Oral-History:J. Lawrence Katz

About J. Lawrence (Larry) Katz

Katz received from Brooklyn Polytechnic his BS in Physics (1950), his MS in crystal physics (1951), and his PhD in crystal physics. He was a mathematics instructor at Brooklyn Polytechnic (1952-56), and then a professor at Rensselaer Polytechnic Institute (RPI). He was inspired in the 1950s by a fellowship year in England to apply crystal physics to biological studies; in the early 1960s, when he got tenure, he began to do so. He has worked on tooth and bone structure, since they are crystalline. He slipped into the field via a 5-year teaching grant (1964-69), to direct graduate students into dental materials research. This allowed him to learn the field with his students. He has done work measuring the anisotropic properties of bones, and uses acoustic microscopy and ultrasound in his work. He set up one of the first biomedical engineering programs that wasn’t subordinate to an Electrical Engineering Program. He believes the interdisciplinary efforts of the field are finally beginning to bear fruit, as it moves towards a “genome to bedside” paradigm.

About the Interview

J. LAWRENCE (LARRY) KATZ: An Interview Conducted by Frederik Nebeker, IEEE History Center, 15 October 1999

Interview # 372 for the IEEE History Center, The Institute of Electrical and Electronics Engineering, Inc.

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It is recommended that this oral history be cited as follows:

Larry Katz, an oral history conducted in 1999 by Frederik Nebeker, IEEE History Center, Hoboken, NJ, USA.

Interview

Interview: Larry Katz

Interviewer: Frederik Nebeker

Date: 15 October 1999

Place: Atlanta, GA

Childhood, family, and educational background

Nebeker:

Can you tell me where and when you were born, and a little bit about your family?

Katz:

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I was born December 18, 1927, in a hospital in Brooklyn. My father came over as a five-year-old from Hungary with his older brother who was seven, just the two of them by themselves, we think it was actually at the turn of the century. He did not have a birth certificate but we got his age, and I suppose he came in the 1900s. We needed to know his age for Social Security when he turned 65. My mother came over with her whole family, including her mother and father. I never met my father’s parents because they still remained in Hungary and were probably killed in the Holocaust. My father came from Sighet, in what is now part of Romania, Transylvania, the same area that Elie Wiesel, the Nobel Prize winner, wrote about Marmarush Zeget. My mother came from Lublin, Poland, which had a large Jewish population. Her family came to the States actually pre-World War I, when she was about five years old. I am really the first generation born American on my side of the family.

We lived in Brooklyn all my life. When I was born my parents lived in Coney Island, which was famous as a summer resort area of the beach and the Boardwalk. I grew up there and went to public school and junior high school there. A great influence in my life is that I went to Stuyvesant High School. I was very fortunate in getting four years of honors courses in physics, mathematics, and chemistry, because I wanted to be a physicist. I feel very strongly about it, as you will find that many of the Stuyvesant graduates feel almost as strongly about the high school as they do their college. I know my colleagues who have gone to Bronx High School of Science or Brooklyn Tech feel the same way because it really gave them a head start when they went off to the university and studied science and/or engineering.

Nebeker:

How did one get into Stuyvesant?

Katz:

Since I went to junior high school that meant I entered Stuyvesant as a third termer, as a sophomore. If you did not go to junior high school and went to ordinary grade school that ended with the 8th grade, you could enter as a freshman. You had to take a mathematics exam, which was quite sophisticated compared to just the mathematics you might learn. For instance, like taking square roots which you generally were not taught, but not just of rounded just numbers; you had to know the techniques. The scientific questions were quite sophisticated. If you look at the people who have won awards or have become senior professors, they come from those schools. The dean I served under as a department chairman, George Ansell, was a Bronx High School of Science graduate, and went on to be President of the Colorado School of Mines. When my son went to Rockefeller University, the president there was a Nobel Prize winner and a graduate of Stuyvesant High School a few years before I graduated. It becomes a very small world, especially when you come from New York City and City College, which was a free school at the time. It was pointed out in one of the early books written in the ’50s that City College produced more people that went on to Ph.D.s than any other school in the country. Of course it has changed over the years since then. But the educational milieu in New York City was very good from the high school all the way up.

Nebeker:

That was inspirational for you.

Polytechnic Institute of Brooklyn; Naval Research Lab

Katz:

Yes. I graduated in 1945 from Stuyvesant. That was just the ending of the war years. I went to Brooklyn Poly, called Polytechnic Institute of Brooklyn then; now it is Polytechnic University. I had applied to City College, passed the exam, but to study physics you had to go all the way uptown and I lived in Coney Island. I also applied to Rensselaer and Rensselaer turned me down. I had a 90 average at Stuyvesant, which was really quite good, but they had so many applicants from Bronx High School of Science, Stuyvesant, and Brooklyn Tech that they would limit the number of people they would take from each in order to get diversity. I was not on any athletic teams or any thing like that, only in the Physics and Math Societies, and they could take only a small number of people. Poly was local and very reasonable. It was very well known then with Ernst Weber there with the Microwave Institute.

Nebeker:

You must have met Ernst Weber?

Katz:

Yes, I knew him quite well. I also served as an instructor in mathematics. The draft was still on, and I passed the Army physical but I wanted to go into the Eddy program in the Navy as an electronic technician. So I enlisted in the Navy, even after being accepted in the Army, not knowing what I had done was illegal. Fortunately, the shooting war was over. While I was in boot camp, my mother got letters from the Coney Island draft board saying, “Where is he? He has not shown up for induction.” I had to get letters signed by the people at Great Lakes boot camp that I was in the Navy for two years. The board said that as long as you are in service, fine.

Nebeker:

I think that was about the same time that Jack Reid was in that program.

Katz:

It could be. I do not know. I might have met him. I started the primary in Great Lakes, then I went to Washington, DC, to the Naval Research Lab for advanced schooling. That is where all the sonar and radar development was. That was a great place. They took me out near the end of the second term in my freshman year at Poly, so I did not get credit for that because they would not give me the extra time. I spent the year going to school and about six months onboard a Destroyer.

Nebeker:

Had you already decided to be an electrical engineer?

Katz:

If you look the Stuyvesant book, it says theoretical physics. When I started at Brooklyn Poly I was in electrical engineering because at that time I was told that there were not many jobs in physics for Jews, whereas in engineering there probably were. When I graduated from high school, the atom bomb work of Einstein and the other physicists was still a secret. By the time I got out of the service in 1948 that had changed and I switched to my first love. But electrical engineering was my minor. I took courses with some of the well-known EEs then who were very active in the IEEE. I became an early member as a student even though I was a physics major.

Nebeker:

You received all this electronics training in the Navy; you nevertheless thought you wanted to be a physicist?

