Presented by the University Archives of the University Libraries, with the Department of Biochemistry of Virginia Tech
Fifty-Year Celebration of the Department of Biochemistry
Robert Smibert: From the development of the Anaerobe Lab to Department of Anaerobic Microbiology


Name: Robert Smibert
Date: June 19, 2002
Location: Sound Booth, Media Building, Virginia Tech, Blacksburg, VA
Interviewer: John Hess
Transcriber: John Hess
[Tape 1, Side 1]

Hess: I am here with Dr. Robert Smibert from the Anaerobe Lab. He is an emeritus professor who had a distinguished career beginning in 1960. We will visit a bit about that career and the development of the Anaerobe Lab and the good things that happened because of that whole operation.

Bob, I would like to begin with you talking about how you became affiliated with Virginia Tech.

Smibert: I got my B.S. Degree in Microbiology from the University of Connecticut and the MS. and Doctorate from the University of Maryland. In between degrees, the war (Korean War) was on and I was in the Army. Most of my time was spent in the Second Army Area Medical Lab, which is like a state laboratory for six states. Then I went to graduate school. After graduation I went to work at Temple University Medical School. Then in 1960, I came down to Virginia Tech in the Department of Veterinary Science. When I was in this department, Ed Moore who had been at Tech since 1953 or '54 was in the Department of Biology. He was on the top floor of Price Hall, the attic. When I came in 1960 Ed had transferred from Biology to the Veterinary Science Department and that was where I essentially got to know him.

In the department, after awhile I was working on organisms called vibrio, which is now called campylobacter. It was mainly a cause of abortion in cattle and sheep. Subsequently, it has also been found to cause diarrhea in people, especially children. The concern had moved over from the veterinary area to the human health area.

Ed Moore had been working with the rumen microbes. Those organisms are very strict anaerobes. The techniques that are normally used to grow anaerobes did not work, because they are very very air-sensitive. The Hungate technique, that Dr. Hungate in California came up with, allowed the growth of these very strict anaerobes. Over in the Veterinary Science Department, Ed applied that technique to the growth of intestinal bacteria, especially in the poultry area. He thought, well this might also work with human and animal intestine. He was able to grow a lot of organisms people hadn't grown before.

Then he decided what might happen was to see if human infection was caused by a lot of the very strict anaerobes. At the time, the common or conventional wisdom was that we knew all the anaerobes that would grow in healthy human; you know human health, disease and infection. There were clostridia that caused tetanus and botulism and gas gangrene. That was about it. We did know in soft tissue infections like liver and spleen and kidney that there were things that looked like infections. You could make a smear of the tissue and look at it under the microscope and see bacteria. They were dead. That is why you could not grow them. A lot of people thought that was not right. So applying the Hungate technique to these organisms worked. They just were very strict anaerobes.

Ed decided to go off to the Pasteur Institute in Paris. There Andrea Prevot had worked on anaerobes and had amassed a nice collection. Ed was able to bring some of that collection home, here to Virginia Tech. He started working on those.

Hess:Do you know what time we are talking about for this work and the visit to Paris?

Smibert: We are talking about the period from 1965-1968.

Hess: Before we go on, who was the department head of Veterinary Science?

Smibert: Duke Watson was head of Veterinary Science and Wilson Bell was Dean of Agriculture at that time.

Hess: Was I.D. Wilson still Head of the Biology Department?

Smibert: I.D. Wilson had retired by that time. Ed was able to grow organisms but found out that you couldn't identify these. Most of them were not described. There was no way to identify any of these organisms, if you looked at any of the books or anything.

Ed and I were at one of the ASM meetings, American Society for Microbiology. Louis Smith was there. He introduced Ed to Peg Holdeman. Peg was at the CDC (Center for Disease Control) in Atlanta, Georgia, where she was head of their anaerobic diagnostic lab. When Ed and Peg got together, it was like two wayward souls getting together, and Louis and I just sat there and listened to them talk. Before we knew it, they had come up with some things they wanted to do with anaerobes. So, Peg left CDC and came up to the Vet Science Department. That is when they started working on a plan to put a project grant in to NIH that would establish the Anaerobe Lab.

Hess: Was Smith on faculty here?

Smibert: No, he was the dean of the graduate school at Montana State University. He was head of the micro department, but then he moved up to become the dean. Peg was his graduate student. Louis was an expert in the clostridia.

