William Duax

Zierler:

Okay, this is David Zierler, oral historian for the American Institute of Physics. It is August 20, 2020. It’s my great pleasure to be here with Dr. William L. Duax. Bill, thank you so much for joining me this morning.

Duax:

It’s my pleasure to be here. I appreciate this opportunity. It has caused me to look over my background, life, etc. And, it’s something I needed to do anyway.

Zierler:

Absolutely. And I’m glad to hear that. Okay, Bill, so to start. Would you please tell me your title and institutional affiliation?

Duax:

Okay, I have a position at the University of Buffalo where I’m a third of a full professor. I’m one of probably, a rarity, of having one-third of a full professor. Three of us here at HWI make up one professor for the university. So, Vivian Cody, Bob Blessing, and I are one full professor. A third each. And I have been at the Hauptman-Woodward for almost fifty years where I was the head of the department. Eventually, I was the research director. And then I was made a professor emeritus. I was identified as the Herbert Hauptman…what is it called? Herbert Hauptman (laughter), sorry…Distinguished Scientist. He wanted to call me a distinguished scientist and I asked Herb, “Could I be the Herbert Hauptman Distinguished Scientist?” And he said, “Sure.” And so, that’s how I became the Herbert Hauptman Distinguished Scientist of the Hauptman-Woodward Institute. Because of my affiliation with the university, the main thing that I do with the university these days is teach a program to high school students that we will get to later, I believe. So, that’s also one of the things that the Hauptman-Woodward appreciates for me. Before, because many of the children, nieces, nephews of the members of the board of directors have taken that program and found it to be beneficial. So, that’s my responsibilities. I had been the CEO of the ACA, but that was terminated a year ago. And I was the editor of the IUCI newsletter. That also I have retired from.

Zierler:

Bill, when did you go emeritus from the school?

Duax:

From the Hauptman-Woodward? Just about two years ago, really. For different financial reasons. As long as I was an employee, and I’m still listed as an employee. But I’m an emeritus employee. So, I no longer had a research lab about, probably ten years ago. So, the last ten years I’ve been teaching this high school student program in evolution.

Zierler:

Well, Bill, let’s take it all the way back to the beginning now with your childhood and even before that. Let’s first start with your parents. Tell me a little bit about your parents and where they are from.

Duax:

My mother and father were both born in Chicago. My mother had Irish ancestry. I think it’s probably her grandparents who immigrated from Ireland. And her parents were lace curtain Irish in Chicago. She began college at DePaul University, but did not finish. That is where she and my father met. My father, his parents came from Wisconsin when my grandfather decided that he didn’t want to be a farmer for the rest of his life. He would rather go into show business. And since that was just the beginning of radio, he thought that radio was going to be a good thing. So, he moved his family to Chicago, and he took singing and dancing lessons. And applied for a job at WLS. He got onto the WLS Barn Dance, which was a precursor to the Grand Ole Opry. And so, on the Barn Dance because my great grandfather had been a honeybee keeper. And my grandfather then learned about honeybees. And honeybees continue today to be an interesting topic that people are willing to talk about.

He went on the radio as Bob White, who did bird imitations and answered questions about honeybees. And Bob White was the bird imitation he was best at. And he became an authority on honeybees and honey. So, because he was on the radio, he’s talking to people every day. Soon he began to raise bees again and became the best-known beekeeper throughout all of Northern Illinois. And he and my father eventually had 500 colonies of bees and were the primary provider of honey to what was the Piggly Wiggly grocery store, that became the Eisner grocery store, that is now Kroger. Our honey, which I helped bottle and process as a ten-year-old kid was being marketed by one of the largest grocery chains in Northern Illinois. And when Illinois needed to have a chief bee inspector because it seemed to be a good idea to have such. Since my grandfather was the authority on honeybees, he got the political appointment. It’s just like Donald Trump gets elected because he has a reputation off of his television show. And therefore, gets to be president. Well, my grandfather only got to be the chief bee inspector.

My brother and I continued to raise bees when I was in graduate school. We had one hundred colonies of them. And today, on my property, here in Buffalo, I have two colonies of bees. I just extracted, or took, this year’s product from the bees. And I got 180 pounds of honey. My sister says, “What are you gonna do with that?” Well, I tend to give it to my friends, and they appreciate it. So, that was my beekeeping. And bees have had another theme through my life because when I was in college, my uncle was at St. Ambrose College. The basketball team was the Bees. And I was the basketball manager caring for the team called the Bees. And St. Ambrose is also the patron saint of bees, because his loquacious ability to give good presentations and everything was attributed to his being stung on the tongue by a bee. So, I have never been stung on the tongue by a bee, but I usually get by with my presentations. That’s some of my childhood.

Zierler:

Now, Bill, you were born in Chicago, but you were not raised there.

Duax:

I lived in Chicago until I was in about fourth grade. I went to a Catholic grade school in Chicago. My father was a very hard worker, but he didn’t stay in any one place too long. He had a lot of different jobs and the point came in which he had to leave Chicago. And he put all of our belongings into a big truck and we drove down to Ashkum, Illinois. Population 400. Where I then began fourth grade and continued my education in a small town of 400 people, seventy-five miles outside Chicago. And the people of the town felt that anyone who came from Chicago was a gangster. And therefore, it made it a little bit awkward to make friends. Particularly because we were living on Main Street in one section of a sales building with plate glass windows.

It had been a shop, now turned into our home. And so, we were somewhat white trash gangsters from Chicago moving into a small town. And I’m sure that that had an impact on my overall attitude toward life and one thing or another. But my mother was determined that her children should go to college. She did not complete college, nor did my father. But she put me into a high school twenty miles away. A Catholic high school that had good college prep courses. And that set me on the way to a college career. Also, I always enjoyed acting and performing. And I was in plays in grade school, in high school, and in college. And that continued through the rest of my life of being a performer. I thought when I was in high school- when I started college, I thought I would like to be either a writer or an actor. And as it happened, I’ve managed to do some of those things in my private life. But one day I was taking courses that would cover almost…make it possible for me to pursue any career. And one day the professor of chemistry asked me if I had declared a major. And I said, “No.” And he said, “Well, why don’t you declare chemistry?” And I said, “okay.” So, that’s how I became a chem major and graduated from college. Where I had not been involved in student government until my junior year when I ran for president of the student body. Because, the year before there had only been one candidate. And I thought that in a democracy there ought to be at least two candidates, so I was gonna be the second candidate. I, at the time, worked in the kitchen clearing dishes and garbage and at a window where all the students brought their tray full of dirty dishes and everything. And I was in that window and I put a sign above the window that said, “Get Duax out of the garbage and into the White House.” And that was my best selling point for becoming elected student body president.

