Oral-History:Clark Colton

About Clark Colton

Colton received his bachelor’s from Cornell in chemical engineering (CE) and his PhD from MIT in CE in 1969. Inspired by Ed Merrill, his research focused on biomedical applications of CE. His thesis was hemodialysis (within the field of mass transfer), involving diffusion in blood, diffusion through dialysis membranes, convective transport, and analysis of performance. He then became a professor at MIT (where he has remained). He first had a wide variety of research interests—hemofiltration, oxygen transport in blood, research into diabetes (acting as a consultant on attempts to develop a glucose sensor and a hybrid artificial pancreas), enzyme engineering, and atherosclerosis (particularly transport of lipoproteins across synthetic survey), which last area got him into animal experiments, therefore biology, pathology, histology, and anatomy. In the process his lab got very large and he drifted more into scientific administration; but from the late 1970s he returned to more hands-on research, with a smaller lab and fewer research interests. More recently he has looked into the physical chemistry of antibody antigen interactions to form immune complexes, and particularly into different sorts of research into diabetes and artificial organs—e.g., research into oxygen consumption and uptake, using NMR to study islet properties in vitro. Colton finishes by discussing the way biomedical engineering is taught at MIT and nationwide, preferring an early emphasis on core engineering disciplines, but only later study of biomedical engineering, as a way to tie together different aspects of core engineering knowledge.

For additional discussion of education and research in biomedical engineering and chemical engineering, see Edward Merrill Oral History.

About the Interview

CLARK COLTON: An Interview Conducted by Michael Geselowitz, IEEE History Center, 20 February 2001

Interview #412 for the IEEE History Center, The Institute of Electrical and Electronics Engineers, Inc., and Rutgers, The State University of New Jersey

Copyright Statement

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It is recommended that this oral history be cited as follows:
Clark Colton, an oral history conducted in 2001 by Michael Geselowitz, IEEE History Center, Rutgers University, New Brunswick, NJ, USA.

Interview

Interview: Dr. Clark Colton
Interviewer: Michael Geselowitz
Date: 20 February 2001
Place: Department of Chemical Engineering at MIT

Definitions of biomedical and biochemical engineering, bioengineering

Geselowitz:
What is biochemical engineering and what do the applications of chemical engineering to medicine and biology mean to a chemical engineer?

Colton:
Biomedical engineering should also be included. There was a time in chemical engineering when a distinction was made between biomedical engineering and biochemical engineering. To some extent that distinction still applies but it’s been blurred by the advent of biotechnology. Biochemical engineering came first, and originally it meant the application of chemical engineering principles to producing drugs and other chemicals by microbiological means.

Geselowitz:
Can one use biological and biochemical processes to produce on a large scale just as chemical processes can be scaled up to produce on a larger scale?

Colton:
Biological processes or biochemical processes. Making wine is a biochemical process and you could call those people biochemical engineers. That would probably go back many thousands of years. The first big fermentation process for drugs of which I am aware, certainly for antibiotics, was penicillin. That was in the forties. Merck did a lot there. That was a field that was developed and has continued. Cell culture, and animal cell culture more recently, has become important. That begins to blur the distinction between that which might be called biochemical engineering and biomedical engineering. It depends upon what one is after. That could all fit within the rubric of biotechnology, which makes it quite vague.

However there was a distinction in chemical engineering between the kind of work aimed at producing useful materials by processes and that of work related to medicine and medical sciences, i.e., biomedical engineering. Things that fit in the middle might have been called either one. With the advent of biotechnology, the meaning of that term originally having been related to genetic engineering, has enveloped both somewhat and the two have grown closer together. There is still a distinction of processes versus medical applications.

Geselowitz:
Would you use the term bioengineering or biomedical engineering?

Colton:
Bioengineering would encompass all of it. Biomedical engineering does not normally encompass biochemical engineering processes.

Geselowitz:
How is the work you do distinguished from work done by bioelectrical engineers who call themselves biomedical engineers? Is bioengineering a field that encompasses both?

Colton:
Bioengineering is a very, very broad term. It is not one field. Nearly 80 percent of what I have done would be called biomedical engineering and the other 20 percent biochemical engineering, whereas a bioelectrical engineer would probably call 100 percent of his work biomedical engineering. The fact that I call what I do biomedical engineering and they call what they do biomedical engineering reflects the fact that there is not a well defined core or descriptor of biomedical engineering. One reason for this is it is engineering applied to medical and biological problems. Engineering is broad and encompasses many different disciplines. Furthermore, there are people who apply physics and chemistry to medical and biological problems and some of that could be called biomedical engineering. There again the lines blur. Biomedical engineering really is the application of physical science and technology to medical problems. Different departments have very different personalities, and that’s one reason why there is no clear-cut definition. It’s a field that is incredibly broad with no one core or uniqueness.

Education; exposure to blood rheology through Ed Merrill

Geselowitz:
How did you get involved in these issues back in the beginning of your career?

Colton:
I was interested in chemical engineering as far back as 8th or 9th grade. It’s in an old junior high school yearbook my kids found. My kids asked me, “How did you know what you wanted to do?” I’m not that sure I did, though it’s what I put down. I think I picked it because of my interest in chemistry. I couldn’t see myself working in a laboratory. I figured that chemists worked in laboratories and engineers didn’t. Since I liked chemistry I decided I would like to be a chemical engineer. That had about as much relevance to reality as the Man in the Moon, but that was the original notion.

