Bruce Carlson

CV | Video (44 min.)

Bruce Carlson

I was born in Gary, Indiana on July 11, 1938 into the Scandinavian family of a Lutheran minister. Life as a small boy proceeded reasonably normally until I was 5 years old, living by then in south Chicago. At that point, I fell ill with rheumatic fever and was confined to bed for a year. Positive aspects of that time were reading the college textbooks of my parents. A negative was being treated in subsequent years like an invalid when at grade school. In 1945 our family moved to Hamden, Connecticut. High points were taking classes at Yale's Peabody Museum after school (Kids could still take a bus into downtown New Haven alone in those days) and illegally fishing in the local water reservoir (I became a fishing addict at age 5, when I caught my first sunfish in Wisconsin). During my time in Connecticut, many foreign visitors to Yale came to our home, and I developed a strong interest in languages. I kept a collection of pages that our visitors wrote in their own respective languages. By seventh grade, our family had moved to a suburb of Minneapolis. Most of my public school career was undistinguished except for major behavioral problems during the first nine grades. Taking Latin in tenth grade opened up my eyes to the fact that formal education could on occasion be interesting. By then I was tired of being treated like an invalid and began to take up sports and running, which continues to this day.

Being a typical Minnesota Scandinavian, I went to Gustavus Adolphus College, where I majored in biology, languages and chemistry and also learned how to play handball, which I continued to do for 50 years. At that point, I was planning to become a fish biologist and put my way through school by working for the Minnesota Conservation Department (now DNR) as an aquatic biologist most summers except one when I worked as a technician at the marine institute of the University of Georgia on Sapelo Island. Two things that happened while at college changed the course of my life. The first was going to a used bookstore one Christmas vacation and finding a used Russian/English dictionary for 50 cents. The second occurred after graduation. I was spending some time in our college library when I ran across an issue of the Journal of Experimental Zoology, to which the library had just begun to subscribe. In it was an article by Richard Goss and Martha Stagg on the regeneration of the lower jaw in newts. I read the article and almost like a religious conversion realized that I wanted to spend my life studying the phenomenon of regeneration. By that point I had already been accepted into a graduate program in ichthyology at Cornell University. I went there, but told my advisor that I really wanted to study regeneration. My advisor understood, but during 1959-60 I finished a research program on the biochemical taxonomy of lamprey larvae (using the "hot" technique at the time of paper chromatography). During that year, I had to work completely independently, since my advisor knew nothing about biochemistry and the person who ran the lab was on sabbatical. Nevertheless, that year proved to be the most valuable of all my post-college graduate years. While at Cornell, I decided to get my money's worth out of the Russian dictionary that I had bought, so I enrolled in a scientific Russian course. Toward the end of the semester, I was poking around in another used bookstore and ran across a monograph resulting from a Russian regeneration symposium in 1952. Although I could with difficulty understand the language, what they said made no sense to me at the time, because all articles began with references to Lysenkoist biology and something called the "new cell theory." During that same year I made a few belated applications to medical schools and was accepted by the University of Minnesota, which had just instituted an MD/PhD program. I was so naïve at the time that in my application I stated that I wanted to go to medical school to become a better biologist. Amazingly, the admissions committee bought that reasoning, so in the fall of 1960 I began my career as a medical student.

During the first year, I took the standard classes with the rest of the medical students and wrote my Master's thesis during the first semester. After the first year, I began to do research for my PhD in the lab of Dr. Charles Morgan, who unfortunately died within a few months of my arrival. Fortunately, the Chair, Dr. Arnold Lazarow, allowed me to continue research on limb regeneration, even though virtually all the rest of the department was working on diabetes. I continued without an advisor throughout my graduate career. A big advantage was that nobody knew what I was doing, such as taking classes simultaneously in three colleges at the University. When confronted by administrators who questioned that, I just told them that I was on a new program and that it was OK. One surprise was realizing after having finished my thesis research that I hadn't yet taken my qualifying exams. That having been corrected, I took the final oral defense of my thesis (done only with the committee in those days – no seminar). When the committee sent me out into the hall to await their decision, I happened to see a copy of Science magazine, which had a brief notice about the newly established exchange program between the US and Soviet Academies of Science. I was so excited that I went to my lab and began writing a letter of application. When my committee members went to the hall to tell me that I had passed my thesis defense, they couldn't find me until after some searching.

