Oral-History:Buddy Ratner

About Buddy Ratner

Ratner was born in Brooklyn in 1947; was a Chemistry undergrad at Brooklyn College; and received his PhD at Brooklyn Polytechnic. There he specialized in polymers, particularly hydrogels, doing his thesis research on a hydrogel membrane for an artificial kidney. He then joined Alan Hoffman as a postdoc at the University of Washington, where he has spent the rest of his career in increasingly senior positions. His first research involved blood compatibility with biomaterials; this turned into research on the surface structure of biomaterials, so as to create a benign biomaterial that will not cause blood clots or other bad reactions. In 1984 he created a National Surface Analysis Center for Biomedical Problems, with NIH funding and equipment from a Shell instrumentation grant. In the early 1990s he began to think improved surfaces weren’t actually providing better results for biomaterials, so he did some new research into modern biology and found out that cells send each other recognition signals. The most benign biomaterial without that signal is still recognized as foreign, so now he had to figure out how to positively encode biomaterials with these recognition signals (or some similar solution to the problem). This led to a new research focus and to founding a new center (University of Washington Engineered Biomaterials). Ratner has been President of the Society for Biomaterials (1990-91) and of the American Institute of Medical and Biological Engineering (2000).

About the Interview

BUDDY RATNER: An Interview Conducted by Frederik Nebeker, IEEE History Center, 5 December 2000

Interview #409 for the IEEE History Center, The Institute of Electrical and Electronics Engineering, Inc., and Rutgers, The State University of New Jersey

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It is recommended that this oral history be cited as follows:
Buddy Ratner, an oral history conducted in 2000 by Frederik Nebeker, IEEE History Center, Rutgers University, New Brunswick, NJ, USA.

Interview

Interview: Buddy Ratner
Interviewer: Frederik Nebeker
Date: 5 Dec 2000
Place: University Of Washington, Seattle, Washington

Childhood, family, and educational background

Nebeker:

Could we start by your telling us where and when you were born and a little about the family you came from?

Ratner:

I was born in Brooklyn, New York, on January 19, 1947. My dad was an electrician. In fact, at that time he was working for the Pullman Company. They were doing a lot of work on luxury rail cars at a time when there was a market for such things. We were quite far from wealthy. I’d say kind of a lower middle class existence. In fact, at first, we lived in a small apartment above a laundromat in Brooklyn. My Dad strongly encouraged education was a great influence on me that way, starting in those early days.

Nebeker:

You weren’t quite under the roller coaster that Woody Allen describes.

Ratner:

No, not quite, but a block or two from the elevated trains. It was 1947, and by 1951 we moved up in the world to a brand new cooperative apartment building in Brooklyn—sort of modern accommodations—which is where I lived until I got married.

Nebeker:

Were you interested in science and in gadgets as a youngster?

Ratner:

I think as early as I could remember I was interested in science, especially chemistry. I’ve always been interested in chemistry.

Nebeker:

Did you have a Gilbert Chemistry set?

Ratner:

I had a chemistry set. More than that, even as a very young boy I quickly outstripped the resources of these limited chemistry sets. So, I’d go exploring in New York. Manhattan was a fertile ground to find most anything, and there were a lot of shops that sold chemicals to amateur chemists, at least back in that time. I think I knew most of them and would go there to buy little bottles of chemicals and things to do experiments.

Nebeker:

Is this like high school years?

Ratner:

Even in junior high—that’s probably where it started.

Nebeker:

What sort of experiments were you doing during these times?

Ratner:

Well, one whole set of them that has a natural appeal to kids is fireworks. I must say it stimulated a lot of thoughts on chemistry because you got to do a whole lot of mixing formulations and wonder why it worked and why it didn’t.

Nebeker:

Your parents didn’t object to you using those chemicals?

Ratner:

Not that they were all that cognizant of what was going on.

Nebeker:

Another thing I know kids love are magic tricks.

Ratner:

Yes. That was indeed another area—chemical magic. But I also think even back in that early era I became intrigued with polymers. I remember as a boy trying to make a urea-formaldehyde polymer, which is kind of like the polymer that’s used for something like a light switch. It’s a hard Bakelite-like plastic. My synthesis was a bit off and the house got rather stinky, if I remember correctly. I was playing around with that.

I also had a microscope and I was very interested in biology. I would go out to the ponds and things like that and take back samples of paramecium and such. I was doing quite a bit of work actually looking at blood smears and staining them in different ways. These were things that interested me as a boy.

Nebeker:

You went to public schools?

Ratner:

I went to public schools, yes.

Nebeker:

How was your high school?

Ratner:

In grades kindergarten through six I received very little science training. I was very, very interested in it, but the teachers were not up to really being able to give much science. So the science I got was at a very limited level through that era. I read a lot in books from the public library to supplement the very little I was getting in class. Once I got into junior high school there were formal science classes. I was very enthusiastic about it and did well.

Nebeker:

Did you have good science teachers in junior high and high school?

Ratner:

I think so. They certainly stimulated me. Particularly in high school I remember a number of very good science teachers, for example, Solomon Feldman at Wingate HS in Brooklyn, that really did stimulate the excitement of science. So, high school was especially a good time.

Nebeker:

Did you decide you wanted to be a chemist in high school?

Ratner:

I had two areas that I was doing well in as I was approaching the end of my high school career. One was science and one was art. I was doing a lot of drawing, painting, photography and things like that. This was the era when the Sputnik had gone up and the U.S. was looking towards how we would encourage people to go into science. There was a future and opportunities in science. Looking at what the options would be in art, it would be very competitive and a very difficult area to make a living in, frankly. So, although I was quite interested in both, a little left and right side of the brain, I chose the science approach and began focusing on that.

Nebeker:

But not specifically chemistry at that point?

Ratner:

Not specifically chemistry. But, again, of all the subsets of science, chemistry, and biology had interested me most at that point. To this day I remember a scene in the movie The Graduate where Mr. McGuire put his arm around Dustin Hoffman and said, “plastics.” It was an era where plastics were viewed as the future. They were viewed as an exciting area. Of course, probably into the ‘90s people started viewing plastic as cheap and junk, and being made out of plastic was almost used as an adjective with a negative connotation to describe things. But back then plastics were very positive. Anything made of plastic was great. It was the highest quality and sort of state of the art and the best thing.

I had gone to a World’s Fair in 1964 in New York. General Electric had a pavilion there. It was sort of a “Better living through chemistry.” Actually, I think that might have been DuPont’s phrase.

Nebeker:

Maybe DuPont’s slogan.

Ratner:

General Electric did have a kind of a “Better Living through Chemistry” -- again, it wasn’t their words -- exhibit where they had a couple of polymer demonstrations making polyurethane foams and things like that. I thought this was just great. I thought it was extremely exciting stuff. It sort of triggered this one area of chemistry and technology, polymers, in my mind as something I might want to pursue later.

Undergraduate chemistry studies at Brooklyn College; graduate studies at Brooklyn Polytechnic

Nebeker:

Where did you go to college?

Ratner:

I went undergraduate to Brooklyn College, and as soon as was feasible I went into a chemistry undergraduate degree.

Nebeker:

This was not Brooklyn PolyTech.

Ratner:

No. This was Brooklyn College, which then was independent and has now become part of the City University of New York. I took the usual courses one needs for a chemistry major. My senior year in a course of study I was doing pretty well at, I got to know one of the professors, Milton J. Rosen. In fact, I did some work for him, just miscellaneous work in the chemistry stockroom and such. It wasn’t research. But I managed to convince Professor Rosen that maybe in one of the advanced courses the students might be interested in hearing a few lectures on polymers and what they were about. Sure enough, he incorporated them into a course. Again, I found this very interesting. It just reinforced polymers as an area I might be interested in studying.

Once that was in my head, I applied for graduate school and looked for where one could study polymers. At that time there were not a lot of places to study polymers. The major option in the world was right in Brooklyn at Brooklyn Polytechnic Institute. Herman F. Mark, was one of the pioneers in polymer science and studied under Hermann Staudinger, who won the Nobel Prize for developing what’s called the Macromolecular Hypothesis, the concept that polymers are made of long chains. Mark made major contributions in the polymer science field. He started the program at Brooklyn Poly, which was the first program of its type in the United States. It nucleated many of the pioneers in polymers in the United States at that point. These people spread the word and started moving out.

