The Genetics Society of America annually honors members who have made outstanding contributions to genetics. The Thomas Hunt Morgan Medal recognizes a lifetime contribution to the science of genetics. The Genetics Society of America Medal recognizes particularly outstanding contributions to the science of genetics within the past 15 years. The George W. Beadle Medal recognizes distinguished service to the field of genetics and the community of geneticists. We are pleased to announce the 2005 awards.
IT is completely fitting that Robert L. Metzenberg be chosen to receive the 2005 Thomas Hunt Morgan Medal. In addition to making a full lifetime's worth of impressive contributions to genetics in his years as Professor at the University of Wisconsin (1958–1996), he has also made stunning research contributions as Emeritus Professor, at Stanford University, at UCLA, and working in his home laboratory. Metzenberg's more than 120 publications include many gems. But equally important are his countless intangible contributions to members of the scientific community. If you have met Bob even just once, you know what we mean. As Bob once said (although not about himself), “The calendar ticks by at very different rates in different people, and here and there, a scientist is a human Stradivarius.”
One remarkable thing about Bob is his breadth of interests and abilities. In addition to being one of the most gifted Neurospora geneticists ever, he is completely at ease with all aspects of biochemistry. Indeed, he was an award-winning teacher of biochemistry at the University of Wisconsin School of Medicine. A partial explanation comes from a glance at his training. Bob majored in chemistry at Pomona College, with minors in physics and biology (which he has pointed out were almost “immiscible” with chemistry at the time). As a graduate student in the laboratory of Herschel Mitchell at Cal Tech, he worked on the biosynthesis of amino acids in Neurospora, and as a postdoc with Philip Cohen in Wisconsin he studied enzymatic reactions involved in urea synthesis in mammals and amphibia. Next, curiosity about the underlying genes led him to spend a year with Ernst Hadorn in Zurich, soaking up developmental genetics. He then made the important decision to return to Neurospora to study “the genetics of regulation of enzyme synthesis in a simple eukaryote.”
He chose to work on regulation of carbon, sulfur, and phosphorus utilization at a time when little was understood regarding regulatory differences between eukaryotes and bacteria. His identification of multiple regulatory mutants that were defective in phosphorus or sulfur utilization and his demonstration that the underlying genes exist in a hierarchy to turn on a family of unlinked structural genes was a major advance. Indeed, Bob was the first to discover a cascade of positive- and negative-acting products of regulatory genes acting to govern eukaryote gene expression. These studies foreshadowed the discovery of similar regulatory systems in other organisms.
In writing about “Thomas Hunt Morgan and His Legacy,” Ed Lewis (http://nobelprize.org/medicine/articles/lewis/) noted that Morgan and his famous students (A. H. Sturtevant, C. B. Bridges, and H. J. Muller) remained at the bench throughout their careers: “The investigator must be on top of the research if he or she is to recognize unexpected findings when they occur.” Bob also managed to stay at the bench, even when it required installing a bench in his office or in his spare bedroom. He is a natural tinkerer, overflowing with interesting ideas to tinker with. As a consequence, his research contributions have been broad and have not been limited to conceptual advances. Throughout his career Bob has also been responsible for numerous innovations and improvements in practical techniques, reflecting his continued activity at the bench and the pleasure he takes in carrying out experiments with his own hands. As examples, he devised improvements in procedures for isolating nucleic acids, preserving Neurospora stocks, analyzing tetrads, recovering and purifying fungi from soil samples, introgressing genes from one species to another, and testing whether particular genes are essential.
In part to ensure that he could stay at the bench, Bob generally kept his group small. One of us (E.U.S.) discovered this personally about 30 years ago. After becoming inspired by a fantastic seminar given by Bob at Reed College, on the phosphorus system of Neurospora, I wrote to inquire about the possibility of doing graduate work with him. He promptly wrote back a kind letter suggesting that I consider another lab in his department because his lab was full. About a year later, while visiting Wisconsin to help establish λ-cloning in his lab, I discovered that Bob's definition of “full” was rather different from that of most principal investigators. His lab was physically quite empty and his group consisted of one technician, one postdoc, and himself. Bob confided that he had recently come to realize that entry into molecular biology may require that he expand his group, but he still felt a responsibility to not add to the population explosion caused by investigators training huge numbers of graduate students.
