KAZIC_T@wums.bitnet (06/02/89)
I have followed the conversation with much interest, and here's what I think. I speak as a geneticist increasingly involved in computational biology (an area which seems rather fuzzily defined, at least to me). 1. I find the notion of the biomatrix interesting, but I do not have much hope that it will be very useful for many years. I think the rate-limiting step is not figuring out the representation, or doing AI, but rather the premise: that there exist first principles in biology to reason from. I'm not sure there are any. Evolution might be the best example of a possible first principle. We know the basic outline of how it works, but we argue still over rates and mechanism precisely because the material evidence supports many rates and many mechanisms. The raw material is mutation, but a mutation is an historical event, only statistically predictable, and subject to its own rules of occurence and 'realization' as a phenotype on which selection could operate. Many mutations never see selection for many, many reasons -- so many that it is difficult and may be impossible to dereive predictive rules for which persist long enough to be subject to selection and which do not. So in the case of evolution we have a general organizing idea (a first principle , if you like) which we can apply to the specific cases we see, but which cannot tell us in any detail which cases we will see. That's not prediction in a sense in which I and I suspect most biologists understand it. Nor will the predictive power be improved until we devise ways of predicting the unpredictable specifically. I think this is wny we reason so much by analogy in biology -- not because we are dimwitted compared to physicists (rare is the phsyicist who appreciates complexity for what is, rather than immediately rushing forward to simplify it away so some calculation of dubious biological relevance can be performed) -- but because nature appears to operate by analogy. Either structures are related by descent, or they have occurred independently -- but we still see analogies. 2. If this is true, what can the biomatrix do? I think it has an extremely important task in the organization and retrieval of information. We have a number of databases of various sorts for E. coli, more are in process, and more are in the planning. An important task we face, and are presently addressing in the E. coli community, is how we can get these things to talk with each other so that information can be shared. It is a big task for us, and we already have some databases with which to start. To do what the matrix project envisions, and keep it current, will be an enormous, gargantuan (I can't think of an adequate adjective) task. Do you guys really understand what you're getting into? 3. Is that all biomatrix can do? (Whaddya mean, ain't that enough?) No, clearly it also has a role in developing tools which could be applied to manipulation of similar data, and the development of ***testable*** simulations. Many important questions on fkinetics and dynamics, for example, lie ahead. If these two tasks are accomplished, the matrix will have made an enormous contribution. Incidentally, we could use help with the collection and organization of the masses of data we're all into generating these days -- simple bookkeeping stuff that's ok on paper when you have a thousand, is breaking down at ten thousand, and forget it much beyond that. 4. The notion of hypertext applied to electronic publishing is interesting, but I can envision it rapidly becoming first, a Talmudic extravaganza as people dump their immediate (not necessarily best) thoughts on line, and slowly an unread resource as everyone gets tired of wading through the commentary. People have problems all the time when they 'clone by phone': the latest thing isn't what the originator thinks it is, or it has some funny properties that haven't yet come to light for the originator because s/he doesn't do that kind of experiment, but the recipient does . . . Would you really put the first or even fourth version of your latest program out there? It will be an acheivement of diplomacy and resources to get what we have on paper online -- and again a vital task. Toni Kazic