Welcome to Adobe GoLive 6

1951-1955 Graduate assistant, Dept. of Biology, California Institute of Technology

1955-1958 Postdoctoral fellow, Dept. of Physiological Chemistry, University of Wisconsin, Madison

1958-1996 Assistant Professor to Professor, Dept. of Physiological Chemistry, University of Wisconsin, Madison

1996- Professor Emeritus, Dept. of Biomolecular Chemistry, University of Wisconsin, Madison

1996-2002 Visiting/Research Professor, Dept. of Biological Sciences, Stanford University

2002-2005 Visiting Professor, Dept. of Chemistry and Biochemistry, University of California, Los Angeles

2005- Adjunct Professor, Dept. of Biology, California State University, Northridge

Robert Metzenberg was born in Chicago, Illinois, on June 11, 1930. In 1951 he graduated Phi Beta Kappa from Pomona College in Claremont, California, where he majored in Chemistry. Between 1951 and 1955, he earned a PhD at California Institute of Technology in the Division of Biological Sciences. His teachers included Herschel Mitchell, George Beadle, Ed Lewis, A. H. Sturtevant, and Max Delbrück. As a graduate student at Cal Tech, he met his wife Helene Fox, who grew up in Pasadena, California. They were married on June 26, 1954, in Vermont.

In 1955, Bob and Helene moved east, to Madison, Wisconsin. Metzenberg became a professor in the University of Wisconsin, Madison’s Department of Physiological Chemistry (since renamed Biomolecular Chemistry), in the School of Medicine. Throughout his career, Robert Metzenberg conducted research on genetic regulation and metabolism with Neurospora crassa, a fungus that is studied worldwide as a model eukaryotic organism. When he was elected to the National Academy of Sciences in 1997, the academy credited him with the discovery that a cascade of positive- and negative-acting enzyme products of regulatory genes, operating together as a feedback mechanism, can act to govern gene expression. In 2005 he was awarded the Genetics Society of America’s Thomas Hunt Morgan award for lifetime achievement.

Following his retirement from the University of Wisconsin in 1996, He became a research professor at Stanford University. Bob and Helene relocated to Northridge, California in 2002, so that Helene and Bob could live near family. His survivors include his wife, Helene, sons Howard and Stan, daughter-in-law Aida, and two grandchildren.

Bob's last experiment

Memorial tribute to Bob Metzenberg

(Perspective by Eric Selker published in Genetics at bottom)

Bob Metzenberg gathered friends and collaborators around him so easily. On the science side, whenever discussions started about some research project or proposal, Bob was immediately entrapped. He could not do other than become engaged, make certain to understand the research questions, and then often to suggest improvements which would confirm and support the investigation. There seemed to be nothing more rewarding and exciting than to imagine a new explanation of some biological/biochemical mystery, and then consider if it might lead to additional discoveries.

To illustrate his considerate and generous ways: he wouldn't accept full credit for his imaginative proposals but often passed the credits on to his collaborators. He wouldn't accept that I was little more than a technician cleaning the glassware in a current project. He proposed that because my name began with a B, I would be first author while he would be in disguise because his name began with M and was in the middle of the alphabet of the five, six, or so suggested authors. Of course he regarded the investigation (his idea) as an extraordinary contribution. It is. And then as the work went on there was a flood of additional questions raised in his mind that would be investigated as follow ups. The day he died he was physically at work with the research stocks, all the while knowing his health was failing.

Bob would put aside or modify his own activities to assist others with their needs, giving up the convenience and ease of working in his own lab at Wisconsin to move to Stanford, then moving on from Stanford, setting up his laboratory at home so that he would be there to assist family members with their needs. Notably, he could not stop inventing and researching. He would nicely pull such a wide variety of others into collaboration and assistance. Though his field was perhaps molecular biochemistry he could and would look through a microscope or across a bunsen burner or, his choice, an alcohol lamp. Grow cultures and make crosses to develop the right mutant strains. Make media and then improve the chemical contents to better support his creations. Test their genetic characteristics and then insert or extract additional genes as needed. He was so complete. I am very much at a loss without him. We need his guidance.

