00:00:00 He's going to, we got a lot of structures that probably can fit in very nicely with some of

00:00:15 this. I looked at part of the tape that we'd done before and there's, there are obvious places where

00:00:23 it would be nice to have structures, but I think that he has some very pretty drawings that could

00:00:28 be used. I mean, I've got all these blown up individually, all of these. And these are some,

00:00:38 this is the ones I've discussed, this is I've discussed, and this is the one I was just discussing.

00:00:44 And they can be blown up or you can use this. Yeah, I can use this. Yeah. Yeah. No, this is,

00:00:50 no, no, no, no, no, but I've got a whole bunch of these. Okay. You know, as, as you go back through

00:00:56 the tape, individual things that you'll want, and then you can either tell me or I'll get these to

00:01:01 lay on these slides and so on. Okay. We can do it on the computer. I don't know. Well, he's,

00:01:07 he's written some of these things up here that we. Yeah, but that's. Would you like some coffee?

00:01:26 Now for the big, sort of big general questions. First, what are the important problems for you

00:01:43 right now? We've talked about the kinds of work you're doing, the isolations, the, where are your

00:01:51 groups going? You have a big group in vision. You've got people working on the tunichromes.

00:01:58 What other kinds of things are you involved in at this particular point? Well, I think,

00:02:09 although I'm not a, most, many of our problems are getting involved with more and more with

00:02:18 proteins, I think. And I don't want to use big, big words, but the rhodopsin also,

00:02:26 it's the interaction between a receptor protein and a small molecule, retinal, you see. And there

00:02:32 are a couple of works we have, we are doing at the Suntory Institute, which is also, again,

00:02:38 interaction between small molecules and big receptor molecules. So that's one big, I mean,

00:02:46 area we are moving into, whether we like it or not. And we're trying to do this by trying to

00:02:55 understand it, clarify the things on a microscopic structural basis. And another thing is totally

00:03:05 unrelated, but the micro-scale determination of glucosidic linkages of oligosaccharides. And

00:03:16 that I'm placing quite a bit of emphasis. And this, shall I just go through this? Okay. You

00:03:30 see, this is at least our goal. You know, the molecular biology has advanced dramatically in

00:03:38 recent years because micro-analytical methods for determining the structures of nucleic acids and

00:03:46 proteins have been worked out routinely, routine methods. But this is not necessarily the case in

00:03:53 oligosaccharides or polysaccharides. And this is the last nasty area which is left, and it's

00:03:59 becoming more and more important because of cell walls and then glycoproteins in general, again,

00:04:08 related to proteins. And the methods which have been used is more or less classical. Not only that,

00:04:15 one had to have reference sugars. And we, the past five years or four years, we've been

00:04:24 concentrating, focusing our attention to develop a micro-method which is more or less totally based

00:04:31 on circled dichroism, the coupled oscillator method, and trying to develop a micro-structural,

00:04:39 micro-scale structure determination for determining the glucosidic linkages of

00:04:44 oligosaccharides on a scale that one cannot use NMR. And I can say that we have finished

00:04:55 clarifying the ground rules, principles, which are operating. And during this process, we have

00:05:02 found some, I think, very interesting, some interesting results which I'll mention in a

00:05:08 moment. And now we have, we are going into the practical application stage. We have started to

00:05:14 work on gangliosides and so on. We want to come out with a simple method, as simple as possible,

00:05:23 and general, so that we don't have to have reference compounds. Just some physical

00:05:31 constants, which is in this case circled dichroism, which you can read from a table

00:05:37 or look at the spectrum, you see. And one important principle that we have found is that

00:05:48 the additivity relation, you have many CDs of complex compounds in a compound. It has many

00:05:55 chromophores, and it will give rise to very complex circled dichroism curve. And we have

00:06:02 found and proven that these can be dissected into pairwise interaction. And then the whole CD curve

00:06:14 can be reconstructed from this pairwise interaction. And this has been a principle,

00:06:21 for example, advocated by Kaufman many years ago. But this was in the D-line era. And it was

00:06:30 almost impossible to prove or disprove at that age, at that time. And we have shown that you

00:06:36 can do it pairwise addition, additivity relation holds in all CD curves, I think. But that's the

00:06:44 basis. Anyhow, it's getting less and less so-called organic chemistry. But the basic techniques,

00:06:57 of course, we are operating as an organic chemist group, working, trying to find out

00:07:04 how mode of action mostly are of these life science related factors, you see. And the real

00:07:14 structure determination per se of a small molecule has usually become quite routine. And that is not

00:07:21 the challenging thing. The challenging factor is once you determine a structure, how does it react?

00:07:29 Of course, there's also a challenge at the other end for you, at least, and that's the isolation.

