Interview with Archer J. P. Martin edled by
ROBERT C. BRASTED
ARCHER J. P. MARTIN Department of Molecular Unwerr~tyofSussex Sussex, England " "
Department of Chamlshy Unwersty of Houston Houston. Texas
by G. Allan Stahl
University of Minnesota Minneapolis. Minnesota
PETER FARAGO Burlington House London. England
Stahi: Dr. Martin, please teil us about your early life. Martin: igrew up in London. Mv father was a general~hysician;Iremember from as ear& as / can, behg faschted to watch anv workmen that came to the house, to remir anything. I k u i d stay with them as iong as they were there and abs& everyihing they did with w t detail. I am told, though i don't re&mbe> it myself, that at the age of 5.1 was replAing tap washem having the maids unscrew the tap which was beyond my strength, but directing the operation and putting the washers on. Stahi: Was there any event or person who led you to your career in chemistry? Martin: i got my beginnings in chemistry from my ywngast sister who was five years OWthan myself. W n g the war. abouf 1915 or 19 16. mv sister and I keut hens, which we sold to mv mother. My father believed that it was very bad to give any simificant amount of monev to children, so we were aiwavs ~ r y s h o r t o f ~ e t m y , ~ a n d w e h a d t o e a m i t s - wiy. And so we kept hens; we spent the proceeds from seiiing the eggs on buying chemi&ls anddoing chemistry She, the time, was 11and had just started chemistry in schwlso she hada textbook In chemistry. and. together. we set up a laboratwy in a tiny potting shed which must have been about 7 feet by 3 feet. w e did= great many standard things. I remember that with the hens, we reared the hens from chicks. or from eggs, and we incineratedour first lot of eggs,having tried to keep them warm over a gas ring. Our next effort using a hot water tank as the source of heat, succeeded in hatching the eggs. Staht What sort of student were vou. Dr. Martin? Martin: Well, I have no difficulty &&er with arithmetic. But i didn't leam to read even a comic until I was 9 years old. And i imagine I must have been dyslexic because three of my four children show some dvslexia to varying . . dwrees. . Staht Did anyone or anyfhing influenceyou in school, or particularly develop your interest? Martin: Yes, i went to Cambridge with the intention of becoming a chemical engineer. There was no chemical engineering course: and I itwught I would do a nahvai sciences t r k u s e for the part one, which you could do in two yean or three years. So i took chemistry, physics, mathematics, andmineralogy for my part one course. Then while i was working on my undergraduate course \met J. 8. S. Faidam who was then not a professor, but a reader in biochemistry. Haidane invited me to visit him on Sundavs. On Sundavaftemocn he hddopen house f w a number of undergraduates, and I went there very often. Mv invitation was indefinitely extended. As a result, I t w k up bicchemistry instead of engineering f a' the m r t two m r t of the course. Stahi: ~ h d y o teil u us more about your days at Cambridge? Martin: i hadn't done parf one biochemistry which normally took two years, and during a long vacation between the end of the spring term and the beginning of the autumn term. I read up parl one biochemishy in order to take the part two bio-
ef
80 1 Journal of Chemical Education
interviewed by
I
G. Allan Stahl University of Alabama University. Alabama 35486
1
chemistry the succeedingyear, This was quite toughgoing. I didget a degree in part two biochemistry, but it was a 2-2 which is a poor degree. Iiike to think that this was because in fact I was very depressed in the third year I was at C a m bridge. I'd been subjected to depressions througbut my life. Thev would come for a vear or 18 months and 40 awav for a few years. During that period I was pretty useless. i didn't receive treatment which was effective until 1968; and by taking the right monoamineoxidase inhibitors. I've been brought onto a pretty normai keel. Stahi: What did you do after graduation? Martin: Well, first I waked with F. P. Bowden andC. P. Snow, In 1932. They were under the cinious misapprehension that they couM clean up a great deal of biochemistry by measuring a few ultravioiet absorption spectra. When ijoined them they had just attained local fame by claiming to have convertedcarotine, befacarotine, into vitamin A with ultraviolet light in an anaerobic atmosphere. After i joined them and heard abwf this in more detail, heard for the first time that they claimed to have done it anaerobically, lasked them where they thought the oxygen, the hydroxide group canfe from, because there was no water in the system in which they had irradiated it, and thevairlvdismissed the problem by . saying . . that they