This project grant, written for NIH, went to Institute of General Medicine. Fortunately there were some people there who kind of championed this grant idea. They felt the same way that all anaerobes in human infections were not cultivated or even known about. We had a whole bunch of study sections on that. Persons would come up here for a site visit and meet in the Veterinary Science meeting room. We would go down and pick them up at the Roanoke airport. Some of these people would say, "This is really out of the way, isn't it? (laughter) How do you get in and out of here?" Some of the people were concerned about putting a lot of money into something that was very out of the way. There is a big difference between Blacksburg now and what it was in the early 60's.

The way the grant developed, each one of us on the grant would have their own separate grant built into it. Then there was one overall section to pay for administrative expenses. It was one of these things we could have five or six individual grants all tied together with administrative funding. So Ed and Peg had one and I had one. I think Betty Cato, who came over from Biology, and was Ed's technician had a grant. Then there was one for Cecil Cummins and Louis Smith and one unnamed person.

We had several site visits. To convince these reviewers about the science was the easy part. The hard part was trying to convince them about personnel, "You mean Cecil Cummins is going to come here? That he is going to leave the London Hospital to come here? Little old Virginia Tech?" "Yes." we said. They didn't believe us, even though we had a letter from Cummins. They still did not believe us, so we ended up with an international conference call.

Hess: During the site visit?

Smibert: At the site visit, we brought the phone in and said, "Here is Cecil Cummins on the phone. He is from London; talk to him." They were convinced that Cecil would come here and they awarded the grant.

The other person was Louis Smith. "Do you mean that Louis Smith is going to give up being the Dean of the Graduate School at Montana State University to come here? To just be a faculty member?" They didn't believe it. We presented a letter, but they still would not believe he would move. At the next site visit, everyone was seated and Louis Smith walked through the door. "Hi guys. I will come here, if you will fund this." They funded.

Hess: Well, it was a huge amount of money for that time.

Smibert: It was a very large amount. Then, for the grant part that was unnamed, John Johnson filled that slot. John Johnson was a graduate student of R. H. McBee at Montana State where he got his doctorate. Then he went to the University of Washington and essentially learned to do DNA homology. That is why we wanted him. That filled up everything so we were in pretty good shape.

The other grant request that was put in was for the building. It was a separate request to build the building that was going to house the Anaerobe Lab. Again we had many site visits before we got the money. It was one of those situations where Tech put up 20% of the cost and NIH would put up 80%. Ed had help from people at CDC who were architects in helping to design the building. That went to Hayes, Mattern and Mattern in Roanoke to get the final design of the building. We worked for a year or two in the Vet Science department, until the building was finished.

Hess: So with Johnson coming around 1967, the building became available in the early 70's?

Smibert: 1969 or something like that.

Hess: That is the building connected to the old veterinary science building on Prices Fork Road.

Smibert: That is correct. I think the vet school now has that building.

Hess: Given the way we build things, was there more space than needed by that group of faculty, or did you have just enough space?

Smibert: We had enough lab space and office for those faculty. Then, downstairs we had a teaching lab, media kitchen, and a spare lab that was supposed to be for visiting people.

Once we got into it, on one project that we had, Tracy Wilkins came as a postdoc. He occupied that spare lab. He was a fortunate pick; he was so good we decided that we would hire this guy as a faculty member. That became Tracy's lab down there.

On the biology side, we had the first electron microscope that was available for agriculture. There was another electron microscope in engineering.

Hess: Was the microscope housed in the new building?

Smibert: That was housed in the basement of the new building.

Hess: Was there a technician available?

Smibert: Yes, there was a technician to run and maintain the microscope. Then the technician moved with the microscope when the lab was set up in the Department of Plant Pathology (PPWS).

Hess: That move was to Price Hall or Saunders Hall. Was Gary Hooper involved in that decision?

Smibert: Yes, Gary Hooper was the Head of Plant Pathology and Physiology.

Hess: I knew Hooper was an electron microscopist, but I did not know the history of the microscope, that it was originally in the Anaerobe Lab.

You mentioned the teaching lab. I remember, probably in the 70's, that you ran the short courses for anaerobe technicians.

Smibert: Well no, it was not just for technicians. The history of the short course is interesting. The laboratory was available, but we were not quite sure how we were going to use it. We thought mainly we would use for graduate students. The NIH people said, "Ok, you guys are publishing articles in journals, but there is a long time lag between when information becomes available and when it is used in a useful way. We would like to cut this time down. We want information to flow from there in a very short time, so it can be picked up by hospital and public health labs."

This is where Peg did a really great job. The first thing was the Anaerobe Manual. It was essentially a manual with everything in it. It started out with a general description of anaerobes, and then each genus of anaerobe had its own little chapter. Everyone in the Lab contributed to this manual. We start off with the genus and the species within it, how to grow them, and how to recognize them generally. Tables were there describing diagnostic tests to identify these bugs. They were presented as flow charts. If an organism ferments sorbitol or not takes you to the next line.