Zierler:

Now Bill, I want to ask. When you were growing up, did you demonstrate any particular aptitude for the natural sciences?

Duax:

No, I had demonstrated an aptitude for singing and dancing and performing. I would do an imitation of the Woody Woodpecker song when I was maybe four or five years old. And everybody applauded and laughed. And I thought, “Well, I must be good at this.” I didn’t realize that I was just a funny, little fool. But I got encouragement for that. Also, it’s my belief that a lot of actors are successful because they grow up with inhibitions and maybe are shy and maybe don’t interact well with others. And when they get in a role to act, they’re somebody else. And suddenly they’re freed of all their inhibitions and are able to just express the feelings of the character they’re playing. And I think from the experience I’ve had working with other teams of actors in local performances, I see other shy people overcome their shyness by being somebody else.

Zierler:

So, when you were thinking about college, you were not thinking at that point about pursuing a career in science. As you said, that only came later on.

Duax:

No. College was because my uncle was the athletic director at St. Ambrose College and offered me a position if I would be the team manager and wash the jockstraps every night. That I could get my tuition paid. So, then I got a job in the kitchen so that I could get my board. And then I got a job in the chem department doing sewer analysis so that I could pay for my room. And then I got a part-time job so I could have some spare change. So that I could work my way through college and have no debts. And I pretty much, from the time of my sophomore year when I was seventeen, I never returned to home. And have had my life since then. I went home to visit, but I usually spent the summers working in the bee yard with my father. Just as my grandfather thought show business is better than the bee yard, I thought so too.

Zierler:

Bill, when did you realize that you were good at science? That you did have this aptitude and that you could make a career in this field?

Duax:

When I went to graduate school- well, I graduated from college at St. Ambrose. And because I did not want to wait and be drafted because at that time you still had to register for the draft. I was lucky. It was after Korea, but before Vietnam. And so, friends decided the best thing would be to sign up. So, I joined the Army Reserves. And I did my six months training and six years of Reserves. And I got an honorable discharge. So, I put in my time for the U.S. government as well. And when I came back from the six months training, a friend of mine said, “Well, why don’t you go to graduate school? Why don’t you apply to University of Iowa? You can probably get an assistantship.” So, there again, if I was gonna get paid to go to school, what could be better? So, I applied, and I got a teaching assistantship in the chemistry department at The University of Iowa. And I enjoyed the teaching. But I had to apply to one of the professors to be my major professor in the career to pursue. When I talked to the guy who was a young, very nice, young man doing quantum chemistry, I didn’t understand a word. And so, I said, “Well, that’s out.” Then I spoke to Norman Baenziger who was an x-ray crystallographer. And he told me that if I studied a crystal, I would learn the arrangement of the molecules in that crystal. I would be the first person who ever saw it. And no one would know more about it than I did. It would be an easy life defending my thesis, etc. So, I was drawn into the beauty of crystallography, it’s reliability. You recently interviewed Helen Berman and at the very end of her interview you discuss why crystallography is special. Why you collect so much data, and if the data all fits together then you really can trust the result that you get.

Zierler:

Right.

Duax:

It is the most reliable type of data. And that’s why the Protein Data Bank and the Cambridge Data Bank of small molecules and all of the crystallographic data bases are considered to be treasures for accuracy. There are no alternate facts. There aren’t two different crystal structures that have the same cell dimensions. That’s the same one. So, we know about real facts and irrefutable facts. So, I was attracted to crystallography. I was given a challenging problem. I still was enjoying teaching, but Baenziger applied to NASA to get a fellowship so I could work on a specific problem and didn’t have to teach anymore. But I loved teaching. But it also I couldn’t turn down this opportunity. So, I began to work on my first crystal structures. One of which has never been published. It should’ve been published. It almost got published. But I didn’t quite finish it. On the other hand, I’ve got plenty of things that did get published. Right now, there are some publications that I need to address concerning the evolution of the genetic code. Those are the next publications I really have to get finished with. But I’m not moving as fast as I should, dissuaded by other things.

Zierler:

Bill, in what ways was your dissertation topic a result of what your dissertation adviser was working on? And how much of it was your own interest and what you wanted to study yourself?

Duax:

It was something he thought would be a good thing to do. But it wasn’t something that he had ever done anything in. The Japanese had published some papers about the thermal motion of molecules of carbon disulfide in the solid-state. Molecules in the solid-state it’s always this puzzle you tell people. Well, all the molecules in the solid things around you are really moving. And they are. But they’re moving and still retain their shape and what we see of them. So, in carbon disulfide, the molecules rotate and translate a little bit, and they vibrate. So, they have all of these properties of an isolated molecule vibrating, rotating, and translating. And the Japanese had determined the structure of powder, solid-state carbon disulfide and they had Raman and infrared spectra to identify the vibration-rotation parameters of molecules in the solid-state. So, Baenziger said, “It would be nice if we would look at the thermal motion and the molecular movement of molecules in the single crystals and see if they would match these measurements by Raman and infrared spectroscopies.” So, here we were trying to bring together data from crystallography and data from Raman and infrared spectra and see how well they match. So, he said, “Carbon disulfide had been studied by the Japanese. You should get single crystals of carbon disulfide and analyze its thermal motion.” It was the first time, and perhaps, I don’t think it’s been done again. But we were able to compare the two and see the correlations. That the thermal motion as seen and evaluated by crystallography agreed with what the Japanese had found for Raman and infrared spectra. And that work got me a lot of attention as something valuable and different and unusual because it tied together different disciplines in science. Once again, it wasn’t one set of facts for Raman and infrared and a different set of facts for crystallography. They matched. And that was very good support for both disciplines that they were doing what they thought they were seeing was in close approximation. As close an approximation as we could make of what was going on.

Zierler:

Bill, when you talk about the value of this research and the attention that it garnered, are you referring to its value just in the sense of basic science or were there practical applications of these discoveries at play as well?

Duax:

This particular application, I wouldn’t say I know of a practical application. But, in a time when people are suspect of science, I think it is a valuable- I think it is important to know that there is agreement within science. And that it is not a matter of different sets of facts. So, I think that that is a more valuable contribution that this work made. Other applications, later on at Hauptman-Woodward, I worked on the relation, the structures of estrogens and antiestrogens.

