Freeman Dyson- LIFE: WHAT A CONCEPT!

Freeman Dyson- LIFE: WHAT A CONCEPT!

An Edge Special Event at Eastover Farm
Freeman Dyson [8.27.07]








You had what I call the garbage bag model. The early cells were just little bags of some kind of cell membrane, which might have been oily or it might have been a metal oxide.  And inside you had a more or less random collection of organic molecules, with the characteristic that small molecules could diffuse in through the membrane, but big molecules could not diffuse out. By converting small molecules into big molecules, you could concentrate the organic contents on the inside, so the cells would become more concentrated and the chemistry would gradually become more efficient. So these things could evolve without any kind of replication.  It's a simple statistical inheritance.  When a cell became so big that it got cut in half, or shaken in half, by some rainstorm or environmental disturbance, it would then produce two cells which would be its daughters, which would inherit, more or less, but only statistically, the chemical machinery inside.  Evolution could work under those conditions.

LLOYD: These are naturally occurring lipid membranes?

DYSON: Yes. Which we do know exist. That's stage one of life, this garbage bag stage, where evolution is happening, but only on a statistical basis. I think it's right to call it pre-Darwinian, because Darwin himself did not use the word evolution; he was primarily interested in species, not in evolution as such.

Well then, what happened next? Stage two is when you have parasitic RNA, when RNA happens to occur in some of these cells.  There's a linkage, perhaps, between metabolism and replication in the molecule ATP. We know ATP has a dual function. It is very important for metabolism, but it also is essentially a nucleotide.  You only have to add two phosphates and it becomes a nucleotide. So it gives you a link between the two systems. Perhaps one of these garbage bags happened to develop ATP by a random process. ATP is very helpful to the metabolism, so these cells multiplied and became very numerous and made large quantities of ATP. Then by chance this ATP formed the adenine nucleotide, which polymerized into RNA. You had then parasitic RNA inside these cells, forming a separate form of life, which was pure replication without metabolism. RNA could replicate itself. It couldn't metabolize, but it could grow quite nicely.

Then the RNA invented viruses. RNA found a way to package itself in a little piece of cell membrane, and travel around freely and independently.  Stage two of life has the garbage bags still unorganized and chemically random, but with RNA zooming around in little packages we call viruses carrying genetic information from one cell to another. That is my version of the RNA world. It corresponds to what Manfred Eigen considered to be the beginning of life, which I regard as stage two. You have RNA living independently, replicating, traveling around, sharing genetic information between all kinds of cells. Then stage three, which I would say is the most mysterious, began when these two systems started to collaborate.  It began when the invention of the ribosome, which to me is the central mystery.  There’s a tremendous lot to be done with investigating the archaeology of the ribosome. I hope some of you people will do it.

Once the ribosome was invented, then the two systems, the RNA world and the metabolic world, are coupled together and you get modern cells. That's stage three, but still with the genetic information being shared, mostly by viruses traveling from cell to cell, so it is open source heredity. As Carl Woese described it, evolution could be very fast.

That's roughly the situation as Carl Woese described it — you have modern cells with metabolism directed by RNA or DNA, but without any private intellectual property, so that the chemical inventions made by one cell could be shared with others. Evolution could go in parallel in many different cells, so it could go a lot faster. The best chemical devices could be shared between different cells and combined, so evolution would go rapidly in parallel. That was probably the fastest stage of chemical evolution, when most of the basic biochemical inventions were made.

Stage four is the stage of speciation and sex, which are the next two big inventions, and that's the beginning of the Darwinian era, when species appeared. Some cells decided it was advantageous to keep their intellectual property private, to have sex only with themselves or with the members of their own species, thereby defining species.  That was then the state of life for the next two billion years, the Archeozoic and Proterozoic eras.  It was a rather stagnant phase of life, continued for two billion years without evolving fast.

Then you had stage five, the invention of multicellular organisms, which also involved death, another important invention.

Then after that came us — stage six. That's the end of the Darwinian era, when cultural evolution replaces biological evolution as the main driving force.