Katz:

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Yes. Since I wanted to make up time I graduated in three years by going summers. I got up through the introductory electrical engineering circuits course, electronics courses, electromagnetic theory. If I had stayed a fourth year then I could have probably received an electrical engineering degree as well. I stayed at Poly. Physics was not well developed at the time. I took a course in crystallography—crystal physics—and they had one of the well-known laboratories. What was very impressive is while I was an undergraduate they had a very important person in that field by the name of Peter Paul Ewald come from England. He left Germany in 1933, where he had been a professor, because of the Hitler regime. In 1949 he came to Poly as the Chairman of Physics. They had a symposium for him and they had Bragg and von Laue, Nobel Prize winners for x-rays; and I think Raman, Nobel Prize winner for Ramanspectra, at our little school. This was introduced by one of the professors, and they were all friends. I said, “wow!” I looked at Poly as a kind of East Podunk type of university—it was a local place you went to. Then I began to find out that there were these key areas. In general most people did not even know where the school was located. It was a small school around the corner from the subway station and the law courts in downtown Brooklyn—it was not very much thought of as a place to be. Weber had the microwave group. Weber was known for electrical engineering. Herman Mark in polymer chemistry, very famous in the polymer area, who really started polymer chemistry in the United States. He was Jewish, so he also came over from Austria. He started a polymer group at Poly, and a lot of the leading elder polymer scientists were either students there or had come through there. Crystallography had world class people. Electrical engineering and chem engineering related to chemistry were key areas also. In the key areas of polymers, electrical, and crystallography, they were on the world scene, and that was exciting.

When I found that out, I started graduate school there in crystallography, looking at the relation between structure and properties in crystals. I was not really doing electrical things there, except I did work on things like iron nickel alloys to understand there is an electrical electromagnetic anomaly in that when you get certain percentages. In fact, a Nobel Prize went to a Frenchman who studied those series of alloys in the 1920s.

I did my Bachelors in 1950, and my Masters under Ewald in 1951. I worked on a theoretical mathematical analysis of how helices diffracted x-rays. Linus Pauling, a good friend of Ewald’s, told him that that was an important problem. We knew no biology or anything to realize that the reason that Pauling thought it was interesting was because he was working on the structure of DNA.

Nebeker:

You worked on that problem of the diffraction pattern of helices?

Katz:

Right. Then Ewald called me in one day, while I was writing up this master’s degree for publication. He was the editor in chief of the Acta Crystallographica, the principal journal, which also had a European and English editor. He said, “Larry, unfortunately we are not going to be able to publish your thesis.” I said why. He showed me a paper that the English editor had accepted by Vand, Cochran, and Crick in which they had worked out the diffraction of x-rays by helices. That is why Crick, when he saw the DNA x-ray picture of Roselind Franklin, said that it had to be a helix. Watson knew about the chargraff pairs, they never really solved the x-ray structural problem by Fourier analysis. They put it together, knowing it had to be helix, and a double helix because that is the way these groups went together and formed it. So I was very disappointed. The name did not mean anything at the time because it was before their publication. I had read their literature; Cochran’s work was well known. This was out of the Cavendish laboratory where Sir Lawrence Bragg was head. If you read Watson’s book, Double Helix, he points out that in 1954 Bragg sent Crick to Brooklyn Poly. That was after they did the work for the Nobel Prize. I remember talking to him at a meeting there then, and he said that my paper was good. By this time he is already world famous. I had developed just pure mathematical notes, a fourier transform of what a helix looked like with different scattering elements. It showed again that you had a Bessel function solution, then you know what the shape of the diffraction pattern would look like. Their paper was the same, but they worked it out more intuitively. They worked out the development by looking at what the diffraction would be of these elements. So I never published that, but I do have my Master’s thesis.

Ph.D. research, n-methyl acetamide (NMA)

Nebeker:

What was your Ph.D. work?

Katz:

My Ph.D. work was in an order/disorder mechanism in another important molecule, which turns out to be the basis of the Pauling alpha helix, called n-methyl acetamide (NMA), which has an amide residue. My thesis professor at the time said I had to become a world expert, even though I did not know very much chemistry. It is the five light atoms: carbon-carbon, nitrogen, oxygen, and carbon, which is a plainer molecule which, when it has side chains on, makes up the different amino acids. It is the backbone of that. Again, Pauling’s group in Cal Tech was world famous for crystallography. That is why he was able to do the alpha helix and get so close on the DNA because they were doing these structures, but on simpler, sub-unit molecules. They had never done the NMA because it had low temperature phase transition. At Poly we had a low temperature laboratory where we could put a cold stream on the crystals and take them down to liquid nitrogen temperatures. It turns out that the material as a crystal is in the real stable form below about eleven degrees centigrade, then it goes into a disordered form and would melt at about twenty-eight degrees. It was a very nice physics problem to look at what was the mechanism. As a physics major that it was I did for my Ph.D. Again, it is the basis of a helix.

Nebeker:

Was this under Ewald?

Katz:

No, I did my Masters under Ewald. I got very disappointed not publishing a theoretical paper as my first publication and I decided to do experimental work. I worked with Benjamin Post, a very brilliant, although comparatively older, man who received his Ph.D. in his thirties after the War. I was his first Ph.D. student. Later he was the president of the American Crystallographic Association and won their award for his outstanding work in certain theoretical aspects. Ewald was on my committee, as was Isador Fankucken, the head of the crystallographic laboratory and the first president of the American Crystallographic Association. David Harker was on my committee, a very well known American scientist who solved the third protein structure after coming to Poly. Then Rudolf Brill was on my committee, who was a very famous German crystallographer who worked up the structure of ice, and went back to head up one of the institutes in Germany. At that time it was kind of a who’s who—one of the few places besides Cal-Tech and some of the English schools where Bragg was and the German in Munich where von Laue was and places like that.

Instructor position at Brooklyn Polytechnic

Nebeker:

Were you happy to remain in Brooklyn?

Katz:

Yes. I met my wife there in 1949 and got engaged later in the year. I say teasingly that she allowed me to be a bachelor for three days—I graduated June 14, 1950, and we got married on the 17th. The year 2000 is our 50th anniversary. Then I stayed on to work with these people. I was one of the bright young guys there who had graduated top in the physics group of the class. I had electrical engineering and math as a minor, and that served me well. My wife quit working when we started having children. I was a protegee for the associate professor in charge of the programming for the department. As an undergraduate I took the top course in partial differential equations and I led the class. I told him the problem I was having and he put me on as an instructor. In those days you did not have to put out advertisements and put out twenty letters to be an instructor of mathematics. I was in charge of developing differential equation courses, vector analysis courses, and complex variables courses for the physics department students. The physics program under Ewald was beginning to grow and they wanted those specialized courses. From 1952 to 1956, when I left to go to Rensselaer, I was an instructor of mathematics. I would have been kept on as a tenure-track assistant professor, which I could not do while I was getting my Ph.D. because it was illegal to do both. I surprised them when I told them I was leaving, because most of the internal bright people, like Ben Post whom I served under and many of the other people there, were home grown. You were born in Brooklyn and you stayed in Brooklyn. I wanted my kids to grow up where there was grass and trees, not cement sidewalks. There was no place to park at Brooklyn Poly as a university professor so I had to ride crowded subways.

Rensselaer Polytechnic Institute employment; crystallography and bioengineering research

Nebeker:

You said you had this position at Rensselaer.