Hess: It sounds like a metabolic key.

Smibert: Yes, you could then identify species. On the next page you had sketches of fermentation products, fatty acid fermentation products from gas chromatograms. Then there may have been photographs or sketches of what the bug looked like in terms of stains for microscopic presentation. At the end, the appendix included all the culture media we used, formulas and everything. We included how to perform the extractions, gas chromatography for fermentation end-product analysis, and where to buy everything. When you got through with that manual, you could set up your own lab. We would update the manual with inserts or revise the whole darn thing.

Hess: Can you recall when was the manual first released?

Smibert: Probably early to mid-70's.

Hess: There are probably some issues or volumes of manual around.

Smibert: Yes, I probably have some.

Hess: I should check with the archives to see that one is in the library.

Smibert: We did not advertise the manual. It was available at just over cost and became known by word of mouth. We sold them and had the lab course. The two-week anaerobe lab course was available in the second summer session. It had graduate level credit, so that graduate students could take it. The main group of students, probably 25 each time, was technicians, MD's, and PhD's. They came from hospitals - big and small, state public health labs, and military health labs - like VA (Veterans Administration) hospitals from all over the country. They also came from all over the world, from England, Germany, Italy, France, Denmark and Sweden. We also had persons from Taiwan and Japan.

I think this type of thing made our reputation. It was a demanding course. They had lectures in the morning and lab all afternoon until about 5:00 p.m. They received cultures and went through the identification process. We had gas chromatographs for them to do the fatty acid end-product determination. They did everything. By the time they got through the course, they could take the manual, go home and start their own lab. Everything was there.

Hess: One of the things I recall was the anaerobe station that was attached to CO2 lines that were operated with foot controls to flush tubes and so on. Did every pair of students have this equipment?

Smibert: Every station in the class had one of these setups. It is very interesting. Ed Moore had essentially worked with the Hungate technique, which was mainly taking a tube of medium that had been boiled and sealed with a rubber stopper. A syringe needle was bent so that it formed a hook so that you could deliver CO2 or nitrogen to flush the tube. Ed was very mechanically minded and could build things.

He thought the tubes with a straight lip would be better, if they were tapered to make it easier to use. He went to Belco Glass Company in New Jersey and had them make these tubes. He went to the hardware store and got some stainless steel brake tubing. At home he bent the tubing and soldered it and made an inoculator. From the scientific distributor, Thomas, we got a manifold, heating mantle and glass tubing filled with copper filings. The copper was heated, so that as the CO2 and nitrogen passed over the copper, oxygen was removed.

Then the gas passed through the tubing into the inoculating device. It consisted of three spring-loaded tubes each with a needle at the end. With a foot treadle, attached with a string, the needle would swing into the Bunsen burner flame to sterilize the needle. Let up on the foot treadle and the needle would swing back so that you could flush the tube of stock culture and inoculate two new tubes. It was great. Belco decided they could make the apparatus and sell it. They not only sold it to us but everybody else who wanted it.

Another thing that Ed did was in the media kitchen. It was a foot pedal operated gizmo to stuff cotton into the end of a glass pipette. When the media kitchen would make the pre-reduced anaerobicly sterilized medium he made a device to fill the culture tubes with a standard amount of medium filled under CO2 or nitrogen.

Hess: It was a kind of production line for culture tubes.

Smibert: When we started, we used wire coat hangers to keep one rack of tubes on top of another. If you autoclaved tubes with rubber stoppers, the stoppers would pop off unless you held the stoppers down. Later he came up with a press made out of aluminum. You could put the rack in and screw down the press to the rubber stoppers to keep them from popping out. Again, Belco made that. Belco made everything we had and it was available for sale to anyone that wanted to by it.

Hess: Do these general techniques persist today for anaerobic cultures?

Smibert: Oh yes. These are still standard techniques.

Hess: The influence of discovery of anaerobes and how to manipulate them are hallmarks of what the laboratory achieved. During this period each of you was pursuing specific interests. Was graduate student education part of each person's career?

Smibert: I essentially started the graduate program at the Anaerobe Lab. I started it when we were in the Vet Science Department. When we moved to the Anaerobe Lab, I continued doing that. I probably had responsibility for the graduate program for 25 years. We had two teaching assistantships, since I also taught Pathogenic Microbiology with Noel Krieg in the Biology Department. Noel and I shared that course. We used the two teaching assistants with the pathogenic lab. Also, in the summer lab they helped Peg set up and run that course.