When I reached graduate school, the polymer science was just spreading. Some of the people who had been at Brooklyn Poly for years and years and had recently left and nucleated programs at other schools. But those programs weren’t yet well structured. At the moment I chose to start graduate school there was very, very little happening out there. For example, there was also a small school called Steven’s Institute of Technology, and they had a sort of polymer processing that was industrially oriented, and it wasn’t really what I had in mind. So, Brooklyn Poly did have the program. It wasn’t all that great an idea in my mind to continue going to school in Brooklyn because I’d been there my whole life, but it seemed I had little choice if I wanted to seriously study polymers.

Nebeker:

It’s a great engineering school.

Ratner:

It was a great engineering school. They had practically the only program in the country that I really wanted.

Nebeker:

I got to know Ernst Weber well, by the way. We did a book together.

Ratner:

He was the president.

Nebeker:

He’s, of course, in the EE department and then was president for many years.

Ratner:

I might have just barely met him. George Bugliarello took over some time after Ernst Weber. In any event, Weber was finishing his tenure there at the time I was just coming into Brooklyn Poly.

Nebeker:

So, you chose Brooklyn Polytechnic for graduate school?

Ratner:

Yes.

Nebeker:

Was this chemistry or chemical engineering?

Ratner:

It was chemistry. Some interesting things happened. Polymer chemistry has always straddled the border between engineering and chemistry. Academic chemistry in those days was heavily oriented to fundamental knowledge, very basic, fundamental studies. The polymers people were interested in fundamental aspects too. But there was always such an immediate application that there was not such a clear defining line.

Emergence of polymer chemistry as a field; Brooklyn Polytechnic polymer faculty

Nebeker:

So, polymer chemistry sort of emerged as this part science/part engineering field?

Ratner:

Yes. It’s a specialty that straddles many disciplines. It’s a very basic science -- a number of Nobel Prizes have come out of polymer chemistry and polymer physics, just to show it’s fundamental importance. From another standpoint, there’s an obvious massive commercial and industrial interest. In any event, I applied and was accepted into this program.

I mentioned that at this point Brooklyn Poly had just started, if you will, spreading the word and sending its formerly cohesive faculty out into the world. James Mark had gone off to another institution and Charles G. Overberger, who has been at Brooklyn Poly since 1947, had gone off in 1967 to another institution. That left the first vacancies in years on the faculty in the polymer area. It was a stable faculty for a long time. These early Brooklyn Poly polymer faculty became sort of the bedrock of American polymer chemistry.

But, there was an opening and they hired an interesting individual—a man named Dan Bradley. Bradley was the head of the Physical Chemistry Section at the NIH at that time (1967). He was working on a subject that back then was very esoteric and now is actually pretty hot in its own right, which is dye binding to nucleic acids. He was basically a physical chemist. DNA, of course, is a polymer.

Bradley basically wanted to leave the U.S. Government in protest over the Vietnam War; he did not want to be associated with the government that was sponsoring this war. He had risen to a position of some importance in the NIH and decided to seek an academic appointment. They hired him as a full professor into the polymer program, which is part of the chemistry department at Brooklyn Poly. When Bradley arrived he wanted, in breaking with his past and with the work that he did with the U.S. Government, to explore new areas.

He chose three areas of research that seemed like they would have great potential for expansion. One was membranes for reverse osmosis. The first reverse osmosis membranes were just developed at that time – there was an engineering focus on what had been done. He started a project studying these structures from a more physical chemistry perspective. The second area of research he started was in the chemical basis of the sense of taste. How do we taste different things? And the third area he started was a project on hydrogels — hydrophilic gels for medicine.

Nebeker:

Were there applications at the time?

Ratner:

There was a paper that came out in Nature in 1960 from two gentlemen in Czechoslovakia, Wichterle and Lim. This paper described the first synthesis of a designed artificial or synthetic gel, that seemed to have very interesting properties for medical applications. This gel very quickly became the first soft contact lens. So, the paper came out in 1960, and by 1967 Bausch and Lomb is already selling soft contact lens. They licensed it from the Czechs, and actually, in communist Czechoslovakia, the royalties from that contact lens became a major income source for funding basic science in Czechoslovakia. In any event, there were only a few papers published on it in 1967.

That was the project I chose. The interesting thing is that Bradley’s projects all were technology oriented. The chemical basis of the sense of taste has perhaps some technology applications —that project was quite fundamental, almost biochemistry. But the other two projects—reverse osmosis and the polymers used in medicine—really had an immediate technology spin.

Nebeker:

What other applications were thought of at the time for the hydrogels?

Ph.D. thesis research on artificial kidney membrane

Ratner:

The use on the surface of the eye, a contact lens, was the important application. But there were all sorts of medical implant applications envisioned. In fact, what I was looking at in my thesis research was a membrane for an artificial kidney with these materials. So, I was working in membrane transport and also, on the physical chemistry side, the fundamental interactions of molecules.

Nebeker:

You decided to work with Bradley?

Ratner:

Yes. I took my thesis project with him.

Nebeker:

Did you do a Master’s Thesis?

Ratner:

No, it was a Ph.D.

Nebeker:

So you went straight to the Ph.D.

Ratner:

Yes. I came into the Ph.D. program. I never wrote a Master’s thesis. I just went straight through. But a tragedy happened about two years into the project. I came into the lab one morning and they told me Bradley had died the night before of a stroke at age 41. He was an inspirational guy to me for his vision and his creativity—he blazed new paths in a lot of what he did. However, I also found myself with the “mechanical problem” of, after putting two years of research into this interesting stuff, wondering how I was going to continue my thesis. I started talking to other professors, telling them what I had done, seeing if anybody might be interested in continuing with this research. The person who did say he thought this was interesting was Irv Miller, who at that time was the Chairman of Chemical Engineering. I continued my thesis research under Professor Miller and slanted the research more towards membrane transport issues.

Nebeker:

When you say the membrane for artificial kidney, was that just a potential application and you were doing more general studies of such membranes, or were you really working toward it?

Ratner:

We were trying to understand how it would serve as a blood filter. How would blood components diffuse through this material and did it have potential as a hemodialysis membrane?

Nebeker:

So, it was quite directed toward that particular application.

Ratner:

Yes, it certainly was. I finished my Ph.D. working with Irv Miller in 1972. However, it was probably in 1971 or maybe 1970 that the Polymer Science program, which was I guess a division of the Chemistry Department, had sponsored a seminar by a professor from MIT named Allan Hoffman. Hoffman was one of the first people to be using this type of hydrogel polymer in technology. I believe he was also looking at reverse osmosis, but he also published papers on transport through this particular polymer.

Nebeker:

What other important medical applications of reverse osmosis are there?

Ratner:

Actually, the reverse osmosis is for water desalination and industrial purification.

It wasn’t so much medical, although hemodialysis, or blood filtration, is not really reverse osmosis. It’s a different process. It’s a permeation process.

Nebeker:

I guess you have high concentrations in the blood of certain materials you want to get out.

Engineered materials in medicine; disciplinary divisions of chemists and chemical engineers

Ratner:

That’s right. You just want to let them go down a concentration gradient. Anyway, about 1970 I attended a lecture at Brooklyn Poly by this professor from MIT, Allan Hoffman. He talked about an approach, sort of a philosophical approach, on how we could engineer materials for medicine—how we as engineers could take the ideas of polymer chemistry and biology and engineer materials for medicine. The philosophy and the work that he was doing was fascinating. When it came time to finish up my thesis research, I wrote Allan Hoffman a letter at MIT. I was very slow to get a response on this letter, but finally, maybe a month or two later, it came back from Seattle. It turned out Hoffman had just moved from MIT to Seattle. The letter basically said “give me a call and let's talk.” We had just one conversation over the telephone and I had a post-doc offer. That worked out well. I had applied at that time also to Bausch and Lomb who were doing the contact lens. They wrote me a nice letter, but said there were no openings.

Nebeker:

Can I ask you a tangential question related to this Hoffman lecture that inspired you about engineering materials? Is there a very clear divide in chemistry between the pure chemists and the chemical engineers?

