Cecil Cummins, Emeritus Professor, Anaerobe Lab
Name of Interviewee: Cecil Cummins, Emeritus Professor Anaerobic Microbiology
Interviewer: John Hess, Professor of Biochemistry
Date of Interview: March 17, 2005
Location of Interview: Sound Booth, Media Building, Virginia Tech, Blacksburg, Virginia
Hess: I am John Hess, and I'm here to interview Cecil Cummins who was a member of the Anaerobic Biochemistry Laboratory called the Anaerobe Lab in the 1970s and 1980s. I am a former member of the Biochemistry Department, and because there was an affiliation of that program with biochemistry, we are making efforts to preserve some of the history for that group.
Cummins: I am Cecil Cummins, and I was a part of the Anaerobe Lab between 1967 and when I retired in 1989. I am here to restore some memory to myself and to John Hess about what used to go on in the Anaerobe Lab during those years. I have some papers here that I will be discussing with him. We will try to find out what actually did go on because it is quite a long time ago now.
Hess: Thank you Cecil. I would like to start by looking back to some of your career before you arrived in Blacksburg and how your interests ultimately crossed with those of persons in the Anaerobe Lab.
Cummins: Well, my original degree was in medicine. I graduated from Trinity College, Dublin (Ireland) in 1943 in medicine. I never did much clinical medicine; I quickly got into laboratory work, and I was a pathologist in the Royal Army Medical Corps for a time at the end of the war. Later for a couple years I was in Palestine with the British forces. I was in charge of a hospital laboratory. When I came back to England, although I was originally from Ireland, I had a job in the London Hospital Medical College, which is in the East End of London. I was employed as teacher for medical students. This was a medical college with medical and dental students. We also had a nursing school. I used to help to take part in the teaching of microbiology to all those three groups, although it was primarily to the medical students.
At the same time it was quite a nice job because we actually had what you might consider three months on and three months off. There were two courses in the year, each of which lasted three months. The other three months you were free and, in fact, expected to do some original research. So this schedule gave you plenty of time to keep that going. In fact, during the three months you were on, you weren't on all week—you had several days free. It was quite easy to do research as well as take part in the teaching.
I got interested in the surface antigens in bacteria. I was looking at the various corynebacteria, and we were trying to find out how many groups there were. In the process for these organisms, it was not very easy to get a useable agglutinable suspension. They tended to be what you called rough. In other words they would not form a nice smooth suspension in water. They tended to auto-agglutinate.
At that time there was an Australian in Cambridge, England called Milton Salton. He had discovered a way of breaking up bacteria by shaking them with very small glass beads, about 100 micron size glass beads. So I tried this to see if I could get useable suspensions for agglutination tests by shaking these organisms with these small glass beads. We discovered rapidly that this totally changed all the properties of these things. In fact they did become suspendable, they gave a smooth suspension in water or saline. But their reactions were all different.
I eventually got to know Milton Salton quite well. He had discovered what had gone on. The shaking with the glass beads simply breaks the bacteria. So you had only the insoluble part of the bacteria, which is the cell wall. So you get a suspension of cell wall fragments, and these are much more hydrophilic than the original organisms, which had a lot of lipids on the surface and so on. I suddenly realized that by shaking these things you could get a suspension of cell wall pieces, and that gave quite good evidence that there were widely shared antigens in these organisms.
Hess: What particular diseases are related to these organisms?
Cummins: I originally started working with Corynebacterium diphtheriae, the causative organism of diphtheria. I was interested in determining whether there were different antigenic groups among these organisms. There was some evidence of this, if you used whole cell suspensions although they were difficult to work with for reasons I've given. When you made cell wall suspensions everything reacted with anything else. So what you were doing as the cell walls broke you got internal surfaces and surfaces at the sides, where the cell wall broke. You got new surfaces exposed, which not only were more hydrophilic so that the organisms gave you a smooth suspension in saline but also you had exposed these new antigens. So that was what we started off with; I discovered we were making cell wall suspensions.