Katz:

I went to Rensselaer (RPI) in 1956. At the annual physics society meetings, they had a place where you could go for job interviews. They had just lost some people who had gone to other universities, one of whom used to do some x-ray diffraction. He ran the lab that Hilliard Huntington, the associate head of the department, needed for his work. He was very well known. He was doing self-diffusion studies in chromium and other metals. You had to orient crystals, and the way to do that was with x-rays. When I told them what my field was, they invited me up and I gave a seminar and they liked it and they hired me. In the ‘50s crystallography and diffraction of x-rays and neutron diffraction for solid state physics was very important. I had my own research area. We went to RPI in 1956. My third child was born in May of 1956, so my view was ego driven—we wanted not to be too far away from both sets of grandparents because of the young ones. I thought I would make a reputation and go off to another place.

It was at the same time as the Sputnik era. Rensselaer decided they wanted to go from just being well known as an outstanding undergraduate school of engineering and science to a real research university, which they have done. Rensselaer is always up near the top of listings of the top dozen or so engineering schools. For a small private engineering school in comparison with the Illinois and the Purdues, it is quite good. In the beginning I was doing straight structure analysis related to properties of metals and alloys and organic crystals, working some with the chemistry department and some with materials. I had developed a big laboratory that was bigger than the one I had come out of because that was ego driven—I was going to show those guys that I could even do better than they did.

Nebeker:

What were your main research questions?

Katz:

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For instance, how did the motion of atoms or molecules relate to elastic properties, a field called lattice dynamics. We worked on zinc from liquid helium temperature all the way up to just below the melt, and measured the properties both in plane how the zinc atoms vibrated and perpendicular, and that gives you a relationship to the internal forces. That started me in good stead. The way I got into bioengineering is I saw this announcement to apply for a Science Faculty Fellowship. I had only been at Rensselaer a couple of years. It was not so much research, but you went some place to learn what to do for teaching. The English system for teaching crystallography was very good. I wanted to go to the University College, London, to work with Dame Kathleen Lonsdale, the first woman member of the Royal Society and a Dame of the British Empire. That is the equivalent of a Knighthood for the male. She was a Quaker, pacifist, vegetarian, and a very brilliant scientist. After she died they named the geology building after her at University College, London, because she was the one that worked out the diamond inclusions in meteorites and moon rocks.

Graduate studies in England is quite different from ours. By the time you are a graduate student you really do not take courses any more. You have had your advanced courses in the equivalent of high school, then you spent three years taking only technical courses. They are ahead of us when they graduate with undergraduate, and we catch up with the graduate because we have more of these advance courses. I wanted to get that idea.

While I was there we got an announcement of a mini symposium at the Cavendish Lab where Perutz and Kendrew were giving their talks on hemoglobin and myoglobin for which they won the first Nobel Prize for the structure of proteins. That is where I met Cochran for the first time (I told you about that early paper). The English group is very friendly and very well known in this field, especially because of the Braggs, the early Nobel Prize winners. So there was a kind of a history of that being one of the key areas of development. I was very excited because both of these men are physicists, trained the same way I was in America in crystal physics using x-ray diffraction to understand the relationship between structure and properties. I knew no biology, having never taken a biology course in either high school or college, but to me their work was very exciting. I was still only an assistant professor, so I went back to RPI with this in the back of my mind. I had quite a number of research projects doing these type of studies of crystal properties related to structure: Atomic Energy Commission (AEC), Army Research Office, Durham (AROD).

Then I get promoted to Associate Professor in 1961 or 1962. Now I have tenure, so now I can take a risk. In 1963 at a meeting of the American Crystallographic Association I saw a friend who got his Masters in the same laboratory. He was a chemist. I knew he was working in the biological area doing these kinds of things. I said to him that I would like to work on living systems. I had kind of an epiphany attending that meeting with Perutz and Kendrew in England where I said, “Gee, fantastic, you can use these techniques and really work on living things.”

Dental materials and crystal physics; research training program

Nebeker:

And you felt real breakthroughs were possible in biology.

Katz:

Yes, that is right. I think these other old-timers had the same kind of feeling. Suddenly they say, “Hey, with the kind of things that I am doing I can make a contribution to understand how it may be possible to improve the quality of life.” I really think that has been the driving force, even with the young ones now who take it up as a career. “I am doing great engineering, but I can also really see what I am doing and how it fits into that.” I said to him, “I would really like to work on that, but I do not know any biology.” He said, “Work on teeth and bone, because they are crystalline and they are solids, and you could use all of your physics training.” This is before I even knew about Potter’s “sidewise lateral arabesque,” when you take your expertise in one field and move it over. My friend said the associate director of the National Institute of Dental Research (NIDR) is coming here to speak to some people because we want to get more of the crystal type of people involved in understanding the development of dentin and enamel and materials to replace them.

So I met with this person and I told him what my background is, and he says research would not be any possibility because you do not know any biology. But he said what we are interested in is training students coming from a crystal physics, solid state physics, and materials kind of background, so they can make developments into synthetic materials as well as understanding mineralization. They had good dental schools that had dental materials programs, and this man himself was a dentist. They were looking at things like improving amalgams and dental composites, and their training was geared very much towards, “these are the present dental materials and this is what we want.” He wanted to train some people with a broader view who could make applications here but have real backgrounds in solid state physics and materials science. I said that I can do it, because we have very bright students at Rensselaer and I had this nice laboratory which was doing just that but in straight physics. He gave me the paperwork and I wrote a proposal in 1963 and submitted it. I had to outline that the students would take biology, physiology, and anatomy on top of the physics and materials. It is a research training grant, the kind of things they still have.

Nebeker:

This is a graduate program?

Katz:

This is a graduate program in the old form of when they had these research training grants, which then supported the students. I got a little over a half million dollars for five years in 1964. If you consider at the time that a graduate student got something like $2,800 a year and a Ph.D. or post-doc the first year received something like $6,800 up to $8,000, a half million then was a like a million or more a year now. I write this proposal which is step wise for a couple of pre-docs and a post-doc and goes up to eight pre-docs and I think two or four post-docs. My support went through the academic year and the summertime for me and another colleague, a secretary, and a technician, and really the whole lab. I received a letter saying that the NIDR Council had met and deferred making a decision pending a site visit. I called this friend of mine who was the one that got me started in the first place and said what is this? Now he was heading the crystal laboratory at the Hospital for Special Surgery, which is the Cornell College of Medicine in New York City. He said, “That is very good. The reason they are coming on a site visit is they know nothing about your laboratory. You are not in a dental school and they want to see if you can do what you have outlined. If they did not want to support you they would have turned you down out of hand.”

I did have a state-of-the-art laboratory. I found out later I had one of the only labs in the world at that time which had a computer-controlled system to measure the crystal properties. This is 1963 and early 1964. I had one of the early DEC-PDP8s, and I had some brilliant freshman and sophomores because we had an honors program where undergraduates could pick a lab to work with. Since I had one of the best computers on the whole campus of Rensselaer at the time, my lab was a focus. The PDP8 was driving this device, and it was dumping the information into another early computer, an IBM 1620, with a tape drive. When we got the money from the Institute of Health I could upgrade it to a card driven computer to speed up the way the Fourier calculations were done.