I include in this e-mail a picture of the Yanofksy/Perkins groups at the time Bob was a member of the Perkins lab at Stanford. I knew Bob from his legendary work in Neurospora but I met him personally during the two summers that I spent at Stanford as a visiting scholar in Charley's lab in 1996 and 1999. At the time, Bob has retired from his University post and had decided that the Perkins lab was a fine place to spend his retired time as an active scientist. I was surprised and delighted by his brilliance and wit and by the interest that he showed to anyone coming to his desk to discuss a scientific problem. Finding him continuously at work and tinkering with fluffy tester plates at his tiny lab bench was an inspiring sight. The presence of Charley, David, and Bob just around the corner at Stanford University was an enriching experience. I'm sure that Bob's presence in the fungal research community will be sorely missed.

The group picture was taken in September 1999 while we were having a small farewell party just before my departure after spending the summer in Charley's lab. The participants in the picture are from left to right: Charley Yanofsky, Feng Gong, Vincent Konan, Bob Metzenberg, Bheong-Uk Lee, Kristin Black, Joe Sarsero, David Perkins, Namboori B. Raju, Luis Corrochano, Janet Elder.

I met Bob in 1961 at the very first Neurospora Information Conference in La Jolla, California. The meeting was free for all, in both senses of the phrase, and Bob and I began talking at the free bar after the last-night banquet. Characteristically, he drank Coke, and I drank Canadian Club. Even as I became less articulate, he became more so, and I remember only one thing from that night: I had made one of the best scientific friends of my life.

He was then at Wisconsin; I had taken a job at the University of Michigan. I kept seeing Bob at meetings, and in the early 1970s, our labs exchanged visits. In Ann Arbor, Bob inspired one of my most daring experiments one I had thought impossible if he had not said, "Why not?" At that point, almost whimsically, he rattled off a protocol that might do the job, and within a month we accomplished the task. This was his habit: using his multitasking imagination to explore, at the speed of light, landscapes of possibilities in ways Mozart might have done to choose harmony and orchestration. As we, his friends, coupled our imaginations to his, we felt that even his hypothetical dead ends were more illuminating than a close scrutiny of quantitative data. He proved repeatedly Francis Bacon's point that the truth is better served by error than by confusion. He remains a model of how much sheer fun science and talking about science could be.

Out of context, one of his remarks about himself might sound ridiculous: "I had no talent!" But the context is illuminating. Having taken instruction in musical composition in earlier times, he had completed several string quartets. He related this to me over lunch one day at Stanford, saying, "They were competent, but they simply followed the rules. Derivative of Haydn and all. But I discovered I simply had no talent!" This not only illustrates Bob's aesthetic refinement, but his curious blend of modesty and ambition, an ambition to use his mind to the fullest. It also explains his symphonic understanding of the complex biochemical systems that he probed with a sensitivity to detail, subtle complexity, and the surprising formal beauty of cascade regulatory systems.

Finally, he became one of the best friends of all of us in our scientific community. Always good humored and anxious to help, he willingly suffered fools, hoping at first he might show them to the light. A lack of success would then bring out advice in an advanced play on words that at least he could enjoy. Finally, the fools would retire, yielding Bob’s attention to others better equipped to enjoy it. I believe Bob made few enemies, largely because he retained a reserve that few people myself included fully penetrated. But what overlay that reserve amounted to an incomparable friend and scientist, one who will glow in the dark for years to come.

I only heard this week that Bob Metzenberg died. It has been quite a year of passage for icons of the Neurospora world. The message I pass along is from February 1984, and I think if provides a good example of Bob's sense of humor. I assume many people received correspondence from him in the typed postcard format, and this was one of those. It was just before I attended my first Neurospora conference. Bob had deposited some strains which comprised the so-called big RFLP mapping kit, as the first paragraph notes. He had addressed the package containing them to Dr. Craig Wilson. I kidded him about awarding me an honorary Ph.D. and his response is in the second paragraph.

Here's a quick story which is also illustrative. One day I came into the office just as Patti Hubbard was concluding a phone conversation. It turned out she had been talking to Bob. She had a perplexed look on her face, and when I gave her a quizzical look in return, she said "Bob Metzenberg is just too nice!"

Bob, like David Perkins, was one of the finest people I have known in science. He deserves a lot of memorials.