Estrogens support cancer. Antiestrogens battle it. So, by looking for subtle differences between estrogens and antiestrogens was useful to try to design more potent drugs to cope with breast cancer. So, that’s a very practical application. The same is true of my students. When I work with my high school students and we try to trace the evolution of ribosomal proteins, they say, “Well, what good is this? Who cares about the evolution of a ribosomal protein?” But when we try to look at the evolution of the enzymes involved in tuberculosis…and they learn that they can detect things from their data. They can look at the evolution of the entire family of proteins that began with the tuberculosis bacteria and see how it’s been modified through time in order to design drugs that will attack the tuberculosis bacteria, but none of its sibling or offspring’s that it gave birth to early on in the course of evolution. So, we look at the evolution of molecular structures in order to identify, how do we target the right member of that large family that may extend all the way from the earliest bacteria to us? And you don’t want many of the side effects that are talked about on TV commercials. They’re not really side effects. In some cases, it’s because that particular drug is interacting with a member of the family of proteins that you’re trying to target. But it’s interacting with the white sheep of the family, instead of the black sheep.

Zierler:

Bill, as a graduate student, were you thinking about the applications to human health research? Was that something that was specifically compelling or motivating for you?

Duax:

As soon as I had my degree in x-ray crystallography, I wanted to think about how can I take and use this technique in biomedical research. So, that right away was what I thought would be the thing to do.

Zierler:

And so, what did you end up doing after you defended?

Duax:

I got my first postdoctoral position with a man named Abraham Clearfield in Athens, Ohio. Because after I got my Ph.D., I applied to one school near University of Iowa. I thought, well, I could teach at that school and I could come back to Baenziger’s laboratory and continue to do research. Then I was interviewed at Athens, Ohio, and the man definitely wanted to give me a job because of my crystallographic skills. He needed a crystallographer to study the structures of sheet like molecules that are used to capture ions and it was related to nuclear- nuclear- I always pronounce it wrong. Where you want to be able to take ions out of a solution that may be radioactive. This is part of nuclear device development. So, Abe Clearfield had a grant to do that. But he needed to determine the crystal structures of the layered compounds that would take the ions out of the solution. So, I went through something completely different. Had to grow crystals in an oven inside of a sealed bomb. Break the bomb open and see if I got the crystals, and then determine the structures of these layered compounds.

I’m sorry, it’s been fifty years since I did this research, or I would be able to explain it better. But anyway, that was a completely different thing. And then I applied…my adviser had told me to apply to Roswell Crystallographic Institute where the first protein structure had been solved. And that I would really be able to work in this is the advice of Baenziger, who said that that’s what I really should try to do. So, I applied, and I got invited to come and talk to someone at the Hauptman-Woodward Research Institute. Which was at the time just the Medical Foundation of Buffalo. So, I go to be interviewed- actually. Wrong, wrong, wrong. I think I’m interviewing for a job at Roswell Crystallographic Center. But the woman who interviewed me had just moved from Roswell Crystallographic Center to the Medical Foundation of Buffalo. She had gotten a grant to study the structures of steroids. And steroids were involved in breast cancer, prostate cancer, all sorts of cancers. And heart disease. All sorts of ailments have connections to the steroid hormones. And so, she interviewed me. And she just won me over immediately. I didn’t need to go to the Roswell Crystallographic Center. I could go to this Medical Foundation of Buffalo and begin to work on structures of steroids.

So, that’s what brought me to the Medical Foundation which was where I thought I wanted to be. And do something related to health. And I believe that my work in the steroids, the estrogens, the androgens, progestins did make a contribution. We developed a model for how all the steroids function. At one end the steroid would bind to a receptor. All of the hormones acted through a receptor mechanism. That was a very well understood paradigm. That what happens is you’ve got a receptor for a molecule and the molecule binds to the receptor and forces it to undergo a change that allows it to express its functional importance. And if you put an antihormone in that site, it will not allow the receptor to undergo the change, so you will stop the action. So, the small molecule, by interacting with the large molecule in the lock and key relationship will be able to either turn a process either on or off. So, that was the biological process underlying many functions. Most of the ones that the steroids are involved in. So, that again was a very satisfying area of research to use crystallography to determine the shapes of the agonists and the antagonists that influence this lock and key relationship.

Zierler:

Bill, did you ever think at this point about pursuing a medical degree? Or becoming more closely involved with clinical research?

Duax:

Well, by the time I’m at the Hauptman-Woodward I’m married and have four children. And I wasn’t about to go back to school. Plus, my father said I had spent too much time in school all along.

Zierler:

A-ha.

Duax:

I didn’t know enough about guts. So, that was not- although, I’ve known a couple of remarkable MD-PhDs, and felt that that was a terrific career because it not only allowed you to deal with patients and apply your knowledge of medicine. But you could be pursuing research to do more for larger numbers of people. So, I often encouraged my students in my student program, I’ve had student programs for almost forty-five years. But only recently I’ve had this really active program of doing basic research and teaching them how to do the research. But before that, I would have summer programs where I would bring in a class of students and show them what crystallography was about. And how it all came together. And then they would have an interview with, by then, Herbert—Nobel Laureate, Herbert Hauptman. And they had a wonderful time. But I always encouraged students. If they wanted to go on to careers in science, then consider a PhD-MD program. Particularly if they’re talking about careers in biomedicine, that they get an MD-PhD so that they can be able to do more. The gratification of working with individual patients, but also the value of trying to advance the field.

Zierler:

Bill, I wonder if you could talk a little bit about your early impressions of HWI? What was it like? In what ways was it unique from, say, a teaching hospital or a university affiliation?

Duax:

At the time, I wouldn’t have been able to contrast with the others. I didn’t know the others. I was impressed with the fact that we were using crystallography to determine these structures. I knew how important the structures were. I knew that there was a department of crystallography in Pittsburgh. But that department was not solely devoted to biological research. It was more involved with the industrial community of Pittsburgh. And the director of that program did very well in developing close relationships with the entire industrial community around Pittsburgh. And helped sustain the University of Pittsburgh, where Helen Berman, and several of the other people that she worked with through the years all got some of their training. At the University of Pittsburgh, from George Jeffrey. George Jeffrey, himself, focused on sugars. And was an authority on sugar structures. So, I knew that there was somebody doing sugar structures. I’d soon become aware of Jenny Glusker in Philadelphia, working in cancer. But what I liked about HWI, was we were working on steroids, which had a wide range of application.