I went to Cornell and majored in chemical engineering, but partway through I lost interest in it. It was a complicated set of factors, but I wasn’t sure what I wanted to do. I actually went to the psychologists in the medical department and said, “I’ve kind of lost interest and don’t know what I want to do. Can you help me?” They gave me a battery of tests, and when I finished them they said, “Well, these tests indicate that you should be a chemical engineer.” I said, “Thank you very much and goodbye,” because that was no help. That didn’t take me anywhere. I thought about law and took a law school course but didn’t like law school libraries. They were too dusty and made me sneeze. Therefore law was out. I also thought about medicine, but thought it took too long. Little did I know, it takes just as long to do a thesis. In those days business was for people that weren’t very bright.

Geselowitz:
That’s still the case. They just make a lot more money than the rest of us.

Colton:
That may be true. I think society is drifting to more consciousness about material things so that business is up front more.

Chemical engineering won out because I couldn’t find anything else attractive and graduate school was like a holding tank. My father had said, “You should be a professor because you won’t have to work as hard as I do.”

Geselowitz:
What did your father do?

Colton:
He was a sales manager. Little did I know that was misconception.

Geselowitz:
You were uninformed there as well.

Colton:
Right. In college I thought that being a professor of chemical engineering was one of the most useless things one could do, because the role models I had – with one or two exceptions – were not good. At that time it was a backward looking department.

I visited MIT. At that time they didn’t recruit, but they directed me to a student I knew from high school. The only thing that really came out of that was that I saw a list of thesis topics. On there was mass transfer in blood. That intrigued me as being way out, and I thought I needed something way out because conventional chemical engineering kind of bored me – at least that to which I had been exposed. The person that showed me around MIT was working for Professor Ed Merrill on blood rheology. That opened my eyes. I’d never had any particular interest in biology. I took biology in 10th grade, but in those days biology was not for smart kids. It was only descriptive and the biological revolution was just beginning. When I came here I took Merrill’s course on chemical engineering in medicine.

Geselowitz:
I understand that Professor Merrill was the first to teach a course on that topic.

Colton:
I think it started in ’60 or ’61 and it may well have been the first course in the U.S. in the chemical engineering department. There were a handful of other people around the country at the time beginning to look at biomedical problems, but I don’t know that any of them had set up a course.

Geselowitz:
Did you have any exposure to biomedical problems at Cornell?

Colton:
None. Zero.

Geselowitz:
You didn’t have any idea that chemical engineers anywhere were working on these medical issues before you took that fortuitous trip to MIT.

Colton:
Right. I was interested in aerospace when I was at Cornell, but that was not viewed favorably. That was another peripheral area. When I took Merrill’s course I was absolutely fascinated. He’s a good lecturer. Our text was a physiology book and it was pretty simple stuff. I saw how physiology is all chemical engineering. It’s about processes in the body and about fluid flow and mass transfer.

Geselowitz:
Is that essentially across membranes?

Colton:
Yes, membrane transport and heat transfer. Of course there is also a lot of electrical stuff. We got into that except perhaps a very little bit, but it was not the direction in which I was heading. However I certainly could see where chemical engineering could be a great contributor in terms of its core areas to a lot of biomedical problems.

Geselowitz:
You said the biological entity is all chemical engineering. Why isn’t it chemistry? Before we talked about scaling up and chemical engineers as looking at large processes. And you said chemists were the ones in the labs, but now you are in a lab looking at a single membrane in a single organism.

Colton:
It is chemistry. Chemistry is very important. What I meant by that is, once you get beyond the chemistry there are processes and diffusion.

Geselowitz:
Is this because the systems are so complex?

Colton:
They are very complex. An organism is a very, very complicated chemical process. Diffusion is going on at the local level and there is a lot of physical chemistry involved in understanding the chemistry in the body. I’ve always been interested in that area, and that is encompassed within chemical engineering. And there is fluid flow – blood flowing through the veins and cardiovascular system – and there is transported mass everywhere – in and out of cells and across many kinds of organelle boundaries. Much of it was chemical engineering, and Merrill picked out the parts that were most related to chemical engineering, for example the lung is a separator transporting gases to the kidney. I found it fascinating and especially found it incredible that he would give homework problems that would be a chemical engineering analysis of some aspect of either physiology or a biomedical problem. We came up with quantitative answers to things that dealt with the human body and medicine. That was a big and exciting eye-opener for me.

Geselowitz:
Did you decide to go in that direction after taking that one course?

Colton:
Well, I wrote a term paper in there about diffusion in blood.

Geselowitz:
Was this as a first year graduate student?

Colton:
Yes. One of Merrill’s doctoral students, Ben Lipps, gave me some help. I used urea diffusion as the model and in the course of it I became fascinated by it. Merrill had just gotten a big grant to work on artificial kidneys and gave a talk, and of everything I’d heard that was the most interesting to me. Merrill was a polymer scientist and wanted to head toward polymer applications. He was interested in developing surfaces that did not cause clotting of blood. I wasn’t particularly interested in that, but at that time he had enough money that he could accommodate me somewhat. I spent nine months in the library reading about artificial kidneys and wasn’t that much in touch with him.

