Norm Pace Faculty Spotlight

Norman R. Pace - Biographical sketch  -

Dr. Norman Pace received an A.B. from Indiana University and the Ph.D. from the University of Illinois.  He has held faculty positions at several institutions, including the National Jewish Hospital and Research Center, the University of Colorado Medical Center, Indiana University and the University of California, Berkeley.  He currently is Professor of Molecular, Cellular and Developmental Biology at the University of Colorado, Boulder, and recently was appointed Distinguished Professor.

Pace works in two scientific arenas.  On one hand he is a molecular biologist, and his laboratory has made substantive contributions to our understanding of nucleic acid structure and processing.  Noteworthy efforts have included elucidation of the structure and catalytic mechanism of the RNA moiety of ribonuclease P, an enzyme composed of RNA instead of the usual protein.  On the other hand, Pace is a microbial ecologist.  His laboratory has led the field in the development and use of molecular tools to study microbial ecosystems.  This work has led to the discovery of many novel organisms and an understanding of some unusual symbioses.  The results have expanded substantially the known diversity of microbial life in the environment.  Current efforts range from high-temperature environments to human disease. 

Pace is a member of the National Academy of Sciences; and he is a Fellow of the American Association for the Advancement of Science, the American Academy of Microbiology, and the American Academy of Arts and Sciences.  He has received a number of awards, for instance the 1996 Procter and Gamble Award in Applied and Environmental Microbiology and the 2007 Lifetime Achievement Award from the American Society for Microbiology, and the 2001 Selman A. Waksman Award for Distinguished Contributions in Microbiology from the National Academy of Sciences.  This is the Nation’s highest award in microbiology.  He additionally is a Fellow of the John D. and Catherine T. MacArthur Foundation.

Pace also is an expert in cave exploration. He has led and participated in numerous expeditions in this country and internationally.  Pace has been elected a Fellow of the National Speleological Society, the Cave Research Foundation and the Explorers Club.  He received the Lewis Bicking Award from the NSS for his contributions to American caving.

Longer, autobiography of life in the microbial world

This is a remarkable period in the history of microbiology because now, for the first time, we have reasonably free access to the natural microbial world. This opens to us an enormous fund of previously unknown biodiversity.  Even though the chemical balance of the biosphere depends upon the microbial world, we have little understanding of the makeup and dynamics of microbial ecosystems.  One critical reason for our limited information in this area is that, until recently, microbiologists generally have had to cultivate organisms to describe them or even know that they exist. We can cultivate, however, only a small portion, far less than 1 percent, of organisms in the environment using standard techniques. Applications of molecular technology have now largely sidestepped the requirement of cultivation to identify, and to some extent characterize, microorganisms. Molecular phylogenetic studies have already made it clear that our knowledge of microbial diversity in the environment based on cultured organisms has been limited and distorted. I find it enormously exciting to know that, right now, microbiologists have only begun to explore the natural microbial world. We have before us a vast, little-charted world to survey and make use of. I feel grateful to be involved in helping to nudge open the door onto this world. How did I come to this opportunity?

It seems as though I have always been interested in scientific things. I grew up in conventional 1950s middle America in a small farming and manufacturing town in rural Indiana. I was (and remain) a voracious reader and my parents encouraged my scientific bent with department store chemistry and microscope sets. The microscope fascinated me and definitely piqued my career-long involvement with microbial organisms. I was intrigued by the concept of an "unseen world." That microscope was a lousy instrument, however, and I didn't know what to do with the bewildering complexity in a droplet of hay infusion. I did some experiments with bread molds, but mostly spent my efforts along those lines building a fairly elaborate basement chemistry lab. Chemistry was more accessible than the microbial world and even more exciting, since one could make bombs! A lot of young experimentalists, myself included, made black powder, rockets and the like, but part of my interest in organic chemistry was the attraction of picrates, fulminates, and nitro-substituted glycerides. Among other mishaps I lost hearing in one ear to careless handling of silver fulminate and buried a rocket motor in a neighbor’s house. I also learned a lot of things scientific. 