There were two other departments, initially. One, in thyroid chemistry and the other in basic endocrinology. So, I was learning about the field of endocrinology, which I knew nothing about. I went to my first Endocrine Society meeting. I was stunned by the decisions that would be made on the basis of a small number of pieces of data. Somebody had three rats; one ran away and the other two did such and such. And so, they wrote a paper about it. I found that the basic endocrinology was lacking in the type of reliability that was in crystallography. At the time I went to my first endocrinology meetings, Vivian Cody was doing thyroid hormones by that time at the Hauptman-Woodward. And the two of us were the only two people there talking about the molecules of the thyroid hormone. The molecules of the steroids. Fifteen years later, the Journal of Molecular Endocrinology came into existence. So, it was those early efforts to try to open people’s eyes to the power of the molecular level interaction of their hormones with their receptors that could be used to understand how to improve health.

And we gained a very good reputation at the Department of Arthritic and Metabolic Diseases at the NIH. We were using the heavy atom method to determine structures. Thyroid hormones already had heavy atoms, iodine atoms, bonded to them but we had to crystallize steroids with molecules having heavy atoms. You can find the heavy atom in certain planes of data. You’d gather the data. You’d create this electron density map and certain planes in that data will show you where a heavy atom is, if there’s just one heavy atom. And that technology was developed by David Harker at the Roswell Park Research Crystallographic Center and by Max Perutz, in England, working on the first protein. So, Harker’s working on a protein in Buffalo, and people in England are working on proteins. And this heavy atom technique is the key to unravelling those structures. But Herbert Hauptman comes to the conclusion that you can determine structures without heavy atoms by looking at the relationships among the reflections that are most strongly diffracted in the x-ray pattern. Because the strongest spots in an x-ray pattern are those spots coming from planes that have the maximum density of electrons in them. So, the electrons are doing the diffracting. The planes that are most dense are the planes that have the most electrons and the intersections of those planes are helping you find out exactly where the atoms are.

So, that is what direct methods was about. And Hauptman figured out mathematical relationships and developed techniques. Herbert Hauptman and Jerome Karle developed direct methods together and tried for twenty years to explain them to crystallographers. I was at meetings where they would be ridiculed. David Harker, who had figured out the heavy atom method, didn’t see what they were doing. In fact, David Harker was confronted with the problem at one time of a small molecule. Didn’t have a heavy atom. Wasn’t sure how he could determine that structure. It was a borohydride and boron’s chemistry was unknown at that time. But Harker and his collaborator, Kasper, noticed that some of the reflections had relationships to one another. So, he saw the relationships between the planes that had the highest density of the electrons in their borohydride and was able to manipulate those by inequality relationships to determine the structure. Hauptman looked at that data and said…what he did is prove that the data contains the phasing information. Prior to that, it was believed that you could gather the intensities of the data, but you could not determine their relative phase.

Zierler:

And what’s the significance of that, Bill?

Duax:

That by developing the formulas, you could solve all these structures that you’d not been able to solve before because it was impossible to get a heavy atom into them. And you didn’t have to worry about whether the heavy atom modified the structure and changed it from making it less likely that you could determine the difference between an estrogen and an antiestrogen that could be used to make the drug. Because at Hauptman-Woodward when I started, we were using heavy atom derivatives to solve the steroids. We didn’t want to put the bromine onto the steroid, so we co-crystalized the steroids with bromophenol. That got a cocrystallization of a bromophenol molecule and a steroid molecule without putting the heavy atom on the steroid, so you could see what the steroid structure was without any contamination. This novel approach taught us about making complexes and it taught us about how to get at a structure that didn’t have a heavy atom on the steroid. Herbert Hauptman provided us with the potential to not have to put the bromophenol in there, to really just look at the steroids. And so, Dorita Norton developed a collaboration with Hauptman.

Hauptman was at the Naval Research Lab and he and Jerome Karle were developing direct methods there. But Hauptman got his Ph.D. And for a while, there were two programs at the Naval Research Lab working on direct methods. Jerome Karle’s program that had been there for years, working with his wife Isabella, and Herb’s program. But the Naval Research Lab decided that they didn’t really need two direct methods programs, so they told Herb they wanted him to turn the laser into a killing weapon. And Herb did not have any desire to go from direct methods in structure determination to turning the laser into a killing weapon. And the offer from Dorita Norton to come to Buffalo to continue direct methods relieved him of the need to turn the laser into a killing weapon. And so, Herb came to the Hauptman-Woodward where I was the head of the crystallography department and he became a member of my department. Which was, non sequitur or an oxymoron. It’s crazy that I was the head of the department with Herb Hauptman in the department. But we worked well together. Along with two of my other colleagues, Chuck Weeks and Steve Potter, who were computer experts. Herb and I were both a loss at computers. Herb was great at theory of methods. I was great at observations. My talent, if I had one, was in pattern recognition. I could see these planes and the interactions of the planes and that atoms were on those planes.

Zierler:

And Bill, can you describe what’s the value of pattern recognition, generally? What does it allow you to do?

Duax:

It allows you to look at the hundreds of thousands of proteins in the gene bank and put them into subgroups of families and classes by looking for patterns that are conserved in all members of a family. Right? Now, with each of the ribosomal proteins, the ribosome is present in all living things.

It’s not in viruses. But it’s in all cellular things. So, the genomes of all cellular things have a ribosomal sequence in them. And each ribosome has from fifty to seventy proteins. So, these proteins are present in all living things. We are able to find all 30,000 members of each family of ribosomal proteins. And each one of them will have a key signature pattern that is retained in all of them. The entire structure will have very little homology if you line up the entire family, but it will have these key residues. Most of the time, the key residues include glycines and prolines. We have discovered this by analyzing families of proteins. So, by the pattern recognition of seeing a specific pattern of five or six or ten amino acids in five or six or ten specific positions in the overall alignment of a family member, it will allow you to place them all in the same family. So, we can take pattern recognition, and this essentially is bioinformatics, and use it to find all members of a family of any protein family, enzyme, receptor, anything. And if that enzyme is a drug target, we know what all the members of the family look like. Where they look similar and where they differ. And how we can use the differences to design specific drugs.

Zierler:

Bill, can you talk a little bit about the funding sources for HWI? How does it operate?