"Cultural" means that the big changes in living conditions are driven by humans spreading their technology and their ways of making a living, by learning from one another rather than by breeding. So you are spreading ideas much more rapidly than you're spreading genes.

And stage seven is what comes next.

The question is whether any of that makes sense. I think it does, but like all models, it's going to be short-lived and soon replaced by something better.

The other thing I was going to talk about was domesticated biotech, which is a completely separate subject. That comes from looking around at what's happened to physics technology in the last twenty years, with things like cell phones and iPhones and the things that I see around me at the table.

Personal computers of all kinds. Digital cameras. And the GPS navigation system. All those wonders of technology, which have suddenly descended from the sky to the earth. They have become domesticated. That has been a tremendous change, something we never predicted.

I remember when von Neumann was developing the first programmable computer at Princeton. I happened to be there, and he talked a lot about the future of computing, and he thought of computers as getting bigger and bigger and more and more expensive, so they belonged to big corporations and governments and big research labs. He never in his wildest dreams imagined computers being owned by three-year-olds, and being part of the normal upbringing of children. It's said that somebody asked him at one point, how many computers would the United States need? How large would the market be? And he answered, eighteen.

So it went in totally the opposite direction.

VENTER: Well, it went in both directions.

DYSON: To some extent, but even the biggest computers are not much bigger than they were in those days. It's remarkable — I remember the very first computer in Princeton, and it was a huge thing — a room about as big as this tent, full of machinery. This was in 1951, '52. It was actually running smoothly around '53.

VENTER: But that was less powerful than your laptop.

DYSON: Oh, much less. The total memory was four kilobytes. And he did an amazing lot with that. Especially a biologist who was there at the time, called Nils Barricelli, did simulated evolution amazingly well with a memory of four kilobytes. He developed models of evolving creatures forming an ecology, and they showed punctuated equilibrium, exactly the way real species do. It was astonishing how much he could get out of that machine.

LLOYD: The problem is that computers get faster by a factor of two every year and a half, but computer programmers conspire to make them run slightly slower every year and a half, by junking them up with all sorts of garbage.

DYSON: Because von Neumann thought that he was dealing with unreliable hardware, he made another mistake. The problem was how to write reliable software so as to deal with unreliable hardware. Now we have the opposite problem. Hardware is amazingly reliable, but software is not. It's the software that sets the limit to what you can do.

My prediction or prognostication is that the same thing is going to happen to biotech in the next 50 years, perhaps 20 years; that it's going to be domesticated. And I take the example of the flower show in Philadelphia and the reptile show in San Diego, at both of which I saw demonstrations of the enormous market there is for people who are skilled breeders of plants and animals. And they're itching to get their hands on this new technology. As soon as it's available I believe it's going to catch fire, the way computers did when they became available to people like you.

It's essentially writing and reading DNA. Breeding new kinds of plants and trees and bushes by writing the genomes at home on your personal machine. Just a little DNA reader and a little DNA writer on your desk, and you play the game with seeds and eggs instead of with pictures on the screen. That's all.

LLOYD: One of the reasons computers became ubiquitous is the phenomenon of Moore's Law, where they became faster and more powerful by a factor of two every two years. Is there an equivalent here?

DYSON: Exactly the same thing is happening to DNA at the moment. Moore's Law is being followed as we speak, both by reading and writing machines.

LLOYD: At roughly the same rate?


VENTER: It's happening faster. I had this discussion with Gordon Moore and I said that sequence reading and writing was changing faster than Moore's Law, and he said, but it won't matter, as you're ultimately dependent on Moore's Law.

DYSON: I agree with that. At the moment it's going fast.

CHURCH: Unless we build bio-computers — right now the best computers are bio-computers.

BROCKMAN: It took two weeks for a 17-year-old to hack the iPhone — and here we're talking about DNA writers and readers. That same kid is going to start making people.

DYSON: That's true, the driving force is the parents, not the scientists.  Fertility clinics are a tremendously large and profitable branch of medicine, and that's where the action is. There's no doubt this is going into fertility clinics as well. For good or evil, that's happening.

BROCKMAN: But isn't this a watershed event because of our ideas about life? What's possible will happen. What will the societal impact be?

