My Life as Written for Graduate Students
My Life as Written for Graduate Students
Diter H. von WettsteinMy Heritage
My father (Fritz von Wettstein, see below) was born in 1895 in Prague (at the time, a province of Austria: Böhmen und Mähren), where he was at that time a professor of Botany. My mother, Else, Jesser was born in 1898 in Marburg (at the time, a part of Austria) on the Drau (now Slovenia), where her father was inspector of the railways. Both moved with their parents to Vienna (Austria), where they grew up independently. My great-grandfather Anton Kerner1 von Marilaun1 (a botanist and an ecologist) had been professor in Budapest, Innsbruck and Vienna, where he died in 1900. My grandfather2 (Richard von Wettstein), who had studied in Vienna, became professor in Prague and succeeded Kerner as professor of Botany and Director of the Botanical Garden.
1Kerner was the first experimental ecologists of the eastern alpine flora, transplanting alpine species into the lowland (from Tirol to Vienna) and its closely related species or ecotypes from the lowland into an alpine garden in the Tirol to find out if the characteristics at their place of origin were genetic or environmentally imprinted. Both cases were found. His two-volume work "Pflanzenleben" was also very popular in the US High Schools and Universities. The translation was by Hansen. [Kerner-Hansen: Plant Life]. We may find it in our libraries. It has nice color pictures of the Primula hybrids growing at the border of limestone and granite in the Alps. They are the parents of the garden primulas bred in the Netherlands and Flamelands.
2Handbuch der Systematischen Botanik, published in 4 editions from 1901 to 1937, was Richard von Wettstein's major work. It was a dominant and most comprehensive phylogenetic system and highly recognized up to the present. It explored the flora of Brazil. He was a highly recognized teacher and active in science and research politics. His plant systematic studies and especially those concerned with "season dimorphisms" of plants in meadows used for making hay twice during the summer made him a neo-lamarkian in contrast to the neo-darwinians. Today these lamarkian adaptations are recognized in the epigenetic phenomena.
My father did his Ph.D. at Vienna University in 1914 and then spent 4 years in the alpine mountains (above 3000m) fighting in the war between Austria and Italy (the first World War). The war ended the Austrian-Hungarian empire, Austria becoming a small country. My father wanted to carry out research in genetics and went to Berlin to work in the Institute of Carl Correns, one of the "re-discoverers" of the Mendelian Laws; he became an assistant to Correns and carried out his seminal work on the genetics, polyploidy, cytoplasmic inheritance and developmental physiology of mosses. My mother studied botany with my grandfather at Vienna during the war and then went for two years to Upsala in Sweden to study algae. They got married in Vienna in 1921. My mother did not continue to carry out research or any other professional activity. They lived in Berlin until 1924. By that the time my father had completed and published his monumental research on the genetics and polyploidy of mosses. He became professor of Botany and Genetics at the University of Göttingen (Germany) and Director of the Botanical Garden in 1924.
I was born in 1929 in Göttingen, at a time when my father and grandfather made an expedition to South and East Africa and collected plants. They had a tremendous time. I was born with a closed/cramped pylarus (muscle between stomach and intestine) and became smaller and smaller instead of growing. I was treated in the children's hospital. One day the doctor came to my mother and said, if she wanted to see me once more she would have to visit in the afternoon. She said there was no use of this but then relented. The doctors hit on the idea to give me coffee and I opened the pylarus and started to grow. My sister was born a year earlier and my brother three years later. In 1931 my father became professor of Botany in Munich and we moved to the Botanical Garden in Munich. My parents hired a British girl that could not speak German, so my sister and I would learn English. I remember us sitting in the winter garden and talking, eventually writing English by playing games.