Mass transfer doctoral research and publication

Colton:

He pulled me into his office at one point and said, “You’re not doing anything. If I don’t have your proposal on my desk by the time I get back Labor Day, you’ve got to find a new thesis advisor.” It was at that point that I informed him I was working on a proposal in the mass transfer area. He wasn’t very interested in that. He was always trying to get me to work on the polymers, but this was what I wanted to do.

He willingly let me do it, but after he saw my proposal he decided to make someone else my primary supervisor because this was not his area of expertise. Ken Smith, who had been gone all that year, then became my primary supervisor. In those days everybody wore a tie but he didn’t wear a tie. When he came and I saw that he was an assistant professor not wearing a tie that worried me a little bit, but I went to work for him and had a great experience. Merrill was my secondary supervisor. There were some things that related to membranes and polymers, and I would go to Merrill for those.

Geselowitz:
Had Smith been doing medicine and biology problems, or was he just concerned with mass transfer?

Colton:
He was doing mass transfer, and he and Merrill had agreed to collaborate. Merrill was very gracious about it and it wasn’t a real problem, but he may have been disappointed that I didn’t work on the polymer end of things. He did a great job of getting me interested and after that I kind of launched. I spent a lot of time on my thesis proposal. He loved the entire literature review when he got it, and he submitted it as a report on his contract to the Artificial Kidney - Chronic Uremia Program of NIH. NIH loved it and published it. That was my first publication. Merrill had it retyped from a Xerox copy of my original. He didn’t want me to take the time to proofread it because I had already taken so much time on my proposal. However I did proofread it, and there were some corrections in there that were done by hand. He wouldn’t let me make any changes, so it was basically verbatim. They printed a thousand copies and they went like hotcakes. It was the first comprehensive chemical engineering analysis of the performance of actual artificial kidneys trying to determine the limiting resistance so where the quickest improvements could be made in the device could be determined.

Geselowitz:
Where could literature on this be found?

Colton:
It was scattered. The early literature was in bizarre places, although some of it was in the very earliest mainline journals. The very first this came out was at Johns Hopkins in 1913. I did a pretty comprehensive survey and think I found almost everything. The recent stuff in the fifties and sixties that was relevant appeared in Transactions in American Society for Artificial Internal Organs, a journal I suspect had been formed in the late fifties. Maybe half of all the papers were in that journal and the other half was scattered around. There was an important paper by Allen Michaels in there. He was one of the first, if not the first, to view it as an analog to a heat exchanger. Another was by Ed Leonard. They had been the first to look at it in this framework. My contribution was finding all the data, analyzing it and making some generalizations about the limiting resistances. There were a fair number of papers, probably on the order of a hundred or so.

Hemodialysis dissertation research; batch dialysis device design

Geselowitz:
Since you now knew all the literature, what did you decide to focus on for your dissertation?

Colton:
I chose to focus on understanding the process of hemodialysis. That involved a multiplicity of things: diffusion in blood, diffusion through dialysis membranes (particularly cellulosic membranes), convective transport in well-defined geometries (I picked the flat plate, which was the most common at that time) and overall analysis of performance. In the course of doing that I began measuring membrane properties in a batch dialysis device I designed. I did the drawings, the whole works. It was modeled after something Ed Leonard had published and he was willing to sell me one of his devices, but Merrill felt that I should design and build it myself, so I did. Ed Merrill was still kind of in charge. My memory is a little vague as to when exactly he transferred me to Smith. It might have been a bit after I finished my proposal.

Anyway, I had taken mechanical drawing in high school and college and he was very surprised when I walked in with complete drawings. He had sent me to an outfit that had done some work for him in Peabody and they helped me, so it was very professionally done. I just gave him the drawings from which they built the device, and Merrill paid for it. I was lucky. He had a lot of money in those days, and I was never constrained by economic shortages. I could pretty much do what I wanted.

Geselowitz:
If money was not the issue, what was the reason he felt you should design and build it on your own?

Colton:
I presume it was for my own edification. Maybe I could build a better device, but I interpreted it that he thought one doing a doctoral thesis should design and build one’s own equipment rather than going out and buying it. I didn’t argue. For me what it meant was a lot more work at the beginning. I went to the library and checked out a book on mechanical drawing written in 1910 to brush up. I had to do things like specify pipe threads. I had never learned how to do that, so I looked in books.

Geselowitz:
You hadn’t done that in high school.

Colton:
Right. When taking chemical engineering the focus was on processes – schematic diagrams of viscous flow sheets and things like that. Building something mechanical with pipe threads and screw threads was something new for me. I had to learn how to specify all of that, and did. I was kind of proud that I was able to do that. I couldn’t do it today, but neither can most of our students today. In any event, I got into how the fluid mechanics and mass transfer worked in the device. That was a kind of side study. I wound up with publications on that. We did a numerical analysis finite difference solution of the convective transport equation. It’s a very complicated system that had never been looked at intellectually. That turned out to be a lot fun.

Then I made measurements with it and had an undergraduate doing measurements of diffusion in blood. I then put it all together in a dialyzer in a very well defined geometry. Another student worked with me on solving the equations for transporting that device. It was like I was running my own little mini-empire. There were two or three students, and two in particular were a big help to me. One was doing a bachelor’s thesis and the other a second master’s thesis.