DYSON: It's not true that what's possible will happen.  We have strict laws about experimenting with human subjects.

BROCKMAN: You can't hack an iPhone either; certain activities along these lines are illegal.

DYSON: But it's different with medicine. You do get put in jail if you break the rules.

BROCKMAN: Not in Romania.

DYSON: There are clear similarities but also great differences. Certainly it is true that people are going to be monkeying around with humans; I totally agree with that. But I think that society will put limits on it, and that the limits are likely to be broken from time to time, but they will be there.

SHAPIRO: I just want to bring in one distinction here, because two things are getting confused. To go to computers, I remember that perhaps 30 years ago there was something called Heathkit and the idea was, why buy a computer when you can build your own computer in your basement? Well I don't see anyone constructing their own computers in their basements any more.

If you purchase from computers from Dell or from IBM they will assemble them for you. But the actual construction, the difficult part, takes place in specialized institutions and then they make their products available. Everyone has a cell phone, but I doubt that most of the people, if they dropped it, could repair their cell phones. And that the new biotechnology — while humans would get the benefit, even now I think, one can contract to put the green fluorescent proteins into all sorts of animals and one artist has done just that and arranged to have specialized laboratories put it in, and then he had an exhibit where he made it seem as if he himself had done it. That isn't the case. DNA sequencing will be done massively, and engineering will be done massively, and new organisms will be constructed. But they will be done in specialized facilities. Only the products will become available to the general public. No child will go into his basement and set up the necessary DNA synthesizers, or DNA sequencers and proceed to make his own new organisms.

DYSON: You're thinking like von Neumann, and I disagree.

VENTER: That used to be a compliment.

DYSON: It's true: what you will sell to the kids is kits — you won't sell the whole apparatus for doing things but you will sell a kit that will do the things that are fun, just as you do with computers that are sold for children to play games. The computers only play games, they don't actually calculate numbers.

LLOYD: In fact there's a good analogy in the history of computation — 30 years ago MIT freshmen arrived having built a computer, and then shortly after that they stopped building computers. Twenty years ago, or fifteen years ago, they arrived knowing how to program computers. But nowadays when freshmen arrive, far fewer of them have actually programmed a computer before, in the sense of writing a program in a language such as Java. But they use computers far more, and they're great users of software. They know vast amounts about how computers work and what you can do with the software.  Why? Because it's a lot easier to do — why program a computer if somebody can enable you to just use the software and program it — of course when you're playing Grand Theft Auto, you're effectively programming the computer at the same time. So I suspect that what Freeman says is right, people will be using this new genetic technology, but maybe there's an analog of programming in the constructing new organisms which will enable people to do it — an analog of software so people will become the users of the software.

SHAPIRO: I see children being able to purchase lizards, say, that glow in the dark — with green fluorescence, but I don't see them creating them in their basement.

DYSON: I think both are going to happen.

SASSELOV: Maybe the question is, what is the time scale for the second thing happening? That is, by then the technology will be so developed that we may be different as a species, and not care as much as we do today whether some kid is capable of tinkering with a human. Because we will have tinkered enough, in the regulated way, by then, so that it wouldn't matter as much.

DYSON: Yes, nobody can ever know in advance; all these things always turn out differently than you expected.

LLOYD: In fact this is a real specter — because as you say, we're not allowed to tinker with humans, but we are allowed to tinker with rats, that we very rapidly will develop rats who surpass us in all abilities. Whereas we're just stuck in the dark ages.

BROCKMAN: Freeman, last night I asked Richard Dawkins if he cared to comment on your chapter suggesting "the end of the Darwinian interlude". He sent the following comment with the caveat that it is a hastily written response solely for the purpose of this meeting. He writes:

"By Darwinian evolution he [Woese] means evolution as Darwin understood it, based on the competition for survival of  noninterbreeding species."?    ?"With rare exceptions, Darwinian evolution requires established species to become extinct so that new species can replace them."





DYSON: Good. Yes, I have two responses.

First, what I wrote is not a howler and Dawkins is wrong. And I have read his book.



