Sunday, May 21, 2006

David Baltimore's perspectives on Synthetic Biology

Here's a rough transcript of Dr. Baltimore's talk:

I helped organize Asilomar. That was more than 30 years ago; none of you were born then, but perhaps you've heard of it. Back then we had no experience with recombinant technology. We didn't know what to expect of it and what kind of guidelines should be in place, and after three days of Asilomar, we still didn't know. Then we essentailly handed the problem off to the NIH, and in retropspect we were very very lucky legislation was a non-player. Guidelines, rules, were developed, but because they turned out to be concerns that were invalid, it was relatively easy to roll them back. That wouldn't have been the case if they had been fixed in legislation.

We focused on safety. We did not focus on ethical issues or bioweapon issues. We didn't have the situation we have today. Terrorists are divorced from central states and certainly will not be concerned with any non-weapon treaties (which we thought, and were, at least in the US, preventing the development of biowepons).

We had some lawyers there. Those were the one's who gave the frightening talks about the liabilities we would be taking home; none of us had really conceived of those until then. But we didn't have ethicists or philosophers. We didn't feel like we were speaking for the public, but from an expert positon.

I've mentioned I have three perspectives on synthetic biology. One of them is that I was involved with Asilomar, with which and tomorrow's policy discussions resonate. Secondly, I'm on a panel at the national academy of science called cscans [spelling?]. We are trying to balance open access to information and research and its potential conflict with national security. And so these two connections are sort of tied together.

The third connection I have is that I think its very likely that viruses are the major concern in infectious systems, and that's because they are esentially small and easily engineered [and lots of nasty templates are naturally available], until I saw this [stuff on bacterial genome refactoring], which potentially makes bacteria just as easy to work with as viruses.

To be honest I'm most concerned with smallpox. It's not a backyard experiment to constitute it, and in fact you would need a very safe laboratory to work with it, so you wouldn't accidentally infect yourself, so I'm not really worried about its construction in clandestine labs, but I think [got behind here... I'll listen to my recording and fill it in soon.]

Now, what is the real danger? What is the danger today? It's the stuff we know about, that exists, the stuff like smallpox that we know can infect people and is extremely deadly and infectuous. I don't put much stock in concerns over designing new, even more dangerous organisms. Nature is a very tough critic, and I think if we tried I would guess we would fail. In retrospect I think those sentiments were present at and help explain some of the complacency that characterized Asilomar.

Take ebola virus. It comes out of its resevouir - bats or whatever - [not very often. You have to wait for that to happen, steal it from a protected lab, or constitute it directly from the sequence online. It's just not that easy to get.]
Bird flu is really not likely to spread until it mutates to a somewhat lower pathogenicity until you go to bed and wake up with the symptoms of flu instead of dying in the night. Viruses are finely tuned to our particular lifestyle, and it's something to remember that [missed the point about non-resevoir human infections]. All I'm trying to say is that we should focus on what we have right now - enough threats already exsits, we don't need to fabricate any more to worry about.

Questions:
Tom Knight: One of the things that has changed is that it's no longer really a question of what's in your freezer, but what sequence you can get online.
David Baltimore: No no, I agree, but there really are not that many things that are not availible in the natural world but are availible in GenBank, and in a clandestine fashion you could recreate that virus.

Unknown Questioner: what can be done now to mitigate [that] problem?
DB: lots of people now have become rich by being involved with biology. So the first thing to do is to admit the reality, but then point out that there's a deeper goal here - the service and betterment of humanity. I can remember when I was getting involved with microbiology, we would write exactly the same thing in NIH grant proposals as you write today, we just never said when. We had faith! But it will happen, and is happening.

Drew Endy: I wanted to get your thoughts on the scope of the community. I remember seeing papers from the 1970s on how to brew botulinum[?] toxin in your kitchen, and it seems there would be a strong negative selection for that behavior. How is it different now, given new [?].
DB:Well I certainly hope we'll see a push towards distributed access, because that's the science, and that's the way we'll be able to release the imagination of people to do great and interesting things. I don't think we should say wholesale "but there is concern." We need to really think about [?]. We find at CalTech today that there is biology in every division, high school students in the laboratory, and what they've been doing, what they know, it's spectacular. No, I think that's all great; I think if there's concern to be had, smallpox. That's my concern.

Rune: There's a lot of people from different communities coming into this, but as someone who's been doing this fo forty years, newness is fine, especially for attracting more interest in the field. So I guess what I'm asking is this: what is new, really? What are its downsides? Its upsides?
DB: Well, you can convince venture capitalists, funding agencies, etc. to get on board, there's definitely that. But I think there really is someting new here, and it's a turning around from sequecing to synthesis, and I must say I'm impressed with the extrordinary facility researchers have in knowing what all the specifics do, what lambda does, this or that promoter does; ten years ago, we knew that would happen. I used to say in those days that there is no question in biology that we cannot answer - it may take a long time - but it can be answered. So it may not be surprising, at least to me, but I think it is new.

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