Ratner:

Back then there was a lot more of a divide. It’s interesting looking at the fields now. We are on the fourth floor of the chemistry building and chemical engineering is actually right below, just outside the window. My appointments are in chemical engineering and bioengineering. I don’t have an appointment in the Chemistry Department that primarily occupies this building. I do have many colleagues in the chemistry department and I find my colleagues often drifting more towards applied problems, and the chemical engineers are very often doing fundamental sort of research that I would say would fit well in any physical chemistry department. About the turn of the century the two fields had a strong divergence. Terms like applied chemistry or industrial chemistry or process chemistry were used. I’d have to check the history, but I think that’s where chemical engineering, in a formal sense, came from. It’s that division point. The two skills were far apart and then gradually they came back together. Yet, if you look at the work of the very earliest chemists they didn’t see a division at all between applied and basic.

Nebeker:

Yes. Of course, when you go back to 19th Century, engineering, physics, and chemistry, very often these people are doing both. I think earlier in this century, in the case of electrical engineering, there was a pretty clear divide between the physicists, who may be trying to understand solid state theory and fields and so on, and the engineers who were trying to build devices. They may be doing work aimed at understanding, but they’re trying to understand how vacuum tubes work. It was pretty clear that if you were a physicist type or an engineer type that everybody’s trying to understand what’s going on. The division between naturally occurring chemicals and materials and engineered ones may not be so clear that the fields would be distinct. So, you accepted a post doc?

Postdoctoral position at the University of Washington; corporations in early bioengineering

Ratner:

Yes, exactly. I came out to Seattle.

Nebeker:

What did you work on initially?

Ratner:

There’s actually an interesting event on the way to Seattle that’s been important in my career, and I also met a lot of people that have been important to me.

Another place I had applied unsuccessfully for a job was a new startup in California. This was an era where high tech startups were almost unknown . Another visionary, a man named Alejandro Zaffaroni , the scientist and industrialist who started Syntex and made the first oral birth control pill, moved to a new company. His new company was called Pharmetrics in the early stages. Now it’s called Alza. Alza pioneered a field called controlled release—delivering drugs in a continuous, controlled way rather than taking a single, large dose by mouth or by injection. This led to device such as a nicotine patch, a device to deliver drugs in the eye over weeks, or an insulin delivery system.

The Alza Company was founded on the idea that there might be an interest in controlling the way drugs are delivered in therapeutic situations. The head scientist was Alan S. Michaels, who was a professor at MIT and moved to be head scientist at that company. I stopped in Palo Alto driving cross country from New York to Seattle where this company was just starting up. One of the post docs from the Bradley lab back at Brooklyn Poly, who left when Dan Bradley passed away, was one of the employees there.

Nebeker:

Of course you knew him.

Ratner:

Yes, Dr. Richard Baker, and that was probably the contact person that I visited at that time. But, it turned out that Allan Hoffman was also a consultant for Alza. I didn’t know that at the time. I met a lot of people visiting Alza in 1972 that to this very day I’m still working with in a scientific sense. Also, these people in a very early era of bioengineering were visionary in using polymers, medicine, engineering principles such as diffusion and transport principles to make new products. This was absolutely seminal work at the time. Now it’s everyday stuff. You can go out and buy a patch for nicotine or for nitroglycerin for a heart conditions, for all sorts of things, even Dramamine patches. Back then, such ideas were science fiction and they were developing all this stuff.

Nebeker:

Would you have preferred working for them over the post doc?

Research: radiation grafting, Atomic Energy Commission, and blood compatibility materials development

Ratner:

It was an extremely exciting environment and I’m sure it would’ve paid better than the post doc. But in retrospect, everything worked out wonderfully that they didn’t give me a job. I came up here and started doing the post-doc. One of Allan Hoffman’s specialty areas at MIT was radiation grafting. It was using radiation, gamma radiation from a cobalt 60 reactor, to graft or covalently attach one polymer to another. Allan had the idea of taking hydrophobic engineering plastics (silicone rubbers and polyethylenes, for example) and seeing if he could graft hydrogels (the same materials I worked on in my thesis) to the surface to make a hydrophilic water-like surface. The basic philosophical idea is, what could be more bio-compatible than water? What would the body like better than water? The body would obviously tolerate water very well. This was a stimulating idea and it used a very interesting polymer technology.

In fact, my earliest research at the University of Washington was for years funded by the Atomic Energy Commission. There were two parts to this. One was using radiation to make new kinds of materials, these radiation grafted polymers. The second part was that the Atomic Energy Commission at that point was funding a plutonium 238-powered artificial heart. They had a concept that engineers could build a heart pump, and in fact they were funding a Stirling cycle engine heart pump at Westinghouse. In the patient’s belly there would be a plutonium 238 nuclear power source that would provide the heat for this Sterling cycle engine. The engineering design called for a core temperature of 1400 degrees C and a surface temperature for this device of about 40 or 41 degrees C. I think the blood was used as a heat exchange medium. Basically they worked out the engineering feasibility of this, but there were a lot of issues, given plutonium 238’s toxicity and fissionability, having people running around with a slug of this stuff in their belly. But we were working on the materials side. We were working on the biomaterials that would be used in the pump to contact the blood. We were studying how we’d make materials that would not clot or would not damage the blood. That was the area that I came here to work on—to take hydrogel polymers I worked with in my thesis and graft them to some elastomers that would be used for a blood pump.

Nebeker:

That was radiation grafting?

Ratner:

Radiation grafting.

Nebeker:

Now is that a technique that was important?

Ratner:

It was. It probably still is to some extent. It never became a huge technique, but it always made interesting materials.

Nebeker:

So you could just get some bonding that you couldn’t otherwise get.

Ratner:

That’s right. It takes some inert plastics and, under the influence of radiation, bonds could be readily broken that allowed you to couple other molecules to them. We made these neat graft polymers. This set of experiments and getting involved in blood interactions and polymers created opportunities to present at scientific meetings and things like that. It’s was a pretty good place to launch a career.

Nebeker:

What was Allan Hoffman’s position here in Washington?

Ratner:

He started here as a research professor.

Nebeker:

In chemical engineering?

Ratner:

In chemical engineering, that’s right.

Nebeker:

Was he associated with that Center for BioEngineering?

Ratner:

Yes, he was. I believe they actually brought him in, although at that time I don’t think they were giving appointments in bioengineering. His appointment was in chemical engineering. He was an associate with the Center for Bioengineering, which was founded by Robert Rushmer, another seminal figure in bioengineering. Allan obviously was the first materials person doing biomaterials out here. His post-docs from the beginning were Tom Horbett, who just got his Ph.D. in biochemistry here at the University of Washington and myself. Tom handled the protein biology side of the program. And, Allan Hoffman hired me as a post-doc in the polymer chemistry side.

Research assistant professorship, U. of Washington; relating surface structure to biological response

Ratner:

The three of us were quite a team for many years in those early days. Personally, I was publishing pretty steadily. I was giving talks at meetings. In fact, I wrote a renewal application of the grant to the Atomic Energy Commission that got the whole grant refunded. That sort of activity stimulated my change in appointment from the role of post-doc to an appointment as a research assistant professor, based upon grants and publications and things like that—the usual sort of criteria that I met for promotion requirements back then. I was a research assistant professor, which meant that I was an independent entity, but I did have to bring in my own funding. So these grants were useful and nucleated my career as an independent researcher.

Nebeker:

When did that research start?

Ratner:

I think that was 1974 or 1975. I don’t remember the exact date, but roughly that. I had been here about two years and then I moved to this next rank. Tom Horbett also got the promotion about that time. We all worked as a very close team—Hoffman, Horbett, and myself—for many years.

Nebeker:

Can you describe the work that the three of you were doing in those years?

Ratner:

Again, we started in this idea of developing materials for blood compatibility.

Nebeker:

Grafting the hydrophilic substance to some other plastic?

Ratner:

That’s right. Initial results looked promising, but when we did a more detailed analysis, what we found was that it wasn’t all that good. This was interesting – we learned much from the unsuccessful experiment.

Nebeker:

The point of view that it wasn’t bio-compatible?

