00:00:00 Yeah, that would look good.

00:00:03 Does he have a lot of usual movements?

00:00:06 No, not really.

00:00:10 I mean, this is the first time we've done, you know, a video with him.

00:00:14 Like, I've just met him in normal ways.

00:00:17 So that's okay like that, then, huh?

00:00:20 Yeah, that looks good.

00:00:22 Just keep it real and simple.

00:00:25 Right. Should I...

00:00:27 I'm trying to think if there's anything else that we need to...

00:00:30 He's going to be drawing something, then, also.

00:00:32 Right. Now, let me show you.

00:00:34 Now, that's going to be...

00:00:35 I mean, now, this time, when he does a drawing,

00:00:37 you definitely don't need to look at me or him, just the drawing.

00:00:39 But the thing is, it's going to be flat, you know, because he's going to be drawing.

00:00:42 So I don't know how you get over...

00:00:44 As you go that way, you'll end up at the swinging door,

00:00:46 essentially where you are right now, except on the other side of that wall.

00:00:49 Then go down the stairs one floor, and it's right there.

00:00:53 That's it.

00:00:58 That's the most difficult thing around, is to describe where you are.

00:01:05 Do you want to talk for a few minutes about the work that you're doing there,

00:01:08 some of these things that you showed me?

00:01:10 Yeah, I can...

00:01:12 Okay. And then we'll be essentially finished.

00:01:15 Okay.

00:01:17 How did you finally get from the airport here?

00:01:20 I'll never do that again. What happened?

00:01:22 I couldn't believe that you wanted to do that.

00:01:24 Am I closing the door? I don't want people to...

00:01:26 Oh, that's to let some air in here.

00:01:28 Oh, okay.

00:01:31 I'd forgotten how long it took to get from Kennedy Airport to Manhattan.

00:01:34 Oh, you came from Kennedy?

00:01:36 Yeah.

00:01:37 Where did you fly in from?

00:01:38 From Washington.

00:01:40 How did you come? Across the Van Wyk or something like that?

00:01:43 I took the...

00:01:45 Or a belt all the way around?

00:01:47 Oh, no, it's terrible.

00:01:48 Well, he called me last night.

00:01:51 And I decided, well, if he feels more comfortable...

00:01:53 I didn't want to scream, don't do that.

00:01:55 No, no, I've never...

00:01:57 Traffic from Kennedy to here is terrible.

00:02:03 If we have to do any more, we'll do it under influence.

00:02:12 And five, four, three...

00:02:20 Since 1979, you've had a fair amount of success...

00:02:24 in the work that's been done at the Centauri Institute.

00:02:27 And what are some of the problems that have been worked on?

00:02:30 What are the problems that you're working on now there?

00:02:34 Just, well, I go there four, five times a year.

00:02:38 And before that, I might mention just one comment.

00:02:43 And before I undertook this directorship...

00:02:46 I knew that they asked me to come there four, five times a year.

00:02:49 And it amounts to about seven weeks...

00:02:52 or eight weeks out of the year.

00:02:54 And that's quite a big proportion.

00:02:56 So I checked with the chairman and my colleagues...

00:02:59 and they all said, why don't you take it?

00:03:03 It's an honour for this place, and you should take it.

00:03:06 Which was very encouraging.

00:03:09 Yes.

00:03:10 Anyhow, and then I go there...

00:03:14 mainly doing, like, consulting.

00:03:18 And broad direction decisions.

00:03:21 And there are groups with which I'm not involved in.

00:03:25 And these are...

00:03:26 We have a very... one of the best synthetic chemists.

00:03:30 We have a synthetic group.

00:03:32 We have a group dealing with plant tissue culture.

00:03:35 And that is also one of the earliest groups to do this in Japan.

00:03:41 We have another group which is dealing with...

00:03:45 what I so-call the water-soluble compounds.

00:03:48 And these are starting to get involved with receptor sites and so on.

