lot more about the various pathways. We prob- 

 ably will start studying the universality of these 

 pathways as utilized by various organisms. 

 For instance, we will like to know how generally 

 the latent message mechanism is being used. 

 It appears now that it is operative both in the 

 sea urchin and in the water mold. We will start 

 asking questions not only about how the genetic 

 program is to be read (by that time we should 

 really know what the genetic program is), but we 

 may also ask, "How did the biological world 

 derive this kind of program?" In other words, 

 in the next five years we would like to link 

 differentiation to molecular biology, and in the 

 following five years we may wish to link 

 differentiation to taxonomy and to the study 

 of evolution. The presentation of Dr. Massaro 

 about LDH systems in all kinds of fish and 

 organisms is an early start of this type. By 

 1975 we may even have some answers from 

 space study about Martian biology. By com- 

 paring Earthly biology to Martian biology, we 

 may start to study developmental biology on 

 different planets. 



POLLARD: I'd like to comment in quite 

 general terms on the message that may go 

 from the cytoplasm to the nucleus. You can't 

 have a message go from the cytoplasm to the 

 nucleus that is physically too big. Almost 

 certainly you're going to have to have some- 

 thing reasonably small which will get into the 

 nucleus. The cytoplasm is unlike the nucleus, 

 which has very large molecules moving out of 

 it. However, to get something out of the cytoplasm 

 into the nucleus you've got to actually drive it. 

 It's like the old question of parking and unparking 

 a car. If you park a car, you've got to put it in 

 a fairly small place and it's fairly hard to do. 

 If you unpark a car, you've got the whole world 

 to go into. You can get big things out, but, I 

 would suspect, you can only put small things in. 

 So you've got to move from the cytoplasm to 

 the nucleus such things as large proteins or 

 ribosomes if a message is to be passed into 

 the nucleus from the cytoplasm. 



TS'O: Yes, in chemical biology we reach 

 the same conclusion that you geneticists do: 

 namely, that this would have a given direction 

 of movement. 



GROSS: I think that it's premature to 

 decide now what informational macromolecules 

 pass only in one direction. 



POLLARD: Oh no, that's not what I meant. 



GROSS: There is accumulating evidence 

 that proteins as proteins can pass through the 

 membrane into the nucleus. 



POLLARD: Yes, they can pass in both 

 directions. It is mainly the question as to what 

 concentration might be necessary and what 

 probability of passage would be. I would say 

 that if you want something to diffuse rapidly 

 and have a high probability of getting inside 

 the nucleus with a message from the cytoplasm, 

 while most molecules are moving out, there 

 must be a high concentration gradient in that 

 direction. 



GROSS: It's feasible, however, that pro- 

 teins that are present in low concentration in 

 the cytoplasm as the result of some previous 

 synthesis, under certain environmental stimuli 

 might, for one reason or another, be carried 

 into the nucleus independently of the concen- 

 tration gradient. 



POLLARD: Well, I would call that a 

 "miracle". 



GROSS: Well, it's possible that there are 

 things that move only by diffusion, to be sure. 

 However, there may also be carriers which 

 themselves diffuse down a gradient. 



TS'O: I would like to know some of Dr. 

 Wright' s opinions, especially after hearing her 

 elegant biochemical experiments. Do you think 

 such a general scheme is suitable for dis- 

 cussion? 



B. WRIGHT: Well, I don't like the term 

 "decision- making". I think it's so complicated 

 that there are many "decision-making" proc- 

 esses interacting and interlocking. One simpli- 

 fied way you could look at it is in terms of the 

 things that I've been concerned with which are 

 going to be essential in all systems. Then you 

 can have degrees of less and less criticalness. 

 I mean, in order to get differentiation, as I said 

 in my talk, you have to have immediate control 

 at the level of substrates and enzymes. The 

 whole small molecule milieu of the cell has to 

 be keyed just right in order to accomplish this. 

 Then, with respect to the time of the differen- 

 tiation process, you have the tendency for less 

 and less dependency in the criticalness of the 

 control as you filter back toward the ultimate 

 message. 



TS'O: You would, nevertheless, say there 

 are cases where the genetic control is a very 

 predominant matter? 



B. WRIGHT: At one time or another it is 

 always of predominant importance. However, 

 even when you can show, as with the nuclear 

 experiment you mentioned, a very striking 

 effect, all of these other levels of control 

 have to be perfectly in shape in order to see 



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