Linus Pauling Interview, August 23, 1991

THOMAS HAGER: [Phone dialing] telephone interview with Linus Pauling, August 23, 1991. [Phone ringing].

LINUS PAULING: Hello?

TH: Hello, Linus?

LP: Yes.

TH: This is Tom Hager.

LP: Yes, Tom.

TH: Hi. How are you today?

LP: Okay.

TH: Yeah? How's your ankle feeling?

LP: Well, it doesn't have so much pain anymore. It's getting better. I can put a little weight on it now [inaudible].

TH: Yeah. So, you're managing to get around sufficiently?

LP: Yes.

TH: Okay, well that's good. So, let's take a little time if now's a good time, 00:01:00and I'll ask you a few more questions.

LP: Okay.

TH: Okay. We had started talking last time about the period when that Chairmanship of the Division of Chemistry and Chemistry Engineering shifted to you, and I wanted to find out a little bit about the time when Noyes was ill at the end of his life. And he held that position until he died, is that correct?

LP: What's that?

TH: He held the position of Chair of the Division until his death, is that correct?

LP: Let me see. Would you say that again?

TH: Yeah. When A. A. Noyes was ill at the end of his life...

LP: Yes?

TH: Did he give up the Chairmanship prior to his death, or did he-

LP: Oh, no. No, he didn't, so far as I know.

TH: Yeah. But his functioning was- I mean, his illness sort of got in the way of his doing his job, did it not?

LP: Well, I don't know that he had very much to do. I suppose he didn't go to 00:02:00the meetings of the Executive Council. Executive Committee. Executive Council, I think it was called. But he was one of the members. I think that there were perhaps three faculty: Millikan, Noyes, and Munro, and three trustees, on the Executive Committee. Executive Council, I guess it's called. And I think that's what there were when I became a member after Noyes' death. So, he perhaps didn't go to those meetings. I saw him I think in his home, which was only two blocks 00:03:00from the institute. And the Chemistry, the Division of Chemistry and Chemical Engineering had been set up, as I mentioned, in such a way that different professors were in charge of committees to make decisions.

TH: Yeah.

LP: I don't remember how long he was ill. Several months after his operation - had a colostomy - so, after the operation that introduced the colostomy, I think that he didn't come to the institute, but perhaps saw people. I know that Henry 00:04:00Borsook, who was Professor of Biochemistry in the Physics Department in the Biology Division, saw him. And he was an M.D., Henry Borsook, and perhaps gave him some medical advice. I don't remember who his physician and surgeon were.

TH: Yeah.

LP: I didn't see him very often. Perhaps only a couple of times after his colostomy.

TH: Now, he made it- would you say that he had made it clear to you that you were his chosen successor?

LP: ...No, I can't say that, except for his appointing me Executive Officer.

TH: Ah.

LP: And then not giving me any duties, so not turning anything over to me.

TH: But he never spoke to you specifically about the Chairmanship of the Division after his, or during the time of his illness, or whenever he was thinking about retiring or whatever? It had never come up as a subject between the two of you?

LP: I don't think so. I think that I was thinking that- well, I... I didn't know that he wasn't going to recover at that time. He was 66, I think, when he died.

TH: Yeah.

LP: And the newspapers said that he died of pneumonia. That was still the days 00:06:00when people didn't say that the death was due to cancer.

TH: Uh-huh. So, then upon his death when the question came up of filling the Chairmanship of the Division, then it wasn't a foregone conclusion that it would be you?

LP: Well, I thought that it was, but [laughs] it turned out, as I've learned only recently about the- well, of course, I knew that I was offered the job as Chairman of the Division, but not Director of the Laboratories.

TH: Yes.

LP: So, there came a time when I realized that it wasn't a foregone conclusion that I would just succeed Noyes. Tolman, by that time, was considering himself 00:07:00more a physicist than a chemist.

TH: Yeah, well he would have been the senior person.

LP: Oh, yes.

TH: Yeah.

LP: As he was 20 years older than I and had quite a reputation. But at that time, he was working, I think working on his big book of thermodynamics, statistical mechanics, and relativity [laughs]. And even in the statistical mechanics and thermodynamics part, he didn't put in much of the stuff that interests chemists. It was mainly... well, I think he was impressed by the way 00:08:00that theoretical physicists [coughs for a bit]... introduced mathematics, and... so, his big, thick book is rather austere in that respect.

TH: So, you think his interests were switching toward the physics side and he wasn't...

LP: Yes.

TH: Who were the other full professors in the Division besides yourself at that time, and Tolman?

LP: Well, Lacey was, I believe, Professor of Chemical Engineering. And I think, although I'm not sure, that Bates had the title of Professor.

TH: Yeah.

LP: And Jimmy Bell had the title of Professor of Chemistry... It may be that Roscoe Dickinson also had that title by that time, too. Perhaps Badger. What I'm thinking back is that I can't remember that I was involved in their promotion.

TH: Yeah.

LP: So, it may be that Yost may have had the title of Professor too.

TH: But as far as you knew, none of them had any interest in the Chairmanship at that time?

LP: Well, I remember... I think that [Joe Caplan?] told me that there was a possibility that Lacey would be made Chairman.

TH: Ah.

LP: ... Well, I didn't have any feeling of uncertainty about it, so far as I was concerned.