00:03:53 I will only mention two, three studies that we have done...

00:04:00 which I have been involved directly.

00:04:03 And...

00:04:06 Well, before that, the water-soluble group is doing with...

00:04:10 dealing with domoic acid and gamma-aminobutyric acid receptors.

00:04:14 Also ADP ribose.

00:04:16 And very biochemical and challenging problems.

00:04:20 Now, also, there's a group that is dealing with marine products.

00:04:27 And there we have had recently quite a bit of success.

00:04:32 Also, I have started a small group working on bacterial adoption.

00:04:39 And there, recently, we have succeeded in measuring this...

00:04:44 taking good quality different spectra proteins.

00:04:53 Now, the marine project, which is headed by Deputy Director Yoko Naya.

00:04:58 And recently, I'll just tell you two things that they have done recently.

00:05:04 One is they have identified the malt-inhibiting hormone of crustaceans.

00:05:11 And this is the paper which is in press now.

00:05:14 And again, it's been...

00:05:21 many groups have tried to identify this.

00:05:24 And quite recently, two groups have identified a peptide...

00:05:32 which also induces the same effect.

00:05:35 What it amounts to is all the malting...

00:05:38 in other words, the shedding of skins of insects...

00:05:41 are controlled by this one compound, which is ectison.

00:05:45 20-hydroxy ectison, to be more precise.

00:05:48 In the case of crustaceans...

00:05:52 No, no, can I use the blackboard also?

00:05:54 Yeah.

00:05:55 Very quickly.

00:05:56 And...

00:06:01 And this is...

00:06:03 I should have...

00:06:04 This is the eyes, okay?

00:06:06 And then here, there's an organ which is called the Y organ.

00:06:13 And this produces biosynthesizers, ectison.

00:06:20 And then there's another organ here...

00:06:23 in the stem of the isotope, which is called the X organ.

00:06:26 And this one now...

00:06:29 somehow interferes with the biosynthesis of ectison.

00:06:34 And there's also this peptide, I think, which other groups...

00:06:39 Chang, for example, has recently isolated...

00:06:43 is the one which...

00:06:46 we don't know, we haven't proven it...

00:06:48 which gives out the message...

00:06:52 order to produce this NIH, malt-inhibiting hormone.

00:06:59 We have not proven yet whether it's a hormone or not...

00:07:02 but at least I can say that we have identified the compounds...

00:07:06 which has a malt-inhibitory effect.

00:07:09 In other words, a compound which interferes with the biosynthesis of this ectison.

00:07:16 And it's this malting hormone and the malt-inhibiting hormone...

00:07:21 they both have a delicate balance...

00:07:24 and controls the life cycle of crustaceans.

00:07:29 And, for example, the soft-shelled crab is the one which...

00:07:34 they just...

00:07:36 there are some symptoms when the crabs are about ready to shed their skins.

00:07:42 Then they are put in a separate tank...

00:07:45 and the moment they shed their skins, they are put on the ice...

00:07:48 so that they slow down their life and then ship to various places.

00:07:54 Now, this was...

00:07:58 since the crabs were cheaper to get in New York and Long Island...

00:08:04 over the years, we have sent to Japan the blue crabs, about 5,000 of those.

00:08:10 And we tried to collect the eyeballs in the chemistry department.

00:08:16 And, of course, in those days, the whole department...

00:08:23 smelled it.

00:08:25 And the smell would be taken up to the elevator on the different floors.

00:08:30 And, yes, but fortunately, after four years, five years...

00:08:34 again, here, the most difficult stage was setting up an assay, biassay.

00:08:40 And, anyhow, we have recently been able to identify this.

00:08:45 And it turns out to be a compound which is called 3-hydroxykinurenine.

00:08:50 And this is a very famous metabolite of tryptophan.

00:08:55 And a further metabolite down the route is xanthurenic acid.

00:09:03 And we think that probably xanthurenic acid is the real compound...