Hess: Was there much anaerobic stuff done in the pathogenic course?

Smibert: I lectured on the anaerobes. They did have laboratories with clostridia and bacteroides. We had some spare equipment that we took over there and left there so that their students were able to use some of the Anaerobe Lab type of equipment.

Hess: Were the graduates in the program awarded degrees through Vet Science or were they through different departments?

Smibert: By the time the building was built, we became the Anaerobe Lab. The status was not quite a department. After a few years we became the Department of Anaerobic Microbiology. We became a separate department. The actual courses and credit for the courses essentially were from the Department of Anaerobic Microbiology. For degrees in microbiology, we were under the umbrella of the Biology Department at that time.

Hess: There may have been a few degrees that came through biochemistry.

Smibert: Oh yes, there were graduate students in biochemistry, biology, and people from animal science.

Hess: There was an ongoing interest in ruminant disease and nutrition. The focus the anaerobe lab moved toward was human health and kept NIH engaged.

Smibert: I think when we first started out interests were human and animal health. They were very intertwined. But since the money to build the building and the money for the research came from NIH the emphasis was more on human than on animal health.

What we found was that all these organisms, when they were isolated, were not named or characterized. It became the purpose of the Anaerobe Lab to sort these out and set this in order and to teach people how to isolate the organisms and to know what to tell the doctor what caused the infection. That meant we had to go into taxonomy, classification and even to the point of naming new organisms - new species. So that is essentially what we did. Later on the scope of work was broadened when Greg Ferry was hired. His expertise was methane and hydrogen producing organisms. It had little to do with health but it was environmental.

Hess: Did Greg come in as a replacement for someone or was this an expanding faculty?

Smibert: Well, it was sort of both. Louis Smith had retired. We were going to replace him when the Dean said we have an extra position for you. So we hired two not one. We hired Chen who was working with clostridia and we hired Greg Ferry. That is how that happened.

Hess: Did Smith stay in town?

Smibert: No, he went back to Washington State.

Hess: Cecil Cummins, on the other hand, has stayed here. He is certainly a "Blacksburgian" after all those years.

Smibert: Cecil Cummins stayed here. He has a son in Montana that he goes out to visit in the summer time.

Hess: I did not realize this connection to Montana, but they have this biofilms institute there. It must have some history and legacy associated with that interest in anaerobic microorganisms that goes way back to Smith. We had a presentation this year (2002) from one of the Directors of the institute out there. I was just amazed at the transformation organisms make when they take on this biofilm micro ecosystem in which they exist. The connection to Montana does make more sense to me now. It was sort of like NIH coming to Blacksburg in the early days. It is very interesting.

Smibert: One of the very interesting things about how the Anaerobe Lab achieved what it did was that it was completely spontaneous. We didn't set out to make a record or reputation. If you do that sort of thing, you fall on your face. We used new technology as it came along and applied it to the work we were doing. Again you need to give Ed Moore the credit because when he and Peg started pulling this together there was the old way of doing fatty acid fermentation end-product analysis. You had a silica gel column and started putting solvents through the column and titrating each fraction. Then get a piece of graph paper put the dots down and connect the dots. Something new had come out called gas-liquid chromatography (GLC). A column was designed for fatty acid separations, so they said, "Well, let's try it." It worked. We could do the volatile fatty acids, and the non-volatile acids like pyruvate and lactate could be methylated. You could inject a second sample on the column. You could get qualitative and semi-quantitative analysis, which was perfect. That type of experiment was a lot faster than titrating maybe 50-60 fractions by hand.

Ok, we had that technology going. Then there was the equipment that was built to make it easier and faster to use than the Hungate technique. It was more convenient. Then later on, when high pressure (performance) liquid chromatography came out, I started to use that because you could get both volatile and non-volatile fatty acids on the same sample. We used new technologies to do the work better and faster. Instead of having a strip chart recorder on the instrument, you had a computer-based record. Then you had a report of what each peak was and how much was present.

Later on, there was another technique using GLC, looking at cellular lipids, long chain fatty acids, and aldehydes. You got a nice profile that reflected unique products for an organism. The profile of long-chain fatty acids was applied so that you could tell that a sample had specific organisms. The reason we had Cecil Cummins come was because he worked on the cell wall of the bacteria. He found that in the cell wall you have a few (4-5) amino acids and several carbohydrates. Each species seems to have a certain combination of those. One species would have three out of four another only two out of four. You could begin to say, for example, that this species always has these three amino acids and this one sugar. That became a way of looking at the bacterial classification. While the study was a huge one, Ed felt we could apply that across the board.