In my opinion, both these responses are valid, but the second one goes more directly to the issue that divides Dawkins and myself.

VENTER: I have trouble with some of the fundamental terms. What's your definition of  "species"? That's something I have great difficulty with lately out of our research.

DYSON: Yes, it is a problem — it's supposed to be just a population that breeds within the population but not outside, but of course there are all sorts of exceptions.

VENTER: That ignores most of biology.

DYSON: Yes, so I don't know what the real definition is. But that's the conventional definition.

VENTER: It's a human definition.

DYSON: It is fuzzy. Like most things.

LLOYD: So for sexually reproducing species, then, it's less fuzzy than for bacteria.

DYSON: Right.

VENTER: But it really comes down to one or two recognition molecules that determine the species — if it's based on interbreeding, it's the sperm recognition sites, right?


VENTER: So that determines the species, then.

DYSON: Well, amongst other things.

CHURCH: Chromosome dynamics, morphology, behavior — many things. Depending on how complex the organism is.

VENTER: It's easy to tell a human from a giraffe, and we can call that a different species.

DYSON: One of the books that I've learned most from, is The Beak of the Finch, which describes evolution as it's observed in the Galapagos by Peter and Rosemary Grant. It's remarkable that they can actually see from year to year species starting to hybridize when conditions are good and then separating again when conditions are bad. So even on a year-to-year time scale you can actually see this happening, that species are not well-defined.

LLOYD: Sorry, I'm not familiar with this work.  So they hybridize when times are good, and when times are bad they separate into smaller populations.  Is this so that they can evolve more rapidly?

DYSON: Yes. So they can specialize. Because in bad times you have to specialize on chewing particular seeds.

VENTER: During droughts, all that was left were these really hard seeds. Finches that survive have Arnold Schwarzenegger beaks.

DYSON: Not only those — you can also have a separate population which specializes on the small seeds, which have small beaks. It happens because of the geography that you have violent swings in climate. During El Niño conditions are wet, and between El Niños, conditions are dry. So selection is brutal — almost every year about half of them get selected out.

VENTER: One of the highlights of my round-the-world expedition was meeting up with the Grants in the Galapagos, and their little tent on the site of Daphne Major. They spent three months on this island in this little tent, there's no fresh water, there's nothing there. And they live off of bottled water and cans of tuna fish. And I took them a bottle of chilled champagne. It became a happier eco-system. Remarkable what they've done.

DYSON: The enormous advantage that they had was that the birds are completely tame. You can just walk up to a bird and put a ring around its leg and it doesn't fly away. That's what made it all possible. They know every bird personally.

VENTER: Better than tame — if you walk on their path, the boobies and stuff will peck at your leg. It's their island. The humans become non-tame after a while. But so that's an important part of the definition. Are the finches with the larger beaks a different species, in your view?

DYSON: Yes, according to Darwin they are. In fact they do interbreed quite extensively.

VENTER: So two base pair change in a genome could be sufficient to create a new species out of 1.5 billion.


VENTER: I'm not sure everybody will buy that definition... So that makes you a very different species than George.

DYSON: The real problem is the lawyers. You have the endangered species act; that means you have to make a legal definition of the species.

CHURCH: That's true.  We're all endangered.

LLOYD: I gather human beings are a genetically very non-diverse species. We take two squirrels on this tree right here — they're much farther apart genetically than we are with any other human being on the face of the earth. So we're inclined to see things in our own light.

VENTER: What's your evidence for that?

CHURCH: It's true for chimpanzees; I don't know about squirrels.

LLOYD: But homo sapiens is a quite recent species — and also the mitochondrial DNA evidence suggests that we're descended from common ancestors in the not very distant past — within the last hundred thousand years or so. So there seems to have been a genetic bottleneck in the human species, compared with hominids as a whole, within the last hundred thousand years. Which makes us much less diverse than, for instance, squirrels.

SHAPIRO: The thrust of what Freeman was saying if we accept most of what he said, which I certainly do, is that concepts like species and interbreeding are about to become in a sense extinct. Because entering the new era, laboratories will exist which will recreate species or combine qualities of one species with qualities of another and it will be up to the designer the extent to which they interbreed or interbreed with existing organisms and so on.  So that perceivably, if civilization continues we will then be in charge of what species may come into being and what species do not.