I had a good friend in the Biochemistry Department there, Harry Harris. We hydrolyzed some of these materials in acid. He was in at the beginning of paper chromatography. I gave him these things, and we discovered some rather strange components in these cell wall preparations. Things like diaminopimelic acid, which apparently only occurs in bacteria. It had been known before, but it had not been associated particularly with the cell wall fraction, as you made it like that. Then we discovered that you could treat these things with say trypsin or pronase or pepsin, and you simplified the pattern, the biochemical pattern that you got when you hydrolyzed it. But these things, the antigens we were working with were still there. These were presumably polysaccharide antigens. It also became evident with a number of different corynebacteria there were similar patterns of rather unusual components like arabinose in sugars and things of this kind.
Diaminopimelic acid exists in both the meso- and the L- form; you have these two different isomers, which you separate chromatographically on paper. Some of these organisms had one, and some of them had the other. Then some had lysine instead. So patterns began to become evident, and it became also evident that if you looked at a lot of streptococci, you found hardly any of the components that you found in, say Corynebacterium diphtheriae, but you found rhamnose as a characteristic cell wall sugar. You didn't find diaminopimelic acid, you found lysine.
So it became evident that this had a taxonomic implication. You could say, well this thing isn't at all like a Corynebacterium. There was one corynebacterium, called Corynebacterium pyogenes, which, in fact, had a pattern similar to the streptococcus rather than corynebacteria. Corynebacteria were a very wide genus at that time—it really was only organisms that stained irregularly. They were not nice straight-sided, square-ended bacilli. They were very irregular looking organisms, and this was about all they had in common.
When we came to examine a wide range of these things, there were several different patterns of cell wall components among the organisms that were called corynebacteria. So this is how I got into the business of using cell wall structure as a thing that had taxonomic use. Harry Harris and I published several papers together. I knew nothing about the chromatography, but I used to make the cell wall fractions and hydrolyze them. Then I would give them to Harry.
In those days we ran them on big sheets of paper about 24 by 36 inches. He had a set up to do that. He had a big grant from Rockefeller. He was a biochemical geneticist; he was interested in the application of patterns of amino acids in urine from children with strange syndromes.
Hess: Well this is a good reflection that interdisciplinary work was characteristic, probably, in every age of our science.
Hess: We talk about it now, but what you have reflected on is your ability to deal with the microbiology and the preparations and dependence on analytical techniques. The period that we are talking about here then is from the late 1940s to the late 1950s?
Cummins: Right, I went to the London Hospital in 1949. We published the first major paper about the use of cell wall composition as a taxonomic indicator. I think it would be probably 1955. It took a while to gel, you know.
Hess: Oh yes.
Cummins: As I say, Harry was absolutely great. He went on to become the Galton Professor of Genetics in the University of London. He was a fellow of the Royal Society; he was quite a fellow. He was in at the beginning of paper chromatography.
Hess: Well then you became a very important fellow in this area of microbial taxonomy based on cell walls.
Cummins: That was the main thing. Now this was obviously not something that a clinical laboratory is likely to be able to do. In fact, in the hospital setup, you are generally more interested in what the organism is called taxonomically, but you are also interested in what strain it is, because sometimes one strain may be much more pathogenic than others. So you are interested in things at a much lower taxonomic level so to speak. This example that I gave, when you examined a wide range of corynebacteria, you found you were able to put them into groups. But these were quite big groups. The whole thing would have no use at the diagnostic level, so to speak, as far as medicine was concerned.
Hess: So then at this sort of same time, a parallel emergence of thinking about the taxonomy of anaerobic microorganisms was being developed by Ed's (W.E. C. Moore, VPI) interest in lipids and fatty acids and things like that, metabolic profiling.
Hess: With the conversation that I had with Bob Smibert (VPI), we enter a period of time when some people interested in microbiology are getting together with the idea of pulling a group of experts from different areas to begin focusing on the anaerobes. This effort was spearheaded by Ed Moore and Bob Smibert. Then Peg (Peg Holdeman Moore) became involved, and I know that they were very excited about your work at the time. They were interested to think about how your contributions might enhance what they were thinking about developing.
Cummins: Right, well I think that Ed was in Paris for a while in 1966. I met him in London, and we went out and had lunch together. He was talking, at that time, about setting up this thing to investigate anaerobes in some detail. There weren't many anaerobes described. Quite a lot of work had been done on Clostridia, but he was, I think, becoming convinced that there were many more anaerobes that were not being grown, and needed investigation. So, I think it must have been then and, as I told you earlier, I went looking for my correspondence from 1966-1967. I can find quite a lot of it, but I cannot find any letters to Ed Moore about this particular thing. They may be somewhere else in my files, but I haven't come across them yet. I believe it was about then, that my wife and I came to Blacksburg to look. I think it would have been in September 1966. We came here.