TH: [Laughs] okay.

LP: As by that time I'd been offered a professorship at Harvard and at Stanford, 00:11:00and at University of London, at Ohio State.

TH: Yeah, yeah.

LP: I just assumed. And I was perhaps the most active person in research, and of course, doing a good bit of teaching too.

TH: Yeah, yeah. Let's switch gears here. I want to ask you about The Journal of Chemical Physics. And I know that in the early thirties when The Journal of Chemical Physics started, there was quite a debate among chemists at that time concerning Wilder Bancroft's Journal of Physical Chemistry, and the nature of physical chemistry in general and the direction that research in that field was going, and there was- I mean, what I had read in that book on physical chemistry 00:12:00that Servos has written, From Ostwald to Pauling, was that the Journal of Chemical Physics sort of arose out of a fear that physics was threatening chemistry. That the integrity of chemistry was being threatened by the expansion of physics, and there was some feeling that there should be a stronger I guess journal out there for the publications in the field to sort of bolster the chemists' position.

LP: Well, I don't think that's right because it's the physicists who set up the Journal of Chemical Physics, and it's continued to be published by the American Institute of Physics.

TH: Uh-huh. But you were on the original...

LP: Oh, yes. Before it was set up, I attended a meeting of about five people, I think, with... Compton, Karl Compton, President of MIT, as Chairman. And Karl Compton probably was the prime mover in setting it up. And so, I can remember his asking me my opinion about the Journal of Physical Chemistry. Well, I was satisfied to publish the Journal of the American Chemical Society, for the most part [unintelligible]. But I had a paper in the first issue of The Journal of Physical Chemistry when it began publication. And I was one of the five members 00:14:00of the editorial committee [inaudible] I think. Well, Harold Urey was the editor, but there were I think five sort of sponsors of The Journal of Physical Chemistry. I was one of them. And it didn't- I don't think this matter of whether chemical physics - this is The Journal of Chemical Physics - whether chemical physics was a part of chemistry, or a part of physics was... a question that I worried about at all.

TH: Uh-huh. What was your feeling about Wilder Bancroft's Journal of Physical Chemistry? Was there a general opinion that that wasn't suitable or able to fill 00:15:00all the needs in that field?

LP: Well, I knew practically nothing about it at that time because we didn't have it in the Chemistry Library. Because I never saw it.

TH: Oh, I see. I see.

LP: Later, when I did see copies of it, I noticed that much of it consisted of book reviews by Wilder Bancroft himself, and his book reviews consisted mainly in quoting a paragraph or two out of the book [chuckles]. So, it was an easy sort of way of writing a review of a book, to give the readers a little idea as to what the book was like [chuckles]. I met Bancroft once in 1938. He invited my 00:16:00wife and me to their home for dinner one evening, and I rather enjoyed meeting him. But I didn't- I knew that Noyes didn't think much of him. And of course, in the Servos book, you see that too.

TH: Yeah, yeah.

LP: That... Well, Bancroft didn't have a very quantitative way of attacking physical chemical problems. His emphasis on the phase rule, which is a sort of qualitative, important qualitative kind of physical chemistry, and phase 00:17:00diagrams... So, I just didn't know much about The Journal of Physical Chemistry, except that it wasn't considered good enough to have in our library.

TH: Oh [laughs]. Did Noyes talk with you about his plans for a medical institution or moving toward medical research within the division, or within Caltech?

LP: I don't think so. My memory is that he didn't talk to me at all about his decision to invite Abel to come from Johns Hopkins. I knew about the insulin work. Well, of course, I knew Albert Raymond and Alles, Gordon Alles well. They 00:18:00were both graduate students at the time. And they were in charge of the insulin work at CIT before Abel came. And I don't think I knew it if Noyes had considered the possibility of getting into medical research. I knew about the insulin work and Abel being there, and [Guy Leighton?] Abel's second in command.

TH: Yeah.

LP: But Noyes didn't talk- so far as I remember, he didn't talk to me about that at all.

TH: About any larger, yeah, larger plans.

LP: Well, that was around 1924 perhaps.

TH: Yeah, that was quite early on. As soon as your work started coming out, your 00:19:00quantitative work on the chemical bond - we're starting with the '31 paper - there started to be a response from Mulliken, and the molecular orbital side of that phase of history was also being worked out and it- people, I've seen, in various books that I've been reading, about people talking about a sort of a debate between the valence bond work that you were involved in, so-called, and the molecular orbital work that Mulliken and Hund and others were working on. Did you see that- at the time during the early thirties as your series of papers was coming out, did you see the molecular orbital approach as a distinct 00:20:00approach that was a debatable... sort of a debatable approach to the same problem? Did you see it as simply a variation on your themes? Or how did you rate Mulliken's work at that time?

LP: Well, I published a paper or two on the molecular orbital method, not making detailed calculations, but determining the expected sequences of levels, so far as the symmetry goes, of diatomic molecules. It was quite useful to do that. I also made, with Wheland, we wrote I think one paper in which we made molecular 00:21:00orbital calculations. So, in- and that was about 1933. In 1931, I published a paper, and Slater published a paper, in which we each said that the molecular orbital method and the valence bond method represented different zeroth-order approximations to its solution of the wave equation and that, if you added further terms to these zeroth-order wave functions, then the two methods became equivalent.