Duax:

HWI has a small endowment, but not a large enough endowment to retain all the staff. When Herb came to HWI in my department, Dorita had the steroid research project funded by the NIH. And very shortly, we got NIH funding, as I say, we showed up at the Endocrine Society meetings and the arthritic and metabolic disease division was pleased to learn what we had to offer. So, they saw what we were doing with thyroid hormones and steroids. So, there were two projects funded by the NIH. About this time prostaglandins became popular, and so we put together a proposal to study the prostaglandins. The NIH had a policy for funding shared resources for data collection. And because we had two programs funded to study crystallography of thyroid hormones and steroids, we were able pretty quickly to apply for a shared instrument. So, usually the shared instrument was placed and would be serving several institutions. But, since we had so many projects working in crystallographic structure determination, we were able to get these shared instruments. And I put someone in charge of the shared instruments to see to it that all the users who were having different funding would be able to get access to that shared instrument. And we ran our shared instrument very effectively. We expanded our studies to include the prostaglandins and pretty soon it was time to investigate proteins. So, we managed to expand ourselves into enzyme studies, so that the steroid project stayed funded for thirty years.

Actually, shortly after Herb came to Buffalo, Dorita Norton tragically committed suicide. And at that point, Herb called me one Sunday morning to tell me of her suicide. I had been with her the day before in the hospital. She underwent an operation for breast cancer. And she was told that she was okay, but she didn’t believe it. And she really was fatalistic. When I went to visit her that day, we talked for about an hour. And I should have understood what was happening because she went through all the staff and told me how I really needed to be more supportive of this person, and I really should watch out for that person. And they may need help. And she was, in fact, giving me instructions of what to do when she killed herself. And so, the next morning Herb called me and told me she had shot herself. In the heart. And we tried to figure out how we were going to salvage the institute.

Zierler:

Meaning that her death was so- she was central to the institute that it posed existential questions?

Duax:

She was the principle investigator on the two grants that were the primary source of support for the institute.

Zierler:

Yeah.

Duax:

So, Herb took over the thyroid grant and I took over the steroid grant. She had been the principle investigator. I was the principle coworker. Dorita was the head on the thyroid as well. Herb took over that and eventually it was transferred to Vivian. I think this is definitely before George Takita comes on board with the prostaglandins. Because we were just figuring out how else to survive it. The people in Washington were very understanding, very sympathetic. We had very good relations with the NIH head of the area that was responsible for our grants. And we maintained and built upon those relationships through time.

Zierler:

Bill, in what ways were you and Herb able to fill her shoes on these ongoing projects? And in what ways were you not able to?

Duax:

Because Dorita had- I had been running the steroid project pretty much single-handedly.

Zierler:

Yeah.

Duax:

There was no difficulty in taking it over. I was giving most of the talks. A couple of times she would give a talk, I would feed her all the information she needed so she could give a talk. So, that was not a problem. And the thyroid problem, Vivian Cody was really doing most of the work. So, Dorita, herself, was the PI, but she was not engaged in the day-to-day. She didn’t solve any of the steroid structures. Or the thyroid structures. They were done by, in the case of the steroid project, Dorita hired an Australian named Tony Cooper. Who was trained in Dorothy Hodgkin’s lab. And was, in fact, in training in Dorothy Hodgkin’s lab when Dorothy received the Nobel Prize. He got the telephone call from Stockholm because Dorothy was in Ghana. So, he was solving the structures with the help of a graduate student, Chuck Weeks. But he found working for Dorita intolerable. The salary was okay, but he was frustrated and unhappy. And so, he left. And Dorita put me in charge of the project. From then on, I was solving all the structures with the help of Chuck Weeks and Steve Potter.

Until Herb comes, and we’re using direct methods and we’re still doing the solving of structures, now using Hauptman’s direct methods. So, the transition of the loss of Dorita was not the problem. The problem was convincing the NIH to transfer the principle investigatorship from Dorita and to me. By 2016, we had gotten grants from the NIH totaling $48 million. That was spread over 1-2-3-4-5-6-7-8…14 different investigators had been PIs, gotten support from the NIH through the total of $48 million. Thirteen million of that went to Hauptman for his direct methods development. Ten million was in the steroid project with me or the ion transport antibiotic project that I also developed. So, we were very successful in getting competitive grants from the NIH over a long period of time. That’s how we stayed alive. By establishing rapport and the valinomycin structure was another breakthrough with Hauptman. We were using direct methods to solve the steroid structures and that was very good. But we kept wanting to do larger and larger structures.

So, the data for an antibiotic called valinomycin came into our hands and it was the largest structure solved by direct methods at the time. And it was solved in the space group P21. Crystal structure determinations are easier if the molecule is centrosymmetric. Then all the data have phases of just zero or one hundred eighty. They don’t have any other phases. So, as I said, you gather the data and the spots- the spacings are a function of the cell dimensions and the intensities are where the atoms are. If you have a centrosymmetric- so, from the x-ray you can get the intensities of the data but not the relative phases. In centrosymmetric structures, all the phases are of one or two values. They’re not random values. Whereas when you go to asymmetric structures like the steroids and the valinomycin and the proteins, the phases can be anything. And therefore, your ability to define them and build upon an internally consistent set of phasing that will show you the molecule is much more complex.

So, with Herb’s methods, you are able to unravel the relative phases. Acentric structures…the structures that are in the space group P2₁…even if you are looking at asymmetric structures in the space group P2₁2₁2₁, at least three planes…the HK0 plane, the 0KL and the H0L plane have only one of two phases. So, you have parts of the data that are limited to only one of two phases. And then you have the vast amount of the data that isn’t limited. In P2₁, you have only one plane that is limited. So, you’re again handicapped as to how do you get started here? How do you establish the handedness of the structure you’re going to get? What is the enantiomer? And so, in P2₁ you had to figure out was there a way to get information on the separation of at least two segments of the data? Half the data in space group P2₁ is enantiomer specific and the other half is not. I figured out how to separate the two halves to determine the structures of the principal mineralocorticoid steroid aldosterone and the antibiotic valinomycin.

But the method used to solve them had a new element that was helpful in the space group P21. And Herb and I wrote the manuscripts on that method. And those are two papers of which I have the greatest affection and pride. Because those are two papers where the authorship is Hauptman-Duax on one and Duax-Hauptman on the other. So, I felt very privileged that we had done something together and I could be a shared author. I have only—

Zierler:

Bill, beyond the co-authorship, what is it substantively about these papers that is also so important for you?

