[Hplusroadmap] Edge 237 - Drew Endy: Engineering Biology

[Bryan Bishop]

I think I'll forward my comments to Drew while I'm at it. I think Drew 
has seen me in the biology mailing lists recently, though don't know if 
he knows about http://biohack.sf.net/wiki/index.php yet.

On Tuesday 19 February 2008, Jef Allbright wrote (quoting Drew):
> The only thing that hasn't been engineered are the living things,
> ourselves. Again, what's the consequence of doing that at scale?
> Biotechnology is 30 years old; it's a young adult. Most of the work
> is still to come, but how do we actually do it? Let's not talk about
> it, let's actually go do it, and then let's deal with the
> consequences in terms of how this is going to change ourselves, how

Agreed.

> the biosecurity framework needs to recognize that it's not going to
> be nation-state driven work necessarily, how an ownership sharing and

*Not* nation-state driven work. Right-- this is science and engineering, 
not politics and you can't legislate about what proteins are and are 
not possible, and we will have to be prepared, not in the sense of 
defenses, but in the sense of gaining access to our own biologies so 
that we may ruthlessly improve. In a recent email I mentioned the idea 
of increasing redundancy, such as by being able to synthesize cells 
from scratch, so that we may bootstrap ourselves on other planets if 
the situation ever becomes so dark and gloomy (or happy, if we're still 
alive anyway).

> innovation framework needs to be developed that moves beyond
> patent-based intellectual property and recognizes that the
> information defining the genetic material's going to be more
> important than the stuff itself and so you might transition away from
> patents to copyright and so on and so forth.

What? The knowledge of what something does will be more important than 
the actual thing?

> You look to your friends, who are going to study electrical
> engineering, and they can learn how to design and build computers, or 
> write computer programs, and the objects that they make don't have 
> emergent properties unless that's what's intended, instead they behave 
> as expected. Then you look at biological engineering and you say, 
> well, yes, I'd like to design and build living organisms, or program 
> DNA to execute genetic programs that behave as expected. But, nobody 
> can teach you how to do that.       

This will likely always apply for amorphous fabricators. In other words, 
you can't know a priori how it will turn out without simulations or 
experimental testing, unless you're using territory that has already 
been mapped out through computer science or graph theory (understanding 
the complexity set that it falls under and so on). 

> We're now thirty years into biotechnology. Are we going to ever get to 
> the point where it's not an exclusive technology, it's not a 
> technology that requires experts? Are we ever going to get to the 
> point where we can make many component integrated systems? Are we 
> going to ever get to the point where we have separation of the types 
> of work in biological engineering, so that one person might be an 
> expert designer, another person might be an expert constructor, as we 
> have expert architects and builders and what not?       

Niche specialization is starting to come about already. For example, 
there are a few sites developing behind the scenes for gene sharing and 
for the aggregation of different biotechers/biohackers.

> The only thing that hasn't been engineered are the living things,
> ourselves. 

Certainly not at the bio level.

> So to zoom out, how to make biology easy to engineer? I don't want to
> talk about it, I want to do it. And, how do we do this in a way that 
> leads to constructive culture around the technologies that's 
> overwhelmingly positive in terms of the consequences of its being 
> rolled out?    

Constructive cultures are important, yes, but that might be a pipe dream 
(we cannot predict its emergence), so we have to be constructive in the 
sense of helping people to specialize and become less dependent on 
hoping wishfully that something bad just doesn't happen to their 
biology. Kinda like this whole operation.

> There is also the issue of addressing the energy needs. A lot of
> people drive investments in biotechnology from the application side, 
> and that's good. There are lots of pressing human needs and problems. 

Right, which all seem to have a general solution, such as self 
replication and empowerment. The functionality of programmable bacteria 
can be brought to those people just by the wind of the earth. And what 
if this bacteria can extract carbon from the ground, or be transformed 
into MNT via bootstrapping?

> Food, which is an energy of sorts for people and animals. Liquid fuels 

Food:
http://biohack.sf.net/wiki/index.php/Meat_on_a_stick

> for cars and jets, and then you've got health and medicine, and then

Transportation: I don't have a witty link for that one. Energy is a 
surface-area problem for autotrophs. Giant solar cells in orbit around 
the sun is probably the answer here, but this goes into the open source 
spacetech scene more than biotech. As for health and medicine, what 
happens when we can deliver self-replicating drugs to the user?
 
> you've got environmental issues, and then you've got materials 

Grey goo. How fast can we convince a philanthropist that we need an 
orbiting redundancy station so that we can reboot life just in case we 
get an outbreak of "convert everything into computronium/goo" ?

> But if you take a longer view on it, in the absence of making such
> foundational investments into technologies that support the 
> engineering of biology, the engineering of biology's always going to 
> be hard.   

Yep. And evolution has a few billion years of investment (not that I 
want to anthrophomorphize the process of natural selection).

> Engineers hate complexity. I hate emergent properties. I like
> simplicity. I don't want the plane I take tomorrow to have some 
> emergent property while it's flying.  

Complexity is not an understanding issue. There's an actual mathematical 
definition, like in algorithmic information theory and Kolmogorov, 
Chaitin, etc. It's based on information physics and statistical 
thermodynamics, and many complexity theorists are working on showing 
how it seems to be a property of the universe (such as Salthe and how 
he points out the 2nd law and gravitational acceleration of the 
expansion of the universe tend to explain a lot, such as the 
thermodynamics-ecology law tie-in). And what happened to wanting to 
hide complexity when you want to, wasn't that your stance a while back?
The (Nelson) Xanadu-like zooming system for complexity and detail.