Bob had an overall knowledge of Neurospora. He was interested in the whole organism from new methods to isolate tetrads, new mapping procedures, biochemcal genetics, moecular biology and new techniques in working with DNA. He was frequent contributor with his ideas to the Neurospora Newsletter and later to the Fungal Genetics Newsletter. His ideas were always useful and unique. He was a wonderful person to talk to you about your reserach. He always had good questions and ways to help you achieve the results you wanted. We shall miss Bob's comments about research and Neurospora in general. His interest in Neurospora did not end with his retirement to California. There is no one else working with Neurospora like him. He made major contributions to the field of Neurospora.

Bob Metzenberg had not a thing to do with why I first started in Neurospora, but an enormous impact on why I am still working on Neurospora. For people such as myself who tend to become tongue tied around “giants in the field”, Bob was a tonic. He’d relish in any good discussion and always cut to the core in the most matter of fact way. This is not to say that Bob suffered fools with what would be described as the milk of human kindness. Bob could be very direct, but was never unkind. But for anyone new to a field, he was just the kind of senior person who personified a field with which you’d want to be associated.

Of course, his knowledge of basic genetics, and of Neurospora biology, was phenomenal. The problem that lacked a genetic solution simply did not exist in Bob’s book. I think everyone can remember one scheme or another that Bob cooked up to solve a problem; they were always really clever (sometimes a bit too clever), presented with an air of genuine and almost breathless enthusiasm, and relied on strains or aspects of Neurospora biology that most folks had forgotten, if they’d ever even learned them. His original invocation of transvection to explain what became MSUD (I remember saying, “huh”, when he first explained this to me), and his extrapolation of this to other problems in genetics (like haplo-insufficiency), was one such example. Another was his novel and ultimately correct interpretation of the QA-1F and QA-1S complementation and heterokaryon data in terms of distinct interacting proteins – in 1979, well before the molecular denouement. And of course his analysis of the genetic cascade in phosphorous regulation was rightly viewed as a tour-de-force; you know something is complicated when the “summary figure” is the first one in the paper rather than the last. Bob thought deeply about problems, cherished the exceptions to prevailing models, and brought to bear on everything he touched both a native and unquenchable enthusiasm as well as a synoptic knowledge of Neurospora biology and genetics. Such are the people that define fields.

Probably the thing I will best remember about Bob, though, is his wonderful word craft. He loved to use words in the way a carpenter loves to use wood. He was an artist with words. I still have notes from talks and discussions where he dropped verbal gems, and some I have since adopted for my own. I remember one discussion about heterokaryons where someone (probably me) advanced (without sufficient forethought) the idea that the final nuclear ratio in the heterokaryon might reflect the relative numbers of homokaryotic nuclei mixed. Bob shot back, “Well, that sounds good if you say it fast”, which was indeed true. It’s a phrase I’ve often since used myself for glibly pronounced but poorly thought out explanations. Another was the phrase “low hanging fruits” to describe the easy scientific pickings available when a field is newly populated.

Always a ready ear, always a new idea, always a novel screen and a mutant that I had never even thought of thinking about, always the perfect word and the apt phrase, and always the word of encouragement for science that he thought was going somewhere – how could anyone not want to work on Neurospora with someone like Bob Metzenberg to talk to?

I remembered hearing Bob's name for the first time from my Ph.D. supervisor, Louise Glass. Bob was Louise's postdoctoral mentor, and she always had the nicest things to say about him. According to Louise, he was intelligent, helpful, kind, and witty. Having known him in person, he was all of the above, and then some.

My first encounter with Bob was in a conference. Like the perfect gentleman that he was, he gave me encouragement and advice on my project concerning mating-type genes (which incidentally, were first characterized by his and Charley Yanosky's groups). Even as the legend he was, he never made people feel intimidated.

Upon retirement, Bob moved to David Perkins' lab at Stanford and began his "second career" as a Visiting Professor. Having been informed of my imminent graduation, Bob invited me to work with him as a postdoctoral fellow. Although I had my mind set on working with another brilliant scientist (Nancy Keller) at the time, I could not pass up the opportunity to learn from my academic grandfather (and risk having Louise be mad at me).

My best memories in science remain to be my tenure at Stanford. I remembered having daily lunch meetings with Bob, Perkins, Jacobson, Raju, and many other visitors (and there were many of them, especially during the Asilomar meetings in March). The conversations were not just about the crazy ideas that he had (many of which turned out to be big discoveries in science). Bob was extremely well-read and he could start an interesting conversation on any topic - history, art, politics, cultures, breweries, and the taste of horse meat, just to name a few.