In 1934 my father accepted the position of Correns at the Kaiser Wilhelm Institute (now Max Planck Institute) for Biology in Berlin and we moved with the au pair girl into the villa next to the Institute located in a big garden and I started school. At the time my father was busy but always kind and my mother was rather severe, scolding me often, and I was afraid of her. After school I sometimes went with a friend to his home to play with his electric trains. Then of course I got late and had to take the underground train for a station to get home in time, although I was forbidden to use it. I remember how angry I was when one day the wife of an assistant of my father came and visited my mother and told her that I was routinely using the underground train. Well I earned a portion of hard blows and was sent to bed without dinner. However my father was always kind, defending us children and was very kind to my mother and spoiled her in every respect. She could get fits of rage and he kindly tried to calm her down. During the holidays in the summer and at Christmas or Easter we went to Trins or other places by car for skiing or mountaineering and on the whole we had a nice and educational youth in a well to do family.
When I became ten I had to join the Hitler youth in uniform. In some ways it was like a boy-scout activity, but it was also the beginning of the war and the leaders were trying to extract from us boys information about our parents, i.e. if they were against the party, etc. Although my parents were strongly opposed to the politics of the day and entertained in their house opposition politicians, they never talked to us children about it, but somehow managed to let us understand that the party and government were on the wrong track. One day I was laid at the Hitler youth meeting on the table and all other boys had to hit me hard with a stick, since I did not want to denounce my parents. I held and soon we had to leave Berlin.
My father died at the young age of 49 in 1945 towards the end of the war as a consequence of treatment for pneumonia with two incompatible sulfonamides.
I finished High School in Innsbruck (Austria) and started to study at Tübingen University (Germany) in 1947. From 1949 to 1950, I spent a year at the ETH in Zürich taking chemistry courses and studying submicroscopic morphology with Professor Albert Frey-Wyssling, who supported my stay at Zürich. With professor Jakob Seiler, I carried out a research project on intersexes of Solenobia disproving Professor Richard Goldschmidt's "Drehpunkt hypothesis" [see J. Seiler, 1951, Analyse des intersexen Fühlers von Solenobia triquetrella/Psychidae, Lep. Rev. Suisse de Zool. 58, 489 495.]. However, I moved to Sweden soon thereafter. In 1951, I had a wonderful time in Stockholm. My mentor Åke Gustafsson had planned two tasks for me. He was working on induction of mutations in barley with various radiations and chemicals at the Swedish Seed Association in Svalöf in Southern Sweden and he was director of the Genetics Department of the Forest Research Institute in Stockholm. The first task was to analyze the erectoides mutants in barley, and to learn why they are more straw-stiff and have more lodging resistance. Most of this work had to be done at Svalöf in the summers. The second task, to be done in the winters in Stockholm, was to grow the M2 generations of the mutagen-treated seeds in the greenhouse and count the chlorophyll mutants as a measure of mutagen efficiency. At the same time, I continued my work with the moss spores for my thesis in Tübingen with Professor Erwin Bünning. So I worked day and night, but mostly at night, since at night, others did not use the equipment. In 1953 I got my Swedish Ph.D. (called Licenciat) with publications on the erectoides mutants and traveled to Tübingen to take my German Ph.D. with an exam and a publication on the polarity of the moss spores.
The Story of the Electron Microscope
After obtaining my two PhDs, I applied in Stockholm for a three year fellowship to obtain a Fil. Dr. degree (equivalent to Dr. of Science degree); it required an independent research like that for an assistant/associate professorship in the USA. The subject of my research was to do electron-microscopic (EM) analyses of wild type chloroplast development and of different chlorophyll mutants. We did not have an electron microscope and there were only very few in Sweden. The one in Upsala was acquired by Svedberg, the inventor of the ultracentrifuge. I found a co-worker in Arne Tiselius (Håkan Leyon) at the Biochemistry Institute, who was working on chloroplasts with the EM. So every week I traveled for three days to Upsala to learn and then to do analyses with my chloroplast mutants. I was allowed to sleep on a couch in one of the scientist's offices. We saw many of the cell structures for the first time with our thin sections that were cumbersome to be prepared at the time.