Hess: What intrigued you about the possibility of working with this group?
Cummins: Well, it seemed, partly because there were obviously a lot of anaerobes that had not been investigated. The clostridia, for example, I hadn't looked at in any detail like we had looked at corynebacteria and things of this kind. Also, as far as I understood it from Ed, it was to be a purely research department. One would be able to be whole time on the job, instead of time on and time off as I was at the time. I think also, the general feeling was that research money was, at that time, more easily available in this country than it was in the UK. I found the idea of working in a university in such pleasant surroundings in the country to be very nice. It seemed to me a good place to raise children. We had two fairly young children then.
Hess: Great! Following negotiations, if you visited in 1966, there was a rather rapid decision about your joining the group. I think they obtained the first really major grant for beginning things in 1967.
Cummins: Yes, as I say, I would love to find that correspondence because then I would be able to give you times and dates. At this long remove, I can't remember any of them, except that we had definitely, by the end of that year, decided we would come. I had notified the London Hospital Medical College. We had agreed to come in the summer. Of course the building had not been built at that time. That took a little longer than was originally anticipated. When we first came, I was working in the old veterinary science building.
Hess: It was still out there on Prices Fork Road.
Cummins: The old building was there. It had already been built 10 years or more before.
Hess: So as you begin work with that group, do you remember the constellation of people who were there at that time?
Cummins: Well, obviously Ed and Peg were there. Louis Smith came about the same time. I think Bob (Smibert) explained Louis' relationship to the whole thing. There were a number of other people who were associated with the veterinary science business. Of course, this was a preliminary training for veterinary students because there was no vet school here at the time. Charles Dommermuth, for example, was in there; he was a virologist. Duke Watson was, of course, the head of it.
Hess: At this point, had the culture techniques that Ed developed for anaerobes become standard for the lab or was that evolving while you were here?
Cummins: It was evolving a bit. But the basic idea that you had a lot of glass tubes of media, and then you gassed them out continuously with either CO2 or nitrogen while everything was happening. So you could inoculate from the top, but that little right angle piece of metal tube leading into the tube (glass culture tube containing medium), continually kept the air out of the tube while you were doing the inoculations. So you could inoculate from one tube to another both of which were being gassed out continuously with something that displaced the oxygen. Then you put the stopper in and took out the little angle tube. That was a modification of Hungate's original idea. Very simple, if you sterilized media, all the oxygen is driven out. The thing to do is allow it to cool under a neutral gas. Then you don't get oxygen back in.
Hess: You had indicated with the corynebacteria concerns about doing this work because they agglutinated and clumped. Did you find this to be the case with the anaerobes that you beginning to work with?
Cummins: Well, I worked mostly with gram-positive anaerobes. I can't remember which organism it was I started working with. John Johnson came very soon after I had arrived. He and I sort of rapidly collaborated because he was interested in and trained to process DNA and do DNA homologies on these organisms, comparing and finding out how much similarity there was between the DNA's in different bacteria. So he really wanted the inside of the organism, and I wanted the outside. It was possible to use it in both ways.
We found very satisfactory agreement between groups that I determined from cell wall analysis, which was partially chemical and also immunological as well. I would make antisera against a crude mixture of cell walls and some whole organisms. We would inject rabbits with that and make an antiserum against that; then use the purified cell wall in an agglutination test. These would give nice agglutination, giving big easy-to-see floccules.
Hess: So that kind of agglutination then was done on your cell wall fragments or did you use the whole organisms?
Cummins: We used the cell wall fragments. With most organisms, the cell wall fragments, because of the new surfaces that had been exposed, were much more hydrophilic. So you could always get a nice smooth suspension that would also agglutinate.
Hess: I wasn't aware until this conversation that there was a need for rabbits and antisera formation over there. Who managed the rabbits?
Cummins: Gosh, I can't remember. We must have had an animal house. I used to regularly inject rabbits in the ear. You would give them maybe half a dozen injections and then leave them for a week. Then exsanguinate them and take the serum. Yes, we used to make antisera there.