00:07:34 Yes. That's never become sort of generalized. That's always. That's another thing. I mean,

00:07:39 people tend to regard isolation as it's not my business and so on. And even if it's a painstaking

00:07:48 isolation, which has taken us three, four years, there are two things. One is many factors which

00:07:56 make isolation difficult. One of the major factors is an assay. When you're dealing with these

00:08:06 life science related factors, it means that these factors have to have a unique assay.

00:08:15 It's not general screening, the factors we are looking after. And many times this assay

00:08:23 is the bottleneck. The next one is the stability, instability. And the next one,

00:08:29 also a big important factor, is the availability of starting material. And I know this is too much,

00:08:38 maybe exaggerating, but unless it presents a challenging problem in isolation,

00:08:46 the problem itself may not be that exciting. It's a little bit extreme, but that's the way I feel.

00:09:04 Where do you think organic chemistry, and in particular, natural products chemistry,

00:09:10 is headed? Where do you think we'll be going in the next 10 years?

00:09:20 I really think it should go, and it is heading towards clarifying these exciting problems which

00:09:27 lie in the interdisciplinary area. But we have to maintain ourselves as organic chemists,

00:09:33 and not to get lost. There's no sense in organic chemists becoming biologists. We have to operate

00:09:39 and stay as an organic chemist, but work on these interdisciplinary problems using our techniques.

00:09:46 And in that sense, it's only the organic chemists who can do this structural elucidation of

00:09:55 interactions between small molecules and macromolecules on a molecular structure basis.

00:10:06 One thing that occurred to me while you were talking was that there could be a fear that we

00:10:11 would become a service organization for biologists and biochemists.

00:10:19 Well, I think if the organic chemist is confident, I mean, I admit it, you can call

00:10:27 yourself technicians, but I don't mind being called a technician myself, so far as you're

00:10:34 not told by the other people what to do, what to do, then you're a technician. But if you know what

00:10:39 you're going to do, and they do not know, and you do it on your initiative, which is always the case,

00:10:44 then I don't care what it is.

00:10:49 You've mentioned Centauri Institute a couple of times, and I know in 1979

00:10:54 you became a director at the Centauri Institute. Maybe you could tell me a little bit about the

00:10:59 Institute and its mode of action, and the kinds of things they're interested in.

00:11:04 Yeah, it's Centauri Institute. The proper name is Centauri Institute for Bio-Organic Research,

00:11:12 and it is almost totally supported by Centauri company, the brewery whiskey making company, and

00:11:25 the president is Saji, is his name. He's an organic chemist, and he wanted to become a professor in a

00:11:32 university, at Osaka University, but unfortunately his elder brother died, so he had to succeed his

00:11:39 family business. And so he has a nostalgia for doing basic research, and then right after the

00:11:47 war in 1947, I think, he set up the so-called Institute for Food Science. This is when food

00:11:53 situation in Japan was very poor, and then it went on until, and several directors and so on,

00:12:02 and then when the previous director was about to retire, my friend, high school friend, who is a

00:12:08 member of the board, Seno, he came to me and asked whether I'd be interested in becoming a director,

00:12:15 and I said, well, I'd like to give it a try. At that time, president Saji's understanding,

00:12:23 they put in a tremendous amount of money into this institute, and built it to what it is now,

00:12:30 which I'll explain to you in a moment. And first of all, they increased the faculty, I mean the

00:12:42 staff members, quite a bit. Currently, it is roughly about 30 permanent staff, and in addition to that,

00:12:53 I started this postdoc system. I will mention that in a moment. And then we bought

00:13:05 many advanced equipment, and I think it is now one of the best equipped institutes

00:13:13 for the type of work I'm doing in the world. And it's a small institute, only a total of 36 or so,

00:13:20 but we have this, well, 500 megahertz, and then 360, and then the 300, and the 200,

00:13:28 and the 100 megahertz instrument. Not only we have it, but they are all maintained in

00:13:35 top condition. That's the big difference. I mean, there are many places who have the instrument,

00:13:39 but it's not running. All of these instruments, not only that, the mass spec, FTIR, CD,

00:13:45 and then many other things. And plus that, we have no restriction in what topics to work on.

00:13:55 Before I go into the topics, let me just briefly explain about this postdoc system.

00:14:00 Okay, where's the home of the instrument now?

00:14:02 It's between Osaka and Kyoto, a little bit south of Kyoto. And the postdoc system,

00:14:14 well, I have to become very sarcastic against the Japanese government. And I even recently wrote

00:14:22 in an editorial that the Japanese Ministry of Education should withdraw itself from all

00:14:32 universities, and we should set up a new ministry. The reason is, I don't think there's a single

00:14:40 PhD in the whole Ministry of Education, and yet they are in control from kindergarten all the way

00:14:46 up to graduate schools. And there's no way that these people, conceptually or knowledge-wise,

00:14:54 can compete with the ideas coming out from the scientists at NIH, NSF,

00:15:03 all the research councils, and so on. So for years, the Japanese professors have been screaming,

00:15:11 we want a postdoc system, we want a postdoc system. There's no way they can understand this,

00:15:17 because none of them have had, know what research is. And the advantage of having a postdoc is,

00:15:23 of course, if you want to, for the people in this country, Europe, it's common knowledge.