Geselowitz:
Did you finish your Ph.D. in 1969?

Colton:
Yes.

Geselowitz:
And you stayed at MIT.

Colton:
Right.

Post-graduate work at MIT; state of the field ca. 1970

Geselowitz:
Back to what you were saying before about the field. At that time would there have been other options if you wanted to keep doing the kinds of things you wanted to do outside of MIT? Had your former professors at Cornell caught on yet to these medical applications or was MIT really the place to be?

Colton:
I really enjoyed MIT. I found it very different from Cornell. The faculty at MIT was connected to the world and did a lot of consulting. Cornell faculty at that time was really reactionary. The MIT faculty was much more enlightened. I wore a beard like you are wearing, and twice at Cornell I was told to shave it if I wanted to graduate. They really were rather old-fashioned in their attitudes. When it got personal like that it really bothered me. At MIT there was none of that. The faculty at MIT was much more open-minded. Because they did so much consulting it was an active and very exciting place. It turned me on.

Geselowitz:
So much for your father’s theory about professors not being busy and having a lot of leisure time. And why did you stay at MIT?

Colton:
I interviewed with classic chemical engineering companies and oil companies, chemical companies. That was all that was available. At that time chemical engineering was hot. I went on eleven interview trips and got ten or eleven offers. I formed a company with two guys with whom I shared a lab plus a third guy who was in materials. We formed a little company we called Tech Recruiting to write a book about how to recruit MIT Ph.D. students.

Geselowitz:
That was very entrepreneurial.

Colton:
We put the head of the MIT Placement Office on our board of directors, had stationery made, and sent letters out to the Fortune 500 or S&P 500, whatever it was called at the time. I think we were charging five hundred or a thousand dollars for this book, and they wanted it. We wrote the chairman of the board of every company. The guy from Allegheny Ludlum Steel who was with the MIT Corporation wrote the chairman of the MIT Corporation saying, “What the hell is this? Don’t we give enough to MIT? Now you charge us another thousand dollars?” What caught his eye was the fact that the head of the MIT Placement Office was something like our chairman of the board. The short story is, he got fired because of that and we got chastised. We were called in and told, “Don’t tread on MIT’s name. Don’t use it in vain. Don’t make use of it period,” we said, “Okay.” We went back, sent letters out, never finished our book, and that was the end of my publishing career in recruiting.

The point is, I was pretty much programmed to do regular chemical engineering. I just happened to be working on this, but I really liked what I was doing. I don’t remember exactly how my joining the faculty came about. I think maybe my thesis supervisor said something to me like, “I could tell you were thinking about it.” The part I remember clearly is that he went to the department chairman and I was told I could have a position as an assistant professor here when I finished my thesis.

At that time MIT had a grant from the Ford Foundation. They hired a lot of their own students and made them assistant professors and Ford Foundation Fellows. That was usually the kiss of death because what it really meant was, “We’re training you to go outside.” I got that and I had it for one year, but when the program ended and I was allowed to stay. Thing were very tense at that time, I’ve got to tell you, because the percentages were poor. When I joined the faculty I had a debate within myself. “Well what am I going to do? I want to do biomedical work, but is it really legit and will it be viewed as legit?” I knew that Professor Merrill was not universally viewed as doing solid work because of his work with blood. There seemed to be an attitude of “What kind of nonsense is this?” I think he had commented about it. I wanted to continue in this direction but I also had to do good engineering. I wanted to pick problems where I could see an engineering component.

Geselowitz:
Did you want it to have an engineering component so that you could explain to other chemical engineers who had no interest in biomedical work the problem in terms they would understand and think of as relevant?

Colton:
Exactly. We would make use of the skills we learned as chemical engineers and apply them to a new system. That characterized some of my early work, although I rapidly became a lot more biological or physiological than I had anticipated in some ways. And at that time I was in touch with a small number of students around the country who had gotten their Ph.D.s working on biomedical problems. When I graduated I knew everybody in the country who was working on a biomedical problem. That was only about three or four people, although it started to grow rapidly. At meetings or talks we gravitated toward one another because we were not part of the mainstream.

Conferences; growing student and researcher interest in biomedicine

Geselowitz:
What meetings or conferences or series of conferences accommodated you?

Colton:
The American Institute of Chemical Engineers was having meetings on chemical engineering in medicine and biology. I presented a paper at one of their meetings in ’68. Also there was the American Society for Artificial Internal Organs. Two government programs were the major fueling mechanisms at the time. The Artificial Kidney Chronic Uremia Program (AKCUP) was where Merrill got his money. There was another program whose official name I don’t remember. It was an artificial heart program. They also worked with blood oxygenators. That was in what is now NHLBI. The other is now NIANDDK, or something like that with a lot of letters, having to do with digestive metabolic kidney diseases. I went to the kidney program as soon as I passed my thesis. They also asked me to join part of their review committee and be a consultant, so I went to all those meetings. And these were the main programs at the beginning, but I’m sure there were some others. There was the Engineering in Medicine and Biology Society (EMBS), which was the IEEE thing and was broadening.

Geselowitz:
Right.