Hess: What about the other chemistry associated with cell wall analysis that you had begun using?
Cummins: Well, I had learned the techniques from Harry Harris. At that time, anyway, paper chromatography was becoming much more sophisticated. We used to do it then on little eight-inch squares of paper in a rack. You ran the first solvent up (the paper), and then you took it out and dried it in a current of air. Then you turned it 90 degrees and ran the second solvent in the other direction. Of course, it got translated into thin layer chromatography you see, which was an additional thing. Sometimes with diaminopimelic acid, which we referred to as DAP, you got better separations if you ran it two or three times - two or three ascents of the solvent. After each ascent you dried it and put it back and ran it again. You got more separation each time.
Hess: So the detection of these was based on ninhydrin.
Cummins: Yes. Then, I think we sprayed with a nickel salt. The ninhydrin spots tend to fade. But spraying, I think with nickel salts gave you permanent red spots, which lasted much longer.
Hess: It is always important, even in this day of image analysis, for gels or whatever to be able to go back a record.
Cummins: Well of course, you could photograph them.There had been a lot of argument about one of the corynebacteria, traditionally the acne bacillus. the one that comes from skin and from Acne comedones and things of this kind. Traditionally it was called a corynebacterium. It looks like one, if you use that criterion of being a gram-positive organism that stains irregularly: it has knobs on it. When I was doing the original work, we looked at some and they didn't have the same pattern as the regular corynebacterium. We picked this up again, when I came here. John Johnson and I looked at a whole lot of things. It goes back to some people in the 1940s, who had shown that for the Corynebacterium acnes actually the major end product of metabolism was propionic acid, which is not like the regular corynebacterium. Ed had shown also, I think, the same kind of thing. I would have to look up which paper it exactly was, but he also and, I think, Betty Cato had shown that this organism differed in metabolism quite considerably. It was like the classical propionibacteria from cheese, where the major end product was propionic acid, about two or three times the amount of acetic acid. Those are the two major end products of metabolism.
Hess: In terms of the actual infection, is the acne infection based on an anaerobic environment?
Cummins: Well, acne is an anaerobe in the sense that, if you put it on the surface of a medium in a Petri dish in air, you won't get any growth. The organisms are not rapidly killed by oxygen, but they needed a microaerophilic atmosphere, at any rate, to grow in. You could use regular anaerobic techniques to grow them. There are at least three major organisms coming from the skin that we were able to separate and identify. They were all what we call cutaneous propionibacteria. When John had come to do the homologies, there were two serological types of acne that I found. These were, I think, if you took standard DNAs and you tested both groups against them. One of them would be 90-95% against its own type and 80-85% against homology to the other type. If you did it the other way around, you got the same result. So they were closely related, but could be distinguished. Then there was a third organism. Propionibacterium granulosum, is what we came to call it. In fact, the homology went way down to maybe 15% or something of this kind. I would get results that divided these three groups.When John came to do the homology, it fitted in so very nicely. The classical propionibacteria from cheese would be way down in homology, compared to the skin organisms.
Hess: One of the things that emerges as you become more sophisticated in being able to differentiate organisms and cell types is nomenclature. How did the group impact nomenclature for these organisms?
Cummins: I think now everyone now calls it Propionibacterium acnes instead of Corynebacterium acnes. At that level it was fairly clear. If you start looking at other properties of the organisms, the classical propionibacteria, they all tend to have similar nutritional requirements. We looked at the acids that were produced as major products of metabolism. The whole thing all fitted together and was quite different from corynebacterium. It is now generally established that these are propionibacteria.
Hess: Then strains within that become just numbers?
Cummins: Well, I was looking largely at carbohydrate antigens. Things that could be extracted with hot formamide or with trichloroacetic acid. You extracted, and then you precipitated out of solution with acetone and used that in an immunodiffusion test –cutting holes in agar and putting the various reagents and allow them to react with each other, you get nice lines. You could detect groupings. It may be quite possible, and I have not done it, that there may be a whole lot of protein antigens on the surface of these organisms. By analogy with things like streptococci and so on, there will be dozens of types. I did not investigate that. We were doing it at a fairly high taxonomic level. We were not down to the identification level, so to speak. You can also identify these things by phage type, bacteriophage. I did have a graduate student here who worked on that for a while.