Ratner:

The issue was that we’d put this novel surface in blood and when we took it out you wouldn’t see clots on it. It looked pretty clean. We figured you obviously want the surface of an artificial heart not to build up clots. This looked good, so we’re saying this is great. But, it turned out that these hydrogels seem to stimulate the formation of clots, but they didn’t stick. It triggered them, they grew and then detached. So, what happened is you have embolic thrombus masses going down stream, which of course was not good. This was actually one of our first major discoveries in that area.

This led us into an exploration of how blood interacts with synthetic materials and how we might design interfaces that work better. There were good engineering plastics out there. There’s polyurethane, for example. Also there are silicone rubbers that are stable, strong elastomers, And, there are companies that know how to manufacture them. We wondered if we could just alter the surface structure of these good synthetic polymers to make them more compatible with biology.

This led me into what has been one of the major focuses of my career, which is how we analyze surface structure and how we relate surface structure to biological response. It turned out that although there was some work on polymers, the best work on surfaces was being done in those days on semiconductor surfaces. The microelectronics community and the petrochemical catalysis community were both looking at the surfaces. These two communities had powerful surface analytical tools, particularly the semiconductor groups, even in the earliest days. I started asking questions. How can I borrow from those areas and bring those powerful tools to biomaterials to look at the surfaces of our materials? I hypothesized that the surfaces were triggering and controlling biological reactions.

Commercialization and applications of surface analysis and blood compatible polymers

Nebeker:

Were there any personal connections, or was it the case that you realized the importance of studying the surfaces and started looking around yourself?

Ratner:

I had read some papers and there were some people in the literature who were doing interesting work. Hewlett Packard was selling one of these surface analysis systems called an ESCA, Electron Spectroscopy for Chemical Analysis. Their system is based on the work of Kai Siegbahn, who won the Nobel Prize in physics in 1981 for developing this. Hewlett Packard had been working with him and evolved his ideas and instrumentation into a commercial machine. I went down to the Palo Alto area and worked with some of the Hewlett Packard engineers who were developing this kind of equipment and published my first paper in ESCA and surface analysis. This was quite early on in the history of ESCA for applied problems.

Nebeker:

When Hewlett Packard decided to commercialize this technique, did they think that it would have many applications in other areas outside of microelectronics?

Ratner:

I think they did, but there was an interesting thing that happened. They started this instrumentation development in what was soon to be called Silicon Valley and were searching for customers. Nobody realized how powerful it would be for microelectronics. Eventually they decided this was not a viable commercial product and they dropped it. Essentially right after that, Silicon Valley sprung up around them and there were major needs for this type of gear. The people at Hewlett Packard who developed it were so excited about this kind of equipment that they started their own company to both do surface analysis and to build the next generation of this kind of machine. So, we talked about influences in my career -- working with these people who developed this instrumentation was quite influential in the direction of my career.

Nebeker:

What company is that?

Ratner:

The people that spun off from Hewlett Packard started Surface Science Laboratories. People like Mike Kelly, Chuck Bryson, and Leroy Scharpen greatly advanced surface analysis instrumentation. These guys were the founders of this company. I am honored to know most of these people and I still keep in reasonably close contact with some of them.

Nebeker:

Did you consult for that company?

Ratner:

No. I went down there nominally as a potential customer to get a demo on the machine. But, working with their physicists and electrical engineers, we all jointly published some very interesting work, surface studies on these polymers intended for blood compatibility.

Nebeker:

So you dragged those people into biomedical engineering.

Ratner:

I guess I did! Really, though, although they were co-authors on this paper, they never really entered the biomedical field. They’ve always been most interested in the physics and the instrumentation rather than specific applications.

Emergence of surface science research community; Society for Biomaterials, American Vacuum Society

Ratner:

What this did work did was start my involvement with the surface science community.

Nebeker:

This surface science community you referred to, were those people mainly interested in microelectronics?

Ratner:

Either microelectronics or petrochemical catalysis.

Nebeker:

Did the Society for Biomaterials bring together people from those two areas?

Ratner:

This meeting I went to in 1974 was (I believe) the Sixth Annual Biomaterials Symposium, which by 1975 or 1976 evolved into what was to be the Society for Biomaterials. It’s now the major society for people studying materials in medicine. Back then it was just a loose confederation of people who met at some of the earliest pioneering biomaterials meetings.

Nebeker:

It was an annual meeting, but not a professional society.

Ratner:

Yes. Now this group, this annual meeting, was dominated by physicians and had some basic scientists and some material scientists, which is how I got in. But there was another group that was dealing with the surface science community, and that was called the American Vacuum Society. This was the vacuums that went to vacuum tubes. It turned out there was a lot of surface science that was needed for vacuum tubes. The production of vacuums was always of interest to this group, and surfaces became very important – surfaces are important to making vacuums and surfaces are studied in a vacuum. Probably the two major technical societies that I’ve been associated with in my life have been the Society for Biomaterials and the American Vacuum Society, which represent the two sides. Both these societies have since spun off sub-groups. The American Vacuum Society has a biointerface division and the Society for Biomaterials has a surfaces special interest group. It’s interesting seeing these interdisciplinary areas come together over this time period.

Research focus, 1970s-1980s

Ratner:

I started taking these various elements that influenced my thinking: blood compatibility, protein interaction with synthetic surfaces, surface analysis, and material science, and sort of fusing them into what really became my career. Again, if you look at your own special contribution, the place where you became noticed, it was the fact that I was bringing these elements together, getting some interesting data that others couldn’t acquire, and making some advancements in how we understood these kinds of materials.

Nebeker:

Could you say a little bit more about that work from the mid-70s on, the results you were getting?

Ratner:

Yes. Part of it was in how we synthesized or created these materials. These first hydrogels didn’t work so well, and because of this we learned about the biological reactivity of the surfaces. We learned how to make new surfaces that might have lower reactivity and be more compatible with the blood. This was work done with grants from the NIH to look at testing the materials. We collaborated with hematologists here on campus.

Nebeker:

Is this still mainly for coating implants of some sort?

Ratner:

Yes, predominantly for that.

Nebeker:

Rather than the membranes.

Ratner:

That’s right -- although one of the major potential applications and one of the driving forces that inspired much government funding for this type of work was the fact that membranes for hemodialysis, were damaging to the patient’s blood. They allowed the wastes to be removed from the patient’s blood so the person with kidney failure didn’t die immediately, but over the period of this treatment their health degraded badly, in part because of the traumas to the blood. You needed strong anticoagulants in the patient’s blood, and there were complications with this protocol. So, although I wasn’t working directly on these membranes, the issue with blood compatibility—what happens when blood interacts with a synthetic material—was relevant to that field that I started out in.

Nebeker:

So, this is in a sense the pure science of it. You’re just trying to understand how blood reacts with materials.

Ratner:

Yes.

Nebeker:

How much of your work was that kind of understanding as opposed to producing specific materials?

Ratner:

I think of there being three components. One component was making the materials. One was learning how we could analyze and characterize them. This was very different from surface characterizing semiconductors, so we had a lot to learn there. The third area was the biological interactions of these. All these three things were going on pretty much simultaneously here.

Nebeker:

That’s pure science, instrumentation, and engineering, so to speak.

Promotion at the U. of Washington; equipment needs

Ratner:

Yes. Anyway, this work went on. I got a few promotions. In 1984, I went from the research faculty line to the teaching/tenure faculty line as an associate professor. Again, I was publishing pretty heavily and getting lots of invitations to speak. People were real interested in this stuff. I did my first experiments, for example, at Hewlett Packard with their gear in 1976. The cost of these surface analysis machines has always been very, very expensive.

Back in ‘76 it was about $150,000, but that was a kingly sum in that era for this machine. I never could afford one. But by the early ‘80s I was using this type of equipment so heavily that I was going out to Xerox Corporation in Webster, New York, and working in collaboration with Dr. Ron Thomas doing these biomedical experiments. I was buying time on instrumentation at the University of Utah. They had a Hewlett Packard ESCA there. I got to realize that I needed this type of instrumentation in our labs at the University of Washington.