TH: Ah-ha.

LP: So, in 1931, the question of the relationship between the two methods of 00:22:00making approximate solutions of the Schrödinger equation were being discussed. And I think both Slater and I felt that the statements that we made just settled the question.

TH: Yeah.

LP: But then what happened is that the molecular orbital method is much simpler to handle mathematically than the valence bond method. It's a poorer order approximation, or zeroth-order approximation, but in the pre-computer days especially, it just wasn't possible to carry out valence bond calculations 00:23:00except for the simplest molecules.

TH: Ah-ha, I see.

LP: Whereas they could be carried out for somewhat more complex molecules by the molecular orbital method.

TH: Yes.

LP: The valence bond method is a better approximation in this simple form than molecular orbital method, but it's a more difficult one to make calculations with.

TH: Yes, yeah.

LP: That's why in our paper on heterocyclic rings... such as pyridine, Wheland and I didn't try to make a calculation using the valence bond method. We didn't 00:24:00have computers then and it would have been- well, we just couldn't do it. But we could carry out the molecular orbital calculations, which we did. So, I wasn't averse to molecular orbital theory. I made use of it. But I thought that the valence bond treatment of... molecular structure is far better for non-mathematical considerations than the molecular orbital method.

TH: Now, when you say better, define the term. Better in what way?

LP: Well... if you have a molecule of any complexity, a dozen atoms, say, it 00:25:00wasn't possible in 1930 or 1940 or 1950 or 1960 [both laugh] to carry out a quantitative solution of the Schrödinger equation, even by molecular orbitals. And if you did carry out a molecular orbital calculation, you'd get some number about single electron energy levels. The valence bond method is just... that is, there are two, two valence bond methods. One is the approximate solution of the Schrödinger equation, and the other is the semi-empirical, semi-theoretical discussion of the structure of the molecule.

Chemists make tremendous use of the valence bond method in the form in which I described it in my book, which doesn't involve trying to solve the Schrödinger equation directly. It's based on quantum mechanics, but it's largely empirically a refinement of the theory of structural chemistry that was developed in the 19th century. And the molecular orbital method just doesn't have any value in this respect. It's useful only for getting some numbers by approximate solution of the Schrödinger equation. It's very hard to apply it to a chemical problem 00:27:00in a meaningful way.

I point out that you have difficulty explaining why benzene is stable on the molecular orbital basis without presenting a rather thorough discussion of quantum mechanics. In the usual molecular orbital treatment, unless you know something about quantum mechanics, you expect eight electrons to give a stable ring structure rather than six.

TH: Ah.

LP: And that is there are four molecular orbitals in the pi type, and two 00:28:00electrons in each means eight electrons. So, a question comes up then: why is six stable? So, the people who do this stuff say well, you can write down these eight, these four equivalent orbitals, and one of them has no planes of symmetry, and the other three have planes of symmetry through the first and fourth carbon atoms, the second and fifth, and the third and sixth. They say 00:29:00it's true you can write down these equations, but if you check them more closely, you find that the three that have one plane of symmetry are not really independent of one another. There are only two of them that are inde- [sneezes] independent of one another. And this seems to me to be a fatal flaw whereas, of course, my discussion of the structure of benzene in a valence bond and a just resonance among the two Kekulé structures, and perhaps also the three Dewar structures, that's very simple and straightforward.

TH: Yeah.

LP: That you can put in freshman textbooks. Actually, the freshman chemistry textbooks, some of them discuss benzene and they just slide over that difficulty 00:30:00about having only two, rather than three, molecular orbitals with a single plane of symmetry. They sort of hide it so that a smart student who really wanted to understand things would just be stymied.

TH: Ah. But as-my understanding is that currently as far as- Actually, again, going back to the question of actually doing calculations that mathematically, because the MO, the molecular orbital method is simpler to use mathematically, that it's gained a certain amount of popularity just from that standpoint, just as a quantitative method for getting approximate solution.

LP: That's right. But during the last 10 years, a number of theoretical chemists, quantum chemists, have been carrying out calculations with the valence 00:31:00bond and-

TH: Uh-huh. Using more-

LP: -pointing out how good it is, and-

TH: Using more powerful computers?

LP: Yes.

TH: Yes, yeah. You had- what did you think of Mulliken personally? I understand he visited your- sat in on your lectures at Caltech at one point, and...

LP: No, I don't think that he did, or at least- well, I remember that he visited Caltech. The Mullikens left their little girl with us.

TH: Oh, yes.

LP: While they were away on a trip. So, she was with us a month or more. I don't remember how long. [Unintelligible] six weeks. And we saw Mulliken I think for the first time while we were in Munich. He and his wife came to Europe. He did a 00:32:00lot of traveling with his parents. He had been accustomed to traveling. He and his wife came to Europe each summer... I think, in '26 and '27. And then we were with him in Chicago and other places. I don't believe that he ever- I don't remember his coming to my lectures.

TH: What I had heard was that- from one of your former students, was that he remembered Mulliken coming in and sitting in on some of your lectures in the nature of the chemical bond class and that, according to this fellow's memory, that you were sort of poking fun at Mulliken and taking the fact that he was 00:33:00sitting there as a chance to poke some fun at the molecular orbital idea.