Bob was not content to confine his work to any one problem and he has made significant contributions in areas other than biochemistry and classical gene regulatory mechanisms. Spin-off projects came naturally from his ability and regular habit of recognizing valuable nuggets in random scientific observations. As Bob put it, “What we call ‘luck’ in research is mostly a matter of recognizing an opportunity … when it comes along.” Like everyone else in the early days of genomic DNA cloning, Bob and his first “molecular” postdoc, Steve Free, cloned ribosomal DNA many times over. But instead of simply discarding this as junk, they examined it in sufficient detail to discover that the tandemly repeated rDNA of Neurospora lacks a gene for 5S RNA, unlike the arrangement in yeasts. Moreover, results of a Southern hybridization suggested that the 5S genes might be dispersed in the genome, a novel possibility. If so, this might reveal whether members of a repeated gene family must be tandemly arranged to maintain sequence homogeneity. Recognizing that he did not have the time to work on all the interesting things he uncovered and that this visiting graduate student's chosen thesis project was on the rocks, Bob offered to turn over this incipient project. We should also note that Bob is a gifted salesman (so good that he can sometimes convince himself when perhaps he should not). Thus he had no trouble sending me home with a new project, which produced enjoyable and productive collaborations for many subsequent years, and which spawned numerous additional projects for each of us. For example, the project led Bob to devise an efficient RFLP mapping procedure for Neurospora and to use this to construct the first extensive RFLP map in fungi. Additional studies on dispersed 5S rRNA genes ultimately led to the discovery of DNA methylation in Neurospora and then to repeat-induced point mutation (RIP). Research on the tandemly arranged rDNA of Neurospora led Bob and his colleagues to discover position-dependent differences in DNA methylation and dramatic premeiotic modulations in copy number of the rDNA.
In another area of research, Bob and his associates examined the structure and function of the A mating-type gene in Neurospora in studies that were coordinated with those on mating type a in Charles Yanofsky's lab. In these pioneering studies, the two labs showed that the so-called mating type “alleles” A and a consist of completely nonhomologous elements. After consulting with a colleague in the Classics Department, Bob proposed to call the genes idiomorphs rather than alleles. In further studies related to mating type, genes that are expressed preferentially during the sexual phase were identified and mutated, and idiomorph-linked sequences were compared in species related to Neurospora.
Immediately before “retiring,” Bob and his postdoctoral fellow, Rodolfo Aramayo, discovered a remarkable and unexpected new epigenetic phenomenon in Neurospora, meiotic silencing (also called “meiotic transvection” and MSUD for meiotic silencing by unpaired DNA). Elegant work by Bob and his colleagues showed that sequences that are unpaired during meiosis elicit an RNAi-like mechanism that silences all homologous sequences for the duration of meiosis. The discovery that meiotic silencing is mechanistically related to RNAi came from one of Bob's characteristically imaginative genetic schemes for selecting suppressor mutations.
A statement by Ed Lewis about Morgan's frugality applies equally well to Metzenberg: “Morgan was very thrifty when it came to purchasing laboratory equipment and supplies—but, according to Sturtevant, generous in providing financial help to his students” (http://nobelprize.org/medicine/articles/lewis/). As Bob wrote in a budget justification, “I have always worked with a fairly modest grant, consistent with my needs.” He spent taxpayers' pennies wisely while enjoying continuous support from an NIH grant renewed repeatedly to cover a period of more than 40 years. Although frugal, Bob has been generous in sharing strains, materials, clones, and, most important, ideas. He seems to generate a continual flow of interesting ideas, new ways of looking at problems, and fresh ways of stating them. This is apparent in his articles, reviews, and lectures, but is most obvious in conversation. A colleague pointed out that “Metzenberg is the type of scientist whose interactions and insights make those around him better scientists.”
Bob's unique style gives a special character to his achievements. His originality is reflected in felicitous figures of speech and colorful use of words. A small set of examples cannot do justice to his style, but here are a few selections from our correspondence with him:Finally, we cannot be permanently content with experimental material obtained by accident.
[Regarding an advantage conferred by heterokaryon incompatibility, this serves to prevent] … corruption or subversion by goldbricks.
Here are some strains—a day late and a dollar short—which you might want to analyze for methylation. Let me tell you about the dollar short part, and maybe you'll feel it's a lot of dollars short.
We are sitting in Kennedy [airport] waiting for our plane to Madrid. I had turned off all thoughts of the lab but something intruded anyway—a possible, remotely possible way to recognize N-6 methyl adenine in conjunction with the Church-Gilbert genomic sequencing method. It requires several things working rather well in tandem, but for what it's worth, here it is …
To my patient and tolerant colleagues: Here is a more than slightly speculative hypothesis … It has only one virtue: It is easily testable.
[Regarding the desirability of publishing details of methodology rather than relying on private communication] … without needing to know the secret handshake.
Bob's discussions have animated seminars and meetings—whether in fungal or general genetics, in biochemistry, microbiology, or biology—with imaginative insights. Much of this is done in a playful, clear, and challenging style that makes observers remember what was said. His command of the biological lore and his deep insight into chemistry and physics enable him to see the “landscape” of a hypothesis quickly and bring it to bear on the subject under discussion.
This is not the first time Bob Metzenberg has received an award named after T. H. Morgan. Nearly 50 years ago, in 1956, he received a Thomas Hunt Morgan Award conferred by Cal Tech in recognition of his accomplishments as a graduate student. His more recent contributions have been recognized by numerous honors, including a Guggenheim Fellowship, an NIH Merit Award, and election to the National Academy of Sciences. He was President of the Genetics Society of America in 1989–1990.
Robert L. Metzenberg
- Genetics Society of America