LLOYD: I have a query: is that actually important, actually? Freeman, you said we reached the end of Darwinian evolution, where human beings are the dominant species on earth, and species that can't co-evolve with humans are probably doomed. But this means that in this end of Darwinian evolution, then genes are no longer so important, and instead ideas, which can be generated more rapidly, and — dare I even say — things like computations and software are more important. Are you envisaging an era where genetic information returns to the predominant position that it had for billions of years on earth?

DYSON: No, I don't look very far. I'm quite conservative as far as human society is concerned. We would be wise to keep ourselves as much as possible the way we are, and I hope we'll be successful in it. I don't see any great likelihood if you monkey around with humans that you'll produce anything much better.

BROCKMAN: This sounds like an engineer's approach, rather than a thinker's approach. As a scientist, aren't you talking about a huge watershed concerning our ideas of what it means to be human or even what it means to be alive? Can you imagine what ideological factions or religious groups would do with some of the statements that have been made this afternoon? 

LLOYD: Ironically many religions are sets of ideas, and one of the things that many religions tend to do is to try to sequester themselves genetically. Keep the gene pool within this religion from people within this religion — prevent intermarriage with people of other faiths. You could say religion is almost an attempt by ideas to get back to the good old days of rapid evolution via genetic engineering in small populations.

DYSON: I'm not familiar with this feeling that culture is collapsing. All these millions of people who are now publishing blogs on the Web are to my mind producing something you might call culture. Of very uneven quality, but it's easier to publish now than it used to be. And that to me is not necessarily a disaster. It may be a step forward.

LLOYD: In fact it's easier to preserve information as well. In the past one of the main problems with culture is it would disappear because there was only one copy. When there's only one copy, things get easily destroyed. And yes, maybe because in the United States we don't have as much culture so we're not so worried about losing it.

Perhaps worrying about the wholesale copying and monkeying with genetic information might open people's eyes to the danger of copying and monkeying with ordinary cultural information — for instance, violating copyrights. While I am usually for any kind of information manipulation I can think of, it does seem a little strange to try to manipulate human genomes. Of course, the primary way of manipulating genomes in the past, which people have been doing for ages, is by breeding. People are rather squeamish about attempts to manipulate human genomes to create perfect human beings just by breeding. This is an old fear among people and an old temptation as well. We may not be so culturally bereft with the mechanisms that we need to cope with these kinds of issues as we might think. It is scary. But anything fun is scary.

PRESS: Is open source sort of an inexorable direction that we're moving in — as people blog openly, and copyrighted music seems to be losing out to open and tradable music — is that the way you expect it's going to be with genomics as well, that ultimately this information is all going to be openly and freely available, and that's the way this whole system is going to progress?

DYSON: Not necessarily. Bill Gates is still around.  But that remains to be seen.  Clearly this is the alternative.

CHURCH: Genomics for the most part has been quite open historically — even in profit-making sectors they will publish papers and so forth, and the genome project went so far as to try to publish things within one week of collecting the data. So it's really quite aggressive so far. Almost every genome that you could possibly want, including some that some people would prefer not to be in open source, like small pox, which Craig helped to do, and the 1918 flu virus — all those things are available. So I think that is a trend.

DYSON: It's unfortunate that small pox is out there — the world would be a lot safer if that hadn't been published.

VENTER: I can disagree very violently with you on that.

DYSON: Good.  That's a minor exception, but as a general rule, openness is by far preferable.

VENTER: Even with that, I think I could convince you openness is far more important. There were two states that were funding an incredible amount of secret research — the U.S. and the former Soviet Union — on trying to modify small poxes, make them more dangerous, et cetera. So if it was not open source, those states would be the only ones with access to this information. There would be nothing out there for either tracking it, understanding it, making better vaccines, et cetera, if it was even a real threat. And on the synthetic biology side, it's a very, very low threat because the DNA is not infective. It's a hypothetical threat that people like to use to scare people, but in reality it's really not one.

