaving school.
So I tried really hard to explore the alternatives for me, because I wasn’t going to give up on what really mattered. So human health, finding cures, it really matters, and we’re not getting to the place that we need to be quickly enough, and there are people like me who want to participate, and some of these people show tremendous promise and brilliance and having so amazed at the people that I’ve met, just trying to learn a bit, but they’re not getting the resources that they need.
I don’t want to feel like the typical academic who says oh, we need more funding in order to explore this problem a little further. It’s really the case that the people who are game-changers are the ones that we’re not aware of and that aren’t pursuing things in traditional ways. So if I were at the White House or just being right here, I think that should be recognized, and if policy-wise, regulation-wise we can do something to enable the individual who doesn’t want to be at a university or at Genentech, then let’s do that. Let’s create some of these regulations and policies.
Hessel: Let’s take a couple of questions, while we still have a few minutes. There’s a question just behind here.
Spiegel: Jerry Spiegel, from New York. You just scared the living daylights out of me. And I am fully aware, as most of the people here are, that these sorts of biological experiments have been going on, but the idea that they’re going on around the world in places that are completely unregulated really scare me to death. I mean, we’ve seen what’s happened with natural species being introduced into our environment and how they’ve taken over and destroyed it. What about these artificial things? How do we deal with the fact that this is going on in a completely unregulated way?
Brand: That’s a common—thank you for asking the question, because it’s a really common one. A gene from a different place is not at all like a species from a different place, and even most invasive species are not a problem. They are a problem in a few delicate kind of places like ocean islands that are basically closed systems and some fresh water bodies that are closed systems.
Genes have been swapped for 3.8 billion years in your and my body at this moment, by the hour, genes are being swapped amongst all of our microbes. That’s what they do for a living. You can’t identify separate species. They call them functional species, because they swap their genomes all the time, and so genome swapping is the norm. We’re still catching on to that.
In terms of actual hazard, the Asilomar Conference held in 1975, when the capability of what was then called recombinant DNA, gene splicing first came along, and there was a weird panic reaction from political bodies, like city councils. So the scientists got together and said what are the actual hazards here, what kind of regulations do we need to generate, what kind of hoods, bunny suits, various things like that, to make sure there’s no real hazards coming out of this.
And they came up with a set, and the federal government stepped in and helped regulate those things. Then they dialed the regulations back year after year, decade after decade. They discovered there was great safety. Since 1975, exactly no one has been harmed by anything that’s gone on in these wet labs. We have had GMO foods since 1996 with alien genes poked into the corn and into the cotton and into the soybeans and the sugar and what not, exactly no health harm has happened from any of that.
There’s various things that come along, so it turns out if they’re an advocate scientist or they got something wrong, then it’s the usual outlier that doesn’t hold up. So we’ve now got a lot of experience of are there bad things that are potentially happening from this kind of scurrying around with genomes, and the answer is not yet.
Craig Venter’s answer is the one time that biotech was really dangerous was when it was sequestered away in bio weapons labs in the Soviet Union and the United States. Since then, it’s been getting safer and safer and safer.
Cochran: Todd Cochran. The GMO folks are going to go absolutely crazy over this, the folks that oppose GMO.
Brand: Strangely silent.
Cochran: It’s interesting they are, but I laugh, because we have all been eating GMO—
Brand: At a presentation I gave in England, and they said mammoths are—bringing back mammoths is a mammoth distraction, which means they aren’t going to focus.
Cochran: But if they hear about manipulation of fish and plants, as soon as that becomes mainstream, people are just going to freak out, and I just—I think your days are numbered before they start hammering the legislation.
Gentry: If we look at food history, a lot of commonly held beliefs about food were due to government, so top-down messaging or interesting results from studies that the media thought were great to write about. And to this day, we have no idea what is good nutrition, honestly.
I recommend the book “Good Calories, Bad Calories”, by Taubes. It’s an excellent read, and it’s not a nutrition book. It presents the real research about why we eat in mass certain categories of food, why we’re high carb, why we’re low carb. The answers are very surprising.
And when we think about people freaking out, I say it’s really going to depend on what the messaging is. It’s going to convince us one way or the other, but I think we’re trying to say you’re capable of doing the research yourself. That’s what we’re trying to do, and the reason that Asilomar worked and the grassroots effort to regulate bio is working is because people are observant, they really care, and what affects everybody else affects them too and if you’re ever interested in hanging out with some people working on this—I know at BioCurious, you are going to find people who will welcome you, be happy to talk to you about everything they are doing. We’re totally open and transplant. And I’m sure Stewart—
Hessel: Perhaps to close on this point, this is an open biotechnology. It’s an open biotechnology that’s global. All the information is out there, as opposed to some of the closed secrets, whether it was done by governments or corporations, and we’re seeing a new wave of people coming in. I remember with the iGym program you mentioned, I would see parents who had been against just kind of had grown up against genetic modification seeing their kids learning this stuff just as 30 years ago think—you might have learned computers, and they were absolutely enthralled. They said I have never seen my children so excited about a technology, so engaged and learning by doing. And so we’re not going to solve every issue here.
Brand: The important point to add is there’s FBI guys at these iGem jamborees. It says weapon of mass destruction on their nametag. Hand out their card to everybody with a big smile, saying you guys, you people are the sensors in this world of potential bio issues. You know what’s going on. You know if anyone’s particularly either wild and crazy or criminal intent or whatever it is, let us know. Here’s our phone number.
This is the opposite of what they did back in the hacker days of computers and—hackers in jail. They don’t put hackers in jail anymore. They ask them to help.
Hessel: Let’s close it out on that. Thank you very much for your attention.