Ninety-nine percent of the failures come from people who have the habit of making excuses.
George Washington Carver
In a SPIEGEL interview, synthetic biology expert George Church of Harvard University explains how DNA will become the building material of the future — one that can help create virus-resistant human beings and possibly bring back lost species like the Neanderthal.
George Church, 58, is a pioneer in synthetic biology, a field whose aim is to create synthetic DNA and organisms in the laboratory. During the 1980s, the Harvard University professor of genetics helped initiate the Human Genome Project that created a map of the human genome. In addition to his current work in developing accelerated procedures for sequencing and synthesizing DNA, he has also been involved in the establishing of around two dozen biotech firms. In his new book, “Regenesis: How Synthetic Biology Will Reinvent Nature and Ourselves,” which he has also encoded as strands of DNA and distributed on small DNA chips, Church sketches out a story of a second, man-made Creation.
SPIEGEL recently sat down with Church to discuss his new tome and the prospects for using synthetic biology to bring the Neanderthal back from exctinction as well as the idea of making humans resistant to all viruses.
SPIEGEL: Mr. Church, you predict that it will soon be possible to clone Neanderthals. What do you mean by “soon”? Will you witness the birth of a Neanderthal baby in your lifetime?
Church: That depends on a hell of a lot of things, but I think so. The reason I would consider it a possibility is that a bunch of technologies are developing faster than ever before. In particular, reading and writing DNA is now about a million times faster than seven or eight years ago. Another technology that the de-extinction of a Neanderthal would require is human cloning. We can clone all kinds of mammals, so it’s very likely that we could clone a human. Why shouldn’t we be able to do so?
SPIEGEL: Perhaps because it is banned?
Church: That may be true in Germany, but it’s not banned all over the world. And laws can change, by the way.
SPIEGEL: Would cloning a Neanderthal be a desirable thing to do?
Church: Well, that’s another thing. I tend to decide on what is desirable based on societal consensus. My role is to determine what’s technologically feasible. All I can do is reduce the risk and increase the benefits.
SPIEGEL: So let’s talk about possible benefits of a Neanderthal in this world.
Church: Well, Neanderthals might think differently than we do. We know that they had a larger cranial size. They could even be more intelligent than us. When the time comes to deal with an epidemic or getting off the planet or whatever, it’s conceivable that their way of thinking could be beneficial.
SPIEGEL: How do we have to imagine this: You raise Neanderthals in a lab, ask them to solve problems and thereby study how they think?
Church: No, you would certainly have to create a cohort, so they would have some sense of identity. They could maybe even create a new neo-Neanderthal culture and become a political force.
SPIEGEL: Wouldn’t it be ethically problematic to create a Neanderthal just for the sake of scientific curiosity?
Church: Well, curiosity may be part of it, but it’s not the most important driving force. The main goal is to increase diversity. The one thing that is bad for society is low diversity. This is true for culture or evolution, for species and also for whole societies. If you become a monoculture, you are at great risk of perishing. Therefore the recreation of Neanderthals would be mainly a question of societal risk avoidance.
SPIEGEL: Setting aside all ethical doubts, do you believe it is technically possible to reproduce the Neanderthal?
Church: The first thing you have to do is to sequence the Neanderthal genome, and that has actually been done. The next step would be to chop this genome up into, say, 10,000 chunks and then synthesize these. Finally, you would introduce these chunks into a human stem cell. If we do that often enough, then we would generate a stem cell line that would get closer and closer to the corresponding sequence of the Neanderthal. We developed the semi-automated procedure required to do that in my lab. Finally, we assemble all the chunks in a human stem cell, which would enable you to finally create a Neanderthal clone.
SPIEGEL: And the surrogates would be human, right? In your book you write that an “extremely adventurous female human” could serve as the surrogate mother.
Church: Yes. However, the prerequisite would, of course, be that human cloning is acceptable to society.
SPIEGEL: Could you also stop the procedure halfway through and build a 50-percent Neanderthal using this technology.
Church: You could and you might. It could even be that you want just a few mutations from the Neanderthal genome. Suppose you were too realize: Wow, these five mutations might change the neuronal pathways, the skull size, a few key things. They could give us what we want in terms of neural diversity. I doubt that we are going to particularly care about their facial morphology, though (laughs).
SPIEGEL: Might it one day be possible to descend even deeper into evolutionary history and recreate even older ancestors like Australopithecus or Homo erectus?
Church: Well, you have got a shot at anything where you have the DNA. The limit for finding DNA fragments is probably around a million years.
SPIEGEL: So we won’t be seeing the return of the caveman or dinosaurs?
Church: Probably not. But even if you don’t have the DNA, you can still make something that looks like it. For example, if you wanted to make a dinosaur, you would first consider the ostrich, one of its closest living relatives. You would take an ostrich, which is a large bird, and you would ask: “What’s the difference between birds and dinosaurs? How did the birds lose their hands?” And you would try to identify the mutations and try to back engineer the dinosaur. I think this will be feasible.