Colton:
I went to some of those meetings in the early stages. That’s where one could hang out with the chemical engineers. There would be a tiny handful of us. It was all electrical EE stuff that none of us understood. They would have a few sessions we’d attend, and I met people there. In the beginning it was a very closely-knit group of people. We all knew each other and knew each other’s work – which is very different from today. I liked it when there was a small number. You’d meet the same people, touch base, learn what the others were doing and then in fact teach it. Courses were starting. I took over Merrill’s course around ’71. I taught what he taught added things, some of which reflected research going on around the country.

Geselowitz:
Was the growing interest due to growing opportunities for students in this field or a growing recognition that it was a useful way to teach because these were complex systems that involved chemical engineering principles? Why were the courses proliferating?

Colton:
I must say they were proliferating slowly. There were just a few places and a few highlights of people doing work. The real growth took off around the mid-seventies when a lot of departments decided they needed to have someone doing this kind of work. A lot of my early students went into teaching because there was a big demand. Yet there were only a few of us turning out people who went into teaching.

Geselowitz:
Was what you were doing in the mid-seventies, chemical engineering in application to medicine and biology, still separate from the traditional biochemical field?

Colton:
Right.

Geselowitz:
This biotech stuff that we now see that I got lost in because it’s all biogenetics. There used to be no biogenetics, and now the program is biogen. I guess that was just beginning to peek on the horizon.

Colton:
No, that didn’t start until the late eighties or early nineties.

Research in membrane processes, oxygen transport in blood, biohybrid artificial device to treat diabetes

Geselowitz:
Going back to when you were still a relatively small peripheral group, to what problems did you turn your attention next?

Colton:
I continued to be interested in membrane processes. My interests bifurcated and trifurcated over the next couple years. Right after my thesis I had a summer job at Amacon Corporation. That was an incredibly stimulating environment. I was out there when fiber ultrafiltration membranes were first developed. They were looking for applications and trying to understand how they worked, and I got involved in some basic work in an application that led to a new process called hemofiltration. That was really very exciting.

When I was a student, I got involved in work on membrane oxygenation through some consulting. I had sat next to a student, Richard Buckles, who had worked on oxygen transport in blood. There was a request for a consultant that came while I was a doctoral student working on a device to take oxygen out of blood to power a fuel cell for an artificial heart. I made use of the work in his thesis in my consulting. That got me interested in oxygen transport in blood.

A couple of days after I joined the faculty I was approached by Bob Lees who in the department of nutrition and food science. He walked into the office and said, “I’m looking for a collaborator. I just went to see Ed Merrill. He’s tied up. He sent me to you. Are you interested in collaborating?” He went on to explain that it was about atherosclerosis and how lipids get into the wall of the artery. I said, “Well, you’re the first guy in the door. Sit down. Why don’t we do it?” It literally happened like that. I read, attended meetings and began to learn about it.

One of the first meetings I went to was a World Congress on Atherosclerosis in Canada. It might have been in Toronto. I met one other engineer there, Bob Nerem, who was also just starting to get involved in this area. As a result of my learning I started to get into experimental work in this area, first looking at the transport of lipoproteins across synthetic membranes. We quickly realized we weren’t going to learn a lot that way, so we decided to do experiments in animals. That was a very painful growth and learning period. We benefited by having a visiting professor at the Clinical Research Center named Don Zilversmith. He had done work on lipid uptake into vessels. He helped us get started with animal experiments. I had animal experiments going on here for about fifteen years, mainly in rabbits and some in monkeys. They got me pretty deeply into biology, or learning a lot about pathology, histology and anatomy. That was another direction.

Geselowitz:
Had this building been built yet?

Colton:
No, not when I started.

Geselowitz:
Where was the chemical engineering department in the early days?

Colton:
Chemical engineering was in what is now Building 12. The arrangement there was horrible. My office was in a central corridor and had no windows to the outside. However it was a fertile place. The experiments at that time were being done at an animal facility somewhere, probably near the Clinical Research Center, which was in what is now an administration building. Later when we moved into this building we did experiments with rabbits and monkeys in the building. We didn’t keep them here, but brought them here for the experiments. We had our own little surgical amphitheater. We used radioactive tracers, euphemized the animals, took their aortas and analyzed them.

Another direction in which I got started early was diabetes work. I don’t remember how it happened. Someone called me up looking for a consultant on developing a glucose sensor. I agreed to work with him and got deeply involved in that. That actually led to a doctoral thesis here in the eighties. That was an effort that continued for a number of years. I also got involved with one of his colleagues at Jocelyn Diabetes Center. He was interested in a biohybrid artificial device – called a hybrid artificial pancreas in those days – with living cells. That opportunity came through Amacon Corp. I agreed to work with him as a kind of consultant. We would go to group and eventually I brought the problem into MIT. In the earlier stages the work went on at Amacon Corporation and then Brown University.

The collaboration we had at MIT working on the biohybrid artificial device fell apart, but I got back into the field and am still working in it – and in diabetes in general. In the beginning it was transport oriented. Now it’s a bit more biological. I went in a number of directions simultaneously, and in those early days I ran several different research groups that had nothing to do with one another. And they were focused in different laboratories.

Laboratory organization and collaboration

Geselowitz:
Would you say that was typical of the field of chemical engineering, typical of the field of chemical engineering in medicine and biology, or just typical of you?