LP: [Laughs] well, maybe. But I would say that it was the sort - if this did happen, I don't remember - that I thought of it as a sort of friendly interchange of comments.

TH: Yeah. That was what the impression that I got was too, was that it was all in fun.

LP: Yes. And of course, we were in Iran together too.

TH: In Iran?

LP: Yes.

TH: Oh, what was that occasion?

LP: Well, meeting of the Iranian Chemical Society. We were all invited. Robert and his wife, and my wife and I were invited. And I... it seems to me that in 00:34:00Iran, Mulliken made some statements about deficiencies in the valence bond method [laughs].

TH: Oh, is that right?

LP: But, you know, he and I were somewhat different in temperament.

TH: How so?

LP: ...Well, he gave people the impression of being sort of rigid and... self-contained. Well, we got along well, I'd say, [unintelligible]. Actually, I was trying to think were there people that I didn't get along with - well with- [laughs], and Fajans comes up.

TH: Yes, Kasimir. Yeah.

Both: Kasimir Fajans.

LP: And he apparently was pretty irritated with me. I wasn't irritated with him, but then that's understandable, that his- he had been having difficulty in making progress in getting recognition.

TH: Yeah. Yeah, I've run across him in the correspondence with him, in which he goes over and over- I believe it was the structure of water, the water molecule entered into that.

LP: Well, I don't remember. He was something like Lawrence Bragg in that when quantum mechanics came in, he was the head of a big chemistry department. He was the professor of physical chemistry.

TH: Yeah.

LP: The Rockefeller Foundation built a building for him, an institute, and he 00:36:00told me that his doctoral theses, the doctoral theses of his students, had piled up during- so that he was three years behind the times in writing them up for publication.

TH: Ah.

LP: He just- this is in Munich, '27 or 1930. He just didn't have time to learn quantum mechanics. But it was evident that you had to know quantum mechanics, or that this was the way structural chemistry was developing.

Fajans and Grimm had published a paper about the electronic structure of the alkali halides, and of course, a year or two afterward, I published a paper based on quantum mechanics and completely different from what they had written. 00:37:00Well, we got along well with Fajans. Had dinner at their home more than once, and they, the Fajans family, loaned us a pair of skis that belonged to their 10 or 12-year-old boy for my wife to use. But then he did start publishing papers about what he called quanticules.

TH: Huh.

LP: Suggesting that he had a way of treating molecules quantum mechanically, and I can't remember the details. I wrote to him, pointing out what I thought were 00:38:00the... faults in his treatment, or the lack of sound theoretical basis. But during the last years of his life, he seems to have spent a good bit of time... trying to show that what I said wasn't right.

TH: [Laughs] yes.

LP: Yes.

TH: Yeah. Can you think of anyone else that you didn't get along with?

LP: ...Well-

TH: Besides the obvious people like William F. Buckley and Edward Teller.

LP: Oh, yes. Well-

TH: [Laughs] besides them.

LP: I was trying to think of people with whom I disagreed scientifically 00:39:00perhaps, and with the discussion becoming acrimonious. I don't know.

TH: What about M- tell me more about Maurice Huggins. Maury Huggins seems to have had complaints. I'm trying to think of where I was hearing about this. It may have been in the correspondence somewhere. There was some question about having worked together on a paper very early on. Pretty early on. And he was complaining about not being proper credit or something like that.

LP: Well, maybe. He and I- he had been interested in covalent radii. Well, he was interested in many of the fields, subject that I was interested in, and we 00:40:00published a paper together. A long paper on covalent radii in crystals based in part on some ideas that he had published earlier. And in the course of that work, I realized that there was some additional information about molecules that... constancy of the [stumbles]-in my opinion, a different method of attack on the interatomic systems problem. So, I published a short paper in PNAS on covalent radii of the atoms without... well, by myself.

TH: Uh-huh.

LP: It wasn't something that had turned up while Maury and I were working together. It was something that I thought of, but it was stimulated by this work on covalent radii crystals. The values of the radii - except for carbon and silicon - the values were different. Not the same set of values. And I heard that- I don't know of when I heard, but sometime later I heard that he had thought that he should have been a co-author of that paper too.

TH: Ah, I see.

LP: So far as I know, it was something that was an idea that I had that he had contributed to.

TH: Yeah, yeah. He was...

LP: So, he, when he got a National Research Fellowship about 1925, I think, he came to Pasadena, essentially to work with me. It turned out that we didn't publish any crystal structure determination together. He'd done some work. I don't remember what he did while he was in Pasadena. And then, he went to Stanford, and after three years, I think he- I don't remember where he- well, they didn't keep him on after three years. And they, actually they appointed in 00:43:00the 1930s, some years later, they appointed Lynn Hoard and kept him for only three years. He's retired professor. He's a member of the National Academy Sciences, retired now at Cornell, Lynn Hoard.

TH: Uh-huh, right.

LP: Probably part of the reason was that, in some chemistry departments, there was the feeling that X-ray crystallography wasn't really important to chemistry [laughs].

TH: Ah, uh-huh. The- hard to understand that attitude now [both laugh].

LP: Yes.