Two things happened about then that were both influential. One was that our chemical engineering department was given an opportunity from the Shell Foundations to receive a grant for a piece of equipment. Of course, this was given to the whole department and people were discussing their needs. I brought up the possibility of the purchase of this machine. I must say mine was the most expensive one, but the Shell Foundation didn’t formally put a cap on the amount for this instrument grant.

Nebeker:

That became a positive argument.

Ratner:

Yes, that’s right. In fact, the other equipment my colleagues were asking for was on the “minor” equipment level. There were other places to find funding for that sort of thing, but it was not obvious where you’d get the money for big instrumentation back then.

Now, it was an interesting situation because Shell was interested in petrochemical catalysis. The people at Shell there who were actually doing this type of analysis work were in essence reviewing my proposal to Shell. They were saying, “Well, as you know, we do hard, inorganic, zeolite supports and metallic catalysts,” which are hard, rigid materials. They were wondering how we could you do this analysis on polymers, given the types of radiation that are used in these ESCA machines. They assumed it would destroy our polymers. I had to go down there to Shell Westhollow Research Center outside of Houston and convince them that you could do good work on organics and this type of work could take you into a whole new area. So, Shell did ultimately fund our first major piece of surface analysis equipment.
At the same time I had applied to the National Institutes of Health. I had become known as one of the proponents of using modern surface tools for biology and biomaterials. A lot of people were gaining interest in this and I was (and still am) personally convinced everybody could benefit from it. I made an application to the NIH to start a national center to make this type of technology available for biomaterial studies. This national center was funded and we gave it the name NESAC/BIO, which is “National ESCA and Surface Analysis Center for Biomedical Problems.”

Shell Grant; National ESCA and Surface Analysis Center for Biomedical Problems

Nebeker:

What year was that?

Ratner:

That was 1984. The two things happened about the same time: the Shell grant and the National Center. The Shell grant provided the instrumentation. The National Center provided the infrastructure, the support to do further research and development.

Nebeker:

Then you could hire.

Ratner:

We could hire professional staff, and also support students, that’s right. We set up a very professional lab for doing surface analysis of biomaterials.

Nebeker:

Was this a long term grant from NIH?

Ratner:

I was the principal investigator for thirteen years and my colleague, Professor Dave Castner, also in chemical engineering, took it over after me and has led the center for the last four years. Castner graduated from the group of Gabor Somorjai at Berkeley. Somorjai is one of the leaders in catalysis and in using these sorts of techniques for studying catalytic surfaces. Dave Castner was one of his Ph.D. graduates. Castner went on after graduation to head the lab at Chevron in Albany, California, doing surface work on catalysts. When I met Dave, he was interested in transitioning out of the industry and getting back into an academic environment. He really liked the focus of our lab, so we hired him as our first laboratory coordinator. Castner went on to the professorial lines. It was clear that he was well qualified for the Professor role.

Nebeker:

The idea of this center was that this tool and other tools would be made available to researchers at other universities.

Ratner:

That’s right. For example, an M.D. could come in who didn’t have any of the physical science or engineering background appropriate to do surface analysis.

Nebeker:

But needed to know the surface structure of materials they were working with.

Ratner:

That’s right. NESAC/BIO was open to M.D.s and research groups throughout the world. I ran the Center for thirteen years, and then Dave Castner has taken over and it is still active and housed in the chemical engineering building.

Nebeker:

Has NIH funding remained here?

Ratner:

Yes. The Center has been successful and fulfilled its mission. I think it has been the leader in developing these tools.

Nebeker:

What is it called now?

Ratner:

It’s still called the National ESCA and Surface Analysis Center for Biomedical Problems. Over the years, we brought in new types of instrumentation, such as a machine called SIMS, which stands for Secondary Ion Mass Spectrometry. It allows you to do a mass spectrum of the surface zone. Also, in addition to ESCA and SIMS, the scanning tunneling and atomic force microscopes were added to the lab. They were developed in the 1970’s and 1980s at IBM in Zurich and a Nobel Prize was awarded for their discovery by 1986. So, this added the other surface tools that the Center uses and we started building on all these things. On one hand I was looking at surfaces and trying to relate them to biology. The other side of it was looking at biology. We were doing biological experiments. We still had grants from the NIH focused on making materials for medicine.

Molecular biology and biocompatible materials development

Nebeker:

These biological experiments, were they concerned with the blood’s interaction with surfaces, for example?

Ratner:

Blood and also implant materials intended for other sites, for example soft tissue implantation. By the ‘90s, I had been doing this kind of work for about twenty-five years. I started having some doubts in my mind about the fundamental basis for what I was doing. Really, for twenty-five years what had I been trying to do? I had done surface analysis and I had done synthesis—my real goal the whole time was to make better materials for medicine. That was the application. In spite of the fact that I and others had become sophisticated in doing these types surface modifications and surface analysis, there was no evidence our biomaterials were getting better. In other words, they basically just healed pretty much the same, particularly in soft tissue implant sites.

I started actually studying biology in a lot more detail just at that time. Biology had awoken from what was almost a sleepy field in the early ‘70s. Molecular biology was THE discovery area in science. In fact, biology essentially pushed the field of physics, which for a long time was consider the prime discovery area in science, into second place. Molecular biology was where the excitement was.  New discoveries were coming along about how cells communicated with each other, about biological recognition, about genetic control and about how things recognized each other. I came to realize that although we’re making better materials and we’re getting very neat medical materials here, there’s no way a living cell could ever recognize a piece of Teflon or one of these hydrogels or a piece of titanium or gold that are used in medicine. Evolution had never provided the recognition mechanisms or receptors for the biological system to recognize these materials.

Nebeker:

Wasn’t the idea that you just needed a benign substance that wouldn’t cause a problem?

Ratner:

Yes, that was the original idea. We wondered how benign we could make it. That did seem ideal.

Nebeker:

You don’t want it to be recognized as a foreign body anyway.

Ratner:

Exactly. It turns out that the body’s response to these materials was to look at it and say that this is benign. But, as it turns out, there’s nothing benign in the body. Consequently, it must be foreign, and the body’s response to it was to put a wall around it.

Nebeker:

In other words, the concept of a benign substance in the body wasn’t a good one.

Ratner:

I’m sure if we went through the technical papers in a 1975 book on biomaterials we’d find everybody talking about how to achieve benign materials. After enough years of doing this, and particularly after I reached the point of making a lot of excellent quality materials, I could create incredible surface structures, but the body found them all benign. The biocompatible materials did not incite an undesirable reaction, but what the body did is see them as foreign and put a wall around them. You got the same reaction as with a splinter or a bullet. That was the essence of the revolutionary idea -- that the reaction we called biocompatible was one that readily occurred since mammalian life evolved—this mechanism to isolate your body from foreign materials.

Nebeker:

In other words, if something is not recognized as part of the body, there’s this response to wall it off.

Ratner:

Yes, that’s right. I’d actually been involved in developing some materials for real clinical applications—eye lens implants and things like that. I’d made some materials based upon what I believed should have given very unique healing responses, and nothing happened. I came to realize that the body just found them all foreign, even though I had this skill for creating specific surfaces, at least for implant medicine. There’s a lot to say here, but for things like blood compatibility, it turns out I could make a difference by creating novel surfaces. Blood turned out to be an exception to most of the other tissues in the body. My surface skills would not be getting me any further for practically any other site but in blood. So, to summarize these ideas, it didn’t matter what the surface structure was. The body found all the surfaces we created to be foreign. It didn’t recognize them because it had never seen them through evolution. The evolutionary mechanisms led to biological recognition and there was no specific recognition with modern surfaces.
On the other hand, in the molecular biology field, people were learning about what recognition is and how cells communicate with recognition-based mechanisms. In retrospect, it turned out to be a much more modern, much more sensible model. In the ‘70s we didn’t have this knowledge, so it wasn’t that we didn’t take advantage of it. It didn’t exist. By the ‘80s and ‘90s the understanding was acquired that when the body heals a wound there are certain signaling mechanisms and trigger mechanisms that turn on normal wound healing. You have the potential to achieve good wound healing and reconstruction.