Colton:
I think it was typical of me. People around here later told me when they were looking back that I kind of exploded. I got really excited and got involved in many things. I benefited by being a young faculty member with some room for expansion in an area that was growing slowly by today’s standards, but growing nevertheless. Ed Merrill was quite busy and sometimes he would send people to me. After a while some just came straight to me.

Then there was yet another area in which I got involved, and that was through our department chairman at MIT who was pushing enzyme engineering. It was part of a larger program aimed at using enzymes to carry out a chemical process to synthesize chemicals. We were looking at antibiotics with enzymes using ATP as an energy source to push the synthesis. That was very exciting and I had a very big lab on that.

Geselowitz:
That’s sort of biochemical engineering.

Colton:
Yes. That’s kind of biochemical engineering, or in the middle. A postdoc here was Barry Solomon that had been at Grace and that was spun out. He is now a vice president at Sursty. Colin Gardner, a vice president at Merck, was another student in the lab, as was Bob Langer. It was very fertile and exciting. Bruce Hamilton, who is now at NSF, was another student in the lab. He is now at NSF. He had been at Grace. The fourth floor was all mine.

I continued that for a while and then decided I didn’t like running such a large operation. I found that I wasn’t as close to the action and the data, and quality control was slipping. I knew I was in trouble when an undergraduate that worked for me in the lab came in to meet with me and I didn’t even recognize her. I decided that I didn’t like running a gigantic lab. I tend to be data-oriented and get really excited about what’s going on in relation to problems and real solutions. I like to work with the students on the data and deciding where to go in the research and its interpretation. I liked administrative work less.

I was deputy head of the department for one term in ’77 or ’78 shortly after we moved in here. I learned at that time what administrative work was all about. It wasn’t a big deal. I’d done everything once – budgeting, tenure cases, that kind of thing – and just didn’t think it was as exciting as working with students. I cut back my lab somewhat and went on sabbatical and when I came back it had been cut back a lot. I built it back up, but I never quite to the level it had once been. Again, when it got really big I found I was doing more administrative work and I didn’t like it.

Geselowitz:
Was your work more focused the second time around or did you still find yourself beginning new groups when people came around wanting to collaborate?

Colton:
I was still getting into new things, but old things were dropping off. The enzyme program and some of the membrane work had ended. I got into new kinds of membrane work dealing with microfiltration and as well as using membranes as infinity supports for separating proteins and later cells. The atherosclerosis work continued. The character was changing and I didn’t have as many irons in the fire as I did when I got started. I also got extensively involved in some physical chemistry of antibody antigen interactions to form immune complexes. That was with Martin Yarmesh who came here to work for me as a student. He already had an M.D. and a Ph.D., so we made him a research staff member and we worked collaboratively for a number of years. He eventually left, but I got into quite a bit of work on antibodies with him.

I have gotten into a lot of different things over the years. I tend to like things at an early stage when there is still mystery, especially when I was younger. I get most excited about the early data, but I’ve changed and I think over the years I have focused a lot more. I dropped off a number of areas.

Current research on diabetes and artificial organs

Geselowitz:
What are your main foci now?

Colton:
Right now I am focused on diabetes and the area of artificial organs that I got started in about 1973. I’ve expanded that work. A lot is going on with islets of Langerhans per se. It might be called cell biology or biochemistry or biochemical engineering, but the obvious application is biomedical. It’s for transplantation. It’s really a blending of everything. It does have a transport flavor. A lot of what I’m doing deals with oxygen consumption and uptake. Someone in the lab introduced me into NMR, and now we’re using NMR to study islet properties in vitro and possibly in vivo. I’m still getting into new things – that doesn’t end – but it’s all now more focused in the diabetes area.

That’s not to say I won’t open something new. I still have one student left who nominally is working on flow in the cardiovascular system, but we took a side path and I’m not sure he is going to get back to it. We’ve had some research going on in rapid cooking using simultaneous convection radiation and microwave. That resulted in a company coming in and wanting to sponsor some work in a course I was teaching, and we did some food engineering research on the side.

I stopped the affinity work in membranes a while ago. That could begin again, but I’d say most of my effort is now centered in the diabetes area. I’d like to enlarge my lab a bit from where it is now, but I don’t want to get too far away from the action.

Students' careers

Geselowitz:
You mentioned earlier that you were one of the people producing students who then taught.

Colton:
Back then.

Geselowitz:
Yes. What would you say most of your students do now? And how has that changed in terms of drug companies versus biomedical engineering companies versus just doing this and then going back to traditional chemical engineering? Where do you see your students going? Has that changed?

Colton:
It’s more of a blend. In the early days there were no industrial opportunities. Some of my early students went to work for membrane companies, but academia was the most popular route at the time. In the eighties industrial positions began opening up, and since then there have been a number of industrial positions. I have had quite a few students go to Baxter Health Care over the years, though most of them have left. I still have one student and a postdoc there. Some of that resulted from the fact that I was consulting for Baxter and I knew a lot of the people and knew of positions that might be good for them.

One of my earlier students went to work for a company called Ceto Therapeutics. They were doing bioartificial organs. Then he left there and went to Alza and developed an implantable pump for humans. He got bored, so left that and joined Millennium. I think he is doing very well there. That’s a totally different area. He was one of the first engineers to be hired by Millennium, initially as a project manager. Their founder and chairman of board, Keith Beyon, is a chemical engineer. I’m not sure what he is doing right now, but he is running some of their programs.