We all had our separate projects. But it was like a team effort on certain things. John Johnson was working with DNA homology, which at that time was brand new. With the particular technique he was using you could define a species that way. It became understood that if two organisms had 70-100 percent DNA homology that defined a species. Then you look at the cell wall chemistry and say well they don't match with the profile of amino acids and sugars. You look at the fermentation products and they have the same fermentation products. Then you start looking at which sugars are fermented and other biochemical characteristics and you can correlate that with DNA homology and you have a species.

A clinical lab cannot do DNA homology or cell wall analysis. There is too much work. However, they can do all the other stuff - the fatty acids, end-product determinations, biochemistry, and growth characteristics. These are all correlated with this key. Then you can construct very accurate tables how to identify organisms. I think that really depends on using up-to-date techniques and applying them in a way that can do it.

Then with Peg doing the manual and the course, she was in charge of doing both. When you put all of that together that is how we got our international reputation. That, plus the regular journal articles that we published.

Hess: You monopolized this research area. You really did.

Smibert: We were the only department in any university that specialized in anaerobes.

Hess: Right.

Smibert: The only ones, there was the federal government at the CDC had an anaerobic diagnostic lab. We worked with them quite a bit. Then, in Los Angeles, CA, there was an anaerobe lab in the VA Hospital. These other two were mainly diagnostic labs and did not do that much research. We were more of a research-oriented lab than a diagnostic lab. Although, people would come to the course and return and find an interesting organism that they isolated and were not sure what it was and would send it to the Anaerobe Lab. That helped with our collection, but it also kept us in contact worldwide with all these people. We acted as a reference lab for them.

Hess: The Anaerobe Lab became a "gold standard".

Smibert: Yes.

Hess: I recall for years that John Johnson's expertise was delivered in coursework. The nucleic acid biochemistry course was the only course with that content at Tech. It was a very important course for so many students.

Smibert: He (Johnson) presented that course so that students would come in and actually work with DNA at the bench. He had the lecture and the lab.

Hess: Right, students used the equipment over there (Anaerobe Lab).

Smibert: They used the same equipment that John used. It was a marvelous course. For coursework we had the Pathogenic Bacteriology that I helped to teach over in Biology. We had John's course on DNA homology and Peg's course on techniques. We also had seminars and for undergraduates we also provided research credits for senior students. That was fun; a lot of times you were trying to pick out a good graduate student.

Hess: That's right.

Smibert: Then Greg Ferry had a course on rumen type of microbiology. I should have mentioned Dennis Dean.

Hess: Was he the last hire in the Anaerobe Lab?

Smibert: He was next to the last. His area was nitrogen fixation. Now that is not strictly anaerobes, but by that time we wanted to broaden ourselves a bit more. He was a good choice.

Hess: He is excellent. Was that hire a replacement or was that a new position?

Smibert: I guess you could call it a replacement. Cecil Cummins had retired and we hired one person who only stayed a few years – Dennis Bazolinski.

Hess: Then the leadership of the lab transferred from Ed to Tracy at some point.

Smibert: Well, about 13 years ago Ed and Peg got married. According to the rules Ed could not supervise his wife. So that meant that Ed had to step down. Ed was just a few years from retirement anyway and Tracy Wilkins became head of the department.

Hess: So the collection itself started out relatively small with some animal-based organisms. Do you know, at the time when the University determined it was unable to support the lab or the size of the collection?

Smibert: Oh, I was working on the treponemes, anaerobic spirochetes, both in animals and humans. We had another long grant, Ed, Peg, and myself on periodontal disease and gingivitis from the National Institute of Dental Health. We would go to Richmond once every couple of week to the dental school (Medical College of Virginia – MCV) to collect samples. We would bring them back and work them up. I know I had one big -80 freezer just full of stuff. Another liquid nitrogen freezer was full of samples. When I retired I went through a lot of it. We sent them out to people who we thought might like them. We couldn't send everything out but good representatives we sent out. Then, I think the rest of the samples stayed there. I guess when the Anaerobe Lab died that they got discarded. Ed and Peg had probably three or four -80 freezers full, plus lyophilized cultures. They had the biggest collection - there were thousands.

Hess: Some probably went to the American Type Culture Collection.

Smibert: Well, we had here the ATCC bacterial back-up. We had it here since the 60's when we built the lab. In fact, there was a big freezer built downstairs built into the lab. It was paid for by the ATCC and they brought their spare collection in case anything happened to the main building in Washington we had one of the spares here of all the organisms that they had, all the bacteria. I think they had to take it back; I don't know where it ended up. I am not sure what happened to Ed and Peg's collection. I am sure that they sent out a lot of stuff, but there was probably a lot of stuff that just got thrown out.