were convinced that vitamin A hadn't any oxygen. i was asked to build them a 30 kW hydrogen . . lamp; . they had a very nice momhromatof, and they were going to use this 30 kW hydrogen lamp in conjunction with the monochrometer to select any wavelength mmugh inadiation of various substances. Well, they designed it themselves and it was a hopeless design. i buik this ming four times andafter anyfhing from two to ten minutes running it always cracked, though it was immmed in a 70-gal tank of water for cooling. At that stage I suneededin transfefring to the Nuiritimi labmatory under L. J. Harris. i may say that doing research at aii was pretty difficun with a 2-2 degee. Nobody in the biochemical school itself would have me with a 2-2 degree. And it was only after Haidanes recommendation, who was surprised that I didn't get a better degree. Stahl: How long did you work at the Nutritional lab? Martin; I wnked there from 1933 to 1938. To begin with, I worked with Tommy Moore on trying to isolate vitamin E. We didn't succeed in isolating vitamin E; it was isoiatedbysomeone else befwe we succeeded. But while I was W e , we didget some enriched fractions, and we published the first absorption spectrum of vitamin E. I built countercurrent apparatus of my own design with 200 iheoreticaipiates. With that we were fint to demonstratethat there were three distinct varieties of vitamin E. Stahi: When did you join Sir Charies Martin and complete your doc-
-
~
just to keep the balance dry. We packeda %-in. diameter torate? Iassume there is no relalionship. tube; lsuppose the column was about 15 centimeters lona, Min: ~ , w ~ ~ ~ . A t ) e r w f i n i s h s d o t f M e w & m v i t ? m i n and we ran chloroformdown th~s,andaddedouracetylammo E. Igot a grant through Sir Charles to do work on the antiacn's to the top Th!s experiment was done ona Fu&y Over pelegra factor in pigs. Ikept 30 pigs for three years, until I the weekend Synge decided that methyl orange was a suitfinished my degree in 1938. By keepingpigsImean Ilwked able indicatw. On Monday we set up our column with methyl after them w!~olly,made up their diet, cleanedout thepens. orange, put on acetylalanine andacetyl valine which formed and even rigged up my car to pump out the sump when the a bright redbandat the top of the column andon developing sump became Waf sewage from the pigs. We were trying this with butanol. we saw the two bands seoaratino deliohtto isolate the antipelegra factor. but before we'd done it. " fully, the alanine movingprobably twiceas fast as the valine Overton discoveredthat the same disease in dogs. called and we were in business straioht awav: black tonoue. was curable bv nicotinic acid. So we tried . we simolv , had to collect the liquids. While the red bands were running out of nicotinic acid on our pigs. We had one pig which we knew the coiumn, we fitrated them. We hada most remarkably frcinexwience wwM die in a muole of davs: it hadn't eaten simple piece of apparatus. It was a better device than the for a couple of weeks, and we injected 60 mg of nicotinic machine which we built over a couple of years, and had to acid. Within a auarler of an how the oio was ravenouslv sit and watch for a week at a time for an analysis. hungry and ate till its sides bulged. It i a i a great Stahl: What was the response of scientists to such a great leap forworking with Sir Charles Martin, He hada thoroughness of ward? approach. I'm sure that it was a great assistance to me. He Martin.' We were rather disturbedto find that when we gave the paper was a man with ~etiwpsIshould say, a luminously simple to the biochemicalsocietythat itpro~kedn~discussionat mind. Whatever he said was entirelyandreadily intelligible; all; nobody appeared to be in the slightest interested. Still he could explain exactly what he meant and his concepts later, the first paper we delivered on the subject of paper were always perfectly clear. Mhe advisedan experiment it chromatography raised not a flicker of interest. always seemed to give an a mwer. Staht HOWdid this subseouentlv Stahl: Sir Charles and Heldane then playeda great part in rounding . . iead to the develooment of oaoer . chromatography? you out, preparingyou for what came next. Martin.: We found we couldn't do the acids with two basic -arouos Martin: Yes. Andit was through Sir Charles that Imet R. L. M. Synge. . or with hydroxy groups very sat~sfaclorilyon the sdica. So, we lstartedworking with him while Iwas still working fora PhD. hunted round for anofher matenal Ne deccrded to use celHe had an Australian governmentscholarship to investigate lulose: we decjded that rt was much easrer to use paper than the distribution of amino acids as their acetyl derivatives to pack columns with cellulose powder. But /hen .ve hadno between chloroform and water. Sir Charles brought us tomethodofdernonsfratrng the amino acid So, to begrn with. g e m so that we c w M discuss my cwnfercwent apparatus which was what was ne&ed for this type of separation. Well, quantitativeaspect. we saa. "well. we won't worry about there was absolutely no apparatus available for counterbut we'll content ourselves with qualitative work." A. H. current extraction. ihad to develop a fresh instrument. The Gordon hadcome to wark with us by this time, and we sent instrument Ihad made was suitable for cyclohexane and him to Idup ail the reactions in Beilstein which gave colon methanol, but not for chloroformand water. So we collabofor amino acids. We decided that the most satisfactory rated on a new design of apparatus for that process. Icab substance seemed to be ninhvdrin. We soraved . . the oaoer . mlated that a 40-plate pocess wouldbe em@. Before this with ninhydrin, and found that we could see spots of about machine with Synge was finished, fhad movedto the Wool halfa m i c r m m ofamino acas. This was two orders smaller Industry's ResearchAssociation, again on the recommenthan the amount we were using on the silica column. This dation of Sir Charles Martin who was on the board of govinvolvedquite a number of changes in technique, and to begin e r m as the Australian government's representative. When with we just ran them on strips. Then one day it occurred to completedthe machine gave difficulties so Icarriedit on my me that we could run two dimensionals on .DaDer . with two car, on the running board, from Cambridge to Leeds, a 170 differentsolvents. And lhar this would be a great advantage mile journey, at about 20 miles an hour; we set if up at the because lhere was no smgle solvent which would separate Wool Industry's Research Association and ultimately did a k comnwn amino acids Fventually, ths first experjment all t very successful separation of the mnoaminomonocarwe nied iw hvo aimem~onswas fo do eleclrol,hwes~sin one boxylic acids. The machine was a nasty one to work with; directionand chromtcgraphy in amther We rsolateda band you had to nurse it for a week while it was running, andyou across a Org sheet of filerpaper by two lines ofparaffin wax. became intoxicated with chloroform vapor. separated by a centimeter. We then put a sodium acetate Stahl: How did these countercurrent apparatus lead to partition buffer on the band between the paraffin wax lines. put the amino acid mixture in the middle andapplieda potentialof chromatography for which you shared the 1952 Nobel Prize? E = 10. Then the acid moved to the anodes and the three bases to the camodes while the monoamino/mmrboxyIic Martin: One day. Iwas thinking the fundamental problems of doing acidstayed in the middle. countercurrent work which were that youneededto get the Staht Is this, to your knowledge, the first known time this type of exdrop size as small as possible of one phase in the other in periment was performed? order to get rapidequilibration, but you neededthe drop size Martin: Yes. Ifwnd the eiecmhwesis as Iwas doim if-nd Iwasn't as large as possible in order to get rapidseparation of the phases. And wimcut buildings centrifugalmachine, this was aware of others doing electrophoresis i n paper at the time--was less reliable than chromatosraphy. So Iwent over exceedinglydifficult The centrifugalmachine to cany 200 theoretical plates wouldbe a formidable piece of apparatus. to chromatography in both directions, first ofaN with phenol, It suddenly occurredto me one day that it was quite unnacwhich separated the amino acids, and then by running .at right angles in coilidine. The common amino acids were entirely essary for me to fry and move the 2 solvents both of them separated into a characteristic pattern, and you could just in opposite directions. If Iwas to fix one of them, then the look at the patternandidentify all the common aminoacids other one could pass through it and Iwould still have the by that picture. Ican remember the first perfect chromatocwntwnnentprmess which lnseded. So,lremgnidthat gram we got on bothsides. This t d overnight for the phenol this was merely another variety of chromatogram. When i and two days for the collidineand we had to come in anddry finally thought that this was what lneededto do with solvent the oaoer in between. We made boxes with controlled countercurrent extraction, the idea immediately occurred of just absorbingif in silica gel. lsoggestedfhis to Synge wtw ato&here in which we couldhangthe chmmatogramshom a olass. A number of mechanicalomblems were encounagreed enthusiastically. The next day we took some silica twed We hada c w i m difficutiy Gich to be specific gel which was residingin a balance case in our laboratory.