Besides the dental people who were there, on the site visit they had an outstanding man who later was the president of the American Crystallographic Association, the key geological crystallographer for the geological survey, whom I knew personally from other meetings. I knew all these people because even as an undergraduate I joined the American Crystallographic Association at its start in 1950, and so I had seen them every year at meetings for twelve or thirteen years. They saw the lab and said it was impressive, and he said there is not another lab like it. He did not know about the IBM lab. There were some people that came out of MIT, also in crystal physics, similarly wanting to get all these measurements under computer control. This is very early work in the early ‘60s.

Nebeker:

You are actually controlling the position of the crystal?

Katz:

You mount the crystal in a four-circle goniometer, and you could orient it to your various angles and then the x-ray beam, so you knew exactly where the space was that the diffraction came from, ie. a certain set of these Bragg planes. Therefore, you can get the amplitude and you know the position and you can put that into your Fourier analysis and work out the structure—all automatically. We never got to the end point because once I got this grant we started to go in other areas. A little later the Council met and approved exactly the amount I asked for. I started to ask for something like $800,000 and I worked it down to $550,000 or $600,000. I should have left the whole thing in. Back then every year the NIH was getting more and more money, and they knew they had to spend it to keep receiving that. Nowadays to get any kind of grant you have to have a history, publications, and development, and so on.

I started this working with very bright students. The beauty of it was that I did not have to write a research proposal. If I wanted to do something, I could take on a student as a trainee. The idea was to train them in how to do research. We began by trying to understand how bone and mineral forms. Very early on that it became clear also that you had to understand something about how to measure these things non-destructively, and that is how I got into the ultrasound work; RPI was a good place to be for that. Dr. Huntington during the War years worked at the MIT lab where they developed sonar for anti-submarine warfare, and he had used those techniques to measure the properties of single crystals. This is the way you measure the elastic properties, the relationship between the sound wave and elasticity. You learn about the wave equation in any kind of instrumentation electrical engineering course. Then the diffraction work to look at structure. It turns out there was important work considering that there was probably an electrical driving force in the development of bone. So this thing began to integrate looking at mechanical properties, electrical properties, and ultrasound measurements.

Nebeker:

You have the capabilities there to do the ultrasound measurements?

Katz:

Yes. We began reporting those in some of the early IEEE acoustics and ultrasonic meetings. I think I am the first non-electrical engineer to get the Career Development Award of the IEEE-EMBS. It says the reason for it is for measurement of the anisotropic properties of bone and developing a model for it. So although it is more mechanics, the basis of it was to understand the things that come out of the electrical engineering background, measuring ultrasonic wave propagation in various directions and be able to do this kind of correlation in that type of development. At the same time the EMBS was trying to broaden its view of biomedical engineering. The journal has papers besides traditional electrical; they now have articles on materials and mechanics, the idea being because these things are so integrated.

My training program started in 1964. I began learning with my students. They took the courses, and we would meet regularly at lunchtime and sit around my nice big laboratory in the physics building built at Rensselaer in the ‘60s and I would learn with them. I started attending these meetings, like Gordon research conferences and learning more about bone and teeth problems. I was also coming from a physics background. For example, 1966 was the first Gordon conference on Biomaterials. The idea at that time was that to develop synthetic materials, you wanted chemists and physicists and other people to come together at that level. Now it is the tissue engineering people and molecular biology. At that time it was mainly people that trained with more microscopic work, down to atomic understanding. I remember one of the well-known orthopedic surgeons, who was co-author of the first book on orthopedic implants, talking about using metals. In our work we had already been working on the components of bone, saying that bone had to be a composite and why don’t you just model it that way. It was kind of a naive question, which you are allowed to ask at Gordon conferences. He said we don’t know the properties of the components. I made a note to myself and went back, and because I now had these students and this funding we started the ultrasound measurements. You could not get single crystals of the inorganic component bone apatite, so we began to measure apatite powders from different species. I worked with good post-docs and began these ultrasound measurements, but not from the viewpoint of imaging. The traditional line of electrical engineers was to use ultrasound for imaging. That is where I deviated. I was interested in using it to measure properties. It is related because it is the difference in properties that allows the image to be seen.

Nebeker:

You are using ultrasound as a way of measuring some of these material properties?

Katz:

Exactly. Because there is a relationship between the velocity of sound and the density of material and its elasticity. It is the basis of imaging as well because it is those differences that allow you to get signal rebounds. You get a different aspect if it is soft tissue and soft tissue with a tumor, or a fetus that has some calcified cartilage. Things show up differently. My interest was more what is the speed of sound in this material, and how can I measure the different directions and put this together.

Nebeker:

You are trying to characterize bone…?

Katz:

I was trying to characterize bone and teeth. That is the way we did it.

Nebeker:

How well was the micro structure known through electron microscopy?

Katz:

There was not a lot of work. People were trying to understand, so there was that information. All of the mechanical measurements that people were doing with these bone artifacts were with large mechanical testing machines. So there was not much work and there was very little known about the anisotropy because it is very difficult to get good size specimens in all the different directions from the tooth or bone. Our publications in the mid to late ‘60s on some of these ultrasound properties were the first saying, “these are the properties, but this is how they relate to structure.” Prior to that was, “here are the numbers, this is the value of the elastic modulus of a bone or the elastic modulus for a tooth,” because they wanted this general information to see how it related to the amalgam. Coming from the solid state, crystal physics, my interest was very basic, as what is the relationship between structure and properties? I essentially first developed the conception that for bone you could not just simply consider it as a mixture of the inorganic apatite and the organic collagen. Because there were so many different levels of structures involved and each one contributed to it, you had to consider it as a hierarchy. That way you had to understand how the apatite crystallites and the collagen organize and how they form their joint structure. I pointed it out in one of my earlier papers with my principle research associate, Dr. H.S. Yoon. He was a materials Ph.D. from Penn State and had a background in crystal physics. We actually wrote a theoretical paper as part of a trilogy on these measurements. We used the term hexagonal symmetry. The engineers call this type of structure transverse isotropic. It means that in the plane is isotropic, and there is one unique axis transverse to that plane. In crystal physics you call it hexagonal. In both cases you need five elastic constants to determine it. Because we use the term hexagonal, sometimes people who read the literature do not understand that we are talking about an engineering term. I had to evolve into engineering type of terms.

When I started I called my laboratory the Laboratory for Crystallographic Biophysics. When I began to go to some of these meetings like the ASME meetings and other engineering meetings, they said you are doing biomedical engineering, and I had to say, “What is that?” In the ‘60s, being a physicist, I said I am working on bio things so it is biophysics. If you are interested in bone as a structure and its properties, then that is engineering. Then eventually the school changed my title from Professor of Physics to Professor of Biophysics and Biomedical Engineering. So early on I had a bioengineering title, probably even before there were any departments of biomedical engineering.

Electrical response of bone

Katz:

At that time we also began to do some serious electrical studies. Rod Lakes, one of my students who last year went to the University of Wisconsin as Wisconsin Distinguished Professor, did a combination of the mechanical properties, viscoelasticity, looking at the behavior over eight decades of the response of bone, both uniaxialy and biaxialy. Early work said that bone is piezoelectric, so there was concern about the electrical influence. It turns out that dry bone is piezoelectric, and that is probably due to the collagen. Collagen is an isotropic structure. If you try to force the bone you have an electrical response, and if you put an electrical charge on it you have a mechanical response. I think Fukada and Yasuda, the Japanese, who first pointed this out, had actually taken the old phonograph records and made a needle out of a piece of bone, and it acts as a pick up.