Hess: Of the anaerobes, is there a percentage that is pathogenic versus benign, thinking about how they impact human health?

Smibert: In human health, probably the main part (70-80%) of the flora of the gums and in the mouth is anaerobes. When you get down to the intestinal tract, you get the same sort of thing. The facultative organisms like E. coli, which everybody knows, are really a minority in population compared to the anaerobes, in terms even of the amounts in there. You may have 107 E. coli, but then for bacteroides or some of these other things they may be 109 per gram.

Hess: Really?

Smibert: Most of those are probably benign as long as they stay in their place. As far as being safe in the intestinal tract, sure, they are fine there. But if you get peritonitis or if they get into the wrong place, soft tissue or out in the peritoneum, then watch out. They are going to get you. Then you have an infection.

Hess: There must be some kind of synergy, since soft tissue is typically well oxygenated in terms of blood supply and such. How is it these obligate anaerobes take over?

Smibert: The conventional wisdom on that is rather proven. Not only do the anaerobes get out but also other bugs too, like E.coli that are facultative. They start growing in the soft tissue and use up the oxygen. They establish a reduced environment so the anaerobes can take over.

Hess: So they are establishing a new community.

Smibert: The anaerobes become established and they are the ones that can do the damage later on.

Hess: What, for your own program was the most interesting aspect of discovery? What excited you most?

Smibert: One was working with the campylobacter. My lab became a reference lab for a lot of public health labs for the campylobacter, especially after they found one species caused diarrhea, especially in kids. Another caused a blood infection, especially in persons with cancer or leukemia who had distressed immune systems. Working with those organisms was getting their identity correct. Those organisms are microaerophiles; they actually use oxygen. If you use 20% oxygen they won't grow, they need a reduced amount of oxygen. They kind of grow at about 5% oxygen.

So there were special techniques in the veterinary field that people knew about. We had been working with those organisms because they caused abortion in cattle and sheep. We knew how to grow the organisms. When it became known that they were human pathogens, it was interesting in terms of the type of organism that causes diarrhea in people that was when I found out in Belgium. When the Belgian Congo went, and Belgians moved out of there, a lot of native Belgians went to Belgium. Of course conditions were not very sanitary. They kept a lot of their farm animals in the house with them. This is where the campylobacter comes from. So their kids were constantly having diarrhea. They found this weird organism and went to a veterinary institute in Belgium. They knew the organism that affects cattle and sheep. That is when it was discovered. The people in our hospitals and state health labs did not really know the trick of growing this microaerophile. What was nice, was when they came to our course, I lectured on this and we showed them culture techniques. Then they went back to show others how to do it and my lab became a reference lab for identifying these campylobacter.

The other thing I worked on was the spirochetes, treponemes. We started out looking at some ruminant spirochetes. When we could grow them, we looked at their nutrition needs and came up with a defined medium for them. Then we looked at the big intestinal tract and other intestinal tracts. Finally we got to the point of looking at periodontal disease and gingivitis. The mouth is full of these treponemes. It was fortunate that there were only two labs in the country, one at CDC, which was more concerned with venereal disease, and my lab, which was more concerned with the oral organisms. When we put this grant in, another one of the large program grants, they wanted to know what the flora was in the mouth and gingivitis and periodontal disease. We came up with shifts in flora and what organisms might be involved in the actual disease process. Of course, treponemes in the mouth were well known but no one could grow them. In my lab we could do it. It was fortunate that we just walked into that one.

Hess: Right, but it's clear from what you just described that your close interaction with Noel Krieg, whose interests had to be inspired by what you were doing. Collectively the interaction was very important.

Smibert: In my lab we were working with the microaerophiles. Noel got interested in the mechanism of microaerophiles. What is going on with growth at 5% but not at 20% oxygen? What makes oxygen toxic? That became his interest. So we shared graduate students on that and wrote a lot of publications together on this topic. He went off real well on the mechanism of microaerophilism.

Hess: Yes, one of the things that amazed me was a slide he showed in a talk that he gave. The microorganisms moved to exactly the "right" concentration of oxygen. That is an amazing story.

One of the things that all of us as educators in science look forward to or think about is the way we have communicated our expertise to the next generation. Are there some notable graduates or persons from the Anaerobe Lab that your feel are carrying on this whole interest?

Smibert: Yes, I think probably more so now with Greg Ferry's people working on methanogenesis. Yes, every now and then you run into people, with people that were associated with the rest of us. One of my graduate students up in West Chester County, NY runs a big anaerobe diagnostic lab.