As an employer, he was the perfect boss - he took care of his employees' needs. Many of his protégés went on to have a very successful career. As a friend, he was as loyal as they come. During Christmas and Thanksgiving, he would open his home to me (and other singles alike) and made me feel like I was a part of his extended family. I remembered singing Christmas carols after the turkey dinner, and Bob would be able to play any song you threw at him, ad lib. That was amazing to me, considering that he never had any official piano training.

Bob was never the prototypic principle investigator. You would never find him paper pushing at his desk, since he was too busy working on the bench. He was the MacGyver of our generation - nothing was too crazy to be utilized in the name of science (e.g. screws joined together as a 96-pin library replicator). He would rather fabricate an instrument himself and not waste taxpayers' money.

Bob was a mentor, a friend, and a father to many of us. He will be sorely missed.

Bob was a very special person to me. My Ph.D. is in Microbiology from the University of Georgia (1975) and my research was under the direction of Branch Howe. My problem involved genetic crosses of N. tetrasperma. As you know, in N. tetrasperma normally each of the four ascospores resulting from a fertilization event has nuclei of both mating types and so is self fertile. This does not lend itself to genetic anallysis and in order to do the research, I had to try to find the RARE dwarf ascospores which would hopefully have only one nucleus. Things were not going well, and I might still be trying to get enough data except for the help of Bob Metzenberg.

Bob had produced hybrids between N. tetrasperma and N. crassa. The hybrids produced asci with eight ascospores allowing for genetic analysis. Bob sent me cultures that were: 3tetra:1crassa; 2tetra:2crassa; 1tetra:3crassa. I was able to cross my tetrasperma mutants to these hybrids and thus transfer the genes) we were interested in to an N. crassa system with eight ascospores/ascus with each ascospore containing nuclei of only one mating type.

From this, my work moved along and I was able to map and analyze the genes we were interested in. And, also, very importantly, to complete my degree.

This help, which Bob so willingly gave to me, is characteristic of the man he was and how dedicated he was to science and how concerned he was about others.

Bob was a wonderful scientist and intellectually adventurous person. He had a remarkable grasp of metabolism and its integration into the physiology of an organism. From the time I began an independent career, Bob was my resource for any baffling interaction that I couldn't make heads or tails of. On one occasion I mentioned a peculiar growth behavior of a mutant in the glyoxalate pathway. Bob always greeted such puzzles with an affectionate broad grin. This was the kind of problem that tickled his fancy, even though it was my problem. Without hesitation, he made a key connection between glyoxalate metabolism and gluconeogenesis that had completely eluded my students and me. The connection he made formed the basis for many important discoveries in my laboratory. Like so many of his colleagues, I found my career influenced by Bob's unique scientific style and generous spirit.

Bob was always very interested in our physical mapping work. He provided advice along the way and always encouraged me to finish it even after the publication of the sequence. We have done so, and he would be pleased to know that we have finished and integrated our physical map of N. crassa with his RFLP map. He remains an inspiration to all of us,

Bob is and has been an inspiration to me, both on a personal and professional level. I first met Bob at a Keystone meeting, where we discussed possible post-doctoral projects. I was semi-comatose (after a week long meeting and rooming with John Hamer and Melanie Yelton), but I remember vividly Bob's passion and enthusiasm for approaching biological issues. I had never met anyone before who showed such a love for biology and experimental science. That passion continued to be apparent when I was a post-doc in Bob's lab. Our lab meetings often dwelled on biological questions other than projects in the lab and how to approach them on an experimental level. Since leaving Bob's lab, I often talked with him about "how Neurospora does it" and the development of methods for genetic research. I will sorely miss those mind-broadening, educational and motivational discussions. He also was a terrific supporter of new scientists in Neurospora biology, including new assistant professors, post-doctoral associates, graduate students and even undergraduates; he always made time for us. In addition to being the most inspirational scientist that I have known, Bob, along with David Perkins, was also the most selfless. He habitually gave out strains and ideas prior to publication and refused to be an author on publications unless he actually contributed experimental work. Now that Bob is gone (in the physical sense), he still remains an inspiration to me. I often find myself asking "How would Bob approach this question?" and "What kind of tools need to be developed to help to address this aspect of Neurospora biology?" and sometimes, I think I hear a few suggestions that help me along the way.