SPIEGEL: Is it also conceivable to create lifeforms that never existed before? What about, for example, rabbits with wings?
Church: So that’s a further possibility. However, things have to be plausible from an engineering standpoint. There is a bunch of things in birds that make flying possible, not just the wings. They have very lightweight bones, feathers, strong breast muscles, and the list goes on.
SPIEGEL: Flying rabbits and recreated dinosaurs are pure science fiction today. But on the microbe level, researchers are already creating synthetic life. New bacteria detect arsenic in drinking water. They create synthetic vaccines and diesel fuel. You call these organisms “novel machines”. How do they relate to the machines we know?
Church: Well, all organisms are mechanical in the sense that they’re made up of moving parts that inter-digitate like gears. The only difference is that they are incredibly intricate. They are atomically precise machines.
SPIEGEL: And what will these machines be used for?
Church: Oh, life science will co-opt almost every other field of manufacturing. It’s not limited to agriculture and medicine. We can even use biology in ways that biology never has evolved to be used. DNA molecules for example could be used as three-dimensional scaffolding for inorganic materials, and this with atomic precision. You can design almost any structure you want with a computer, then you push a button — and there it is, built-in DNA.
SPIEGEL: DNA as the building material of the future?
Church: Exactly. And it’s amazing. Biology is good at making things that are really precise. Take trees for example. Trees are extremely complicated, at least on a molecular basis. However, they are so cheap, that we burn them or convert them into tables. Trees cost about $50 a ton. This means that you can make things that are nearly atomically precise for five cents a kilo.
SPIEGEL: You are seriously proposing to build all kinds of machines — cars, computers or coffee machines — out of DNA?
Church: I think it is very likely that this is possible. In fact, computers made of DNA will be better than the current computers, because they will have even smaller processors and be more energy efficient.
SPIEGEL: Let’s go through a couple of different applications of synthetic biology. How long will it take, for example, until we can fill our tanks with fuel that has been produced using synthentic microbes?
Church: The fact is that we already have organisms that can produce fuel compatible with current car engines. These organisms convert carbon dioxide and light into fuels by basically using photosynthesis.
SPIEGEL: And they do so in an economically acceptable way?
Church: If you consider $1.30 a gallon for fuel a good number, then yeah. And the price will go down. Most of these systems are at least a factor of five away from theoretical limits, maybe even a factor of 10.
SPIEGEL: So we should urgently include synthetic life in our road map for the future energy supply in Germany?
Church: Well, I don’t necessarily think it’s a mistake to go slowly. It is not like Germany is losing out to lots of other nations right now, but there should be some sort of engineering and policy planning.
SPIEGEL: Germans are traditionally scared of genetically modified organisms.
Church: But don’t forget: The ones we are talking about won’t be farm GMOs. These will be in containers, and so if there’s a careful planning process, I would predict that Germany would be as good as any country at doing this.
SPIEGEL: There has been a lot of fierce public opposition to genetic engineering in Germany. How do you experience this? Do you find it annoying?
Church: Quite to the contrary. I personally think it has been fruitful. And I think there are relatively few examples in which such a debate has slowed down technology. I think we should be quite cautious, but that doesn’t mean that we should put moratoriums on new technologies. It means licensing, surveillance, doing tests. And we actually must make sure the public is educated about them. It would be great if all the politicians in the world were as technologically savvy as the average citizen is politically savvy.
SPIEGEL: Acceptence is highest for such technology when it is first applied in the medical industry …
Church: … yes, and the potential of synthetic life is particularly large in pharmaceuticals. The days of classic, small molecule drugs may be numbered. Actually, it is a miracle that they work in the first place. They kind of dose your whole body. They cross-react with other molecules. Now, we are getting better and better at programming cells. So I think cell therapies are going to be the next big thing. If you engineer genomes and cells, you have an incredible amount of sophistication. If you takeAIDS virus as an example …
SPIEGEL: … a disease you also want to beat with cell therapy?
Church: Yes. All you have to do is take your blood cell precursors out of your body, reengineer them using gene therapy to knock out both copies of your CCR5 gene, which is the AIDS receptor, and then put them back in your body. Then you can’t get AIDS any more, because the virus can’t enter your cells.
SPIEGEL: Are we correct in assuming you wouldn’t hesitate to use germ cell therapy, as well, if you could improve humans genetically in this way?
Church: Well, there are stem cell therapies already. There are hematopoietic stem cell transplants that are widely practiced, and skin stem cell transplants. Once you have enough experience with these techniques you can start talking about human cloning. One of the things to do is to engineer our cells so that they have a lower probability of cancer. And then once we have a lower probability of cancer, you can crank up their self-renewal properties, so that they have a lower probability of senescence. We have people who live to be 120 years old. What if we could all live 120 years? That might be considered desirable.
SPIEGEL: But you haven’t got any idea which genes to change in order to achieve that goal.