Åke came usually after dinner back to the lab to do some analyses or writing and stopped by my lab to inquire about my results. Of course I showed him the newest EM pictures and explained excitedly about the new results. The first few times he was somewhat negative, because I had no new data on erectoides, but then he got very excited. It was at the time, when he got a new building for the Genetics Department and he asked about the best electron microscope we can buy. I replied a Siemens, manufactured in Berlin, and off we took for a week to Berlin, for me to learn about the instrument and for him to talk to the business people. It turned out that there was a long waiting list and we kept inviting the manager for dinner several times with no result. On the last day, Åke said, this is bad since the Swedish King was going to inaugurate the Institute and we will have to tell him that Siemens could not deliver the most important instrument. The manager jumped from his chair and said but we have to have a picture of the microscope with the King. So I will telephone tomorrow to headquarters and get you moved up on the list of delivery, so the microscope will be there in time. When we got back to the hotel I asked Åke, if it was arranged that the King will come to the inauguration. He looked at me and said NO, but we have to arrange that now, and so it was done.
With the chloroplast work published I obtained in 1957 the degree and a docentship (dozentship) for 6 years at Stockholm University. I worked most of the time, but I also went skiing in Northern Sweden (in the Lapland).Of course I took the opportunity to visit my mother and traveled for skiing and mountaineering to Trins, to Switzerland and Italy and attended my first scientific Congresses.
Research and Teaching
In 1958 I obtained a Rockefeller fellowship to carry out research and training in the USA. I went to work with Frits Went at the California Institute of Technology, Pasadena, California, for 3 months, then in the summer to Cold Spring Harbor to learn bacterial and phage genetics offered in their excellent courses. The last part of the year I spent at the Carnegie Institute of Washington at Stanford to work with J.H.C. Smith and C. Stacy French on chloroplasts in various mutants. In between I went to visit the National Parks and was invited to several Universities to give talks on my chloroplast work.
After my return from the US being a docent (associate professor) in Genetics at Stockholm University I had to teach 75 hours per semester. I decided to give a 3-week practical laboratory course in bacterial and phage genetics basically on the lines of the two courses I had taken at Cold Spring Harbor. So I went to the professor of Genetics (a Drosophila researcher) and told him my intention. He answered: That is of no interest to genetics. I responded that it is the docent who decides what he wants to teach. His answer was: "Yes you are correct but I won't give you a teaching laboratory". My laboratory was still at Åke Gustafson's Institute but there were no teaching laboratories. I found out that at the new Microbiology Institute of the Karolinska Institute (the Medical faculty of Stockholm University), there was a most fancy new teaching laboratory. I made an appointment with the professor and his closest co-worker and told them that I wanted to teach this practical course. They looked at each other and then said: That sounds very interesting and I gave the first course to some 15 students. I had to prepare everything and sometimes the instructions were not accurate. Especially the transformation experiment was a problem until I found out that they had forgotten to mention that vitamin B had to be added to the medium. Niels Ole Keldgaard (the discoverer of lambda lysogeny) came from Copenhagen to find out about the course since he wanted to establish one in Copenhagen. Everything went fine. A week after the course was finished the assistant of the professor called and said that all their cultures in the big fermenters, they were working with, were lysing. The problem was that we made experiments with all 7 T phages and I didn't know that T5 survived in air and it had escaped into the fermenters. Well I made T5 resistant mutants of their strains and promised not to use this phage in the future. I gave this course for the following several years until I left for Copenhagen.
Much later in 1994 the professor of microbiology (Lars Rutberg) from Lund came to Copenhagen to discuss some experiments on porphyrin synthesis as he wanted to do research with us. When we were eating lunch in our canteen, he looked at me and said "Do you know who I am" and I said "not really". He then said I took your first course at Karolinska Institute and that was quite embarrassing. "He continued: it strikes me often that most present day professors in molecular biology in Sweden took your courses".
I had a good time with the electron microscope, got some grants, two technicians, a postdoc and two Ph.D. students. Åke wanted a Phytotron similar to the one in Pasadena. He obtained the money and I had to make the design with the engineers. It became a building with growth chambers and two greenhouses where one could grow axenic higher plants i.e. with no bacterial and fungal contamination. All seeds for the plants had to be sterilized and the people working in the Phytotron had to change clothes. The air was sterilized at the intake. It was a fantastic facility and we made experiments with barley and trees. (I wish we had such facility in Pullman, Washington). I worked mostly with my chloroplast projects and in the summer with the barley mutants.