Hess: Who was that?

Smibert: That was VanHorn. So there are people out there who are carrying on the work. But they are only single individuals working in a department somewhere. Whereas, we had eight to ten people working in concert as a team. That is why we could do so well, because we did have the teamwork, besides our individual projects.

Hess: It has to be a model that NIH reflects on as being a very successful way of getting work done and results in short order.

Smibert: The project grant we had for at least 15 years, renewed every five years. After that we went to more individual grants and there was no problem getting those. Then we had another 10 years or so with the dental school at MCV, through the National Institute of Dental Research. We had the microbiology part of the work and MCV had the medical and dental evaluations on all these patients. There were some people in biochemistry and immunology at the medical school that had another grant section. So it was an innovative sort of thing. It was amazing, when we read the request for a grant, it seemed that they wrote this just for us. (laughter)

Hess: It is good to be that side of things. I remember, as you were talking about the dental project, a student Frank Jimenez, and being on his committee. I learned a whole lot about the flora in the mouth. Do you know what he is doing?

Smibert: No, I don't.

Hess: As we think about the education of international students generally, you had a fair share of those or were they mostly U.S. citizens?

Smibert: Most of our graduate students were from the U.S. The postdocs were also mainly U.S. citizens. We did have some from China, both Taiwan and Mainland China. They usually worked with Chen. We did have Louis Anthenon do a sabbatical with us from England. We did have those people in too.

Hess: Ok, well there are certainly some events that punctuate the accomplishments of the lab. Your personal relationship was mainly with biology and biochemistry. That was probably true for most of the faculty out there.

Smibert: We used to go to the biochemistry seminars and worked with Mick Gregory and Noel and they served on a bunch of our committees. Earlier on with Charlie Engel and Joe Fontenot and Kendall King. We had some early publications with Kendall.

Hess: It is interesting how things change. I remember Kendall being interested mainly in cellulases. It is obvious he had a heavy interest in human nutrition as well. Was the work of the lab related to how an understanding of how these organisms can be regulated, say with antibiotics and that sort of thing? Did that happen elsewhere?

Smibert: In terms of antibiotics, it was mainly sensitivity studies. It was all that was needed by a physician sometimes. That is the antibiotic your start off with. In terms of regulating, let's say, populations or something like that, we did not get into that sort of thing. Although I think that, if we had carried on and they had replaced some of us who retired, would be the right area to get into.

Hess: Thinking about the current trends in manipulating organisms and understanding their interactions, it is almost a return to metabolite analysis. We now call it "metabolomics". However, it is very similar to these early characterizations - what are the metabolic products that these organisms produce?

Smibert: We were more interested in organisms as individuals. There was work out there a long time ago where people were putting 2,3, or 4 organisms together and seeing how they interacted. They asked, how did that change the population and the metabolism?

Hess: Once you have all the genomic information, which is being "belched out" by these sequencing groups, you still don't know how the organism will interact in the environment.

You haven't talked too much about university politics. I guess Ed Moore probably did a good job of insulating the faculty there from the concerns of what the college relationships were.

Smibert: Well, being out on Prices Fork road, we sometime had the best of things because we were out of the main stream. We did some committee work on campus, but we were not overloaded with it like a lot of people on campus were. That kept us out of a lot of things. In terms of what was happening on campus, we knew what was going on, but chose not to worry about it. We just did our job.

Hess: Well, your funding was quite independent.

Smibert: Some people in other departments were envious that the university gave us a budget. Our grants were 3-4 times that budget. We probably had a lot more outside grant money than a lot of other departments singly or put together. So when a budget crunch hit and people couldn't travel or couldn't buy this, we still had money to do what we wanted to. We had two teaching assistantships. All the other graduate students, 15-20, were paid for on grants. The postdocs we had were paid for on grants. Probably 30-35 technicians were paid for on grants. So we did not worry about money.

Hess: You probably did not have many state-funded technical positions. All of them were supported by grants.

Smibert: The idea was to have one technician per faculty, but it did not quite turn out that way. Downstairs in the media prep room they started out as state technicians. Then we had two other people because we had to run our own building. So we had to hire our own janitor, buy our own janitorial supplies, pay our own electric bill, and our own water bill.

Hess: So there wasn't really much reason to be worried about what was going on on campus.

Smibert: No, that is true. At first, they didn't pay for anything. We were considered off campus.

Hess: Was that true of the vet science department that was in that building as well?

Smibert: Yes, that was off campus too. Duke (Watson) had to deal with the same thing. He had an oil furnace and had to buy oil out of his budget - electricity, everything.