Nebeker:

That’s proof of piezoelectricity.

Katz:

But you can’t say it is not piezoelectric because you are in wet bone and the thing does not behave the same way. They started talking about things such as streaming potentials, the fact that there is fluid motion with ions, which somehow the cells may sense. Rod developed a very clever bridge with my other colleague, Richard Harper, and then used it to make these measurements electrically as well as the mechanical measurements. He was published in the Review of Scientific Instruments. With the publication of the series of papers with him, we modeled the different things that might control the transfer of energy in bone, and one of them was the electrical consideration. That was based on being able to measure these bone specimens as a function of frequency using this very clever four-element bridge. You did not get surface charging going all the way down to low frequency. It was like the measuring of electrical properties on other tissues that Herman Schwan was doing at the University of Pennsylvania. I was invited to a symposium to give a lecture on that, and he was in attendance. I pointed out that this was the first time that he would accept the measurements on bone at low frequency because there was not charge build up because of this clever design of the bridge. We were coming back full circle to try and understand the electrical-mechanical interactions.

Nebeker:

That is interesting that you are getting into electrical measurements.

Katz:

Even though we were looking essentially at elasticity theory. But the electrical response is important because of that. We had very bright students getting their Ph.D.s and put out a lot of publications. I did not have to wait to write a research grant for each new thing. For instance, if I wrote up a proposal for the work that Rod Lakes did, we probably would not have gotten it funded because there were already measurements of some aspects of viscoelasticity in bone and teeth in the literature. It turns out that they are really insufficient. If you want to relate these different properties, the amount of information you need was much larger than in any of those studies. We did not find that out until we began working with it. He got a Ph.D. and his Ph.D. thesis is still considered the seminal work in the field. In any of the recent books on the mechanics of bone, the viscoelasticity theory presented describes our work. But if I had put in a research proposal with what we knew at the time, it probably would have been turned down. “Why do we need this? You should be aware of the literature.” And we were. That is the basis of what we said, if you look at the literature and do the mathematics you will find out that you cannot relate this scientist’s work with that scientist’s work because neither of them did it over a wide enough frequency range to fully understand the properties. This comes back again to understanding the wave equation and the interaction with some of the IEEE type of aspects. So that worked out very well.

IEEE and societies

Katz:

Meanwhile, my title had become Professor of Biophysics and Biomedical Engineering. Sometime in the late ’60s or early ’70s, when we were up for accreditation with the old ECPD (Engineers Council for Professional Development), they wanted to have the proof of biomedical engineering. We did not have a department then. I was one of the people that they listed. You had to have so many teaching equivalents. At the time Theo Pilkington from Duke University, who was very well known in the IEEE, was our site visitor.

We got to be very friendly because I was in the IEEE as well. I was in the two societies of IEEE and ASME, and also one of the founding people of the Biomedical Engineering Society.

Nebeker:

What about biophysical societies?

Katz:

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I do belong to the Biophysical Society. In fact, in the early days some of us tried to get kind of a bone biophysics going, but the interest there was more on cellular and molecular biology, so there turned out not to be too much. Eventually I stopped going to those meetings, although I am still a member of that society. The principal ones I went to were the IEEE-EMBS, BMES, and ASME, which has this biomedical engineering subset. Several of the people here at the earlier meeting of our Board on the BMES Annals have come from the biomechanics type of groups. In the beginning the Annals traditionally were almost all electrical and systems type, but they have spread the view of that as well.

I received a phone call from the National Institute of General Medical Science right after receiving the NIDR Training Grant. The grant was listed as a biomaterial/biomechanics type, and there were not too many of that type at the time outside of the dental materials program. They wanted to know if I would be available and willing to go down to Houston to look an artificial heart program between Debakey and Rice University. It was still Baylor Medical, although it was in Houston rather than where Baylor is, and they were very close to Rice. I said I do not work on artificial hearts, and he says they need somebody who knows something about mechanics and biomaterials. I said okay. It was an interesting visit.

Then I get an invitation to join the study committee for biomedical engineering training the National Institute of General Medical Science with a bunch of the old-timers. We wrote an article when they wanted to drop training that appeared in the IEEE Transactions. It was a critical paper because that was when Nixon was President. He said why should the government pay to train people, because they can go out and make money afterwards? They used the argument of the free market place: if you are a farmer selling tomatoes cheaper than the other guy, people are going to buy yours. We pointed out that people do not go into fields just to make money; you do it because the thing excites you. So the free market idea is not the way you get good scientists trained. Otherwise everybody would want to become a lawyer or physician or stockbroker or something like that. It just does not work. The title of the article was "The Future of Training and Biomedical Engineering 1972," IEEE Transactions of Biomedical Engineering, Volume 19, Pages 148 to 155. Our committee consisted of Bill Siebert, chairman of the committee; Ernst Attinger was out of Virginia; Cox was the head of computing and biomedical computing at Washington University in St. Louis; Dowd, and I forget where he was; Grodins from Southern Cal, who headed up the biomedical engineering program; and Hobstetter, who was vice provost for research at the University of Penn, a material scientist. Penn had one of the other training programs something like mine. Even though they had a dental school, they brought in the material science people. You see some of the old-time leading names in biomedical engineering on that committee. I served on that committee from late ’60s until the early ’70s. This article was published even after my five-year tenure went off.

Development of biomaterials field

Nebeker:

This is I suppose when biomaterials is becoming recognized as an important field. Is that right?

Katz:

Yes.

Nebeker:

I am wondering about the roots of that. The dental research must have captured a lot.

Katz:

Dentistry was well ahead of orthopedics and the others at that time. Caulfield  designed the first artificial kidney when he was in the Netherlands under Nazi occupation. They had a big tobacco industry so they had cellophane. He made his first one in the bathtub with giant amounts of cellophane as a diffusing membrane to make an artificial kidney. That was one area by itself. The people who were too concerned about the artificial heart were like Debakey in the late ’60s or early ’70s.

Nebeker:

They were concerned with materials that they could use…?

Katz:

People already know that you can have stainless steel because it did not corrode too quickly. Cobalt chrome alloys were good because you have chrome oxide coating which pacivated the material. Titanium was not used until much later.

Nebeker:

This is the beginning I suppose of implanting new materials.

Katz:

Yes. Dentistry was the leading cause because they already knew about amalgams and they already had the polymers to make impressions, and so they knew these things could be used inside of biological tissues. Already, some orthopedic implants were being made out of steel and cobalt chrome alloys, even produced commercially, because some of the post World War II people began to try implants when people had accidents and so on in order to replace damaged tissues. There was also the neat external orthotics materials and prosthetic materials for all of the war injuries which happened after World War I, but even more after World War II.

Nebeker:

The solid state physics, the physics of materials came in the War years.

