Dr. Alexander Tzagoloff recently retired after more than four fruitful decades of research and teaching in the Department of Biological Sciences. He has been a beloved mentor and professor, and his research has contributed to an understanding of the genetics and biogenesis of mitochondria. Faculty Spotlight talked with Dr. Tzagoloff about the unbearable buzzing of tape recorders, serendipity and life’s path, and his decades-long love affair with mitochondria.
Faculty Spotlight: What was your undergraduate experience like and how has that informed the way you teach?
Dr. Alexander Tzagoloff: Both my undergraduate and graduate years at Columbia were very influential in shaping my own approach to teaching. The first semester of the undergraduate physics course, for example, was taught by professor Polykarp Kush, who just a few years earlier had been awarded the Nobel Prize for his determination of the electron’s magnetic moment. The class met in an auditorium-size room of Pupin Hall that had 8 vertically maneuverable blackboard panels. The chalk talk began on the lower leftmost panel and ended with each of the panels filled with neatly written and clearly explained equations that would have made Newton proud. If my memory serves me right, the blackboard eraser was not used by Professor Kush in any of his lectures that semester. This experience was an early lesson on the importance, especially for undergraduate students, of a well-prepared and memorized lecture. To this day I retain a very clear memory of the many outstanding instructors I was fortunate to have had in my humanity and science courses.
FS: What was your path to Columbia, and how long did you work in the Biology Department?
AT: My path to teaching at Columbia began at Columbia. In 1958, a year after the USSR launched Sputnik, I was a graduate student in the then Department of Botany located on the top floor of Schermerhorn Hall. It was the year President Eisenhower initiated a host of government sponsored and supported programs to stimulate scientific training and research in the United States. One of these programs, run by the National Science Foundation, was meant to expose high school students to more advanced topics that were not covered in their normal science courses. I had the good fortune to have the opportunity to teach a Saturday course on energy metabolism to a group of high school students. As I knew next to nothing of the subject, the benefits of the course were shared equally by the instructor and students. There were no suitable biochemistry textbooks on the subject at the time, which necessitated preparing the lecture notes from research and review papers. Some of these were written by Dr. David Green, who first introduced me to the world of mitochondria and their importance in supporting all the energy demanding processes of cells. Following graduation, I spent 5 years working on these fascinating subcellular organelles in his laboratory at the University of Wisconsin. This was followed by another 10 years at the Public Health Research Institute of New York and finally back home at Columbia in the then recently formed Department of Biological Sciences, where I continued my love affair with mitochondria for four and a half decades.
FS: What is one of your favorite stories to tell from your time teaching at Columbia?
AT: The one that comes to mind took place during my first lecture for the Biochemistry course I taught after my appointment in the Biology Department. The lectures in the first half of this course, on the structure and physical properties of biological molecules, were given by Charles Cantor of the Chemistry Department, who was an excellent instructor with a tendency to lecture at near-to-supersonic speed. Cellular metabolism, comprising the second half of the course, was my responsibility. All the lectures were given in a large room of the Schermerhorn building. After the first few nervous minutes of my first lecture, I became aware of an annoyingly continuous whirring sound emanating from the long table that separated me from the hundred or so students in the class. The mystery was resolved when I noticed that the top of the table in front of me was completely covered with tape recorders of various shapes and sizes. Fortunately, my dawdling pace of lecturing removed the need for the recording devices, which by the fourth class had all been repossessed by the students.
FS: What is the most surprising thing discovered in your field during your scientific career?
AT: One of the most surprising discoveries is the chemic-osmotic hypothesis formulated by Peter Mitchell that clarified the mechanism by which mitochondria synthesize ATP, the universal biologically utilizable currency of energy. As often happens with new ideas, it took Peter Mitchell many years to garner the evidence needed to convince the large number of skeptics who championed a more conventional chemical mechanism, similar to one known to operate in making ATP during fermentation in the absence of oxygen. The existence of a mechanism that bypasses chemical intermediates is also surprising because it is one of the very rare if not the only clear instance when nature invented two radically different ways of achieving a fundamental process essential to life.
The second important finding, particularly relevant to my own research interests, was the demonstration of the presence in mitochondria and in chloroplasts of small genomes and of the machinery needed to express their genetic information. This discovery opened up a whole new realm of studies aimed at understanding the function, if any, of these extra-nuclear genomes. Our studies and those of numerous laboratories around the world have helped to understand the roles of mitochondrial and nuclear genes in the propagation of mitochondria during cell growth and development and how the spatially separated genomes coordinate the expression of the genetic information needed for this to occur.
FS: What do you see as the most interesting open question in your field?
AT: Modern-day eukaryotic animal and plant cells are thought to have arisen endosymbiotically by the physical incorporation into primitive nucleated cells of unicellular bacterial-type cells with a much more efficient chemi-osmotic or photosynthetic means of making ATP. According to the endosymbiotic hypothesis, mitochondria and chloroplasts are the descendants of the bacterial progenitors that partook in these evolutionary events some 1.5 billion years ago. Although there is a large body of evidence supporting the endosymbiont hypothesis there remain many intriguing and still unanswered questions regarding of the evolutionary steps that were required to establish a genetically and biochemically stable symbiotic co-existence of the two different cells types.
Of equal interest is an understanding of the selective pressure(s) that drove the massive transfer of genetic information from the symbiont to the nucleus of the host cell. Did an accidental random transfer of an essential gene to the nuclear genome of the host foster the symbiotic relationship?
These are examples of questions that will be answered by present and future generations of scientists concomitant with increased clues gained from studies of yet-to-be discovered organisms that may shed light on the process that led to a conversion of bacteria into organelles. I should also point out that our maternally inherited mitochondrial genome has helped to elucidate questions related to the evolution and migrations of our ancestors on this planet. Finally, mitochondria, by virtue of their importance in energy metabolism and other essential cellular processes, are targets of mutations with devastating consequences. Although the genetic basis for many mitochondrial dysfunctions has begun to be understood, future efforts are required to find effective therapies to alleviate this class of inherited human diseases.
FS: If you had never been a scientist, what would you be?
AT: This question can only be answered by someone with the ability to see into the future. My deficiency of such powers makes the choice of an alternate existence a futile enterprise. But I did imagine myself to be incarnated as a cowboy, superman or musketeer when growing up, depending on the comic book or book I was reading at the time. Good teachers that came into my life later dispelled these ambitions in favor of a métier that would contribute to an understanding of the molecular processes underlying life as we know it on earth.