Hess: Let's talk a little bit about lab personnel. Were you working pretty much on this aspect of discovery by yourself or did you have a technician?
Cummins: I had a technician; in fact, I had two at one time.
Hess: Who were they?
Cummins: Oh dear, I would have to go back in my records. Well, I have got some names here but I would have to make a separate list of them. [Acknowledged technical assistance from: Habiba Najafi, Patricia Lahoda (1973-74), Barbara Francis (1970-73), Wendy Barrick (1967-70), Sandra Slomon (1972-74), Carol Jones (1971-73), Cynthia Gross (1974-78), Dan Lin (1975-77), Bruce Bishop (1981-84), Cacia Shabdach (1983), Patrick Hall (1985), and Liz Goodsell (1987-89)]
Hess: Well the other thing that was happening that the lab became well known for was the application of analytical techniques to diagnostic procedures and the training of persons in the lab techniques. Did you have some of the work that you were doing come to that application?
Cummins: Not very much. I was not so concerned, than perhaps Ed was, with working out diagnostic schemes that could be immediately applied say in a hospital laboratory. I was more interested in doing the more general stuff with John Johnson. We worked on clostridia and lactobacilli, but it was all the same kind of thing. I was doing cell wall analysis of the kind I have described and John was putting the same organisms into homology (DNA) groups. There was nearly always a good correlation between the two things. In the first place, this was done mainly on gram-positive organisms. Except for the clostridia, Ed was mostly interested in things like Bacteroides fragilis and other gram-negative organisms that came from the gut. I didn't work very much with those. So I wasn't working with stuff that was designed to make it easy to identify a particular strain. I was working at a slightly broader taxonomic level mostly.The other thing came out of all this. There was a strange organism that was called Corynebacterium parvum. Professor Prévôt in Paris, whom Ed had contacted and knew quite a lot, was working on this organism. These were called skin diphtheroids or cutaneous diphtheroids. Diphtheroids meaning an organism looking like C. diphtheriae, in general a coryne-form morphology. This strange organism had been discovered way back. Some one had isolated it from a uterine infection back in the 1920s, and it has been called Corynebacterium parvum, parvum meaning little. I am not sure how it was discovered that a vaccine made from a suspension of this organism was very stimulatory to the reticulo-endothelial system in experimental animals. I mean, for example, I had a friend who was working with this thing in mice. He was able to show the clearance of carbon particles in the mouse was very stimulated. If you injected a suspension of carbon particles in the tail vein of a mouse, they are cleared at a certain rate from the blood. That rate was tremendously increased, if they had been given some of this vaccine. The cells responsible for picking up these carbon particles had either become much more active or there were far more of them. Somebody else, then, discovered that if you gave tumor cells, which always produced a tumor in the mouse, mixed together with some of this vaccine, the tumor did not take. So that was interesting because when we came to examine a lot of these propionibacterial strains, and quite a few of them were from Prévôt's collection, we found that this organism, Corynebacterium parvum, were actually a strains of Propionibacterium acnes.
Hess: Very interesting.
Cummins: So I, having a medical background, got rather interested in this. I got a grant from the National Cancer Institute to see if we could investigate this phenomenon. We had a test system with an inbred strain of mice that we could get from Jackson Labs at Bar Harbor, Maine. We used to get this single strain, so we were working with a highly inbred strain. Somebody here at VPI, and again I forget the name, had produced a tumor in this mouse. So we had the mouse, and we had the tumor. We would make a suspension of tumor cells. You can separate the tumor cells from other things by differential centrifugation in a gradient. Put that into the thigh of the mouse and then measure the thigh diameter. You can tell how the tumor is growing.The tumor will eventually spread and kill the mouse. If you injected those tumor cells together with some of the vaccine made from this organism, then the tumor cells didn't take. This was interesting.
Hess: Yes, it certainly was.