The opportunities have expanded and students go a lot of different places. A recent student went to a membrane company. Another recent student got a job with a local patent law firm. They’re putting him through law school. I haven’t lost anyone to finance, but I have one student who I think is going to work for a software company. The education that we give here should allow students to go to a wide variety of places, and that is still true. There are academic openings, but the industrial openings are far broader than they once were and I’ve seen more students go in that direction.

Chemical engineering, biomedical engineering, and bioengineering pedagogy at MIT

Geselowitz:
What is MIT’s attitude toward the field from an overall undergraduate educational perspective? Is a typical undergraduate chemical engineering student coming out of here exposed to medical and biological applications in chemical engineering?

Colton:
Within chemical engineering we have made an effort to bring bioengineering applications into homework problems and things like that.

Geselowitz:
Is this is in the mainstream chemical engineering courses?

Colton:
Yes. We don’t teach things that you’d call biomedical engineering within the mainstream courses right now, but some fraction of the homework problems deals with biomedical applications. Some of these are naturally very good problems.

Geselowitz:
When I was an undergraduate in the seventies, Benedict and Bielers were two physicists introduced the physics sequence everyone was required to take. It was a separate physics with biology applications. There were no biomedical applications taught in the regular 801/802 Physics I and II sequence. I don’t know if that has changed and those are now routinely taught. Medical applications have become such a huge field in physics, electrical and mechanical.

Colton:
Are you speaking of undergraduate courses?

Geselowitz:
Yes, the 801/802 sequence.

Colton:
A lot of our undergraduates can take graduate courses. There is a course that Langer teaches about biotechnology, examples of development of drug processes. He and someone in chemistry teach that. All students at MIT are now required to take a biology course. I don’t think we have any other undergraduate courses within chemical engineering. We have had a biochemical engineering course for a long time now. Undergraduates probably could take that, but I think it’s a graduate course. We now have a biomedical engineering minor and there is also now a master’s program in bioengineering and environmental health. It has expanded in that direction. I’d say fully a third of our students intend to go to med school, are biology double majors, biology minors or in effect chemi minor. We have a 10C program. There are a lot of students in our program who get a big dose of biology, and I think that’s a very good thing.

Geselowitz:
It sounds like it is still not completely mainstream. For instance one could still receive their education at MIT and go to work for an oil company without ever having been exposed in a serious way to the kinds of problems on which you are working. Am I reading that correctly?

Colton:
That’s true. However there are not many jobs at oil companies these days. Not like it used to be anyway.

Geselowitz:
Right. Maybe that was a bad example. Obviously there are more jobs in biotech.

Colton:
Numerically, that depends on how things are going in the economy. Certainly the oil companies are not where they were years ago. There was an implication in what you said that every student should be exposed to what I’m doing.

Geselowitz:
You don’t think that’s necessarily true?

Colton:
No. I think every student should have some working knowledge of biology. I think it’s very important to be able to read whatever is on the front page of the New York Times and understand it. By the same token, they should have physics and know some of astronomy and whatever. Biology is very important and they need to have an understanding from a relatively basic level. Beyond that, I don’t think it’s necessary that every student be exposed.

Geselowitz:
Unless they are going to pursue biomedical engineering?

Colton:
Yes.

Geselowitz:
You mentioned that Professor Merrill started that course back in ’61 or ’62 and that you took it over. Is that basic course still taught?

Colton:
It is no longer taught with the same title. I had a course on artificial organs for a while that part of the HST program with Harvard. I co-taught with Bill Dean for a while and we taught a course called biomedical transport. And sometime in the early to mid-nineties I was asked if Linda Griffith could modify and teach that course. She modified it into a course on tissue engineering. She taught that in the department and I stopped teaching it. I don’t remember if that is still a department course or a BEH course. A lot of the concepts she teaches are similar to what I covered years ago, though the applications are not all the same.

I was asked to resurrect our undergraduate lab course about five years ago. Then I got involved in our undergraduate transport course, so I’ve been doing both of those for the last three years and I’ve not been teaching a bioengineering course. I enjoy those courses, so it’s been a conflict.

Bioengineering and chemical engineering texts; student preparation and interest

Geselowitz:
If you wanted to teach an undergraduate course tomorrow, an introduction to bioengineering with chemical engineering applications to medicine and biology, could you order textbooks for that or would you have to write something yourself? You have created many different things. Someone who doesn’t know a lot about it who hears of these different areas might find it difficult to see all the threads that tie these together. They seem very diverse. Could you sit down and write textbook and tell undergraduate chemical engineers about biomedical applications – and put it all in one place? Is that possible? Or has that been done?

Colton:
It depends on what you want to teach. There are a few books of which I am aware related to things that I have done. There could be something written on biomedical transport, and there’s a handbook of bioengineering. However from my standpoint, in general, the answer is no. There isn’t anything out there. I don’t think there is agreement even as to a core. There is no core. The core of bioengineering is the core of different engineering disciplines. It depends on the painter how he’s going to paint the details around it. It’s different things to different people, and in different departments it’s different things. The biomedical engineering departments around the country certainly have different flavors. The older ones are dominated by EE.