Engineered biomaterials, University of Washington Engineered Biomaterials center

Ratner:

We started asking whether biomaterials, instead of being inert, should be recognized by the body. We, as engineers, should be able to control the healing reaction, the biological response. So we started looking at subjects like normal wound healing – which proteins or signaling molecules are involved? Then, using our surface knowledge and skills, we ask if we can take existing medical devices—they’re FDA approved, familiar to surgeons and manufacturable—and put on them the right biological recognition elements. Instead of making them inert we turn on and control specific biological processes to engineer biological reactions, for example good healing.

This set of ideas was the reason why I resigned as Director of the NESAC/Bio Center. I had this idea to start another center, namely an engineering research center through the National Science Foundation, to see if we could take the field of biomaterials to another level or a new paradigm -- from inert materials to bio-active, engineered surfaces. We called this new generation of medical implant surfaces “engineered biomaterials.” The center founded around this idea is UWEB, University of Washington Engineered Biomaterials. UWEB is now working in collaboration with some twenty-two investigators including material scientists (my academic roots), fundamental biologists that know little about materials (it was never their area, but they certainly know a lot about wound healing and proteins in biology), and physicians and people involved in healing. This engineering research center raised the following question, “Can engineers working with experts in these rather diverse disciplines take biomaterials from their existing state and go to the next level and make materials that control the biological responses with precision?” We’d reached a high level of sophistication, but it wasn’t going anyplace further. It didn’t matter what kind of neat surfaces we did. The body reacted to the materials the same at this point.

Nebeker:

To try to understand it better, it’s not only a matter of tricking the body, or is it? I mean, it seems like a valuable thing to trick the body into not trying to wall this off, trying to just ignore it. Or, are you trying to get the body to bond to it, you know, have cells that bond to it?

Ratner:

It could be bonded to tissue. From an engineering design standpoint we’ve set up a series of design criteria. So, if you want a bone to bond to a hip joint, it would. Or for a catheter, you’d hardly want the body to bond to it. You want it to go in and come out easily. There’s a lot on just the engineering design side. But, the important point is work with the body rather than working against it. Work with the body’s own mechanisms.

Nebeker:

It sounds like you’ve got to give some signals to the body.

Ratner:

Yes. The body knows how to heal things, and what we want is to do is turn it on – send the correct signals.

Interactions of engineering and biology in shaping research and research centers

Nebeker:

To better understand this Center, is this a matter of coordinating work of people who already have positions at Washington?

Ratner:

Yes, they’re all faculty. Let me just take a step back and talk about an engineering research center. In the early ‘90s, I started more seriously learning about some biology where, in the past, I’d been pretty much focused on the materials end and mostly dabbled in the biology. Based on the evolution of molecular biology, I started seriously reading about what’s going on and really studying and learning about some of the new things that were being learned that were just revolutionizing our understanding of how biology works. It was interesting that you could see that biology also works by what looks like “little machines.” If you start looking at how the surface of a cell does its communications functions and transport functions, it looks like a nano machine. It’s perfectly reasonable to say one could engineer with this kind of system.

Then I realized that to implement this, to do the biological discovery, to learn the biological facts—not the curiosity driven paths the biologists were studying, but the information we needed to generate new biomaterials—there were some fundamental biological discoveries that had to be made. Furthermore, with the expense of working with animal models in focused studies, I realized that there had to be a much greater level of resources than I had available to me to do this at that time.

Funding and industrial support

Ratner:

One of the mechanisms that the National Science Foundation made available was engineering research centers (ERCs). The engineering research centers had a few criteria that had to be met to be an ERC. It started with the requirement that an ERC just can’t make an incremental improvement in an area. You really have to look at how you could have a major impact on a field that is both important intellectually and important to Industry. Advanced biomaterials certainly seemed to fit that. If we succeed in our healing biomaterials, indeed we will make a major impact. For example, the medical devices are at the moment somewhere between a forty and a one hundred billion dollar business. There’s a major industry/commercial side, a humanitarian side, and a very significant intellectual side. We had to show that to the NSF. It had to be interdisciplinary. This obviously fit that criterion pretty well. It had to have a major educational component. We had to show how we could use the ideas that we developed to turn on students to be involved in engineering; to educate the general public and K through twelve; to provide training to industry in these sorts of new areas.

The other major component is industry. All these engineering research centers have some sort of a science technology base, they have an education base, and they must have an industry base. You may never succeed in impact if something is seen as just a crazy idea. It was very important if industry could buy into your vision. We have twenty-six medical device and biomaterials companies that are now in partnership with the UWEB Center. At this moment there are maybe twenty-three professors. There are about 100 students that are actively involved in these sorts of programs.. There are major programs going into K through twelve schools, into engineering programs focused on diversity, and other interesting programs.

Nebeker:

What does it mean for a company to be part of this? I assume they do more than just keep an eye on what you’re doing.

Ratner:

One thing they do is they do buy in financially. They have a membership fee. As part of what they receive for that fee, they participate in our governance and research planning. We have an active industrial advisory board.

Nebeker:

They have some say in what issues are investigated.

Ratner:

Yes. They have a vote in how some of the money is spent. They give us critical feedback on how useful our studies are and which directions we’re going in. They also evolve specific research projects based upon our core technologies that are of interest to the companies, which get our students working with industry. Since most of our students are being trained to go to industry, this is appropriate that they get exposure to the real world concerns that engineers have to deal with in industry.

Nebeker:

So part of this is you convince this company this could lead to a successful product and then the company initiates work.

Ratner:

Yes, that’s right. There’s a core technology within the program with central ideas in what we call biomaterials that heal and controlling biology with precision. These are central ideas, but what stems from those are the interests that the companies have in using some of these ideas on their own products, which often tends to be proprietary, or at least they want exclusivity for their own products.

Intellectual property management; collaborations of academia and industry

Ratner:

Another large part of these engineering research centers is working out issues of intellectual property management. We have a full time intellectual property management person. We also have a large education office that is building these exciting ideas into educational programs. There are some intrinsically very exciting ideas in UWEB. Kids are interested in medical devices and stuff like that. We can use this to stimulate them to want to learn science, to want to get involved in engineering. We’re hoping that we can save some of them from lives as lawyers and MBAs and get to some intellectually stimulating work.

Nebeker:

Then there’s not any serious problems. I mean, often there’s something of a conflict between industrial mindset and the academic mindset. The academics wanting to just investigate and make known and the industrial person wanting to make a profit, wanting to develop an exclusive product.

Ratner:

We strive to get a common ground. Perhaps intrinsically a conflict is set up. We’re managing it, as each side has their own skills, all of which are critically important. How can we get both sides to work together, meeting the needs of both groups? How can the academics meet their needs for communication, publication, and intellectual excitement? How can the industry people meet their needs for proprietary and commercial and things like that?

Nebeker:

Some of the biomedical engineers that I’ve talked to have said things like I had this wonderful technique. I just couldn’t convince any of these companies to do anything with it. So, I can see that a close contact between industrial people and academic people can be important.

Ratner:

Yes that’s right. That certainly facilitates taking the basic ideas and getting them all the way down the chain into real products, which is the only way an engineer ever does any good. It’s to get a real product out there.

Nebeker:

When did the center start?

Ratner:

In 1996 is when the center was inaugurated. These are eleven-year programs. They come with over the eleven years more than thirty million dollars in NSF funding so it’s a very substantial living. Plus the University of Washington saw the excitement in this and they put in a substantial sum of money for remodeling, positions, and things like that. Then industry of course has contributed additional money. We’ve got things like private foundations contribute to education and other grants from the NIH and the NSF. The UWEB Engineering Research Center is quite a growing enterprise.

Combining administration and surface engineering research

Nebeker:

Does this mean that you’re an administrator much of your time?

Ratner:

Well I do have a major administrative role. It’s something that I enjoy is scientific administration. I must say I’ve never aspired to be the department chair or dean -- these things have, at this point, little interest for me. But to administer an exciting piece of science, especially I must say, the thing that stimulated me and has kept me growing intellectually, has been a very good place for me at this point in my career. In other words, my administrative activities can leverage a lot more research than I could ever possibly do on my own.

Nebeker:

Have you been able to continue research yourself?