Katz:

The things like having the evolution of outstanding technologies with ultrasound with devices that can measure down to microseconds and nanoseconds. You can measure the quick time of flights and things like that. Look at the chemist who won the Nobel Prize in chemistry this year for doing quadrillions of a second imaging of actual atomic—some kind of multiplication of fast speed. So you are actually looking at inter-atomic interactions. If you think of the equivalent then, the ability to measure things in the megahertz region so you can measure wave velocities and start to do medical imaging.

Nebeker:

There is also the chemical side. Polymer chemistry developing and evolving.

Katz:

Exactly, people began to realize that you could get better resistance type of materials. Suddenly besides the electrical engineers they now had some material mechanic expertise. All these other people I mentioned, Attinger was an M.D. from Switzerland who got his Ph.D. under Schwan. Dowd, Grodins and Bill Siebert were electrical engineers. Almost the whole committee were electrical engineers. I was appointed, and so was John Hopstetter, because he was the PI of the training grant that Penn had just gotten, not really with the dental school people but with the materials science and physics people at Penn. They said this is not just all the old time electrical engineers involved; now we are talking about synthetic materials.

That time period in the ’70s was when the space thing went down and they began to fire a lot of the solid state and material scientists. The National Academy of Science (NAS) had a special meeting in Washington to see what could be done in applications and material science. I was invited to speak about biomaterials. They had a whole session on bone and they had some other people there. Starting in the late ’60s, when all the societies had their annual meetings they had a symposium on biomaterials—chemistry, physics, and the old Institute of Materials and Mining Engineers. It was almost the same working group, giving the talks at each symposium.

Nebeker:

The idea was that some of these materials people were no longer employed in the space race.

Katz:

So they wanted to find out where to go. Even before the National Academy of Engineering (NAE) existed they were concerned, because a lot of them were scientists, chemists, and physicists. Biomaterials at that time was beginning to blossom. Sam Hulburt was one of the people. He is now the president of the Rose Holman Institute of Technology and started the idea of ceramics; he is very well known in ceramics. I was on it for bone. Ed Korostoff from the University of Pennsylvania Dental School was one of the speakers. It was almost the same group because each of the societies saw they can have someone speak about dental materials. I spoke about properties of bone, Hulburt spoke on ceramics of biomaterials, and someone who spoke on cardiovascular. We had a traveling road show. Out of about ten people, generally there were at least six of us who were always there and then a few other people were added. There was this interest, and the different societies saw this was an area to go into.

Nebeker:

Was there a real influx of people into materials--

Katz:

Yes. Because of the training programs, and then graduate schools began programs if they did not have departments. I was invited to the University of Michigan to be the external reviewer of their graduate BME program. At that time every five years each graduate program that gave out degrees that was not a department had to be reviewed externally. I met people in electrical, mechanics, and materials because graduate students had to have some type of homebase. They recently went to a graduate department of Biomedical Engineering. Wisconsin, on the other hand, now has a full undergraduate and graduate department in biomedical engineering. Electrical was very strong and it was the major component there, and also human factors for whole body motion. Rod Lakes, now a Wisconsin Distinguished Professor, was brought in from the University of Iowa. Because of his background, his appointment is 75% in engineering physics 25% biomedical engineering. The way they formed the department is they took the electricals who were quite well known, someone like Rod, and have assigned 25% up to 50% or maybe 75%. With the new money from the Whitaker Foundation, they are actually hiring people full time in this department. More and more you are finding either graduate departments or full departments where there once were only programs, which were a lot looser without guidance at the top or with a chairperson and so on.

Nebeker:

How big was biomaterials in this establishment of biomedical engineering?

Katz:

Very strong. In the early days this group of people who were involved in these meetings, like Sam Hulburt, when he was at Clemson started international conferences out of which evolved the Society for Biomaterials. We were very egotistical. The feeling was that since these were international conferences, this was going to be the major world society. The Europeans formed the European Society of Biomaterials, Canada has the Canadian Society of Biomaterials, and Japan has the Japanese Society of Biomaterials. The Society of Biomaterials is just the American, without the word American. That was formed back in the ’70s, so it was the first of these professional societies in biomaterials in the entire world. There are all these subsets now.

Nebeker:

In that very early period of the ’70s, what were the areas of biomaterials that attracted the most attention?

Katz:

Orthopedics and dentistry.

Nebeker:

Orthopedics for the implants?

Katz:

Mostly for the implants, although people began to look at substitutes when you had a tumor where you had to take bone away and you wanted something to replace it. That is how Hulburt got involved. His Ph.D. was from Alfred University in upstate New York, which is one of the very famous ceramics places. His point is that a ceramic is already the highest state of oxidation so that you would get very little corrosion, and its mechanical properties were good enough that it could support loads. Even though it might be quite brittle, eventually you could make them with very good, low uniform microstructure and even have good impact properties.

The artificial heart program had to have blood compatible materials and for replacement for clogged arteries besides transplants and other operations to look for blood compatibility. Debakey and Coonley used artificial heart valves. The first one was the poppet valve, a silicon base polymer bouncing up and down for the valve. Now you have leaflet valves made out of graphite. Independently they took different kinds of backgrounds. If you worked in an orthopedic implant, it was more mechanical with finite element analysis and some materials trying to get a better material, as opposed to the heart valve where you were interested in blood flow and biofluid dynamics as opposed to biosolid mechanics.

Nebeker:

What about the prosthesis application?

Katz:

In prosthesis application, you had people that were interested in blood flow and the people that were designing orthopedic implants. But they began to come together because the ASME had its own subset, a biomedical engineering division, just as IEEE had formed the EMBS. People had interactions, and that is the way the field has evolved. In material science you were trained somewhat like a solid state physicist because you started with atomic structure, symmetry and asymmetry. Zinc is an hexagonal structure so there are two directions that you have to be concerned about with 5 elastic constants as opposed to nice noble alloys, gold, silver, copper, and those which are cubic structures and therefore have only three independent elastic constants. That section evolved as mechanics came into the materials field to try to understand that.

I do not say that I am the first materials person or solid state person in the field, but probably the first to try and develop a school that actually trained people as opposed to where electrical engineers were trained. You had Jacobs at Northwestern and Grodins at California, who in Electrical Engineering departments were training biomedical engineers mostly at the graduate level. My program was also the graduate level, so I was a little bit behind them. That committee I mentioned already existed when John Hobstetter and I were appointed to it in the ’60s, because we were kind of the new breed coming in with classic training in our own fields, just the way the Grodins, Schwans, and Jacobs were classically trained in electrical engineering, and seeing there is a problem they can solve because of their background.

Applications of crystallography and electrical engineering to biomedical engineering

Scanning acoustic microscopy

Nebeker:

Is the kind of training you received in solid state physics, crystallography, and so on, an important complement of training in biomedical engineering today?