A number of the new ones are populated by chemis. A number of the chemi applications have become the trend. I don’t know what it’s going to be in ten or twenty years, but lately there are a lot of things that chemis have worked out. It’s grown, yet it doesn’t exist in that it doesn’t have a central focus. That’s its strength and its problem. What that has meant on this campus is that we don’t have an undergraduate bioengineering program per se and the philosophy has been to develop expertise in one area to the point where one can intelligently go forward and bring it to biology or medicine. Otherwise, the expertise cannot be developed.

I could tell you stories about students that we get from other places. I would have to say that in many cases the students who come in with biomedical engineering undergraduate training are at a deficit with respect to their competence in areas that we consider important. The question is, “What is it that you are going to train?” I have no problem with bringing in biology and medically related courses, but I think the engineering must be learned to a point where one is competent and can apply it before bringing in bioengineering. Bioengineering can be brought in too early. Engineering is something where one doesn’t really get it the first time around. That’s a characteristic of engineering, and it’s true of all engineering disciplines. Students have a horrible time in the core areas because they don’t get it. They don’t get it because engineering is not pure equations; engineering is also judgment. And when you get into judgment you get into art, because there really is an art to the judgment.

I’ve been trying to figure this out because I see students having so much difficulty. When they are given a problem, it’s a problem in words and pictures. Understanding how to relate the mathematics to the problem is very, very difficult. I certainly struggled with it. I’m no different than anyone else. A common experience in the courses I teach in mass transfer is that when students do well they think they understand. Then in graduate school they realize that most of the time they didn’t really understand what they now understand. Okay? They get it the second time. I’ve heard from other departments this is true in all engineering. Then they do a thesis and realize, “Wow. Now that I’m really getting into it, I realize how little people know.”

It’s a problem no one has ever solved. And of course the thesis is focused on just a small area and one becomes an expert in just that area. Then when they go teach it, they have to teach it more broadly and they begin to have a much bigger perspective of how little we know. Practitioners as well as teacher begin to fully understand the art in approaching a problem; how to simplify problems so they can be reduced to what is often relatively simple mathematics or it’s idealizations.

How does one know when to apply the idealizations? How does one figure out what is important and what is not? This is art, it’s judgment, and it comes with experience. It’s why students have such a hard time with that material the first time through. Every engineering professor who teaches a higher order course will tell you that when the students come in it is really as if they never took a prior course. This is common. It’s not that they didn’t work hard. It just doesn’t stick very well the first time and the judgment one needs in order to know how to go about analyzing a problem takes experience. Synthesis? It’s harder for me to figure out what that requires. That’s another area and another way of doing things.

The point is, this stuff is hard to learn. If you give students just a bit of engineering and get into the applications too early, you have stolen from them the opportunity to develop some competence. For that reason bioengineering is a really tough thing. I think that in most cases it’s been a mistake to develop large numbers of engineering programs. Graduate programs? Yes. Those are appropriate. And there you focus in certain areas and develop confidence in certain areas. The students can choose when they decide where they want to go in what sub-areas a department should be active, because every sub-area is a bit different. That’s dangerous at the undergraduate level, because you run the risk – which I think has played out – of training people who are only modestly competent, if at all, in fundamental areas.

I’m not alone in that opinion, though I don’t know how popular a view that is today. It certainly was the dominant view at MIT when I came in as an assistant professor. Maybe I’m brainwashed. However it’s an opinion that I continue to have because of the students I have come across who were trained in biomedical engineering. With few exceptions their level of competence is lower.

Geselowitz:
Looking back at the past fifty years, how do you see the field of biomedical engineering emerging in regard to both how it is taught and its accomplishments? Well, I think we’ve pretty much covered that. Is there anything else you’d like to say about your career or biomedical engineering for the record?

Colton:
It’s certainly something that attracts a lot of students. There is a lot of enthusiasm about it.

Geselowitz:
Do you think that is due to the fact that it’s a hot field now with job opportunities or do you think it’s the same sort of fundamental things that attracted you years ago?

Colton:
I don’t know how hot it is in terms of actual numbers of jobs compared to many other areas. I’d be careful. These opportunities come and go. In the biotech field they tend to be small companies. There are bursts of hiring, but it can quiet down. For example many companies hired students with experience in separations. That hiring has quieted down. The people are out there now, and there is less of a demand.

I think people are motivated in part because it’s one of the few areas where you can feel you are doing some good for mankind – even though people don’t always verbalize it. Some do. When I got started one of the things that appealed to me was the fact that this research ultimately might contribute to the betterment of mankind as opposed to just “making money.” Those two motivations meshed a lot these days. In the beginning I think a certain amount of idealism went with it. I think students may be motivated in the environmental area that way as well, but I don’t think that has quite taken off. However since we don’t have an undergraduate program here in the environmental area I should be careful what I say. I think other places may be more active than here at MIT.

Geselowitz:
Environmental engineering.

Colton:
Yes.

Geselowitz:
Is that usually following more the civil rubric than the chemical or both?

Colton:
It depends on the department. We definitely have environmental work going on at MIT on the undergraduate level. Some of it is related to energy. However we don’t have an environmental engineering program per se. It’s a little bit like the bioengineering area. Why don’t you shut it?

Geselowitz:
Are you all set?

Colton:
Let me think for a minute.

Colton:
Okay.