In 1957 something wonderful happened to science education in the U.S.: the Soviet Union launched the first orbiting satellite, Sputnik. At that time the U.S. space program was faltering. Part of the political response of the U.S. to our perceived weakness was the insertion of a large slug of funding into science education at all levels. Federal programs were invented to draw youth into scientific careers. I benefited enormously from one of those, an NSF-sponsored "High School Science Institute," at Indiana University. That program introduced me to the concept of a molecular-chemical side of biology and provided me with a summer job in a real university research lab, the phage biochemistry lab of Dean Fraser. I was hooked by the exposure to the university environment and to molecular biology, then a new field. I was captivated to realize that there were important unknowns in biology at the molecular and chemical level, and that the way to illuminate them is through the fascinating process of laboratory research. I needed to do that.

Also in my teens I developed a persisting interest in caves. Over the years I have explored, mapped, studied and visited caves around the world. One of my most cherished awards is the National Speleological Society's Lew Bicking Award, for contributions to exploration and study of caves, received in 1987. Caving was personally formative for me and it taught me important lessons that every scientist must know deeply: that there are new things to be discovered; that the frontier of knowledge is all around us; that looking at known things in new ways can reveal new vistas.

When I entered college, in 1960, if you were interested in molecular biology you went, as I did, to a department of "bacteriology." The research advances were being made in Escherichia coli and its phages, as model systems for all of life. As an undergraduate at  Indiana University I continued to work in labs. For a senior honors thesis under Howard Rickenberg, who had discovered lac permease only a few years earlier, I studied membrane-bound ribosomes in E. coli and Azotobacter vinelandii. During the course of that I developed another long-abiding interest, in RNA. This interest led me to graduate school in microbiology at the University of Illinois, specifically to work with Sol Spiegelman, a leading RNA molecular biologist of the time. I was exposed to the little that was known about microbial diversity as an undergraduate, but did not get very excited about it; there wasn't any handle on just what "diversity" reflects.  I recognized even then that culture was a challenge and that the conventional identification of microbes was a pretty haphazard business.  Even most professionals in the field did not (and mostly still don’t) have a clear concept of microbial diversity.  The field of microbiology then did not have the organization of the phylogenetic framework. The traditional microbial taxonomy, grouping organisms on the basis of morphological and nutritional properties, although pragmatic, had resulted in an unwieldy and messy collection of anecdotes, not relatable on the larger scale in a meaningful way. I was intrigued by the biochemical diversity of microbes, much as I was fascinated by my first glimpses of the microbial world through that rudimentary microscope. Nonetheless, I couldn’t organize that diversity in any way; I had no concept of any way to articulate “diversity.”

I arrived in Sol Spiegelman's lab just as the phage Qb viral RNA replicase project was opening up. This was the first experimental system in which in vitro replication of infectious viral RNA was achieved. My Ph.D. studies involved various aspects of the enzymology and mechanism of that replication process. Following an additional bit of postdoctoral work milking the same system, I took my first job, in Denver, as a joint Assistant Professor at National Jewish Hospital and Research Center, and University of Colorado Medical Center. The first contributions from the lab were in RNA processing, then a newly emerging field. We studied the maturation pathway of ribosomal RNA, showing among other things that the rRNA genes in E. coli are transcriptionally linked, and characterizing sequences removed during processing. We also established a purified system from Bacillus subtilis for maturation of 5S rRNA in vitro, RNase M5, still
the best-characterized rRNA processing nuclease. In turn, this led into studies of RNase
P, a tRNA processing enzyme with a catalytic center composed of RNA. RNase P RNA, is a ‘ribozyme’, an enzyme composed of RNA.  My lab has been significantly involved in the analysis of the structure and catalytic function of RNase P RNA, work that remains a major involvement of my lab. During the course of all that, I rose through the academic ranks to full professor. I also foundered about a bit, as we all probably should do. For instance, during the course of my early academic career I spent a year in medical school, but could not settle into the culture and so quit. I learned a lot and bsically (retrospectively) enjoyed that process.  Nonetheless, I concluded that I am irrevocably a lab rat.