TH: Let's go back to proteins for a minute now. Again, I had read in an 00:44:00interview that you had given somewhere where you had said, "By 1934 very much information had been obtained about the dimensions of a great many rather simple substances, and for some reason, I decided the time had come for me to be interested in the very complicated molecules that make up the human body."

This is a discussion of your move out of simpler crystallographic problems into the more complex, larger biomolecules. And do you- we had talked a little bit about the hemoglobin work a couple of days ago and your interest in hemoglobin. I guess I want to make sure I'm straight on that. It sounded to me, from what we had talked about, that your interest was actually spurred by the magnetic studies in the iron components rather more than, perhaps, simply the question of 00:45:00protein structure, or that stuff. It's almost as though you sort of backed into that, the direction of looking at magnetic influences above the question of looking at protein structure. Now, is that sound right?

LP: Well, I think that's an oversimplification. Coryell and I, in our magnetic papers, discussed also the ionization of proteins, the acid-based relationship, titration curves. And I mentioned that I probably knew, in 1929 already, about Conant's stating that the imidazole rings of the histidine residues in the 00:46:00protein, the globin, were responsible for two different ionization, acid ionization constants. And we mention that. We discuss that, Coryell and I, in our papers in 1935 or '36, so that I was cognizant of the whole problem of polypeptides or other structures for proteins. And interested. And so, by 1937, I made the efforts to find the secondary structures of proteins.

TH: Yes.

LP: Unsuccessful.

TH: Yeah.

LP: And Corey, Corey also had done some X-ray crystallography on proteins when he was with Wyckoff. [Tape ends].

LP: -him where he'd like to go. They knew about me because I had got Mirsky. I'd gotten to the Rockefeller Institute to send Mirsky to Pasadena for two years-

TH: Yes, yes.

LP: -to work with me, and to support him, too. So, Corey decided that the thing to do was to come to Pasadena and talk with me about protein structure, I guess, 00:48:00in 1937. So, we formulated the program of determining the structures of amino acids and simple peptides.

TH: Yes. Yeah. Why- I'm interested in why, in terms of the macromolecules - apart from the work you did with Corey on the subunits - why you focused on some very complex proteins. The hemoglobins and antibodies, for instance, as classes of proteins are quite large and quite complex compared to, say, collagen or keratin, or perhaps some of the simpler structures. What was it that drew you to these more complex molecules rather than the simpler proteins?

LP: Well, I didn't focus on antibodies with respect to possibility of 00:49:00determining their structure, so far as the polypeptide chains go.

TH: Ah.

LP: In 1929, I had become interested in the whole general problem of biological specificity.

TH: Yeah, okay.

LP: This is what several of the-well, the geneticists, of course, their genetic investigations all dealt with the biological specificity. A strain of living organisms can reproduce a progeny year after year, for generation after generation, essentially identical. So- and then something happens, a mutation, and you get a difference. Perhaps a different species.

TH: And this is with-

LP: [Unintelligible] "specificity" coming in from the word species. In fact, you talk about species-specificity of hemoglobin, see.

TH: Yes.

LP: I knew the work of Brown and Reichert. I'm not sure about [inaudible]. I think that's right. They had published I think three big volumes that I saw about 1924 in the Caltech Chemistry Library, on the form of crystals of hemoglobin from the blood of different species of animals. Classical crystallographic investigation. So that even rather closely related species, a goat and a sheep, can produce hemoglobin crystals that differ from one another crystallographically.

TH: Yes.

LP: So, I knew there was specificity in these protein, big protein molecules, and I judge I was sort of thinking- well, many other examples, of just genetic examples, but you have the specificity in action of enzymes that will accelerate what a particular chemical reaction that - and sometimes not a chemical reaction - involving a closely similar molecule. So, I think I was sort of on the lookout of some more chemical way of studying biological specificity, and when 00:52:00Landsteiner talked to me in New York in 1936, I immediately, pretty quickly, at any rate, thought this is a fine technique for studying biological specificity by changing the nature of certain small molecules or the atomic groupings that are involved in the immunological reactions.

TH: Uh-huh.

LP: So, the work on immunology I carried out to see if I could find and be assured of a molecular mechanism that accounted for biological specificity-

TH: I see.

LP: -in this one example.

TH: Right.

LP: And that was thoroughly successful [laughs]. After the eight years when we were working vigorously on that problem, 1940 to 1948, at the end of that time there was no doubt that biological specificity, at least so far as it shows up in antibody-antigen or hapten interactions, is determined by detailed molecular complementarianism. Of course, already in 1940, just from Landsteiner's work, I had reached that conclusion, my 1940 paper...

TH: Yes.

LP: ...on antibodies that was based on it. And the paper that Delbrück and I wrote about...

TH: 1940, I think.

LP: 1940, yes. So, it took from 1936 to 1940 for me to, without doing any experiments of my own, to decide that biological specificity did not involve interaction of identical molecules, which was one idea that's been expressed. The gene forms a duplicate of itself, but rather interaction of a molecule with another molecule that is complementary in structure. So, the gene, you have to go through two steps. This is what I pointed out. The gene forms a dupli- or a 00:55:00complementary structure, and the complementary structure then forms a complementary structure to it, which is the original.

TH: Yeah, I thought that that was an amazing insight, and I don't think that that has been fully recognized, either.