Katz:

Yes. Especially now because we are getting down the hierarchy. I just came back yesterday from a meeting in Germany on a mixture of micro and nano mechanics—scanning acoustic microscopy—which is what I do now. It is the interaction of electrical engineering with wave propagation. Calvin Quate at Stanford’s Electrical Engineering Department co-developed atomic force microscopy and the scanning acoustic microscope. The idea there is to look at the properties and mechanical response of cells using state-of-the-art electronic equipment. The interactions now begin to come together. Most of the work in those older days were macroscopic in mechanics and materials. But coming from my background and the material science people where you started from the atomic level and built up is why I began to consider the hierarchy. If you make a mechanical test and you get a mechanical property, that number is important so you know something about a material’s response. But if you want to understand the properties of the quality of the bone, then you have to understand how the inorganic and organic come together and how it forms a super structure on the micro scale. Those micro dimensions are just the right dimensions to be examined by ultrasound, just as atomic dimensions are right to be examined by diffraction of x-rays or neutrons. You need the right wavelength. You are back in terms of a spectral concept. Ultrasound at high megahertz measures things in the micrometer range. The way bone organizes structurally is at a micrometer level kind of construct. You use x-ray diffraction and all these other things to understand atomic and molecular configurations, and then you go to things like ultrasound at high frequencies. My Olympus acoustic microscope goes up to one gigahertz; the Germans make one that goes up to two gigahertz. You are talking about resolutions that are better than a micrometer. You are looking at individual elastic properties now at a spacing of no more than a micrometer. The interest is not to give those numbers, but that gives you an idea of understanding homogeneities and the way these tissues form.

Nebeker:

Is this all related to the visual data these days?

Katz:

Yes. Because you can do optical microscopy at that scale, you have an optical figure of bone which the histologist stains and you can see the bone structure. It does not tell you anything about “quality,” which is the elastic response that you then measure with these other techniques, the acoustic microscope or the atomic force microscope, or by indenting and looking at the response so that you can also measure things on a nano scale. That is where the future is now. With tissue engineering we are trying to replicate the way the body organizes tissues, which means you have to know cell properties and measure cell dynamics: How did the cell respond to a force? What is the signal that turns on a cell, say in bone to produce the bony material? How does a cell move when you get cancer? Why does it move? Is there a way therefore of stopping the move? Because it is the metastasis that kills people. A localized cancer can be treated, but if the cells migrate you have problems. Knowing how and what makes a cell move may enable working out drug modalities. Not that we know all the microscopic properties, but we understand that you have to go down in scale. A colleague of mine in a very well known cardiovascular engineering group has said that the theme for biomedical engineering should be from genome to bedside. Start with why the body organized something, and work a continuum all the way up to know the proper drug modalities. So if you are doing cardiovascular you know about implants and you know it may cause thrombosis, or what causes an arrhythmia because you have done the mathematics and the analysis. But you know why and what makes the cell not work properly and so on. That is what biomedical engineering is today. From genome to bedside is a good model. The end result is to improve the quality of life, which means to be able to do away with heart failure, strokes, Alzheimer’s disease, Parkinson’s, etc.

X-rays and ultrasounds

Nebeker:

It is impressive to me that you approached these questions with two quite different modalities: the x-ray crystallography techniques and the ultrasound, and maybe others.

Katz:

It was part of the training. The x-ray techniques give you some idea of atomic structure and their structure relations. I do very little x-ray diffraction now, but with the technology at hand I applied that rationale. To study what I studied then, I used x-ray diffraction at a wavelength which is comparable to the scale of the structure, because you cannot see atoms directly but you can get the information from the x-ray diffraction pattern. It is a mathematical relationship, the Fourier transform, the atomic structure and the way that the diffraction pattern are related mathematically.

Sydney Lang published a paper that preceded my own work, and we stopped the work at the time, where he used ultrasound to measure the anisotropy of bone. He also did not come from engineering but more from material science. He used only five elastic constants because he assumed bone is hexagonal, and he said the reason it was hexagonal is because the inorganic component is hexagonal—the apatite crystals—and collagen at that time was thought to have three-fold symmetry. When you have something with just threefold symmetry it would fit with sixfold, and therefore bone itself has to be hexagonal. Then Dr. Yoon, who was trained at Penn State in material science, used ultrasound to measure the properties of fluorapatite as part of his Ph.D. thesis. It was suggested to him that he come to work with me because I was working on apatite and measuring it. Talking to him, I said that we have really done so much work. The size of the crystallites, we knew from x-ray diffraction and transmission electron microscopy appeared to be very small—much too small to affect a megahertz response which is 100, 200 micrometers wavelength. You are talking about a crystal that is so small that there is no way you are going to see the atomic structure with ultrasound. The same thing with the collagen molecule. I already had students working on the microstructure. By this time scanning electron microscopes were available so we had very good pictures of what the bone structure looked like at the micro level. I said if you look at this, then the micrometer scale that ultrasound measures is this microstructure of bone. Because of the training that I had, and Yoon appreciated it also, and had done x-ray diffraction in material science at Penn State, you knew that it was the size-frequency dependency. The wavelength of ultrasound that we are using was the right wavelength to sample the micro-structure of bones. We took the early work that had been done and redid it, and then wrote a series of three papers stating in detail that although the values that Lang had gotten were probably correct because he measured them properly, the reason was not because he was measuring the crystals or collagen. What we were measuring was the bone micro-structure. The important thing about that is that you can get bone from young animals which is not the same kind of structure where you get cylindrical arrangements, but you get something that looks like plywood. But it is made out of the same components of organic and inorganic. When you measure with ultrasound, you get differences in the three directions because of the anisotropy. With plywood, when you stack the wood you get a difference when you go through the wood in series or parallel. Just like with series circuits or with springs, you get a difference if things are in a series or in parallel. The same thing with anisotropy. When I teach I show the electrical mechanical analog between capacitors and resistors and springs, which is a mechanical response. We called it hexagonal but the people in the field know. For the first time in these early papers we said the reason that you can measure the anisotropy is because the ultrasound measures the right structural scale. Again, it was the confluence of a technique which is based on understanding wave propagation, which has a mechanics and materials response, but also in terms of measuring is making the right type of transducers, understanding the frequency response, and things of that sort. That is where the training comes in. Different from the mechanical engineers who would understand the wave equation, but are trained in continuum mechanics that every piece of material is the same as every other piece when you do the modeling. We said no, that you have to work at each level, a kind of hierarchy. That is why this conference I was at involved both nano and micromechanics, because you can now measure on an angstrom or a nano scale, as well as on a microscale. This is how the thing has evolved, and why I feel that you can train undergraduates properly in biomedical engineering. It is not a scatter course where you take a little of this and a little of this. Our students start in our department with courses in physiology and biophysics, that they take as sophomores, and then they take courses that integrate that with the engineering. The Mechanical Engineering Department at our school has courses where they teach mechanics of implants. Outside of biomedical engineering there are, for example, people in Mechanical Engineering Department who are doing biomechanics, and you find that in many schools, so that you really intensify the education.

For instance, I got into acoustic microscopy because an electrical engineering colleague at Rensselaer, who worked on surface acoustic waves, was developing a transmission system in the early days and he thought it might be useful for us in bone. I said, “You bet it is useful!” Before we were only measuring average properties. We would take transducers and put it across the material to get its property on the average. In that case the resolution went down to 100 micrometers as opposed to millimeters. This was very exciting, and that led us into acoustic microscopy full time. To show again the influence of cross-breeding, recently another electrical engineering colleague, Massood Tabib-Ayer, has invented and developed an evanescent microwave scanner from one gigahertz to ten gigahertz, which means we can now measure the complex permitivity of materials. He developed it for composites for the Air Force, because if you have very tiny cracks that can then fill with moisture, that really makes the machine response jump because you have changed the permitivity. We have some papers in press now: one in the IEEE Transactions in that area, and also in a new journal called Biomedical Microdevices. We are using it for early detection of caries. Once again, a cavity would change the electrical properties and its resolution is down to micrometer scales. So we are doing a combined acoustic microscopy and evanescent microwave microscopy to look for our electrical-mechanical properties. Again, showing because of this interaction how new instrumentation may be developed.