At that time in Sweden, one could be reappointed 2 times for 3 years and another 3 years as research docent. If one did not get a full professorship at the end of this period, one's career at the university was finished. So in 1960 and 1961, I applied to three places for a professorship, at the universities of Gothenburg and Lund in Sweden, and Copenhagen in Denmark. Competition was stiff, with many other applicants.
Professorship at Copenhagen
I was at the top on the list in Copenhagen as professor and head of the Genetics Institute, mainly because of my teaching experience in molecular genetics and my chloroplast research. So in 1962, I moved to Copenhagen into an apartment (i.e. a flat). Then in 1963 I bought a house in a suburb close to a big forest and lake about 20 km from the institute which was quite new and located in the Botanical Garden in the center of the city. Niels Ole Kjeldgaard (and his professor at the Institute of Microbiology) were teaching the phage and bacterial genetic courses, so I had to find some new laboratory course. Therefore we did establish a genetics course with Aspergillus and Neurospora, while Associate Professor Ove Frydenberg (population geneticist) handled the Drosophila genetics course. I also had to teach the general genetics lecture course (3 hours per week), which I did until 1975, first in Swedish and then in Danish.
By that time there were 150 students per year. Every hour of lecture took 3 to 4 hours of preparation because I updated the lectures as genetics developed and did this by adopting every year a new textbook and accordingly updated slides and subject matter. The students liked the lectures but not the exams and felt that I was teaching too advanced subjects. Later when I no longer taught the course, it happened that I met a former student on the street, who say "in your lecture we really learned a lot". By the way Penny, my wife, now does the major biochemical and genetic teaching at the Genetics Institute and she is a much more talented teacher than I ever was. There is one thing with teaching: If you keep up with the development of the subject you learn much more genetics and molecular biology, than during your own studies and Ph.D. preparation.
Professor Mogens Westergaard, who had taught before me, became a good friend of mine; he had to retire for health reasons and moved to the Carlsberg Laboratory. During the first years, I continued work at the phytotron in Stockholm, but I purchased a new electron microscope in Copenhagen, and one of my technicians who made thin sections for electron microscopy moved from Stockholm to Copenhagen. At the time the faculty consisted only of the full professors and once a year the budget was discussed. At these meetings, Professor Niels Bohr the famous nuclear physicist would get up and say that he had already talked with the Minister of Education, who had agreed that "so and so many millions" would come to his institute (which was quite a large amount compared to other institutions). Mogens told me that he never got any budget for 'excursions', and since he loved to look at plants, he would go to the biological station in Greenland to study chromosome counts of plants. So when the question came to dividing the excursion budget, I raised my hand and explained that it was very important for graduate students of Genetics to study the evolution of plants and animals in the field. Three physicists agreed that this was very important and I was allotted a budget of 120,000 DKK (Danish Krona) which I got every year as long as I was at the university. This meant that once a year, the whole institute could go for a week on excursion. We went to Greece, to Italy, Iceland, the isles of Gotland and Öland in the Baltic ocean, Trins, and many other places. This had a very important function for the working climate of the institute. Since at an institute of some 20 or more members, students, assistants, and technicians, small animosities and fights developed during the year. However at the excursions, we walked and studied plants and insects; cultural objects like the Acropolis in Athens, and climbed mountains like mount Olympus. In the evenings, the participants enjoyed disco bars and dances and talking with each other. Everybody had a good time and became friends. Thus, the excursions served a good social purpose as well as fulfilled educational goods.
Mogens was an outstanding scientist who had discovered the mechanism of sex determination in the plant Melandrium, that has an X and a Y chromosome. After the war he worked on the biochemical genetics of the fungus Neurospora that generated the one gene-one enzyme hypothesis that gave George Wells Beadle and Edward Lawrie Tatum the Nobel Prize in 1958. During the occupation of Denmark by the German army, Mogens and some other professors were prominent resistance fighters and had to hide. Some like Mogens were caught and interned in camps or prisons.