Ratner:

I do. I have a very active research group actually. Again, my research focus was sort of the materials related to component of this bigger unit, asking questions about how we can make improved biomaterials. We have some world class biologists participating in this program. And they might, in fact have, discovered a protein, but how can we implement that on the surface of a material in a way that’s manufacturable, that delivers the signals that we want, that has the durability and stability? These are engineering concerns. My group is focused on the materials end of this. But in the excitement of working with important biomolecules and using them in a precision sense, this is opening very, very exciting horizons. We still use ESCA and SIMS, the surface analysis techniques. They’re still our foundation. I’m a user now in the NESAC/BIO center that I started.

Nebeker:

What specific work has your own research group been doing in recent years?

Ratner:

As I said, it’s still very surface-oriented. As we discover proteins of interest that turn on interesting biological reactions we realize how difficult it’s going to be to sell a protein covered medical implant. We’re asking if surfaces can be engineered to send those same signals without the proteins there.

For example, we did a very interesting study that was published in Nature last year. My Ph.D. student, Galen Shi (now at Merck), took protein molecules and stamped them into a polymer surface and made pits or imprints in the shape of the proteins. Within those pits or imprints there were receptor grooves that kind of gave a lock and key interaction with the proteins. So, instead of trying to sell a medical device with proteins on it, we might sell a medical device with “nanopits” in it and those pits would attract or interact with proteins in your own body to turn on the signals that we want at the surface. This is one example.

Another place we’re working that’s actually very interesting is in what we call nonfouling surfaces. These are surfaces that resist picking up biological molecules. These might be bland, non-interactive materials that are sometimes used. The terminology “stealth” is sometimes used for these kinds of materials. We’re working in materials that may be invisible in the body. Rather than being inert, they’re invisible.

Nebeker:

Again, the signals idea. But, the inert materials always sent the wrong signals.

Ratner:

Right. They weren’t chemically reactive, but they non-specifically adsorbed proteins and thus they never sent the right signals.

University of Washington research centers; Bioengineering Research Partnership

Nebeker:

Have we named the most important things in your own work? Have we hit those along the way?

Ratner:

I think we’ve touched on a number of them, but there are others. These engineering research centers are viewed as growth areas and new areas for me are cropping up. I think an important thing to put these centers into context is that when we applied for this engineering research center, medical related biology was viewed as being a little bit suspect at the National Science Foundation. The central idea was that the NIH was in charge of medicine, and why were they messing with it. Our argument was that there’s a huge industry out there and NSF addresses industry. NIH never addressed that side of it. But we wound up in competition with 117 other universities, and four of these centers were funded out of this competition.

So, obviously the ideas, the vision, and the team we pulled together were quite impressive. Indeed, the University of Washington has over the years become one of the leading Health Science Centers in the world. We have the world class biologists here to make these things happen. It turned out to be the right time with the right set of skills for it, and a lot of things were put together. At one point during the steady growth and evolution of our UWEB Center one of our partner companies came over to us and suggested we partner on a new NIH plan for a “sub-project” using some of the ideas we’ve developed in the Center. This has led to a program called a Bioengineering Research Partnership. It’s an NIH funded program that’s quite large and also a 10 year program. The goal of this program is to ask if we can tissue engineer a piece of living heart muscle. Can we make a piece of heart muscle that a surgeon might use to replace a damaged section of your own heart?

Nebeker:

Culturing human heart muscle cells?

Ratner:

Yes, using three-dimensional porous scaffolds to control these cells. Using biology to control the development. Of course the heart is not just muscle cells. The heart is blood vessels, nerves, and support structure. We have to turn on or engineer the tissue to reconstruct portions of the heart.

Nebeker:

That sounds enormously ambitious.

Ratner:

It’s enormously ambitious, but it’s also an enormously exciting area. Again, it’s allowed us to bring in some fabulous cell and developmental biologists that we hadn’t been working with before.

Nebeker:

Do you think something like that is possible in ten or twenty years?

Ratner:

Yes, I really do. I think the more we’re learning about biology, and from the quality of the team that we have, we can do this.

Nebeker:

Are there any other aspects of your career that we haven’t named here?

Service as President of the Society for Biomaterials

Ratner:

I became President of the Society for Biomaterials, in ‘90, ‘91, so it’s been quite some time.

Nebeker:

Has that society been important?

Ratner:

Yes. As I said, I think it’s the leading society in the world by far for the use of materials in medicine. It’s interesting that I became president at that time—and I’m not saying this had anything to do with me—but, about that time the society went from a very small society that produced a little meeting at Clemson to a very large national society that has much, much larger meetings and all. I was made president at the cusp of this growth.

Nebeker:

It must have been that there were a lot of people who didn’t really think of their work as being biomaterials and saw okay, here is a society.

Ratner:

That’s exactly right. A lot of new areas came in. People would do, for example, the gene chips and diagnostic array chips. In one of the other groups that we now bring into the UWEB program, they’re not medical device oriented, but they are using diagnostic DNA chips for understanding the human genome for diagnosing diseases, for forensics, and things like that. This is surface control of biology. Many of us are going into these sort of new developments that stemmed from surface ideas we pioneered over all these years.

Nebeker:

It does seem like an absolutely fundamental field you’ve been working in. I mean, everything must be interaction with the surface, ultimately.

Ratner:

Yes, well not everything. The strength of a hip joint prosthesis involves the mechanics of materials. There’s another group that deals very professionally with mechanics, but when it comes to how the bone sees the surface of that titanium hip joint, there’s a place we can make a contribution.

American Institute of Medical and Biological Engineering

Ratner:

Also, in terms of my career, I was one of the founding fellows of an organization called AIMBE, which is the American Institute of Medical and Biological Engineering. EMBS is one of the sub-organizations in AIMBE. In fact AIMBE represents some 30,000 biomedical engineers, and I’ve just been elected as president.

Nebeker:

And this functions as kind of an umbrella organization for all of these more specialized groups?

Ratner:

Yes, exactly. We provide information on bioengineering and really study the field, looking at the growth of the field of biomedical engineering. We provide information to Congress and other Federal agencies. In fact one of the accomplishments that AIMBE can take credit for was launching an Office of Bioengineering at the NIH. That led to the National Institute of Bioimaging and Bioengineering (NIBIB) at the NIH. One of the things that AIMBE has done is taken what might be called a peripheral field in engineering, biomedical engineering, and brought it to center stage as one of the core engineering disciplines. We have electrical, mechanical, chemical and civil, and now we have bioengineering right in the center of the engineering community.

Nebeker:

With AIMBE, is it fair to say it’s principally an outward looking organization that represents the bioengineers and that field to the public at large and to government, rather than being one that’s trying to foster communication within the field?

Ratner:

It does to some extent, but basically the function of AIMBE is to promote, to foster, to educate, to advance biomedical engineering as a field within government agencies, to the public, and within the communities that employ or address these fields. But also to develop unity in the field.

Nebeker:

Thinking about professional societies in engineering, originally they were mainly inward looking. You know, you’re advancing the field by fostering the work, readings, publications, and so on. Something that came later was that it’s very important how others perceive us and so on. But from what you were saying, it sounds like AIMBE from the beginning was very interested looking outward.

Ratner:

Yes. We ask some questions about training and curriculum issues as the field evolves. We look for growth areas and try to promote them. We’re very interested in public policy and how federal agencies and the general public perceives this new field that’s evolving. The ethical issues are obviously very central any time you talk about biomedical. There are misleading perceptions that we’re going to address.

The role of biomedical engineering in the engineering field

Nebeker:

I’m interested in the discipline history issue here, especially what you said about biomedical engineering emerging as a new fundamental engineering field. Right now, or at least earlier, you had people in lots of different places doing things that some people called biomedical engineering. Do you think that there’s enough coherence to this that, say fifty years from now, really will be seen as one of the basic engineering fields?

Ratner:

It’s happening and I don’t know the exact number, but I’ll bet at the moment there’s 150 departments of biomedical engineering that have sprung up, most of them in recent years. Our department goes back to the ‘60s. We were certainly one of the pioneers, but there are others that go back that far. We’re not the first.

But what has happened is the realization that there’s a real profession here. There’s a certain way we have to educate our students. There’s a core knowledge base that gives us commonality. A person that does electrical engineering, a person that does the mechanics of a hip joint, the person that designs a pacemaker that goes into the body and designs the electrodes for the pacemaker, the biomaterials person, the person doing a chemical sensor or biosensor—there’s a commonality within what all these people do. They borrow from other engineering disciplines, but there’s a central core that is the biomedical engineer.