-
-
-
~
.
.
.
Volume 54, Number 2 February 1977 1 81
to our laboratow. When we ran the amlno acids in phenol, below the blue&h which ihe nlnhydrin gave we $uldsee a kindofpink beard: if you imagine the blue s p t a s the face, there w& a long pink beardbeneaih It. li t w k us a very long time to find out what this was due to. The answer eventually came when one evening I was investigating the change h the rates of running on the paper by including ammonia in #?aatmasphere wng phenol. W t m we lwkedat the paper the next morning it was covered wiih dark spots, very very &rk spots indeed. WeSuWenlyrealired that we were dealing with a catalytic effect due to metal ions on the paper. We searched the literature, and found indeed thatphenol is oxidized in the presence of ammonia to give a dark colored compound in the presence of copper. Our laboratory was hrN ofpartlcles of copper whlch came both from the Leeds atmosphere-ihere was a copper works quite close to usbut also, chiefly, fmm a badly sparking commutator of the motor that we used for driving the fan in the drying box for the paper chromatogram. The time we were doing fhis was during the '40's. WWII was very much still on. We had to use anv OMeouiomeni that we m I d find or build. and his w .o e r problem &s the explanation for the pink "beard" under the spoh. The copper complex of the aminoacidran faster than the amino acid, and ihe color it gave with nlnhydrin was pink instead of blue. Therealter we had to include in the atmosphere in the box some substance whim wwM complex wi6, the copper such as cyanide. Slahl Is th,s the work for whtch youandR L M Synge wereawarded the Nobel Pnre m 19521 If so, how dld dl lead to your vorC in the discovery of gas chromatography? Martin: Yes. we were awarded the Nobel Prize in 1952 for~artition chromatography, which covered both the original sNica column work and paper chromatographv. Throuqh the use of paper chromatography we had reduced the fime for a qualitative analysis of proteins from about two man years, which it twk by the m e w before we started, to ihree &ys with two man hours of work. We reduced the quantify from haMa kilogram of protein to about half a milligram. Later, when I went to the National institute of Health in 1950, working with A. T. James, we developedgas chromatography. Synge and I. in 194 1, in our first paper on the silica predicted that gas chromatography would be possible and it would have many advantages, such asspeed. Stahl: And no one followed up on this? Martin: No one followed up until lstarted my work at the National InStifUte with Popiax, hebinq . .him in his analvsis of the fanv acids. He was Investigating the biologicalsy~ihesisof amino acids in mammals, andhadfeda goal wiih radioactive acelale was necessaty lo achievea very mmplele separalm. This was my iirsl real practical appl!cat,onand need for gas chromatography James and I succeeded in making it work inaboul eight weeks. By that rime we hadseparaledalilhe isomers. the fany acids up lo C, anda mixture of some 20 am~nes,something which was a1 that lime impossible by any other means. Stahl: What did you use for a detector on that first gas chmmatograph? Martin: Titration. The gas was bubbled into a test tube containing an indicator solution, and when the color of the Indicator changed, a drop of alkalior acid, accordlno to whether one was separating amines oracids, was dropped in. In the first experiment James sat beside me with a stop watch, and timed the drops and recorded it on graph paper, and Iput in the dmps when the indicator changed color. We .wt perfectlv satisfacrory separations which &re qwntitahe t o abmi 1% and the whole apparatus could be made, if you lefl out the stopwatch, for half a dollar. Stahi: Wouldyou describe your work in the development of electmphoresis ? Manin: Well. I started working with elecirophwesk when I was trying to isolate the antipelegra factor. I made a muliibaih and cell wiih cellophane membranes hanging as a succession of
.