After the end of the occupation of Denmark by Germany in 1945, these scientists and some other prominent personalities and politicians became very influential and provided the universities during the 1950s and 1960s with new buildings and considerable funds. In spite of the prevailing animosity against Germany (and, thus against Germans), I did not encounter any of that, due to my Swedish language capability and proficiency in Danish. Also, the scientific prominence and political integrity of my father was well known to the Danish scientists and I was careful to try to integrate into the Danish Society and habits. With Mogens, we started a project on the ascomycetes cup fungus Neottiella rutilans that grows on the sandy shores of the Baltic ocean. It cannot be cultured, but it is an outstanding object for cytology and DNA measurements and electron microscopy. Its chromosomes are always condensed at all stages of the life cycle. Mogens and a student, doing quantitative DNA spectro-photochemistry of the premeiotic and meiotic stages, with the microscope, discovered that the DNA was replicated in the crozier nuclei before the haploid nuclei fused to give the diploid nucleus entering meiosis. This lay to rest the then popular copy choice hypothesis of chromosome pairing in connection with a DNA replication at meiotic prophase. I concentrated on the electron-microscopic analysis with the ultrastructural characterization of chromosome pairing with the synaptonemal complex. My unique micrograph of the synaptonemal complex is in many textbooks (e.g. Benjamin Lewin's Genes). Of course the work with the chloroplast mutants continued.
Penny and I met in USA
In the spring of 1966 I was invited for a three month visiting professorship to the University of California in Davis. I had to give lectures on the genetics of chloroplast inheritance and started a research project with the prominent plant lipid biochemist Paul Stumpf on the biosynthesis of chloroplast lipids in my barley mutants. I met Penny there. She was doing her Ph.D. on carotene mutants in tomato studying the synthesis of these compounds with tissue culture and carrying out genetic allele tests. Her professor Charley Rick was a very nice eminent tomato geneticist, who collected wild tomato ancestors in South America to retrieve resistance and other genes for the cultivars. He and George Ledyard Stebbins, Jr. had arranged my visiting professorship. Penelope (Penny) Knowles asked highly appropriate questions after my lectures and I found her very attractive. We started to play tennis and badminton in the evenings in the lighted courts, and went for dinners outside the campus. One weekend I asked her, if she would like to go skiing on Mount Shasta in Northern California (4,700m) and she said that would be wonderful and got some equipment. I had some spare skins, needed to climb the mountain slopes. Off we went by car on Saturdays and stayed at a motel at the foot of the mountain. Next morning we started climbing the mountain with the skis equipped with skins. It was a beautiful sunny day and we kept walking up this huge mountain enjoying and enjoyed it. At four in the afternoon it was time to get down and as we took of the skins. Penny said: I have never skied down a mountain like this. But I making tracks, she caught on soon the slalom way, we made it down and had a good dinner. Thereafter we started back to Davis a several hours drive, but the car battery gave out as well as the generator and no repair was possible on Sunday evening. So I bought a new battery and we drove with it, but two more batteries had to be bought to be able to arrive at Davis at 2 in the morning within walking distance of where we were staying. I had to give a lecture the next morning at 8. It was not too good but Charley Rick smiled.
After her Ph. D. exam on tomato genetics, Penny came to Copenhagen for postdoctoral work. She worked on the eceriferum mutants in barley, which lacked the wax coating on different parts of the plants and there was a collection of over 1000 of them in more than 30 genes by allelic tests. The purpose was to determine the chemical steps in wax synthesis that was blocked in the mutants and their function. Penny did and does a marvelous internationally acclaimed work on this job with her students. She obtained a professorship at the Genetics Institute a year later, a position she will retire from next year. We were married in August 1967.