00:09:08 which interferes with the biosynthesis of ectysol.

00:09:12 And now we're going into more reaction studies and how does it interfere.

00:09:16 And it is an oxygenase inhibitor.

00:09:20 So we're trying to prove what's happening there.

00:09:24 Now, the other compound which we have recently done is...

00:09:32 it is a compound which leads to symbiotic relation...

00:09:36 between a very common sea animal...

00:09:42 which is called the anemone or sea anemone.

00:09:45 And it's a very colorful thing.

00:09:47 And some sea anemone species live symbiotically...

00:09:56 and very species-specific with another common tropical fish...

00:10:02 which the common name is called clownfish or anemone fish.

00:10:06 These are striped with orange stripes.

00:10:10 And you can see them in aquarium.

00:10:12 And when these, the newly hatched ones...

00:10:17 and they come straight to this particular...

00:10:20 I'm giving you one particular example, a particular species of sea anemone.

00:10:25 And then from there on they live symbiotically.

00:10:28 The newly born fish go directly to the anemone.

00:10:31 Yes. So it's an instinct.

00:10:33 It's not learned. That's what I want to say.

00:10:36 And genetically controlled.

00:10:38 And what is the substance?

00:10:40 And again, the difficulty was...

00:10:43 What was the substance that attracts them, you mean?

00:10:45 Yes. And what is the substance which induces this symbiotic behavior...

00:10:49 between the sea anemone and the anemone fish?

00:10:54 And we had to hire a postdoc...

00:11:01 who got a degree on the behavior of anemone fish.

00:11:08 And it's not trivial, these kind of things.

00:11:12 And it took us seven years to get a degree and so on.

00:11:17 And incidentally, she's what we call an ethologist.

00:11:24 And just to show you that there are couples like this.

00:11:28 We had to send her down to the Okinawa Aquarium...

00:11:34 because it had to be done where they had natural anemone fish.

00:11:39 These are not so easy to raise in the lab and so on.

00:11:42 And then it had to be done in a dark room.

00:11:44 And we had to have lots of young, newly hatched anemone fish.

00:11:49 It's a very exhausting thing because the assay is not trivial.

00:11:55 They are delicate fish.

00:11:57 And they had to be done in the dark room under the red light.

00:12:01 And it's terribly hot.

00:12:04 There's no air conditioning at the Okinawa Aquarium...

00:12:08 where they had the labs for sparring.

00:12:12 And she would go there periods of one month, two months.

00:12:18 Then she would get exhausted and say,

00:12:20 I'm going to join my husband.

00:12:22 And her husband turns out to be another ethologist, animal behaviorist...

00:12:29 who is specifically studying the mating behavior of mosquitoes...

00:12:34 who live on glaciers.

00:12:37 And so she goes to Patagonia on top of the glaciers and joins her husband.

00:12:42 Just to cool off.

00:12:44 She told me later that if you keep these mosquitoes on your palm...

00:12:48 after two or three minutes they are dead.

00:12:50 It's too hot for them.

00:12:52 And so, anyhow, this woman...

00:12:55 and because of the difficulty in bioassay...

00:13:01 and because of the extremely small content...

00:13:04 finally we succeeded after four years...

00:13:07 followed by this very, I would say, frustrating assay...

00:13:13 positive and negative and so on...

00:13:15 until she established a way to do this.

00:13:17 From 15 kilograms of a particular species of sea anemone...

00:13:22 which we have to ask the collectors to collect...

00:13:25 and they don't like it because they have to dive rather deeply...

00:13:30 and it's stuck to the rock.

00:13:32 Anyhow, 15 kilograms of this coupled with two or three years of assay...

00:13:37 we were able to isolate this active factor...

00:13:42 a total of about 40 micrograms.

00:13:45 And it turns out to be a new structure, a new peptide...

00:13:52 a dipeptide containing a quaternary pyridinium moiety...

00:13:57 hooked onto a lysine and...