LP: No, that's in my papers, or in a number of papers that I published around 1948. A number of addresses. The address that I gave at Leeds, the Sir William [sic, Jesse] Boot lecture, is a clear expression. But it was in a number of my other papers.

TH: Yes. Yeah, the immunological work is very interesting to me because of the- that's where I have some more expertise than perhaps in quantum mechanics. And 00:56:00the development of your work during the war period where you were handling not only immunological studies but doing all of the other war-related work that you were doing with blood plasma and explosives and so forth was an incredibly productive period for you.

LP: Yes.

TH: Yeah. In terms of the blood plasma substitute, I understand that there was a meeting just prior to America's entry into the war where a number of problems were outlined in Washington D.C.

LP: Yes, that's right.

TH: And was that-it was I believe at that meeting where you decided to work on blood plasma substitutes or saw that as an area of concern.

LP: Where I decided to what?

TH: Where the blood plasma substitute idea came up.

LP: No, I don't think so. We were presented- there were about 20 chemists there. 00:57:00Irving Langmuir was one. I don't remember who the others were. And we were presented with a list of about 20 problems that the armed forces wanted solutions to.

TH: Oh, it was the oxygen meter. That was where that-

LP: That was the oxygen.

TH: Yes. Yeah, okay.

LP: So, one of them was an oxygen meter that would detect, determine the amount of oxygen in a mixture of gases. So, on the way back on the train, I thought about these 20 problems, went over them one after another. And about halfway 00:58:00back to Pasadena, I thought of building the oxygen meter.

TH: That was a quick one [laughs].

LP: Yes. And within a week, we had built one of them.

TH: [Laughs]. And then Beckman produced those, is that correct?

LP: Yes. The institute arranged, at the end of the war, it was- we built them in the laboratory. Sturdivant and Wood were in charge, and we built several hundred of them. That was the secret instrument through until the end of the war.

TH: Ah.

LP: So, around 1946 perhaps, the institute made a deal with Beckman to manufacture it. So, the institute got some royalties, and Sturdivant and Wood, and I also got royalties.

TH: Sturdivant and Wood and you took out the patent on this device?

LP: Yes.

TH: Yeah. Tell me, what other things have you patented?

LP: Well, let's see. I patented, during the war, a class of composite explosives. Propellants. And it may be that they are used to some extent now. I never got any royalties from that because the government had an irrevocable royalty-free license, and nobody else was interested in the powder for propelling bazookas and things like that. And I patented... I think that one was just by myself. I patented, with a couple of other people in the laboratory, the oxypolygelatin.

TH: Oh yeah, yeah.

LP: I don't remember when I had the idea of making oxypolygelatin. Perhaps 1940 or thereabouts.

TH: And oxypolygelatin really never caught on, did it? As a plasma substitute?

LP: Well, it wasn't approved by the Plasma Substitute Committee. And it was manufactured for veterinary use. My understanding is that it's still being manufactured in some places, but I don't have information. The Committee on 01:01:00Plasma Substitutes said that it shouldn't be administered because it wasn't homogeneous, molecularly. It involves a range of molecular weights. I felt that what difference does it make if there is a range of molecular weights if it works?

TH: Well, it's not as though there aren't a range of molecular weight substances in plasma anyway, [inaudible].

LP: Yes. Blood in the... in the plasma, you have serum albumin with molecular weight about 65,000, and serum globulin with molecular weight of 160,000 [laughs].

TH: Yeah, yeah. Exactly.

LP: So, what difference does it make if there's a range of molecular weights?

TH: Huh. Now, what I had- when you talked with Landsteiner in '36 about antibodies, the note that I had is that Landsteiner had asked you to- about the question of accounting for antibody formation and specificity in terms of molecular structure. Do you remember, in your discussions with Landsteiner in '36, if that direction came out of his mouth, or was that your own insight?

LP: Well, my memory is that I didn't know about his work, except, of course, I knew that he had got the Nobel Prize for having discovered the blood groups.

TH: Yes.

LP: I don't think I knew more than just the most elementary aspects about- of 01:03:00immunology at that time. When I gave my lecture on hemoglobin at the Rockefeller Institute for Medical Research in 1936, probably August or September, Landsteiner asked if I would come to his laboratory the next day to talk to him. So, I said yes, and I went to his laboratory. And he told me something about what he was doing, making azo proteins by coupling small atomic groups onto a protein and injecting it, and then testing an antiserum by 01:04:00combination with these small atomic groups. And I was quite interested in what he was saying. I just didn't know very much. He said that he had called me in to tell me about this to see if I could develop an explanation of his observations.

So, I said I would think about it. I bought a copy of his book, first edition of his book on immunochemistry, and read it carefully and thought about it. And read other literature in the field. And by 1940, perhaps 1939, I had pretty much 01:05:00formulated my ideas about complementarianism and had eliminated, I thought, the idea that a molecule could direct the synthesis of an identical molecule.

Then, in 1938, before I had these ideas well-formulated, but while I was in the process of thinking about it, I went to Cornell. And Landsteiner came up and stayed for several days in- to Ithaca, just to talk with me about the same problem. Find out what my thoughts were. So, my thoughts were still somewhat 01:06:00confused, I think because of the fact that the immunological literature, just as with much medical and biological literature, contained contradictory statements from different authors. Even experiments that seemed to be- to contradict one another. And I have said that during these days, three or four days, I probably had the best course of instruction in a complicated field that anyone ever received.