Even more recently, my students went to one of my colleagues in electrical engineering who is a transducer specialist in ultrasound because he had the equipment that we did not have, and we wanted to make some measurements on individual materials that we can use for calibrating the acoustic microscope by measuring the density and velocity of well known materials, so that you know their properties. The recent colleague, Dov Hazony, says he has developed a device that might be good for implantation. It is a miniaturized ultrasonic transducer, and we can make them even smaller in titanium, which is a biocompatible material. You need a good, high quality digital oscilloscope. It is self-calibrating because you get the rebound of the signal from the first cut, and you know the speed of sound in titanium. You get signals from the second cut, so that calibrates the size of the cut, or little cage at the end of the device. As the tissue grows into it, you get the wave velocity in the tissue as well as the attenuation of the sound wave. We now have another area to cross over between the electrical engineering aspects to try and measure for the first time ultrasonic properties in vivo, and to relate that to these external devices that are trying to measure properties clinically. We are planning to make one now. There are expenses, so we are starting to put in some research proposals to make it as small as two millimeters in diameter by half a centimeter long, so you can implant it in animals, but it could also go into humans. In spinal cord injury they are concerned about the loss of bone quality, like osteoporosis. There the only thing that you have to worry about is the possibility of infection. That is why we have animal experiments so we can work about a better way of measuring through the skin. It can be made into an orthopedic screw, so it serves a double purpose. By having these serrations internally, instead of having a smooth internal surface to get the rebound of the ultrasound signal, you get the scatter of noise, and the only really good signals that come back are the ones you need for the internal calibration. In your oscilloscope you can get rid of the noise by averaging or sampling and get beautiful echoes. People know that I am interested in ways of measuring bone properties. First there was the acoustics that I started with, then the scanning acoustic microscopy for high resolution, which again is a state-of-the-art developed by electrical engineers. And then the scanning microwave work, and now implantable transducer. I am not taking credit for being the originator of the idea, but very quickly seeing how these things can be applied and having the background knowledge on a very fundamental basis across the spectrum of the hierarchy of the bone to see just how something like this fits in.

Katz's bone structure formation research

Nebeker:

Most of your work in the last decades has had to do with acoustics, with ultrasound?

Katz:

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Almost identically both the bulk wave propagation and the acoustic microscopy, but related to things like optical for histology as well as scanning electron microscopy to look at density distributions and structure. Although I have used acoustic techniques mainly, I have always said that you need all of these other methods as well. You need something to measure structure and something that measures properties, and there are different ways of looking at properties. Although I cannot do all of it, I can see how it all fits in, and I do my thing. My major interest is still to understand how and why the bone structure forms, and how it relates to the properties. Any tool or device that will do that, I will either work with those people who use it or work with it myself. Each case is like a bug zapper that attracts bugs to it—because of my interest and of having a history of publication and being at the cutting edge in this, my colleagues who themselves are not biomedical engineers but who have something like this will say, “I have this thing and it looks like it should be related to your work.” I say you bet it does, and we start working on it, then we merge our expertise. I make no claims to be able to develop the scanning evanescent microwave device because I do not have that kind of background in microwaves. But I know the restrictions and how the measurements should be done, and what is required in order to correlate those measurements with my acoustic measurements. Neither have I designed the acoustic microscopes, but I have evolved to the point where I understand what wave propagation will do and how that relates to those things of interest to me. That is why I am interested in what is being done inside the body that relate to the measurements that people are doing externally and what we do ex-vivo. You must cut samples for all the measurements in the acoustic microscope, so you know it is no longer the way it was in living bone in order to at least understand what you are measuring. For instance, in a distraction experiment, you make a person’s bone grow by cutting the bone at a millimeter and putting in a device on the outside with very rigid screws that each day you pull slightly. Each day the cells are trying to close the gap. You can actually grow people several centimeters. It was invented by a Russian named Alizirov off in Siberia as opposed to Moscow or Leningrad, which were the scientific centers. He took Wolfe’s Law, which is a phenomenological law developed by a German anatomist/physiologist at the turn of the century who said bone function and form are related—the way that the bone develops (not the shape because that is genetic), but the quality of bone depends upon the forces on bone. You can measure the ultrasound velocities and within 100% can tell you if you are right-handed or left handed, even through the skin. You put a transducer at one end and receive the signal at the other end; the fast echo will come through the bone. It will be on the surface of the bone; the soft tissue will not affect it. There will be a difference between the two bones because the density is quite different. Also the bone properties will change with age. He took it literally, and became world famous; it was called the Alizirov Technique, or distraction osteogenesis. Osteogenesis meaning the growth of bone, and distraction because you are literally pulling it apart after making the cut. People are applying it on teeth, cutting in jaws where the teeth overlap, and doing the same thing. What you can do is make the mandible open up and the teeth move with it. It is just fascinating how these things get picked up.

With the external device, you do not want to have the external device on too long, because if it is on too long you shield the bone from getting all the forces that the cells need. After they fill in the gap you want it to form into normal bone. If it is on too short a time and you take it off, you get a pseudo arthrosis and the bone will break again because it has not filled in. We are talking about implanting one of these miniaturized transducers because you can make it into an orthopedic screw, and then look at the tissue growing in. You would not do it in humans at first but test it in animals. A group that I work with in Germany are hoping to do it in sheep. You can look at the callous formation and see how long it takes on average for the callous to form and then bone to develop.

Nebeker:

You will know exactly when…

Katz:

Not exact because there is always a distribution. But you have some idea what the range is. Then you translate this to humans. By doing the observations with x-rays, you now have the relationship between what you see in x-rays of the bone and its actual ability to withstand loads. You are using a combination of catscan, again an electrical engineering product, with this type of acoustics. It is really why no longer you can be just a material scientist or a mechanical engineer if you are trying to understand such problems. That is why from the motto is from genome to bedside. Because of the spectrum, if we understand how cells respond to forces and how they then put out the material to make bone. Maybe we can duplicate that even in synthetic materials, so-called biominetics, tissue engineering, to get the body to do it. The same thing with neural systems, where you have people really coming from electrical engineering to understand transmission of signals, trying to bridge broken nerves by using tissue engineering, so that you reconstitute the nerve.

To me it is a very exciting field, even though I am not working in it; I’m excited by working with young students and educating them and pointing out where things are now and where things can be. I know that at Case we are in the top three of undergraduates popularity along with mechanical and electrical engineering. We have nineteen and half full time faculty now and will be increasing to 21 or 22 tenure-track faculty. The only bigger department, because they recently merged computer, electrical, and systems, is EECS (Electrical Engineering and Computer Science). They have about thirty-plus faculty.

Nebeker:

You have certainly given me an enthusiastic view of biomaterials and how this has developed.