CHURCH: DNA is not infective but you can make infective viruses with the DNA in the lab?

VENTER: Hypothetically. But nobody's done it yet.

CHURCH: With other pox viruses you can do it — so it's not that hypothetical.

VENTER: There are probably a few thousand pox viruses out and very closely related species that could easily become small pox. I'll argue for open source of information — my genome is on the Internet, but I'm much more selective who I share my biological materials with. There's open source and there's open source.

SHAPIRO: You did raise an interesting point there, though, because genetic privacy is something which is often debated — the rights of individuals to genetic privacy, not to have their genomes known.

VENTER: But that's driven by fear, not by knowledge.

SHAPIRO: But what I'm saying is, that genetic privacy actually maybe impossible. Let us say that I wish that he hadn't put his genome on the Internet and wanted it secretive, say he was running for public office and had some gene for some mental instability, and therefore wanted no one to have his genome; yet someone wanted his genome.  All I'd need to do is swipe your glass, and shake your hand.

VENTER: This is issue that we could talk about that George and I have been facing that's counteractive to what our government is doing. Francis Collins is setting up data bases, where you have to have retinal scans and finger prints to have access, and we're publishing our data on the Internet. So, open source is not a guarantee of any means at all.  We hope by making human genetic data available, people will find in fact that it's almost impossible for your scenario, wherein you can look at one gene and say this person's going to have mental illness. Even the entire genetic code doesn't provide that answer. You have to know the environment; you have to know a lot of other things.

Perhaps 50 years from now we can get much closer to those answers of predicting things, but we are not just genetic animals. My dangerous idea is that we're probably far more genetic animals than society is willing to accept. But we're not purely genetic animals, so I don't think it's going to be as predictive as some people think.

SHAPIRO: Well, certain specific things will be predictive — for example, Huntington's disease is due to a repeat of certain letters in DNA.

VENTER: There are some very rare exceptions, yes.

SHAPIRO: You can even tell what onset is likely at what age by counting the number of repeats that are present.

VENTER: But that's the exception that doesn't make the rule. That's what every geneticist has used as the few early examples of success in genetics of single gene disorders.

SHAPIRO: But there are cases where individuals themselves didn't want to know whether or not they had inherited the gene for Huntington's disease, or if they did, whether they were going to have a severe form. Yet if some external person wanted to inform himself as to whether that individual did carry the gene, it would almost be impossible to prevent that individual from getting the information. You would practically have to live in seclusion, with all of your clothing, all of your artifacts destroyed on contact.

LLOYD: It's interesting because in fact the digital nature of genetic information, the fact that it's seven billion bits that can easily be written into a computer hard drive, makes genetic information much more like the information in computers and it can be manipulated in that way. Whereas strangely enough, our mental information, the information that's in our brains, is much less digital in a fashion, and much harder to get hold of.

And in fact it does suggest that, since this information has been digitized, and will continue to be digitized and manipulated, and be more available, the question of how secrecy and privacy for genes is rather similar to the privacy of your iPhone? How privately are you allowed to keep the information in your iPhone? How privately are you allowed to keep the information in your genes? Because it will be available, and it will be possible to get it and to digitize it so then the question is, do you need codes for protecting your genetic code? Maybe everybody should be issued their own public key cryptic system so they and only they can have access to their own genetic code.

CHURCH: We're kind of in a state of change where we're deciding what's the right thing. For example, consider our faces. Some people keep their faces completely masked; in most situations it's considered anti-social to keep your face completely masked. Like walking into a bank, for example. But it's extraordinarily revealing — it not only reveals something about your physiology, your current health, your relationship with the person you're talking to, whether you're angry or very happy — it's very revealing. And so we've made a conscious decision in society, for the most part, to not keep that private. We might do the same thing for genomes, it could be, who are we protecting? But it's an open question.

SHAPIRO: Well we shed cells so easily unlike faces that it's almost impossible to keep your genome private, if there is someone out there determined to have it.

CHURCH: I agree with you. We'll all become bubble people, living in our little hermetically sealed bubbles so nobody can get in.

LLOYD: Who steals my genome steals trash, right?

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