Cummins: The same thing had been shown by other people; this was not a totally original observation. We discovered a number of interesting things about this vaccine. One was that, if you used 12-hour cells, then killed by heat, these cells were pretty inactive. Well, if you let the thing go so that you were at the end of the growth curve, you were at the end of the logarithmic phase, the thing had leveled off –the 48-hour cells were highly active. So something was developing. I forgot to tell you the easy way we used to determine whether or not these things were active or not, was to inject the mouse intraperitoneally with the vaccine. In about a week, we would kill the mouse and weigh the spleen. You expressed spleen weight per 20 grams of mouse. It is normally 70-80 mg or something. You could get spleen weights of 500 mg.
Hess: A tremendous increase.
Cummins: It was a tremendously stimulating material, the spleen being the major source in the animal of cells of the reticulo-endothelial system. So I did quite a lot of work on that.
Hess: Were those animals treated that way with the vaccine and then subsequently injected with tumor cells, would the tumor take?
Cummins: We didn't do it that way. Initially we were interested to know how widely this stimulatory property was spread among different organisms. We found that it was mostly a property of the strains of P. acnes.
Hess: Were those organisms also part of the flora of the mouth?
Cummins: I don't think acne is part of the flora of the mouth. Acne comes from practically anywhere on the skin. There is another organism called P. avidum. That actually comes mostly from the glands in the axilla. Some of these strains of P. avidum were quite active as a stimulatory agent. There was another organism called P. granulosum, which you get mostly from the skin area around the nose and on the forehead. It is hardly active at all. But avidum and acnes were fairly closely related by both my test and by John's test of DNA homology. Granulosum was much further away and it wasn't active.Another thing was that the cell walls were not active. If you injected cell wall suspensions you did not get this big spleen development.
Hess: So it required the intact organism.
Cummins: It required the intact organism, but if you grew organisms with chloramphenicol, which is a protein synthesis inhibitor, they would still become active. If you started them off with chloramphenicol and then added penicillin, the material became inactive. Now penicillin inhibits cell wall synthesis. This activity was, in some way, dependent on the integrity of the cell wall, but cell wall fragments wouldn't work. This was a mystery.
To cut a long story short, I had a graduate student who was doing her Ph.D. on it. We discovered effectively that, if you allowed active vaccines to be phagocytosed by polymorphonuclear leucocytes that you can get by putting starch granules into mouse peritoneum. The exudate has a lot of polymorphs in it; you can take those polymorphs out and separate them. If you allowed them to phagocytose the vaccine, after a while—I forget for how long, but I have it in the paper here, the supernatant from the phagocytosing mixture was toxic to tumor cells. The active material is a result of what happens when things are phagocytosed is that you get lots of oxidative products of one kind or another. Obviously some of these were toxic.
In fact, we showed if you injected tumor cells into the mouse together with the vaccine and then killed the mouse after 12 hours and took the tumor material out and put that into another mouse, you got no tumor. Normally you would get a tumor. So the tumor was producing circumstances probably because of its phagocytosis. The toxic material from the phagocytosis was killing the tumor cells. That is about as far as we got.
Hess: What student was that?
Cummins: That was a girl called Elsa Murano.
Hess: Do you know what she is doing these days?
Cummins: The last I heard of, she was working in the Department of Agriculture. She completed her master's degree with me and then went on to Food Science for her Ph.D. Who is head of Food Science now? I forget.
Hess: Susan Sumner.
Cummins: This work was before that; it was Merle Pierson's time. She went on to Texas and did very well. Then eventually became a spokesperson, I think, for the Department of Agriculture. It may have been another department. Is there a department of Food?
Hess: Yes, the Food and Drug Administration.
Cummins: Well it might have been, but she was talking primarily about infections in meat getting into hamburgers and things of this kind. I think that's where she is now.
Hess: Well, the one clear message that you help us with is the freedom and focus that you had to do research. Do you recall any political issues associated with the university or the town over that period?
Cummins: No, I don't. The anaerobe lab was a well-designed building, I thought. Everybody had a lab with an office beside it. The building was designed with a spine down the middle, where all of the services were. The gas came in from there and the electricity came in from there. It was wide enough so that you could put a tank of special gas in there and then get a tube run into your lab. So the tank was not in your lab; it was held against the wall in the central spine. It made it a very flexible design.
Hess: Was that building, in part, a design that Ed did or was it Tracy?
Cummins: I believe that he (Ed Moore) was responsible for that design. Another thing, the corridor ran all around the outside. None of the labs had access to windows on the outside. But it didn't make any difference at all really.