TH: [Laughs].

LP: I could ask-I could mention to Landsteiner two different investigations that I was having trouble with, and Landsteiner would tell me that he had confidence 01:07:00in one set of authors but not in the other.

TH: Yes.

LP: So, I got some of these problems clarified by Landsteiner when he came up to see me in Cornell. That impressed me, too, that he would make a trip from New York up to Ithaca and stay for several days just to talk with me and find out what my opinions were. So, that's what happened. Then, in 1940... possibly 1939, '39 to '40, Dan Campbell came to work with me. He had been given a Rockefeller Fellowship to spend a year in Europe. He was Assistant Professor of Immunology 01:08:00in University of Chicago. So, because of the war, it was decided by the Rockefeller Foundation that he should not go to Europe, and I think they said the place for you to go is Pasadena, to work with me. So, during that year, he did work with me. We started some experiments. And he had to return to Chicago for a year. He felt he was obliged to go back. I offered him a job as Assistant Professor of Immunochemistry.

TH: Yeah.

LP: And I was able to do these things because of my Rockefeller money, and money 01:09:00from National Institute- National Foundation for Infantile Paralysis... as I recall. So, and perhaps... yes, I guess that that's where much of the money came from. Mainly the Rockefeller money.

TH: Uh-huh.

LP: So, then he came back at the end of the year, and we- and was involved in that expensive series of experiments.

TH: Yeah. Now, you- regarding-

LP: So, it was Landsteiner's idea that I see if I could understand, interpret his results on a molecular basis.

TH: Yes. In the immunological work, as it went along, you began, it appears, to 01:10:00take a view that antibodies could form around a substrate and take on a complimentary structure- say around an antigen, and take a complimentary structure that would account for the specificity of the reaction.

LP: Yes.

TH: Yeah, and that this occurred if-now again, this is me just working from memory here, so correct me if I have this wrong, but the theory was that the proteins, the globulins existed in a somewhat denatured form, and then as they formed around the-to create the complementary positions at the end of the globulin molecule, they-

LP: Well, not in a denatured form, but in a form that had not yet assumed its 01:11:00final structure. And this is called the instructional theory of antibody formation.

TH: Yes, yes.

LP: I'm considered to be its principal supporter at that time. And the alternative is the selection theory, the clone selection theory that we have the capability of making perhaps a million different kinds of antibody molecules. And there may be only a few cells for each kind, but stimulated by the antigen, the proper kind of cells begins to form a clone to produce the proper antibodies. And that's accepted now.

TH: Yes. And of course, it would have- at the time you were working on the 01:12:00problem, though, it was impossible to test adequately for the clonal selection alternative because there simply wasn't the genetic knowledge or the molecular biological technique in place.

LP: No. The... well, I think there's something to what I said, that I have continued to say, that cells manufacture the specific antibodies only in the presence of the antigen and that there's a complementarianism between the haptenic group and an antigen that stimulates the cell to produce the antibodies, and also to multiply and produce a whole clone of cells. But I think 01:13:00that also there must be haptens for the individual cells of the clone.

TH: Yeah.

LP: And some immunologists seem to question that. But I continue to feel that antibodies are produced only in the presence of the antigen.

TH: That in fact there's a strong instructional component at play.

LP: That's right.

TH: Yeah. The-

LP: The cell is instructed to produce its antibody.

TH: Yes. There was a debate over whether or not you had actually produced artificial antibodies.

LP: Yes.

TH: Yes, and you still, you maintain that in fact this- that this occurred?

LP: Oh, yes. Well, I say that we did succeed in producing artificial antibodies. 01:14:00Very weak ones, yes, but still with specificity.

TH: Uh-huh. And this was done by denaturing existing globulin and reforming it in the presence of antigen?

LP: Essentially, yes.

TH: Have subsequent studies borne that out? Have other people tried to duplicate that work?

LP: Yes, other people tried to duplicate it, and reported that they failed.

TH: I see.

LP: [Laughs]. May have been something like Don Yost on the xenon fluoride.

TH: [Laughs]. Now-

LP: And I never have felt that it was worthwhile to repeat the experiment.

TH: Yes.

LP: Partially, of course, because there was always something else that 01:15:00interested me more. But I did get one of my students to carry out a somewhat similar experiment with positive results. His name was Frank Dickey.

TH: Dickey with a D?

LP: D-I-C-K-E-Y. Frank Dickey. He was at my 90th birthday party. I hadn't seen him for 50 years, I guess [laughs]. So, what he did at my suggestion - he published his paper in PNAS - what he did was to repeat our experiment, but not using protein to make the antibodies, but using silicon. Sodium silicate. He 01:16:00took three different antigens and added... some of each of the three, to three samples of solution of sodium silicate.

Then he added acid to the sodium silicate so that the sodium silicate would condense to silicic acid. Hydrated silica gel. He dried the preparations to get 01:17:00a powder and eluted them with water to dissolve the original dye away. See, my prediction was that he would have then a preparation that would combine with the specific antigen. Then he determined the combining power of the three antigens with each of the three gels, silica gels, carrying out nine experiments. And each of the antigens combined strongly with its homologous silica gel and weakly 01:18:00with the heterologous.