00:14:01 Oh, we have the structure here.

00:14:03 We have the structure. It's this structure on the...

00:14:08 It's here, this one.

00:14:10 And this is lysine and this is a pyridinium moiety.

00:14:14 Which is a new amino acid.

00:14:16 A new amino acid, yes.

00:14:18 And we are now synthesizing this.

00:14:20 And during this course of studies we also identified the other factors...

00:14:26 which lead to this symbiotic behavior.

00:14:28 It involves they're attracted and then they go up and down...

00:14:32 they meaning the fish...

00:14:34 and then at the same time do sort of a hula hoop.

00:14:37 They sway their bodies.

00:14:38 We have identified the other factors...

00:14:41 and they all happen to be neurotransmitters.

00:14:45 And this structure looks... it could be a neurotransmitter.

00:14:49 So from this, very specific at this stage...

00:14:52 but after we synthesize this...

00:14:54 we would like to look into its effect...

00:14:58 as other pharmacological effects.

00:15:01 And I wouldn't be surprised if it has some other effects...

00:15:04 but at this stage we don't know.

00:15:12 Well, I can just tell you one more thing.

00:15:14 Okay.

00:15:15 There's another thing which was published recently...

00:15:18 and I don't have the structure...

00:15:20 but this is... it may provide a new source of natural products.

00:15:25 And that is... there is a group of insects...

00:15:30 which is called the plant hoppers.

00:15:34 And these are sap-sucking insects.

00:15:38 And some of them, in this particular case...

00:15:43 we worked on a plant hopper...

00:15:48 which is a pest to a rice plant in Southeast Asia.

00:15:54 And in this particular case we found that...

00:15:58 not we, some microbiologists in Japan...

00:16:05 had published this some time ago...

00:16:07 that the eggs...

00:16:09 you can incubate the egg for 37 degrees for a certain period...

00:16:13 and then the eggs will hatch normally.

00:16:15 But the insects which come out of this...

00:16:18 either they are totally undeveloped...

00:16:20 they become fertile...

00:16:24 or the wings missing...

00:16:27 or in some cases the whole body becomes covered with white mold.

00:16:31 Okay.

00:16:32 And these people...

00:16:35 it's Dr. Kita and his co-workers...

00:16:37 developed and secured at...

00:16:40 this is a government agency...

00:16:42 a big lab.

00:16:43 We collaborated with this group...

00:16:45 and they were able to develop a method...

00:16:48 in which you can culture these symbiotic microorganisms.

00:16:53 And at first it was not so easy...

00:16:56 but then once you know how to do it...

00:16:58 we started screening for a lot of these...

00:17:00 and looking for specific antibiotic activity...

00:17:04 against agricultural pathogens.

00:17:07 And by this way we found another tripeptide...

00:17:12 which is just published in a recent issue...

00:17:15 of American Chemical Society...

00:17:17 which contains a polyene structure.

00:17:21 And this is specifically active against a pathogen...

00:17:27 which causes the rice plant to...

00:17:32 it induces the so-called white blight disease.

00:17:40 And in other words...

00:17:42 what we think is this insect...

00:17:44 while it's sucking the sap from this rice plant...

00:17:48 must transmit this symbiotic microorganism...

00:17:52 into the rice plant.

00:17:54 And then this microorganism...

00:17:58 which is a pseudomonas we think...

00:18:00 produces this antibiotic...

00:18:02 which is specifically active against the pathogen...

00:18:06 which would destroy the rice plant.

00:18:08 And maybe it is a way of...

00:18:12 protecting their own food source.

00:18:14 At the same time...

00:18:16 they're protecting the rice plant as well.

00:18:18 This could be very exciting...

00:18:20 for protecting a number of...

00:18:22 We found quite a few other antibiotics...

00:18:24 but most of them were known.

00:18:28 They had been isolated by pharmaceutical companies...

00:18:30 from the common soil and so on.