Nebeker:

Because the field is so advanced in all these individual areas, wouldn’t a person still have to be trained as the electrical engineer or the chemical engineer or the mechanical engineer with this interest rather than a core field of biomedical engineering?

Ratner:

Yes. The students choose pathways. Some of them are more interested in mechanics, some of them are more interested in electrical circuit design, and others are interested in materials. These students choose pathways, but there are common areas of education just as in chemical engineering there are many sub-specialties. There’s environmental and all sorts of things in chemical engineering. We’re looking for core curricula and we’re looking for specialty pathways. We’re concerned and responding to the idea that we understand our students must ultimately come out as competent engineers. For example, chemical engineers that gets a good part of their education from a petrochemical model have driven chemical engineering for the last forty or fifty years. That’s used as the central model to determine if students learn mass transport, kinetics, and thermodynamics. We’re saying, “Why not learn it with models that relate to biology, and why not be learning the biological fundamentals, using a biological model as part of the core?”

Nebeker:

It’s very interesting historically how fields evolve and electrical engineering has sort of hived off computer engineering in recent decades and that’s emerged as almost a separate field in professional societies. We have these tensions of groups pulling apart. Do you see so much commonality between, say, electrical engineering and chemical engineering in the biomedical field that you think the biomedical engineering could be the fundamental? The way of perceiving the field?

Ratner:

Just as we were talking about engineering and fundamental science originally being spread apart, now I see both sides coming back together again. I see all the engineering disciplines also are really getting closer and closer. In fact, biology is going to dominate them all. I see the electrical engineers looking at neural and protein computing as they reach the Moore’s Law size limit. I mean, the laws of physics and the laws of the universe are going to stop those circuits from getting smaller. Molecular engineering and biological engineering do this very elegantly.

The electrical engineers are going to start looking to biology. The material scientists already find incredible mechanical properties of materials processed in aqueous and at ambient temperatures rather than in smelters and things like that. So, the material science that comes out of biology is brilliant. Biology is the master of chemical processing—processing exactly the molecule, exactly the stereochemistry with “clean and green,” if you will. Biology does that wonderfully. You can take practically all the engineering disciplines and what you see is that the biology, what is called the biomimetic model, really does provide what might be a future direction for almost all the engineering disciplines.
Just to give you an example, I collaborated with our Dean of Engineering, Denice Denton. She’s an electrical engineer by training. What we’re looking at is surface coatings for MEMS devices that might be used in sensors and diagnostic instrumentation. It brings together the semiconductor fabrication that came out of electrical engineering, going into making channels that we float fluids through. We have chemical engineering principles, but it’s biomolecules with biological sensing. The walls of these channels have to be engineered. All of these things are coming together in what’s often called MEMS. It’s just one of many examples of the merging of disciplines. It’s kind of scary when you appreciate how many subjects are involved to build such devices. What it means is you have to collaborate You have to speak the language. It’s a communication thing. One of the things we’re teaching is communication skills.

Pioneers in biomedical engineering

Nebeker:

Could I get you to name a few people in the areas of biomedical engineering. You know best who’s been most influential over the last forty or fifty years.

Ratner:

Sometimes the founder of our department, Robert Rushmer, has been called the father of biomedical engineering. Rushmer was a cardiologist; he’s not an engineer. In the ‘50s and ‘60s he believed that engineers are critical to make advancements in cardiology and deal with cardiovascular disease. He wrote a very seminal text book called Cardiovascular Dynamics. It brought engineering ideas and medical ideas together, and he’s the founder of this department. He had quite a vision. He was very influential.

Of course, I mentioned Dan Bradley, my thesis advisor. I went from the mentorship with Dan Bradley, who tragically passed away at such a young age, to Irv Miller. Irv Miller was really one of our earliest biomedical engineers. Irv was always working on proteins and interfaces on the artificial kidney and things like that. So Irv Miller has been a mentor, a major influence. I met Allan Hoffman. Allan Hoffman is an immensely exciting and creative guy. Allan and I are still good friends and still collaborate together this very day.

Nebeker:

Are there people that you haven’t known or worked together with that in this type of biomedical engineering that you’re concerned with have been knowing some things?

Ratner:

Yes, people that I haven’t directly worked with. At the time when I started my graduate work, the ideas of a man named Robert Baier were extremely exciting to me. He’s a professor now at the University of Buffalo. He was thinking about surfaces and biology very early on. His ideas have always been very, very influential in my career. There was a chemical engineer named Ed Leonard, a guy who’s always very excited about the possibilities at Columbia. Ed’s still at Columbia and I still know him. There were people like Alan Michaels, who started as an MIT chemical engineer. Alan formed this company called Amicon, which is still a leader in membrane and filter technology. But then, Alan Michaels then went on to be the Director of Research for ALZA, which opened tremendous horizons in controlled drug release for use of materials in medicine.

At the same time there were groups doing surface engineering with people like Gabor Somorjai who was using the surface tools to study interesting problems. One of the pioneers who took this surface technology and first realized that you could do other things than semiconductors and catalyst is a man named David Clark, who was a professor at Durham University. David Clark’s work was very important to me. One of my earliest collaborators was one of David Clark’s Ph.D. students, Ron Thomas, who was a researcher at Xerox when I met him.

Nebeker:

Ed Leonard is actually on this short list of people to talk to.

Ratner:

He’s a stimulating and exciting guy and a pioneer in bioengineering.

Nebeker:

Anything else you’d care to comment on?

Ratner:

Probably a lot of things. I actually wrote sort of an informal history. It’s not too long. This is the industry magazine for our UWEB research consortium. A couple of years ago I won the CMA Stein Award for the American Institute of Chemical Engineers, which was an important material science award and a nice honor. They asked me to write up my award address, which I call "An Irreverent Guide to Biomaterials as Materials: Autoparts to Robocop." I sort of talk about the field in very personal terms. Let me give you a copy of that.

Nebeker:

As I say, there’ll be a chance later if you find you’ve forgotten to include somebody’s work who was very influential or have some thoughts, you can always add them later. If you have any now you might as well mention them.

Ratner:

There certainly are so many people because I think my work has again borrowed from polymer chemistry. In the polymer chemistry field, there are people starting with Herman Mark, who brought polymer chemistry to the United States. His office was near my office as a graduate student, so I got to see one of the great pioneers. Other very well known polymer chemists who influenced me were people like Herbert Morawetz and Murray Goodman, who were professors at the time at Brooklyn Poly. Polymer chemistry is one area that has influenced me.

A number of people have really opened my eyes to modern biology. Tom Horbett, my long time colleague in Chemical Engineering and Bioengineering at the University of Washington, first exposed me to biochemistry, proteins and research methodology ideas. Also, I will give credit to one of my Ph.D. students, Ann Schmierer. Ann was a BS biologist working at a startup company called Immunex, which was one of the hot biotech companies in town now. We all wish we had stock in this company in the early days. Ann was at the company in the early days. She was a BS biologist and I guess not terribly pleased with the sort of work they gave her to do with the BS degree, so she came to do a Ph.D. in bioengineering. Most of our bioengineering students are engineers. Ann came from the biology side, but she was very influential in opening my eyes to the possibilities of biology. Suddenly I had in my group, instead of a chemical engineer or a bioengineer, a biologist. She opened my eyes to things that were going on in modern biology, so I give her very direct credit as an influence. I suppose it’s very appropriate to have your student’s as a major influence.

Nebeker:

Of course, biology has been enormously influenced by the engineering model and been part of what biomedical engineering is, viewing biological systems and engineering systems with feedback, signaling, self regulation, and all this.

Ratner:

Nature is a fabulous engineer, and happens to do it a lot better than an electrical engineer or a mechanical engineer or a chemical engineer. We can watch with admiration and envy how well nature does it’s job. Talk about systems engineering, the living organism has the most fabulous systems engineering. Information coding and information technology—it’s all in biology. It’s got the whole thing.

Nebeker:

It’s kind of like the systems engineering that Bell Labs had to do was a kind of intellectual preparation for us to grasp what systems engineering in the biological world was doing. Well, thank you very much.