-
82 1 Journal of Chemical Education
shallow basins each of whlch dlppedlntoeach offwand wi6, liquids being pumped through as a callout. You could then Impress a very large current Andagain, because of s h g e of funds, I'd had to make everything myself: I even had to blow my own mercury rectifier to supply the current. This apparatus worked, more or less, but i didn't understandhow to obtain a pHgradiant which was what I wanted, actualiy I never succeeded in doint this. The need for the apparatus ended when the nicotinic acid was discovered. But I stM t d an intwestln elecbOphoresis to the W w l Industry's Research Association. lrebuilt a similar piece of apparatus to try and isolate a peculiar basic amino acid from elastin, until the director of the association told me that this was going t w far horn waolandl was wasticgmytime. Reacld wasrremr identified. Later, when we were doing the work on separation of ihe pept&s, we needed mwe ihan paper chromatography for the separations, so I developed chromatography in slabs of Silica Gel which was the first varieiy of zone separations that I know in a gel layer. This was a very simple and sucCessfulpiece of apparatus. Wlth A. H. Gordon and R. Conston, I published a theory as we had done with the chmmatography. ialso workw'on oiher methods of electrophwesis during this period and began work on the displacement electmphoresis and demonstrated that I couldseparate sodium andpotasslum with a nice front. This apparatus was t w Clumsy so just before llefl the Woolldustry's Research Association, I set it up in a form much more similar to the present day form of displacement electrophoresb. i used long capillary iubes and with high voitage sources supplied. in fact, by war surplus dynamos. Stahl: Well, p r e g a r d p r s e l f a s a b i o c h s m ~ t ; ~ s o m a n y o f ~ conhibutions are in the analytical field. Do you think a scientist should be multidisciplinary? Martin: I think it's a matter for the individual scientist. As Isay, I was interested in engineering from my earliest days; lhada gwd knowledge of mechanical and electrical engineering, and a reasonable one ofphysics. So I was able to wwk in aiifhree flelds. While I was stillan undergraduateidevlssd techniques to help my sister, who was a PhD shldent in c~tallography, to grow anddo crystalstudies on very hydroscopic crystals of the trihalides (encapsulated in glass) of various metals. i devised a method for detecting pyroelectriciiy by putting certain of these crystab in liquidair andseeing whether they wouldadhere to their elechic image in a metal plate. Thai's a method thai's still in the textbooks. though it was done as a first year undergraduate. Staht Can yousuggest changes in the structure of the chemishydepartmen!, or even in the University, that wwld produce greaterproductiviiy while maintaining betterandimproving the quality of education? Mariin: I think it's highly desirable that courses should be made that stimulate thlMing. One is not stimlated to think in University courses that seem to be mostly potted formulae. In Cambridge, both the lectures and the laboratory work were very much concentrated on the fundamental ideas behind what you were being taught. I feel the buildings in American UnC versifies are altogether too luxurious and that the money Is being wasted instead of being spent on people which are more important than buildings. Stahl: Or. Martin you've now had the unique opportoniiy to compare the European educationalsystem wiih the American. Could you do that? at the m n f is b&gahr& Martin: The English system of &tion under political pressures, to be very much more similar to the Amerlcan system. And in my opinbn itS being ruined The selection ofpoplls intogroups ofability is being largely abolish&; veiy wide ranges of abilityare taught in the same class which I think is a basically most undesirable method. The result is that the poorest student usually learns nothing at all, and the best students don't learn nearly as much as they should, andgetprofoundly bored. Whereas, ifyou have proper segregationp can make sure that all m e capable