When Carl Woese's first results from using rRNAs to infer the phylogeny of microorganisms emerged in the mid-1970s, I was enchanted. I had long known Woese; he was on my Ph.D. qualifying exam committee at Illinois and we had developed a friendship.  Woese's Big Tree, the sequence-based phylogenetic tree relating all modern life, gave us a way to articulate all that bewildering diversity in the microbial world. The results of molecular phylogenetic analyses were not speculation, the hot air upon which most thought on microbial evolution had been based. Rather, sequence comparisons are discrete experimental observations of evolutionary relatedness. The results are a picture of the course of evolution unclouded by historical speculation. We can paint our understanding of biochemical diversity onto the roadmaps presented by phylogenetic trees and begin to think meaningfully about the biochemical course of the origin and evolution of life.  Woese also discovered a new form of life, Archaea (formerly archaebacteria), right under all our noses. The phylogenetic signature of Archaea proved unquestionably that they are unique, fundamentally different from the familiar organisms such as E. coli, Saccharomyces cerevisiae, or Homo Sapiens. I was thrilled with this discovery. What else new was out there?

An important aspect of the molecular phylogenetic perspective, not appreciated
Initially but developed by my lab, was that we no longer needed to characterize the physiological properties of organisms to detect and identify them. This was the key to being able to study the makeup of microbial ecosystems without cultivation. The notion was to isolate directly from the environment and sequence rRNAs or rRNA genes. Phylogenetic analysis of the sequences then could be used to identify organisms present in that environment. Some properties of otherwise unknown organisms could be inferred on the basis of the properties of their cultivated relatives, and the sequences could be used as hybridization probes to monitor the organisms in nature, and for other purposes including cultivation. For the first time we had, in essence, free access to the natural microbial world!

We began molecular phylogenetic studies of ecosystems in the early 1980s. For technical reasons we first focused on 5S rRNA, but invested a lot of effort in developing 16S rRNA-based methods such as "universal primers" for sequencing and PCR; and "phylogenetic stains", fluorescently labeled hybridization probes that identify organisms in nature. I have been blessed with the participation of a talented and enthusiastic group of students and postdocs, several who now are leaders in environmental microbiology. Geothermal environments and unusual symbioses were early themes of the activities of the lab. However, it is not necessary to travel to exotic places such as submarine hydrothermal vents or Yellowstone to find new things; there are intricate and unknown ecosystems all around us – including our own bodies and our immediate surroundings.  It is clear from even the small number of environments so far studied that our understanding of the makeup of the natural microbial world is rudimentary, and that many organisms out in nature are profoundly different from cultivated ones. I believe it is important, even essential, that we undertake a representative survey of biological diversity in the natural microbial world. With what kinds of organisms do we share this planet? What are their roles in our biosphere? What model systems should we choose for laboratory studies of environmental processes? How extensive is the fund of biodiversity from which we can draw useful lessons and products? The sequence based
methods now provide a way to survey biodiversity rapidly and comprehensively.  rRNA sequences gathered from the environment are snapshots of organisms, different types of genomes, targets for further characterization if they seem interesting or useful.

I am deeply enthusiastic about the future and promise of microbial biology. It is curious that university programs in microbial biology are on the wane in the U.S. They are being folded into departments of 'molecular and cellular biology', or 'biology'. It is argued that this amalgamation costs the identity of microbial biology as a coherent academic unit. Many microbial biologists lament that development but, frankly, I think it healthy in the long run because it integrates microbial biology with the rest of biology. Beyond the boundaries of academic organization, microbial biology is intrinsically a coherent academic discipline, united by a common suite of techniques and experimental strategies, and with a unique perspective on an unseen world.

Because of its importance to all of biology and its opportunities, the microbial world needs to be prominent in any modern curriculum of biology, at all levels of education. I believe that the just-beginning avalanche of new discoveries and applications will bring a renaissance to microbial biology.  In that light, I close with a translation of a famous statement by the pioneering Dutch microbial biologist Martinus Beijerinck: “Fortunate are those who are starting now.”