Hess: Let's see, the vet school took over that department.

Smibert: Yes, they took over the department when the vet school came around. The veterinary science department was integrated into the vet school. So the vet school took over that building. A lot of the people stayed there. Then we were connected to it. When the Anaerobe Lab was merged with Biochemistry, the vet school took over the old anaerobe building.

Hess: I can remember having gone to some seminars in the Anaerobe Lab and seeing that there was a collection or library. Was that an important resource to the group to have an independent library?

Smibert: Yes, it was. That library was essentially from journals of individual subscriptions.

Hess: It became a compilation of journals.

Smibert: We all got the Journal of Bacteriology. Ed or Peg put their copy into the collection. For some other journals, someone would get one and someone else another journal and they will go into the library. It was very convenient to be able to go in there and sit down and do that rather than go over to the main library and find a parking space. You could spend half a day doing that over there, whereas, with our own library we could go in and do that in half the time.

Hess: It was really something that all of us try to instill in students is accessing the literature. Having it there, the barriers were less. As we look at the way things have changed, electronic media now makes student have access that was practically unheard of in the time we are talking about. Are you a "web-active" person now?

Smibert: Not that much, no. Of course, before I left, we had the service where you could buy a diskette and load it on a computer and run a search.

Hess: That was an ISI product or something.

Smibert: That was marvelous. You could write for reprints.

Hess: Now we are advanced to the point in time where you click and get an electronic file copy. It is like the transition you talked about use of technology for very useful things. The whole idea of what you can do with search engines and accessing stuff so quickly and very high quality material. There was the time I was very skeptical that you were going to get good information off a computer. It is all there right now, not all of it. Of course the historical part is not there.

Smibert: For something published 10-20 years ago, you still probably have to go to the library. If it's recent, say the last five years, is it available?

Hess: Oh it's probably at least 10 years, certainly since 1990.

Smibert: That is about the time I got out, I retired. I have to confess that I have not kept up with anything since I retired.

Hess: That is what retirement is about.

Smibert: Exactly. Now I can go and read all the mystery novels and the other things that I didn't have time to read when I was working. You find out when you are working, after awhile. When I first started out in the 60's you could kind of keep up with a bunch of journals and broadly. By the time I retired, you couldn't. You were just lucky to be able to keep up with a little narrow field, never mind broadly what is going on other fields. It is an explosion of information.

Hess: That is really a loss, because persons we have as role models had this ability to be global information centers. They could think very creatively and in broad terms. I think we are trying to get back to that a little bit, but we rely so heavily on computers to do a lot of the assembly work that is important. That work people used to do in terms of pulling stuff together.

Well, I am trying to think if there were any other things that I wanted to visit with you about. We have talked mostly about the important issues. We are going almost full circle here, so we are almost done. Where was the Army lab located where you initially worked?

Smibert: That was at Fort Meade, MD, the Second Army Area Medical Lab. That was essentially a reference diagnostic lab. It took in every Army, Navy, Air Force base in the second Army area.

Hess: How is it that you and Ed Moore actually connected? Did he recruit you?

Smibert: No, Duke Watson did. I was at Temple Medical School and decided that Philadelphia was not my cup of tea. I wasn't going to be a big city boy. At one of the ASM meetings, I looked around and there was somebody I knew who said they were looking for somebody at VPI. I decided to give it a shot. When I did my Ph.D at Maryland, I was in their veterinary science lab where I physically did the research. So, I thought that was not bad. So, I interviewed down here and they hired me. When I walked in, that is when I met Ed Moore. He had, either at that same time or the previous year, moved from biology to vet science. Both of us being microbiologists we were kindred souls.

Hess: Then getting Cecil here from London. How did that actually happen? What encouraged him to come?

Smibert: Ed and Peg got together and worked on the approach and did a lot of good thinking about it. They came up with some good ideas. Cecil had published the cell wall stuff. They thought it might fit here. They talked to him by phone and wrote to him and everything. They convinced him of this team-type approach. He decided that he would come here, if we got the money.

Hess: Had he visited Blacksburg?

Smibert: No, he didn't.

Hess: So he was really coming site unseen from London. That is astounding.

Smibert: Louis was the only one who had come down here to visit. That was the thing that convinced the study section people that he was serious. He would actually give up being a dean of graduate school in Montana State just to become a professor and do research. I think he was getting tired of being dean and wanted to get back to the bench.

Hess: Let us conclude here unless there is something else you want to reflect on.

Smibert: No, I think we got it all.

Hess: We will transcribe the material and get it to you for review. When we have a final copy, we will put it in the archives.



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