Church: In order to find out, we are now involved in sequencing as many people as possible who have lived for over 110 years. There are only 60 of those people in the world that we know of.
SPIEGEL: Do you have any results already?
Church: It’s too early to say. But we collected the DNA of about 20 of them, and the analysis is just beginning.
SPIEGEL: You expect them all to have the same mutation that guarantees longevity?
Church: That is one possibility. The other possibility is that they each have their own little advantage over everybody else. What we are looking for is protective alleles. If they each have their own answer, we can look at all of them and ask, what happens if you put them all in one person? Do they cancel each other out, or do they synergize?
SPIEGEL: You seriously envisage a new era, in which genes are used as anti-aging-cures?
Church: Why not? A lot of things that were once left to luck no longer have to be if we add synthetic biology into the equation. Let’s take an example: virus resistance …
SPIEGEL: … which is also achievable using synthetic biology?
Church: Yes, it turns out there are certain ways to make organisms of any kind resistent to any viruses. If you change the genetic code …
SPIEGEL: … you are talking about the code that all life forms on Earth use to code their genetic information?
Church: Exactly. You can change that code. We’re testing that out in bacteria and it might well be possible to create completely virus-resistant E. coli, for example. But we won’t know until we get there. And I am not promising anything. I am just laying out a path, so that people can see what possible futures we have.
SPIEGEL: And if it works in bacteria, you presumably could then move on to plants, animals and even humans? Which means: no more measles, no more rabies, no more influenza?
Church: Sure. And that would be another argument for cloning, by the way, since cloning is probably going to be recognized as the best way of building such virus resistance into humans. As long as it is safe and tested slowly, it might gain acceptance. And I’m not advocating. I’m just saying, this is the pathway that might happen.
SPIEGEL: It all sounds so easy and straightforward. Aren’t biological processes far more complicated than you would like to lead us to believe?
Church: Yes, biology is complicated, but it’s actually simpler than most other technologies we are dealing with. The reason is that we have received a great gift that biology has given to us. We can just take a little bit of DNA and stick it into a human stem cell, and all the rest of it is self-assembled. It just happens. It’s as if a master engineer parked a spacecraft in our back yard with not so many manuals, but lots of goodies in it that are kind of self-explanatory. You pick up something and you pretty much know what it does after a little study.
SPIEGEL: Do you understand that there will be people who feel rather uncomfortable with the notion of changing the genome of the human species?
Church: I think the definition of species is about to change anyway. So far, the definition of different species has been that they can’t exchange DNA. But more and more, this species barrier is falling. Humans will probably share genes with all sorts of organisms.
SPIEGEL: First you propose to change the 3-billion-year-old genetic code. Then you explain how you want to create a new and better man. Is it any wonder to you when people accuse you of playing God?
Church: I certainly respect other people’s faith. But, in general, in religion you wouldn’t want people to starve. We have 7 billion people living on this planet. If part of the solution to feed those people is to make their crops resistant to viruses, then you have to ask: Is there really anything in the Bible that says you shouldn’t make virus-resistant crops? I don’t think there’s anything fundamentally more religiously problematic about engineering a dog or a cow or a horse the way we have been doing it for 10,000 years versus making a virus-resistant crop.
SPIEGEL: Virus-resistant crops is one thing. Virus-resistant humans is something altogether different.
Church: Why? In technology, we generally don’t take leaps. It’s this very slow crawl. We are not going to be making a virus-resistant human before we make a virus-resistant cow. I don’t understand why people should be so deeply hurt by that kind of technology.
SPIEGEL: Apart from religious opposition, biotechnology also generates very real fears. Artificial lifeforms which might turn out to be dangerous killer-bugs. Don’t we need special precautions?
Church: We have to be very cautious, I absolutely agree. I almost never vote against caution or regulations. In fact, I requested them for licensing and surveillance of synthetic biology. Yes, I think the risks are high. The risks of doing nothing are also high, if you consider that there are 7 billion people who need food and are polluting the environment.
SPIEGEL: Mr. Church, do you believe in God?
Church: I would be blind, if I didn’t see that faith in an overall plan resulted in where we are today. Faith is a very powerful force in the history of humanity. So I greatly respect different kinds of faith. Just as I think diversity is a really good thing genetically, it’s also a good thing societally.
SPIEGEL: But you’re talking about other people’s faith. What about your own faith?
Church: I have faith that science is a good thing. Seriously, I’d say that I am very much in awe of nature. In fact, I think to some extent, “awe” was a word that was almost invented for scientists. Not all scientists are in awe, but scientists are in a better position to be in awe than just about anybody else on the planet, because they actually can imagine all the different scales and all the complexity. A poet sees a flower and can go on and on about how beautiful the colors are. But what the poet doesn’t see is the xylem and the phloem and the pollen and the thousands of generations of breeding and the billions of years before that. All of that is only available to the scientists.
SPIEGEL: Mr. Church, we thank you for this conversation.
Interview conducted by Philip Bethge and Johann Grolle.
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