Fortunately, I was accepted into the exchange program, and in December, 1965, on the day I was supposed to get my degrees, I was on a plane heading for Moscow in order to work in the laboratory of L. V. Polezhaev, one of the real pioneers of regeneration research, but most of whose work was almost unknown in the West. My time in the USSR was fascinating. Nothing of great note happened in my laboratory research while there, but I became acquainted with anybody of note in the USSR who worked on regeneration. I got along well with Communist bureaucrats and because of that, was able to do some amazing things and travel extensively throughout the country. My most valuable scientific contact was with Prof. A. N. Studitsky, a brilliant, but very complex individual. He was a Lysenkoist and wanted to use a mammalian muscle regeneration model (at that time almost nobody in the West believed that skeletal muscle was capable of regeneration) to demonstrate the validity of the "new cell theory," according to which new cells arose from a proteinaceous soup celled "living substance." To do so, he decided to take entire muscles from rats and chickens, grind them up into tiny fragments and then replace the fragments into the site from which they were taken. He reasoned that if new muscle formed, it would prove the validity of the new cell theory. New muscle did, in fact, form, and for 15 years his lab conducted some remarkable research on muscle regeneration that was completely unknown in the West. It wasn't until I had visited his lab and saw his preparations that I realized that he had discovered something amazing, but was interpreting it according to a totally incorrect theoretical basis.

My own research on muscle regeneration had to wait until I returned to the USA as an Assistant Professor in the Department of Anatomy at the University of Michigan in 1966. At this point, I began a research program that was divided equally between amphibian limb regeneration and mammalian muscle regeneration. During the late 1960's I was able to validate Studitsky's minced muscle model of regeneration and related that to the regeneration of muscles in regenerating amphibian limbs. This research was summarized in a monograph on minced muscle regeneration that I published in 1972. In 1968 I met my wife, Jean, who at the time had just finished her first year of medical school. By the end of the summer we were married and have had a wonderful relationship ever since.

Around 1970, I discovered by accident that rotating the skin in certain directions around the stump of an amputated axolotl limb resulted in a very complex supernumerary regenerate that might contain as many as 15 digits. For several years I devoted considerable effort to delineating that phenomenon. Much of my best research in that area was conducted at the Hubrecht Laboratories in Utrecht, the Netherlands, when on my first sabbatical. This led to the concept of positional memory, according to which certain tissues of the limb are imprinted with a memory of their original position. Even when transplanted, this memory remains, and conflicting signals during regeneration are the basis for the formation of supernumerary regenerates. To this day, we do not know the molecular basis for positional memory.

At about this time, Dr. Bradley Patten, who had been writing embryology books since the 1920's, took me under his wing and asked me to work with him on an upcoming edition of his Foundations of Embryology. Although he died about a year after we began working together, he taught me much about the textbook business and how to write a book. Every Friday afternoon I went to his home, where we worked on the revision in an almost grandfather/grandson relationship. After eight or nine editions of embryology books, I still value my time spent with him.

In 1971, I was working on an academic year salary with no summer salary, and rather than teaching histology to failed medical students, decided to do something different for the summer. That something was to go (with Jean) on another inter-Academy of Sciences exchange visit – this time to Czechoslovakia. Through some unknown mechanism, I was paired with Professor Ernest Gutmann, whose laboratory was actually my second choice. This proved to be one of the most important accidents of my life, because he and I got along like ham and eggs. He was a brilliant scientist, but with a series of most unfortunate life experiences. During World War II, he escaped Czechoslovakia and spent that period in England, working with the cream of the British biomedical research community, all the while supporting his studies by teaching evening classes in Marxism. A committed, but romantic Communist, he got into trouble by officially protesting the Russian invasion in 1968 and was living on borrowed time ever after.

Gutmann was a muscle physiologist and proponent of the neurotrophic theory of nerve-muscle interaction. During my first summer with him, we conducted the first studies of the development of contractile properties on regenerating minced muscles. Because mincing was not a good regeneration model on small muscles, we devised a new technique of transplanting entire small muscles in rats. These muscles degenerated and then regenerated, and we were able to cross-transplant fast muscles into the beds of slow muscles and reinnervate them with slow nerves, and vice versa. At the same time an English plastic surgeon independently used free muscle transplantation as a technique to deal with some of the problems associated with facial nerve paralysis. This led to a long association with plastic surgeons who transplant muscles and an interesting series of meetings in Vienna in which clinicians and basic scientists compared notes. My association with Ernest Gutmann was abruptly cut off when he was finally allowed to visit England and died there of a heart attack, which I'm convinced was the result of Communist-induced stress in his later years. During the 1970's, I spent at least a month each year in Prague, working first with Gutmann and then with Milos Grim, who is now Professor of Anatomy at Charles University in Prague.

For about 20 years from the mid-1960's I served as a pipeline of communication between regeneration researchers in the Soviet bloc and the West and made many trips to the USSR and Eastern Europe. Such trips were always fascinating and informative. I have frequently been asked whether I was also working for the CIA. The answer is no, but every time I returned from such a trip I found either a CIA or FBI agent (or both) at my office door on my first day at the University. I have had many fascinating interactions with intelligence agents on both sides of the fence, so to speak.