00:18:32 But this one is new.

00:18:34 So I think there is some promise...

00:18:37 as a new source of antibiotics...

00:18:41 with specific activity.

00:18:45 It's fairly obvious that you're doing...

00:18:47 some very, very exciting work.

00:18:49 Obviously we're always looking for...

00:18:53 young new blood to go into science.

00:18:55 Would you have any advice for...

00:18:57 young people who are interested...

00:18:59 in a career in science today?

00:19:01 Frankly, I become much more talkative...

00:19:07 when I drink.

00:19:09 And I'm quite sober now.

00:19:11 So let me see.

00:19:15 I think...

00:19:21 The young people obviously...

00:19:23 are all very intelligent.

00:19:25 And they have a good memory.

00:19:29 But I can mention...

00:19:31 a few interesting things.

00:19:33 I mean important things, which I think...

00:19:35 is to always have your...

00:19:39 antennas stretched out...

00:19:43 so that you can explore...

00:19:47 what's going on.

00:19:49 And to be very sensitive...

00:19:51 so that they can catch anything...

00:19:53 which the student can translate...

00:19:57 in terms of coming up with a solution...

00:20:01 in terms of organic chemistry...

00:20:03 or structure.

00:20:05 And for that, they have to be...

00:20:09 very curious about the things.

00:20:11 To have a very sensitive antenna...

00:20:13 means to have a tremendous amount of curiosity.

00:20:17 And also it turns out that...

00:20:19 try to pull out some interesting...

00:20:23 to extract an interesting subject...

00:20:25 while you're talking with your colleagues...

00:20:27 in other fields.

00:20:29 And you have to have a concerted effort...

00:20:31 to do these kind of things.

00:20:33 Otherwise, I don't think you can come up...

00:20:35 it's very difficult to come up...

00:20:37 with the projects that I've been discussing...

00:20:39 so far.

00:20:41 And in some cases, as I mentioned...

00:20:43 it's quite true that...

00:20:45 we don't know where the exciting projects lie.

00:20:47 The biologists don't know that...

00:20:49 they know that there's such a phenomenon...

00:20:51 but they do not know that...

00:20:53 this could be a chemical problem.

00:20:55 So when you meet with biologists...

00:20:57 to have a good conversation...

00:20:59 when we started these projects...

00:21:01 I mentioned the Suntory, for example...

00:21:03 and the first thing we did...

00:21:05 was to...

00:21:07 we asked the biology professors...

00:21:09 at the University of Newcastle...

00:21:11 and fortunately ten of them came...

00:21:13 we sat around the table...

00:21:15 and we discussed some things...

00:21:17 and that's where some of these projects came.

00:21:19 And from that meeting...

00:21:21 came out a project...

00:21:23 which we solved the problem...

00:21:25 of a shark repellent...

00:21:27 which was secreted by a flat fish...

00:21:29 and this was done by Tachibana...

00:21:31 and papers are still coming out...

00:21:33 but from this...

00:21:35 we also isolated...

00:21:37 Tachibana isolated and clarified...

00:21:39 32-33 peptide...

00:21:41 which is also amphiphilic...

00:21:43 and it's going to have...

00:21:45 very interesting biochemical properties.

00:21:47 But again...

00:21:49 this all started...

00:21:51 through the conversation...

00:21:53 with the biologists...

00:21:55 and to have not only that...

00:21:57 not only our straight questions...

00:21:59 but lots of imagination...

00:22:01 could this be translated...

00:22:03 into an organic problem...

00:22:05 and so on...

00:22:07 and also to have...

00:22:09 a very broad mind...

00:22:11 and also very critical...

00:22:13 when you read papers...

00:22:15 don't think...

00:22:17 don't accept...

00:22:19 the things written there...

00:22:21 take it for granted...

00:22:23 and I think...

00:22:25 it's...

00:22:27 try to retain...

00:22:29 I mean, this is all ideally speaking...