00:15:28 If you want to go into a new field, you can get a postdoc from that group, and then you can

00:15:33 immediately go into a new field. But in Japan, it's not so. The professor or the assistant professor,

00:15:39 the assistant, has to start that field themselves. So the starting base is quite different, you see.

00:15:46 Anyhow, and it's good for mixing blood, and makes it more fluid, dynamic. Japanese tend to be in a

00:15:54 small island, they're all solidified, they're all glued to their own places, you see. And I mean, it's

00:15:59 horrible, the situation. And so the president had a good understanding, and this is the advantage of

00:16:07 not being government, and I don't like bureaucrats at all. And so he let us do whatever we wanted,

00:16:15 and fortunately, we have extremely good postdocs. And from this country, I can mention,

00:16:23 we've had from Harvard, Yale, Columbia, UCLA, Caltech, Kansas, all these places. And we've also,

00:16:33 from mainland China, Korea, and European countries, and it's been quite successful. And of course,

00:16:42 we had lots of difficulty, just to give you some idea, to tell you about the mentality of the local

00:16:49 Japanese police. And when we had a poll, and the mainland Chinese, the police would come once in a

00:16:57 while and check, are they okay? Unfortunately, right in front of the institute is a fire station.

00:17:04 There's no fire, because it's a very peaceful residential area, so they're bored, they don't know

00:17:09 what to do. So they come once in a while across the street to check what's going on at our institute,

00:17:14 and are those people from eastern or the Chinese okay? Then my deputy director, who is a woman,

00:17:23 Yoko Naira, she asked, why do you keep on checking those people? It has become very unpleasant.

00:17:30 They said, well, once they want to, what do you call, emigrate or leave the country, we are here to

00:17:42 protect them. That's the excuse they made. But anyhow, Japan is still, it's not, it's undeveloped,

00:17:50 I would say. It's not even developing in that sense. Anyhow, I should calm down now.

00:17:57 The postdoc system is going fine, and then... How many postdocs will you have in a given year? Six.

00:18:03 Six postdocs? Yeah. So it's a very competitive kind of... Well, there's some waiting list. I see.

00:18:10 Yes, and yeah, it's lucky. But you see, the postdocs come, I mean, in Europe and this country, it's fine,

00:18:18 but when there is, when they come to a country where, in which there has been no formal postdoc

00:18:26 system, it's difficult for the receiving side also. Most of the staff members are postdocs,

00:18:32 they have postdoc experience, but it's different when you are on the receiving side, you see, and

00:18:37 it took some time for me to clarify the situation in terms to make it clear that the postdocs come

00:18:50 to do their postdoc as a stepping stone for the future, and which is quite different situation

00:18:57 in Japan. You don't worry too much about your job because the professors usually arrange it.

00:19:02 But in this country and European countries, when you're interviewed for a job, you have to

00:19:10 describe what you did for your research and so on in the postdoctoral years, as well as your

00:19:16 doctorate. So it's quite different. Anyhow, the topics, there's no restriction.

00:19:25 So if you put it, if I mention it in one word, we're trying to do topics, research topics,

00:19:33 which cannot be handled in a single, by a single group at the university. And so,

00:19:42 but we have to be very selective because after all, the total membership is only 36,

00:19:48 and quite a few, and about 10, 12 of these are senior people. So they all, I mean, they are all

00:19:55 associate professor level people, you see, and they only have one assistant or they work together

00:20:01 with one postdoc. So we have, I call this the pair system. It's, that's the way I started,

00:20:08 that pair A and pair B and pair C, they could collaborate and overlapping where they can,

00:20:16 and then thus maintain some fluidity in the collaboration within the institute.

00:20:29 So there's a whole series of different interests, and you try to get.

00:20:33 Yes, yes, yes. But now it's eight years now, and it's somewhat changing, and we start and get some

00:20:42 structures, three or four big groups within. But still, the basic unit is senior, junior,

00:20:50 or a permanent staff and a postdoc. Postdocs, of course, we do not consider as juniors. These

00:20:56 are colleagues. Also, recently, we have employed on a permanent staff an Irish,

00:21:03 also, which is again, not so usual in Japan. Yes.

00:21:07 He came as a postdoc, and he fitted in nicely. So we have employed him as a permanent,

00:21:14 and he's in charge and handles our mass spectroscopy.