> 2008 is our 1995, if you will; this is the year where a bacterial
> genome's been synthesized from scratch. Ahead of that work, 
> chloroplast genomes, mitochondrial genomes, have been constructed ; in 
> fact a project from Japan a couple of years ago made a ten million 
> base pair fragment of DNA from existing fragments, which is 15 times 
> larger than anything getting attention these days.     

Is it really a victory if the technological advancement is closed source 
or not open access and unavailable to the general amateur? It's just 
news hype at that point, with only a few distant people out of billions 
able to do the new feat, with catch-on taking decades and many new grad 
students to train to become professors and distribute the knowledge to 
new schools ... in the old way of things (not that I'm saying it 
doesn't have its place in the emerging era of 'open').

> So, what happens to the science of genetics as a new set of tools come
> online that let us build whatever DNA molecule we want, you get to 
> make changes and see what happens. Instead of being called genetics, 
> this is called reverse genetics, and the mathematics driving this is 
> probably going to be perturbation design. What changes do you want to 
> make, and how do you choose what to make?. So, first genetics goes 
> from pre-sequencing technology and it's based on logic. Then it's 
> post-sequencing and it's pattern recognition. And next there's going 
> to be post-synthesis genetics, and it's going to be, make whatever you 
> want. Perturbation design becomes the mathematics. And the whole 
> field's going to change.          

I'd like to doubly emphasize how "at that point it's all mathematics" 
(or programming) -- I think namely graph theory comes into play, 
especially for protein folding, but then there's also lots of fun 
cryptology stuff that we can play with and topology in general (set 
theory etc.). And what about when we start digitally sharing our genes 
and new theorems in mathematics to guide our creation process? 

> How do you recognize this exponential and serve it and bring more
> people to participate in it? The rewards of doing this are greater 
> than any one group’s project.  For instance, the team from Melbourne, 
> Australia showed up with a 6,000 base pair fragment of DNA that they 
> found, which somehow, I don't know how this actually works, folds 
> up ... the proteins get made and the proteins self-assemble into a 50 
> nanometer, very tiny, sphere that is filled up with gas. The protein 
> shell is somehow gas-impermeable, and these little balloons, these 
> protein balloons, get booted up inside the cytoplasm, the insides of 
> cells, and you can control how many different balloons there are. 
> Depending on the number of balloons, the cells will either float or 
> sink or be neutral.           

Ref?

> The IT framework based on patents isn't going to scale

esp. with combinatorial possibilities of genetic material

> The more serious situation is that these issues of human practice
> don't get resolved in a six month conversation; it's not like what 
> happened in Cambridge, Massachusetts in the '70s, where recombinant 
> DNA work got shut down for a little bit, and then became okay. The 
> technologies are being developed and distributed so quickly, yet 
> there's still so much more to do in improving the work of biological 
> engineering. The conversations we need to set up are conversations 
> that need to persist in ways that are constructive for decades.       

Natasha Vita-More has mentioned that we will need to convince the people 
and politicians that there is a human right to self-transformation. But 
I see many parallels with what you're calling for here, and am 
interested in what sort of public discussion we're going to have to 
start up in a way that shows people that all of this tech is really 
here *now* (perhaps some parts inefficiently) and that the cat is 
already out of the bag, but that health and understanding and 
intentions can still be maintained etc.

> But, the real value associated with being able to engineer proteins
> that bind DNA are in the uncountable applications people could use the 
> proteins for. It's like a programming language where it would be a big 
> downstream economic cost if you owned "if/then" and you were the only 
> person who could use it. We need to be able to reuse this stuff in 

Not only that, but "if/then" can *still be written* by any programmer, 
and the same with biology, and this is where politics and "social 
contract theories" and "intellectual property" fall flat on the ground. 
One guy 'owning' "if/then" wouldn't be feasible. But, the further 
argument that there is more value somewhere else is an interesting 
distractor to this fundamental issue, which reminds me of the recent R. 
U. Sirius interview I critiqued in the ausint mailing list.

> combination. Note that the ownership of biotechnology will play out in 
> a landscape that is surfing along a technology transition where, as 
> automatic construction of DNA gets better and better and better, 
> you're going to care less about the specific material you have, you're 
> going to care more about the information on a computer data base and 
> the computer design tool that lets you organize that information, 
> compile it down to a DNA sequence, and print it. As soon as you start 
> to manage information, all sorts of new ownership, sharing and 
> innovation schemes become allowable.             

> That took me to Austin, Texas, at UT, I worked with Ian Molineux, who
> had done the early PCR work at MIT, he was running one of the last 
> bacterial virus labs in the country, and still is, and he taught me 
> how to map and clone DNA and do my experiments. I then spent a summer 
> in Madison, Wisconsin and went to Berkeley, California, where I ended 

Interesting! UT Austin and Wisconsin-Madison are my two remaining 
university options (for one reason or another). 

> It is interesting for me to learn how difficult it is for folks to
> appreciate what an exponential technology really implies. 

It is math and programming in general and their intersections.

Thanks for linking me, Jef.

- Bryan
________________________________________
Bryan Bishop
http://heybryan.org/