Duax:

That it was a way to define the enantiomorph in the space group P21. Other people subsequently found other ways to do that and were very pleased to do so, but when they bragged about it, they were told by another one of my colleagues, “Well, Bill already did that.” Because it was a relationship within the data that had not been detected. And it was laid out in a way that it was possible to use that in hoping to solve other structures. It was a scientific accomplishment done in collaboration with a wonderful Nobel Laureate. I have only in my entire collection of published papers, I have only one single authored paper. All of my other papers have multiple authors. And one of the papers that was the most important in my research funded by my projects was another ionophore called gramicidin A. And David Langs was a brilliant young scientist here. He’s since died. But as a young man, he was brilliant with regard to direct methods. And when I got continuation funding for my ionophore work, it started with my determination of valinomycin. But one of the challenges was to solve gramicidin A. A far larger, more complex structure. So, I gave the data to David Langs and I said, “David, only you can solve this structure. So, see what you can do.” And David did solve the structure.

Some of the solution may have been mystical. He was pretty mystical when he talked about it. But he did solve that structure. And so, when that structure was published, I did not, although I was the principle investigator on the grant, my name did not appear on the publication. My grant was acknowledged, but my name was not there. My project manager wanted to know how could that be? Why wasn’t my name on the paper? And I said, “Because David Langs did all the work and he deserves all the credit.” So, Helen talked about how they didn’t put their mentors’ names on papers because the mentor didn’t do anything. I voluntarily did not put my name on David Langs’ paper. And I think David appreciated it. I certainly appreciated him.

Zierler:

Bill, can you talk a little bit about the quality of the instrumentation at HWI? Did you get a sense that you were working with state-of-the-art equipment?

Duax:

Yes. The shared instruments that we applied for were state of the art equipment. So, when I came into the institute I worked on a diffractometer that Dorita Norton had brought from Roswell Crystallographic. And it was so wonderful to collect data. You had to dial three dials and then push a button and take an intensity. Then you had to dial three more dials and push another button. It seems tedious now, but at the time it was wonderful. I didn’t go to lunch. I just worked all day long gathering data because the data was so easy to get by comparison and so important to me to get that data to solve the structures. Then when we applied for our instruments, we got state of the art.

When we solved the valinomycin structure, an additional complication was that the Russians had a reputation from their institute called the Shemyakin Institute that they were the leaders in the field of synthesizing decapeptides, peptides, octapeptides, etc. They were the authorities. And they published a paper about valinomycin in Science in which they said that this was the only way that uncomplex valinomycin could be found. When we determined our structure by direct methods, we found a different conformation. We found a conformation that seemed to suggest what uncomplexed valinomycin would look like. And that we had a mechanism for ion capture based upon our structure coupled with the heavy atom structure that had been previously reported. And Science was very pleased to publish this paper in which we were able to state that the Russians were wrong about this. I had no idea at the time. I thought it was the science that was valued. What was valued was the anti-Russian aspect of our work. So, Science was happy to publish something critical of Russian work.

And it’s only in the last couple of years that I’ve thought this through. Ovchinnikov, who was a vice president of the Russian Academy of Sciences, came each year, or every other year, to meetings in New York of the Peptide Society. I saw that he was coming to the Peptide Society and so I wrote him an invitation and I said, “While you’re in New York, could you come to Buffalo and give a talk?” And he said, “Sure.” He would come. I didn’t know he was the vice president of the Russian Academy of Sciences. I only know that he was somebody who worked in the spectroscopy of valinomycin. When he arrived, we had a reception for him. I picked him up at the airport and brought him to my house for the reception. And offered him wine and, “Would you like white or red?” “Red, of course.” He was a handsome, tall, wonderful man. And he was just very gregarious. Enjoyed coming to the U.S. Would go back to Russia bringing magazines, comic books, whatever, to his people there because they were interested in getting U.S. stuff.

So, the next day Ovchinnikov was to speak. I had him in my office interviewing him to do the introduction. He tells me he’s the vice president of Sciences. He tells me this, he tells me that and I’m really thinking, “Oh, this guy’s really important. I didn’t know all these things.” By the time we go downstairs to our very small seminar room, the hall was clogged with people from Buffalo all of whom knew who he was even though I didn’t know who he was. So, he got a good audience, made his presentation. Then he went to lunch with Herb and Edie Hauptman and my wife and I, and at the lunch he invited all four of us to come- he would pay all expenses for us to come to Russia. And that he wanted to start a collaboration with us on methods of structure determination. He had wanted to start this collaboration with Jerry Karle at the Naval Research Lab. But that was impossible because he was from Russia. So, he was unable to take up the collaboration with Jerome Karle that he hoped to do, and he had to settle for us. So, he went back to Russia. He purchased five, at the time it was a Syntex diffractometer. He purchased five $50,000 diffractometers and put them in five institutes in the Russian community. And then when I visited later, he had me go to each of those places and give talks on how to use the data. Meanwhile, he sent another colleague of his to us. First of all, he sent this guy to Syntex. These were Syntex diffractometers at the time. He sent a guy to California to learn how to use the diffractometers. So, Vladimir Pletnev was designated by Ovchinnikov to be the person who knew how to collect the data. And then he sent him to Buffalo to learn to be the person who would solve the structures using the methods we used at HWI. So, that was the basis that built up the new modern crystallographic capabilities of Russia. All going back to a single paper on valinomycin. In the front of the institute in Moscow which I’ve visited on more than one occasion, there is a huge iron statue of valinomycin.

And along one side of it, is the place where Linus Pauling and Dorothy Hodgkin planted trees. The trees haven’t survived, but the monument has. And Pletnev, although there were some ups and downs, is back at the Shemyakin now where he continues to run the crystallographic group. Oh, we’ve had controversies with them about the conformation of valinomycin, yada, yada, yada. No point in going into that. But this was how I got engaged in more international activities. And in particular strong- Vladimir Pletnev is a good communist, but I think he basically has a belief in religion that he hid all the while until communism collapsed and he could go back to church again. Which disappointed me because I didn’t see why he would want to go to church! Anyway, Pletnev is one of the people in the scientific community that I have the greatest confidence in. And trust. I would like to trust all the collaborators I’ve ever had, but that’s not realistic.

Zierler:

Bill, I want to go back a little in the chronology and talk about your work at SUNY Buffalo. So just to be clear, when you joined HWI in the late 1960s, SUNY Buffalo was not part of the consideration? This was separate?