The next few years we made trips to Africa to see the animals and climb the Ruwenzori (5000m); we had renovated and completed the house in Trins. Also the house in Copenhagen was built on with a wing and Penny insisted that we do the garden ourselves. In 1970, Heidi was born and in 1973 Kim. Penny kept working uninterrupted throughout these years with her mutants and clarifying the biochemical pathways of cuticular and epicuticular wax synthesis and kept teaching her course. It was a wonderful time. We spent every summer, potato holidays in October, Christmas holidays in December, as well as Easter holidays in April, in Trins with the children. We hiked the mountains with them (at first carrying them on the back as well as an umbrella overhead). They felt at home there as much as in Copenhagen and they spoke good German in addition to Danish and English, the language Penny insisted we talk at home.
My Move to the Carlsburg Laboratory
In 1972, the Genetics Institute had grown and the research output by the staff, the postdoctoral fellows and Ph.D. students had increased to the extent that financing became a problem. The universities previously financed research and there was only a small research foundation. Actually my grants from the research foundation amounted to 80%of their total expenditure at that point and it was clear that this could not continue. I had an offer to move to the Max-Planck-Institute in Köln, which became the Institute of Jeff Schell (discoverer of T-DNA) but I did not want to move to Germany. At this point a stroke of luck hit on me. The Head of the Department of Physiology at the Carlsberg Laboratory Heinz Holter had to retire. This Laboratory was one of the flagships of Danish Science since 1876, founded by the successful beer brewer Jacobsen who felt that basic science was the key to industrial development. He founded and financed the laboratory and a foundation to support Danish Science. Subsequently he gave the brewery as income to the foundation and so did his son who had established a brewery in competition with his father. Milestones of the laboratory are the first pure culture of yeast and its application in 1882, the Kjeldal procedure of nitrogen determination in 1886, the establishment of the pH scale and its use for buffer solutions by S.P.L. Sørensen, the discovery of the mating type of yeast by Øjvind Winge and the basis of protein structures by Kaj Linderstrøm Lang. After the second world war prominent US protein researchers (subsequent nobelists) were postdocs with Linderstrøm Lang. The laboratory was no longer up-to-date and the Trustees of the Foundation asked me, if I would take over the Department of Physiology and rebuild the laboratory to its former high standard. I was asked to go to the Director General of the Breweries and negotiate what was needed in finances. So I did. The Physiology and Chemistry Departments had five positions each. I suggested that each department should have 27. He said that sounds reasonable. Then he asked what kind of equipment is needed. I said an electron microscope. That was reasonable he said. I said the building dates from 1894. A modern laboratory should be added: He said yes, we will design the outside and you have free hand to design with the architects and engineers the inside. Then I said a department for applied research and barley breeding should be added and a field station closer to the laboratory than the present farm should be obtained. He said that we will provide all this, but you have to bring the research and application of brewers yeast and malting barley at the basic and applied level to be the world's best. I said that is reasonable.
Reviews of my research results from the Carlsberg Laboratory are listed below in reverse chronological order.
Von Wettstein, D. (2007) From Analysis of Mutants to Genetic Engineering. Annu.Rev. Plant Biol. 58: 1-19.
Von Wettstein, D. (2006) Fascinations with Chloroplasts and Chromosome Pairing. Introductory Review. Progress in Botany 67: 2-28.
Von Wettstein D. (2000a ) Chlorophyll Biosynthesis II: Adventures with native and recombinant enzymes. In :Discoveries Plant Biology. S-D. Kung & S-F Yang, eds. (World Scientific, Singapore) 3: 95-139.
Von Wettstein D. (2000b) Chlorophyll Biosynthesis I: From analysis of mutants to genetic engineering of the pathway. In: Discoveries in Plant Biology. S-D. Kung & S-F Yang eds. (World Scientific, Singapore) Vol.3, 75- 93, 2000.
Von Wettstein D. (1987) Molecular genetics in the improvement of brewer's and distiller's yeast. "Anthony van Leeuwenhoek" Journal for Microbiology 53: 299 305.
Parts of the above account were presented at a the 2009 LTAAward ceremony of the Rebeiz Foundation for Basic Research, on September 18, 2010. I thank Tino Rebeiz and Govindjee for inviting me to present this part of my story to be made available at the web site of the Rebeiz Foundation.