Hess: They were very bright hallways.
Cummins: They were very bright hallways because there were lots of windows down the hall.
Hess: Did you have interactions with subsequent faculty? Greg Ferry came and Chen and Tracy.
Cummins: I didn't have much contact with Greg. He was more interested in intermediary metabolism, and I was more interested in the products of that metabolism, really in terms of the cell wall. Then I got into this business of the corynebacterium and the antitumor effects of it. The problem too, as things progressed it seemed as though the attitude of the granting agencies was subtly changing. They wanted more evidence that what you were doing was going to be useful with a capital "U". I was more accustomed to it being intellectually interesting. What you needed to do you couldn't find a use of anything until you established it with some degree of certainty. This was really putting the cart before the horse a bit. That seemed to be changing.
Hess: There must have been some real interest on the part of the Cancer Institute in terms of your work.
Cummins: Yes, I think there was. I don't know whether it came to anything; I haven't followed it since then. You certainly could show that the stuff was very cytotoxic when this material was phagocytosed. What I would have like to have done was to get on to finding out why, for example, 12-hour cells were almost inactive in this respect. It obviously was something to do with the degree of organization of the wall because12-hour cells are rapidly growing. Things may not have been as completely cross-linked, for example, as they were in later cells.
Hess: How many graduate students did you work with?
Cummins: Over the years, I suppose maybe half a dozen or so.
Hess: Did you serve on committees with other students that were being advised by other faculty – advisory committees for other students?
Cummins: No, I wasn't in on that very much. There was one other thing we did. Bob White, was he in biochemistry?
Hess: Correct, he is in biochemistry.
Cummins: He and I collaborated on it, because I had found a strange blue spot in ninhydrin developed paper—a bright blue like aspartic acid, but it wasn't in the position of aspartic acid. He and I eventually, yes there it is, characterized a 2,3-diaminohexuronic acid. He identified the thing, and he and a graduate student synthesized it.
Hess: So, that certified its identity then.
Cummins: Yes, that certified its identity. It has occurred in some gram-negative, I think, pseudomonads. I didn't really follow that up any further. Again, I was interested that the distribution of this thing was in almost all the propionibacteria except, oddly enough, the one that had been designated as the type species.
Hess: Isn't that interesting!
Cummins: Well the type species is known to be different. It has a different type of diaminopimelic acid, for example. It differs in a number of ways. It is an unsuitable type species.
Hess: (Laughter) Well that was one of the characteristics of the era. As you defined and learned more about organisms, they, in fact, turned out to be different from what they should have been.
Cummins: I was not a chemist, you see. So I had to rely on people like Harry Harris at the London Hospital or John when I came here. Or people like Bob White, if you had a special problem. You had to get collaboration with somebody who understood these things. I didn't work at all, except very peripherally, on the structure of peptidoglycan, which is, of course, the backbone material that holds the cell wall together. The reason that diaminopimelic acid and lysine and so on are there because you need a diamino acid so that part of the amino acid chain is the one that crosslinks a hexosamine. You need the two amino groups to link the two chains together.
Penicillin works by preventing the synthesis of that material. I never worked into that at all. I wasn't sufficiently into the chemistry of the thing to work into the structure. When this was hydrolyzed, it liberated these components. The pattern of the components was what I was interested in.
Hess: Well, being an Irishman in Blacksburg, did you make often or frequent trips back to Ireland?
Cummins: I actually don't have any very firm connections now with Ireland. I have three brothers, but they are all in England, or one is in the north of Ireland, and two are in England. My son-in-law and granddaughter and I go back every now and then and connect with the family.
Hess: During this period did you do a fair amount of international travel with your work or was it mainly reported here in the states?
Cummins: We used to go to international meetings of the International Society of Microbiology. There was one in Mexico City for example. That is the only one I remember going to outside of the United States. There was an international meeting in Moscow in 1966, but that was before I came here.
Hess: When the renewals for funding for the lab came up on a periodic basis, were you involved in the site visits at all?
Cummins: Yes, we all got to meet the people who came. I don't remember any specific feeling that what I was doing was any more important than what anybody else was doing or anything of that kind.