Duax:

Yeah. I came to the Medical Foundation of Buffalo.

Zierler:

Right. And so, when did you join, or when did it occur to you that this would be a good thing for you to pursue? An appointment at SUNY Buffalo?

Duax:

I contacted people in the medicinal chemistry department because again, they were developing medicines. I met people in the medicinal chemistry department, and I got compounds from them and I determined crystal structures for four or five members of the medicinal chemistry department. So, I started doing crystallography for one department of the university. And also, because Roswell Park had an affiliation with the biochemistry department of the university, the valinomycin structure came from someone over there who gave me that compound. Someone at Roswell Park who was also in the biochemistry department at the university. So, those came together. In the medicinal chemistry department, they ran an annual symposium on topics of medicinal chemistry. And they would bring in eight or nine scientists to talk for three or four days. And I had become an adjunct member of that department. I offered to run the symposium one year. When I did that, when I was the chairman of that session in…[leafing through papers] the date of it is in here somewhere. It was the twenty-fifth annual meeting. And I said I would run the meeting and it would be on using structure to do drug design. [looking around office] Sorry for this. The twenty-fifth annual meeting of the medicinal chemistry department in June of 1984. I redesigned the program and entitled it Recent Advances in Techniques for Drug Design and Confirmational Analysis. HWI had nothing to do with this. This was entirely done in the medicinal chemistry department. I invited thirty-nine world leaders in the field, appointed session chairs, and allocated only thirty minutes to each speaker. The speaker’s list remains impressive thirty-five years later. I used a rubber duckie as a timer and the duckie never had to quack. If the duck came out on the podium, they would pretty much stop in five minutes or the duck would start to quack. I still have the duck over there on my shelf.

That reminds me, I noticed that in Helen’s there were no figures running down the column. I will want to put figures throughout this, after we get the final copy. I will put the appropriate figures.

Zierler:

Certainly.

Duax:

So, the speaker’s list, they followed the rules. I contacted Olga Kennard before the meeting and told her that she had to send someone to show these people coming to this meeting how to use the database so we could promote wider distribution of the Cambridge Database. That they could use it in designing drugs in these various pharmaceutical companies. After I became an adjunct member of the medicinal chemistry department, I had contact with a lot of people from medicine. By going to these annual meetings, I met all of these people from drug companies and I already had distributed the database to some of them but there was a huge audience that wasn’t getting them. I solicited support from fourteen corporations, had ten stations in the exhibited hall, an evening of computer films, thirty-eight posters and a banquet at the Albright-Knox. So, it was a very splashy meeting. Very successful. It went on to the point where the subscriptions to the database rose very nicely. Somewhere in here- [leafing through papers].

Anyway. So that’s my connection with the university. Then when the Hauptman-Woodward became the site of the structural biology division of the medical school, so the medical school took on the structural biology department as a member of the medical school and they offered us two salary lines were promised. They gave two and promised four more. The four more never showed up. But the two lines that they gave to us for the structural biology department were divided into thirds. That’s how I became a third of a full professor. Bob Blessing a third and Vivian Cody a third. The other thirds, one third went to Herbert Hauptman, one to George DeTitta, and one to Walter Pangborn. All three of them- well, Herb died. The other two have retired from their positions. But Bob, Vivian, and I retain our one third of a position which is a nice piece of change. A university professor at UB is now making about $150,000 a year. I have no trouble making ends meet on $50,000 a year.

So, that was a final complete affiliation for me with the university as one third of a full professor. Over the years I had graduate students. I had Bobby Huether, one graduate student. I had a master’s degree student. I had a postdoc come in. But I think I’ve only- I know- one, two, maybe I’ve had three students over the full time. But I’ve had good collaborations here with other staff scientists. My student Bobby Huether needed to be trained in protein crystallography. He came to me out of a computing program position at the university. And he was not doing well at that. But when he started analyzing the evolution of proteins, he became much more interested and then decided what he needed was more than bioinformatics. But he needed basic crystallography as well. So, he took up doing x-ray crystallography proteins under the supervision of one of my colleagues and got his degree. And that, too, was very helpful because when he went out to get a position and could show that he was experienced in protein crystallography and bioinformatics, he got a $4,000 signing bonus. They gave him a higher salary than any of their other starting postdocs. First year starting postdocs. And he’s gone on to have a successful career, moving more and more into bioinformatics. He’s in a laboratory in Chicago right now. So that turned out to be a good additional…again and again, it’s clear as when we talked earlier about an MD-PhD or bringing together different disciplines. Skilled in more than one discipline is a very important factor in today’s scientific community.

Zierler:

Bill, it sounds clear. Even if it wasn’t part of the original plan coming to Buffalo, that this appointment at SUNY Buffalo was absolutely critical for your own research.

Duax:

Yes. Every step, I can look at the connections. I’m fortunate to have a fifty-year connection with crystallography, that I have never had…it’s always been at the center of my research and my activities. So, the research went on and my involvement in the ACA, the International Union of Crystallography, the Cambridge Database. All of these things grew naturally out of the focus here at the Hauptman-Woodward on crystallography that really was established very early on with the endocrinological applications. The Cambridge Database…there was a point at which Olga Kennard, she wanted to distribute the database and she indeed sold copies of the database to every nation that could afford it. She did all the work of gathering all of the data on all solved single crystal small molecule structures into the Cambridge Database.

At the same time, we had begun to do the same thing with all of the steroids, so that eventually we published two atlases of steroid structure in which we present a comparative analysis of all the steroids and then an introductory section to help endocrinologists understand the information that was in steroids. So, they could understand the difference between an estrogen, an androgen, by looking at this atlas of steroid structure. Well, Olga was very complimentary of our doing this compilation of a subset of the single crystal data, the subset of steroids. She was doing everything but found that we learned from each other. And then when she was needed to support the database, she offered it for sale to different countries where crystallographers were who could use it. England did not have to pay anything because they had provided the support to her lab to get the Cambridge Database organized. She distributed it to the academic community, and I think it was the NIH that paid the subsidy. The NIH had some staff who were to provide a copy of the database to any academic in the U.S. who wanted it. But they weren’t getting the job done very effectively. And Olga needed to distribute to the for-profit community, and she wanted to charge them $5,000 a piece for giving them the database because they had made no contribution to it. Any of their crystallography was held in secret. It was not provided to her. So, Olga wanted to sell it to them, but they were all using Fortran and in England, in Cambridge they weren’t using Fortran and we met at a meeting and she said, “Do you think you could distribute the database in Fortran?” And I said, “Yes.” I didn’t know if we could, but I felt confident that Chuck Weeks and Steve Potter would figure out how to translate the database files into Fortran. And then my very good colleague Phyllis Strong would make copies and send them out.