of leamino to read do so. and can do simole arithmetic. Whereas &se who are &able ofgoing fukher can move reasonably fast and their interest in schcol is maintained. Stahl: Are there special respoll~lbilltlesa scientist shouldbear toward society Other than those normally encountered in the c o r n munity? Martin: I think not. Scientists making badpredictions are w e than scientists not makino oredictions. And most anv . imole. mentation of socialmeaswes has to be underiaken bypoiiticians anvwav. . . If a scientist wanh to olava . . .mlitical~artas well as a scientific pafi, he just has to become a politician. Staht Then he's no longera scientist? Mariin: Not as a poiitician. Sfahl. Can a scienttst make a good social or political leader? Martrn I thmnk rt's mprooable The scentwt normally has too much concern for truth. He will be an inefficient politician. Stahl: Many gwdscientists have immigrated in their younger years to this m h y . !Waf is bringingyw to this country aftersuch a long and distinguished career? Martin: Weli. I had many opportunities to immigrate to this country, butl~thatlhsdapabioticdufvtostayinEng~ndtohya~ he10 the English scene. Now, the situation has c h e n d : A. in England me situation has become quite appalling&~dthe poiitical direction is such that I can only fwsee disaster, and B. Houston offered me a post without a retiring age. Stahl: This is the Robert A. Welch Foundation Chair? Marfin: Yes. The opportunity to continue work with a well-equipped labaatory is exiremely importam to me. I have enough ideas to keep me going for however long I live, and I hope I can continue to do useful work for many years. Staht Do you feel that there's an optimumage at whicha scientist is most productive? Martin: Well, I think probably one's intelligence decreases from the late teens onward but that one's knowledge increases thrwshwf this pwnd which gives one some balance. i hope I can continue to work as effectively as Sir Charles Martin did; he was stillactively at work in his 80's. Stahi: What activities do you Indulge in besides scientific research? Martin: in my younger years I went in for mountain climbingandjudo and gliding. But these days I can do very little except research. Stahl: Have your interests hadan effekf on the education or the profession of your children? Martin: Very little I'dsay. None of my children wants to pursue a research career.
-.
Stahl: What are your current research interests? Martin: Well, I have a number of very diverse ones. One is to test out a hypothesis I have for the sense of smell. This would inM)Ive separating what I believe would be the sensitive materials for the different smells, dlfferent odorants, from oilfactory tissue. Another one is to develop the technique of microengineering. I've already spent five years of my life trying to do this. i believe that it can be possible to make a very sophisticated micro-manipulator with which it would be possible to do most of theactivities that one does with one's hands, on a smaller scale. And most importantly, to make smaller micro-manipulators, so that one could work successiWcbwn h scale. Atpresent I'malso hying to improve the technique of protein isolation, and to employ these for the isolation of a number of hormones, particularly those concerned with diabetes. lalso have an interest in an antiInflammatory substance which I think is not currently recognized. Stahl: What do you feelare the majorproblems confrontingmankind at this time? Martin: 1think ovwwheimingly the most importantproblem in the wwM at the moment is human population. ft seems to be that, like every other species, we have to limit our population. Of course Malthus will eventually limit the populalion, but we shallallbe exceedinglyunmmfombleif we leave it to natural fwces. We should take a hand in our own population control, and it wouldseem to be wholly ridiculous just to reduce the fertiiity of everybody. We should select the better members of society to survive. The method that I wouldsuggest would be to offera volunfary bonus to anybody except those below a certain age to get themselves sterilired. 1 think in this way it would have a rapideffect in removing those who foundlife difficult in various ways. The bonus would be more attractive. Stahl: Professor Martin, based on your wide experiences, whatadvice would you give a youngerperson just begining a career in science. Marfin: The advice you give depends on the individual circumstances. That which fits one doesn't always fit another. fdy career has depended totally on chance. I've applied for a number of completely dissimilar jobs, andhad 1gotton one of them, my life would have been different. For example when with Sir anxiow to apply for a job as a chemical Charles Martin, 1I engineer, Sir Charles was against it and engineered my joining the W w l Industries Research Laboratory. Without his effoiis, I might now be an engineer. 1 must say that I feel the most important consideration should be the long term result.
Volume 54, Number 2 February 1977 1 83