To go back to the earlier thing (the interview with Bob Smibert), I don't recall the international call that Bob said was made to me. It is quite likely that it was. I didn't take part, as much as other people did, in the whole business of devising identification schemes for bacteria. I was more concerned earlier on with the taxonomy on the broad sense.
Then later I got mixed up with this potential cancer use of this thing. People had tried using the vaccine to treat patients, but they had given it to them, maybe intravenously or they had given them the vaccine intramuscularly. Judging by this little paper, which was the last one we published on it, the whole effect of the vaccine was very local. Those things worked because the phagocytes were phagocytosing this vaccine material. That process was taken in the presence of the tumor cells. The oxidative products, whatever they were, (pause to look at the reference paper) we added things like azide, catalase, superoxide dismutase and mannitol to that mixture. I think azide neutralized the whole thing. In other words, made that phagocytosis mixture non-toxic to tumor cells. We were in on that kind of thing. To have any effect, it would have to have been given as locally as that. In other words, that phagocytosis would have had to taken place in the presence of tumor cells. Which pretty well means, that to make this effective you would need to have injected it directly into the tumor. That would be pretty complicated, if you had intestinal tumors and so on. I could see a lot of difficulty using it in a practical way in human medicine. We were under highly artificial conditions using experimental animals.
Hess: One of the really interesting revelations as I discuss things with you here today was the role that live animals played in some of the work of the anaerobe lab. I really didn't know that vaccine development and the use of mouse models were part of the way exploration occurred there.
Cummins: That is only because I got into it because of being interested originally in Corynebacterium parvum, which we showed was the same as Propionibacterium acnes. That was already of interest. If you read the literature on that, it was already of interest because its reticular stimulatory effect had been discovered. I guess, having a medical background I picked up on that and went into it in some detail.
Hess: I think the breadth of the group that was present all the way from straight microbiologists to people with real interests in medicine made the anaerobe group a really unique population of scientists.
Cummins: Yes. Well, I had a number of graduate students and I was trying to think what they worked on. I mentioned what Elsa worked on. I had one lad (Jim Babb) who ended up in Abbott Labs in Chicago; I think he is retired from there now. He worked on bacteroides and we showed that many strains were capsulated, for example. He worked on some of the various polysaccharides that were present in different strains.
I had another graduate student, Steve Stimpson, who is now working with Glaxo down in Raleigh/Durham area in the Research Triangle Park. We were interested in trying to determine the nature of this substance that produced this reticular stimulatory effect. He published a thesis about that.
I had a post-doc, Don Ferguson, who is now a professor in East Tennessee Medical School. He is about to retire too. People are getting old.
Hess: That's right! It happens to all of us. (Laughter) Well, it has been a good conversation to think a little bit about this piece of history. Are there any other thoughts you would like to close with?
Cummins: I found the Anaerobe Lab a very pleasant place to work in. My views of research were a bit different to Ed's (Ed Moore). I was more, sort of, in the background style and he was anxious to make sure that things could be identified at a level that would be useful in a medical context. These are not in any way incompatible in the same department. Because of that, his interest and mine didn't really mesh a great deal. It was a very pleasant place to work in, a nicely designed building.
He and Peg had this tremendous collection of organisms. I think that it a pity that it got either destroyed or dispersed. I am not honestly sure what happened to it. I am sure Peg knows much more than I do, because she was much more concerned with it. I contributed very little to it, except that we did put some identified strains of some of these propionibacteria in it, as strains we had worked over.
Between them (Peg and Ed Moore), they really put the place on the map.
Hess: With your help.
Cummins: Well, I don't know whether we helped or not. I would like to have known more about the people. We organized this meeting in 1969. I think it was called The Use Of Cell Wall And Membrane Composition In Bacterial Taxonomy. I think it was published in the October 1970 issue of the International Journal of Systematic Bacteriology. I thought I had a copy of that, but I can't find it.
Hess: Well maybe we can do that research and get a copy and put it with the transcript for this interview.
Cummins: Well I am hoping something will come of that. They remain unheard so far.
Hess: Ok, well thanks so much.
Cummins: You are very welcome John. I am glad to find that somebody is still interested in what happened in the Anaerobe Lab.
Hess: Oh yes, it is an important part of history for sure.
Cummins: It is nice to think it is going to be part of the record.
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