TH: Huh.

LP: ...I've said antigens; they were dyes. Methyl orange, ethyl orange, and isopropyl orange.

TH: Yeah.

LP: Using these dyes with three different algio groups [?]...

TH: Well that, you know-

LP: That the dyes were to give, permit easy determination of the amount of combination, just by measuring the surface factor.

TH: Yeah. You know, and theoretically, you can see that using a sort of a homogeneous preparation, say rather than the proteins, using the sodium silicate as the pseudo antibody, you could see where the- it makes more sense to me to 01:19:00see that as, quote, "artificial antibody," end quote, than to think about using real antibodies and denaturing and renaturing them when we know now that the active site on the antibodies varies in primary structure; that the order of the amino acids is different in the active sites of different antibodies. So, I'm wondering, when you're doing your original denaturation, renaturation work, you'd be working with a diverse group of antibodies I assume, or did you have a homogeneous batch of antibodies that you were using?

LP: Well, they didn't have homogeneous then [laughs].

TH: No, of course not.

LP: For preparations then. Well, it wasn't the antibodies we worked with, but just globulin.

TH: Yeah, yeah.

LP: Gamma globulin from blood.

TH: Right. And then- but given the variety of active site formations that would 01:20:00have been present there initially, I guess you would have only expected a weak response since upon renaturation they would tend to form different active sites anyway, is that right?

LP: Well, the silica gel is sort of like a liquid, in not having a well-defined structure. And the denatured protein that folds up I would say is also somewhat similar in not having a single well-defined structuring, but having a great multitude of structures, determined perhaps largely by chance. But in the presence of the antigen, I contended, there would be this instruction on the folding.

TH: Yeah.

LP: Of course, I felt that Dickey's results were- just showed that I was right in contending that you can get this sort of instructional effect in which a molecular structure is made to be complementary to some atomic grouping.

TH: Yeah. And that still sounds correct to me in theory, that-

LP: What is?

TH: I mean, it certainly sounds commonsense that that sort of instructional event could take place.

LP: Yes.

TH: Yeah. Linus, let me ask you one last question about your wartime work. You said that when you got your citation for the Presidential Medal of Merit, the-

LP: Medal for Merit.

TH: Yes, for Merit. The citation mentioned some things, but you had said in an interview that it did not mention the most important of your contributions because they were classified at the time, in terms of the wartime work. Is it possible for you to outline what those contributions were now?

LP: Well... Paradowski says that I was in charge of 14 different investigations. And someone connected with the War Department came to see me a few years ago, perhaps only three years ago. Duncan. I'm not sure that that's his name. I hadn't seen him since the war, but he said my most important contribution - and 01:23:00Corey and Verner and many others were involved in this work - was on the stability of double base powders. Nitroglycerin and nitrocellulose powders; that we found a much better stabilizer than had been used, and that this is used in all powders now.

TH: Ah, okay.

LP: So, I didn't take out a patent on that. We set up a laboratory, an installation for measuring the stability of powders at elevated temperature, so that we could speed up decomposition, and carried out chromatographic analyses 01:24:00to find out what was happening to the stabilizers and other powder constituents. We sort of revolutionized powder chemistry by introducing chromatographic analysis.

TH: Aha.

LP: Then I was approached with the problem how can someone who wants to communicate with the government send a message, let's say in the form of an ordinary letter, a sheet of paper, that no one would be able to decipher?

TH: An unbreakable code.

LP: Yes. So, I had an idea, and we worked for two or three years on this, and then one of the people with me was disappeared from view. He was taken by the government. So, my secret writing, I don't know what happened to that. And I still don't say what the method of secret communication is.

TH: Have you ever had a chance to use it since then? Was there anything you wanted to transmit in code?

LP: No. You have to set up the system. I have several books, research books, containing messages that were written and then transcribed, but I never heard 01:26:00whether this was used or not. Although, I did turn over the materials to the government.

TH: So, the powder, various kinds of powder research, and propellants and explosives. The oxypolygelatin work, the oxygen meter, the immunological studies, and the coding work, secret writing. Anything that falls outside of those categories?

LP: Well, let me see. I had Bill Lipscomb working on a separate contract dealing 01:27:00with aerosols, determining size distribution in aerosols. And I had Kent Wilson - no, not Kent Wilson - Norton Wilson, I think, working on the project of growing aluminum phosphate crystals to replace quartz crystals.

TH: Oh, yes! Oh yeah, I saw mention of that somewhere.

LP: ...Well, what the 14 projects were that Rob Paradowski referred to [inaudible].

TH: Yeah. We can figure that out. Well listen, this is terrific. I won't take up any more of your time today, but I'm glad that we had a chance to talk...

LP: Okay.

TH: ...a little bit more, and maybe I'll check in with you next week, see how 01:28:00you're feeling.

LP: You could look up the paper by Frank Dickey.

TH: Yeah, I will do that.

LP: PNAS about 1940. Well, early 1940s or-no, late. About 1948 or '50. Something like that.

TH: Yeah. I will take a look at that. Okay Linus, thanks so much.

LP: Very well.

TH: Bye-bye.

LP: Bye.