By the end of the 1970's, research on positional memory was getting to the point where it was important to try to figure out what was happening at the cellular level. At that time the in vitro culture of amphibian tissues and cells was not very well developed, so I decided to see if some of my experiments on amphibian limb morphogenesis could be repeated on embryonic chick limbs. For my next sabbatical, I went to the University of Helsinki and learned how to operate on chick embryos in the laboratory of Prof. Lauri Saxen, a world expert on kidney development. By then Jean and I had two sons, Marty and Jim, and as a family we had a fascinating year, especially since Helsinki had the most snow that it had seen in over 100 years. We could cross-country ski from our house to the Baltic Sea during the dark Finnish winter evenings.

Upon returning to Michigan, I decided to see if we could use monoclonal antibodies to find out something about positional memory in limbs, and hired Jean, who had a Master's degree in immunochemistry, to work in my lab. We had an NIH grant to fund this research, which proved in most respects to be quite unproductive, but a serendipitous finding probably gave the NIH its money's worth anyway. For a positive control, we used one of our antibodies, which brightly stained the quail cells that we were working with. It was not until well into our project that we were also testing our antibodies on chick wing buds and found that our positive control wasn't working on them. It soon dawned on us that this antibody (QCPN) stained all quail cells, but not chick cells. We then let some colleagues who were doing quail/chick grafts in neural crest research use the antibody, and it soon became apparent that this antibody was a perfect marker for grafted quail cells. Its use supplanted the more cumbersome Feulgen staining that was standard before that.

In 1988, I was named Chairman of the Department of Anatomy and Cell Biology at the University of Michigan, and at that time decided to close down my limb lab, which was housed in the Department of Biology, and concentrate on research on mammalian muscle regeneration. At this time, my long-time colleague, physiologist John Faulkner, and I had gotten interested in the biology of aging muscle. Muscle in old animals regenerates much more poorly than muscle in young individuals. We devised a cross-age transplantation model, in which entire muscles from old inbred rats were grafted into young rats, and muscles from young rats were grafted in to old animals. The purpose was to see if the poor regeneration was an intrinsic property of the muscle or if it was a result of the old tissue environment surrounding the muscle. It turned out that old muscle grafted into young hosts regenerated as well as young muscles, and young muscles grafted into old rats regenerated no better than old muscles, thus showing that the environment, rather than intrinsic properties, is an important determinant of the success of regeneration. During the last 10 years, much of my research was directed toward understanding the tissue biology of long-term denervated and very old muscle. There are great similarities in both, and the overall tissue environment is very complex, with degeneration, atrophy and regeneration all occurring simultaneously.

During the 1990's, I was very active in AAA affairs and was elected to be the first two-year president of the Association. During this time, I had the great fortune to interview Andrea Pendleton for the position of Executive Director of the AAA. Fortunately, she accepted, and the rest is history, and a happy one for the AAA.

In 1990, I was on the Executive Committee of the Medical School, and after one meeting, the Dean asked me if I would be willing to go to a meeting held at the Fetzer Institute in Kalamazoo, because they were holding an international meeting and needed someone who could speak with Russian scientists. That began a 20-year association with Fetzer. During the 1990's, I was on and then chaired their Committee on Bioelectricity and Biodynamics, and since 2000, I have been on their Board of Trustees, a job that presently takes about 90 days per year.

In 1999-2000, Jean and I spent our last sabbatical working on isolated long-term denervated muscle fibers in the laboratory of Dr. Ian McLennan at the University of Otago in New Zealand. We had a wonderful time there and spent every weekend exploring the South Island, with which we both fell in love. By then I had stepped down as Chairman of the Anatomy Department and was planning to spend the last several years before retirement concentrating on research. However, a few weeks before returning, I was asked if I would be willing to consider acting as Director of the Institute of Gerontology at the University of Michigan and reluctantly agreed. It turned out to be a fascinating period, and I thoroughly enjoyed directing a research institute, which is a much more free-wheeling exercise than running an academic department. During that time, I was shutting down my lab in Anatomy, but directed a large multidisciplinary study on exercise effects on aging human muscle.

I'm not quite sure when I officially retired from the University of Michigan, but in the couple of years after that, I wrote books on regeneration and lake biology and the fourth edition of my medical embryology book, as well as the yet unpublished manuscript of a popular book on regenerative biology and medicine.

After almost 45 years in Ann Arbor, Jean and I moved back to Minnesota, where we now spend summers at our lake cabin and winters in the Twin Cities. I have returned to my first professional love and am now a fish biologist again. I'm now finishing the second year of a fascinating 10-year study on the growth of northern pike in a pristine northern Minnesota lake. Part of the field "duties" is to spend two days a week fishing for pike and tagging, measuring and taking scale samples from all pike caught. To date, we have tagged about 1,400 pike. The down side is aging fish scales, using a microfiche reader, during the winter. I'm also in the middle of a two-year stint as president of our lake association, which amazingly has taken up more time than being president of the AAA. When not doing these things, Jean and I are spending as much time as we can travelling to various parts of the world and are enjoying every moment of retirement.

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