In comments after being awarded the 2005 Thomas Hunt Morgan Award at the 23rd Fungal Genetics Conference, Bob Metzenberg took a moment to acknowledge the role of the Fungal Genetics Stock Center in providing an even playing field for scientists interested in fungal genetics. He called the FGSC an "open source" for fungal genetics, comparing it to the open source software movement. This was not just a passing comment, but rather the culmination of a career of support and use of the resources at the FGSC.

Bob Metzenberg has deposited 254 strains into the FGSC collection including 231 Neurospora crassa strains as well as N. sitophila, and N. tetrasperma strains, interspecific hybrid strains and even Gelasinospora strains. The first strain Bob deposited, FGSC 1769, reached the FGSC in October of 1969 in a group of eleven strains. They were described as hybrids between N. crassa and N. sitophila useful for transferring genes between species (Metzenberg and Algren, 1969). Demonstrating the value of long-term collections, most of these strains were not requested from the FGSC until after 2000 but have been distributed a number of times since then.

Correspondence between Bob and Bill Ogata, the first FGSC curator, suggests that strain 1226 which has the genotype rib(76R5) and which was deposited by Walter S. McNutt in 1965 may be Bob Metzenberg's first strain deposited into the FGSC. This is the level of detail that early correspondence between Bob and FGSC director Ray Barratt included.

The next group of strains deposited were aryl sulfatase mutants of N. crassa which were the first of a number of mineral metabolism strains Bob developed. These ars-1 strains were the result of UV irradiation but also coincided with a description of variation in aryl sulfatase proteins among wild strains from a number of Neurospora species.

Many later strains were specific purpose strains such as RFLP mapping, heterokaryon maintenance or manipulation or even transformation strains. These were all useful and widely used.

Bob was also very supportive of the evolution of the FGSC into a repository for molecular genetic materials and first suggested this in a January 1980 letter to Bill Ogata. The FGSC collection of molecular clones now numbers nearly 650 plasmids. Of these, up to ten percent were deposited by Bob Metzenberg or his academic progeny (or theirs).

Bob also used the resources in the FGSC collection. Since 1987 he ordered 317 strains, including mutants, wild type strains, and many strains with translocations or inversions. Bob also used the molecular resources he promoted and received nine plasmids and three gene libraries.

Bob supported the FGSC in other ways. He donated a supply of the cell wall synthesis inhibitor polyoxin B to assure that it would remain available. He was generous with his energy, ideas and time. This is truly a remarkable heritage and establishes Bob Metzenberg as one of the giants upon whose shoulders future generations will stand.

Bob and Colleagues (Mary Anne Nelson, Tom Randal, _________Bob, his car, Mary Anne Nelson and Seogchan Kang

Jeff Grotelueschen and David Butler) on a collecting trip_________on a collecting trip

I’ve known Bob since the second Neurospora Information Conference, at Rice University in 1964, when I was a young graduate student. That’s a long friendship, and I’ll certainly miss him. He was one of the giants of our community, with a phenomenal intellect and a propensity for thinking out of the box. He gave us sulphur and phosphorus uptake and metabolism, regulatory cascades, RFLP mapping, tRNA and rRNA genes, and so much more from his own work. He gave so many of us, so freely, novel insights and suggestions regarding our own research. Over the last few years, I’ve really appreciated his support and encouragement as the e-Compendium has been developed, but that was typical of Bob. He was one of the key people who set the style of the Neurospora community – that of cooperation and mutual support, and that may be as important to us in the future as his research output.

My meeting with this noble soul was very short, but his work is of great influence. My first attempt to meet him in Wisconsin could only materialize with a brief telephonic talk. He was gentle and apologetic that he cannot meet on that day (in 1988), but was willing to help with the lab protocols for preparation of protoplasts and transformation. Only in 2003 I got the oppurtunity to meet this extraordinary scientist with a pleasing smile.

Bob and Helene were married for 53 years. Helene was an important contributor to Bob's love of life and the pursuit of science.

(Perpsective for Genetics)

BOB METZENBERG: GENETICIST EXTRAORDINAIRE AND "MODEL HUMAN"

by Eric U. Selker