So, we immediately began distributing copies to the for-profit community, charging them $5,000. And Olga let us keep $1,000. But each year, the price went up. She got more money from the drug company for a copy and she paid us less for making the copy. That’s the way finance works. And Olga was brilliant at it. Eventually, the academic community in the U.S. learned that we were distributing copies of the database in an effective manner. And they were willing to pay us $500 per copy instead of waiting to see whether the NIH would ever get around to sending their copy. So, we began being the distributor to the academic community and was another source of income for us. That went on for a while until Cambridge decided they could do everything from England and cut out the subsidies that they were getting from countries or subsidies from us for the for-profit community. So that was the end of that source of revenue. But each time there was a loss, we would scramble around and figure out where do we go from here? But it’s always been connected with crystallography one way or another.

Zierler:

Bill, I wonder if you could talk more broadly about some of the advances that have been made in steroid structure over the years? What are some things that were big question marks when you got involved? What’s understood really well now? And what might be some ongoing mysteries with regard to steroid structure?

Duax:

The first steps were we had this model for a steroid function proposing that the A-ring bound to the receptor and the receptor changed shape, stabilized by the D-ring. So that was our A-ring binding D-ring model. But you couldn’t really test that model unless you had crystal structures of the receptor. So, it was essential that we move, at HWI, into protein crystallography. And I went to England and spent some time getting some basics, but I never really learned to be a bona fide protein crystallographer. I learned more about it and what was going on, but when I came back to Buffalo after a sabbatical, I hired a trained protein crystallographer, Debashis Ghosh, to work on protein structures here.

Even at that time the receptors were not isolated and purified well enough to be able to undertake a receptor structure. But there were a number of enzymes that modified metabolized steroids and they were the dehydrogenase enzymes. So, there was a number of dehydrogenase enzymes being studied that could be purified. So, Deb Ghosh purified and crystallized and gathered the data for a couple of steroid dehydrogenases and for a cholesterol enzyme. So, we had three different enzymes that we worked on and solved. I played little role in any of these determinations except for the first dehydrogenase where I did make a minor contribution from my knowledge of symmetry relationships. There were four molecules in the asymmetric unit and there was only a certain way that those four could be present. Dorothy Hodgkin made some early observations based upon the cell dimensions of cholesterol that refuted prevalent…what was believed to be the structure at the time. She said, “The structure that you’re proposing can’t possibly be fitting into a cell dimension of this shape.” So even the cell dimensions are valuable in how they can show you how multiple molecules can come together. At any rate, in this case with the dehydrogenase, we solved the structure, and this actually led to my ultimate interest in the gene bank and trying to improve the gene bank. Because we found that our dehydrogenases were members of a family that could be traced back to the earliest bacteria. So, this was very revealing. Again, it was pattern recognition. We saw in these dehydrogenase enzymes a pattern of amino acids that was a threonine-glycine-XXX-glycine-X-glycine. This arrangement of a threonine-glycine separated from a glycine-X-glycine was present in every one of the members of this family and not in any other protein in this family. This was a signature for what turned out to be one of the most primitive Rossman folds.

The Rossman fold was one of the first crystal structures ever determined by a man named Michael Rossman. One of the first protein structures, about the third protein structure. And Rossman saw this fold, saw how stable it was. It was an arrangement of beta strands into a beta sheet surrounded on either side by alpha helixes. A nice compact group of globular structure that Rossman said will probably be seen again. It was. It was seen again and again and again. It is the protein fold that is most common in the entire protein data bank. Over time, this Rossman fold had the core in common, but there would be strands that would stick off of it. Or there’d be an extension to the one terminal or the other. There was elaboration on this Rossman fold, but the fold was there. And so, we were able to trace the evolution of the protein having the pattern TGXXXGXG all the way back to the earliest bacteria as a beta-keto acyl carrier protein reductase that is critical to membrane components in all bacteria.

So, here was a strength of pattern recognition being able to define all members of a family. And that family turned out to be the most primitive Rossman fold. It had less stuff hanging off of the edges as shows up in later Rossman folds. With that ability, I tried to persuade people that you could evaluate this entire family. People wanted us to do additional crystal structures of dehydrogenases. And we would look at the sequence and we would look at the structure and we’d say, what are we going to learn by doing another one of this for which we already have good examples in an entire family defined? We should be working on problems that have yet to be fully defined. That gave us insight into two things. One, our ability to align an entire family and two, how once you align them and break them into families determining exactly how many families of different proteins are in the entire gene bank. Right now, the estimates range from low estimates of maybe 25,000 different families to high estimates of 50,000. But that’s better than the millions of structures that are occurring in the gene bank.

So, by using bioinformatics, family tracing, pattern recognition, we should be able to take the gene bank and break it down into fifty families that covered it all. Fifty models. But I was trying to persuade people by showing them the consistency in the steroid dehydrogenase family going back to the beta-keto acyl carrier protein reductase in bacteria and realized that I would be on safer ground if I looked at the ribosomes. Because the ribosomes are present in every species. Trying to establish an evolutionary tree goes back to the time of Darwin. Darwin drew his idea of an evolutionary tree. The separation of the plant world from the bacterial world from the eukaryotic world. Another guy whose laboratory I visited in Germany, Haeckel. Haeckel had a lot of ideas about evolution a hundred years ago and he drew trees. And I’ve shown these trees to my students and we were trying to come up with a tree based upon the ribosomal proteins.

Once DNA became recognized as having the information about the sequence of all proteins. Woese tried to take the DNA in an early stage and see if he could see separations between the DNA of eukaryotes and bacteria. And he was able to separate eukaryotes and bacteria, but he had a small subset of data for which DNA was available…genomes were available, and it didn’t fit either of them. So, it seemed the sequences looked somewhat what like the RNA, he was using RNA. He had sequences that looked somewhat like the RNA of the bacteria, but they also looked like the RNA of eukaryotes. And so, he said, “These are the archaea. These are the oldest species and they are the base of the evolutionary tree.” Although his idea that they were at the base of the evolutionary tree has been refuted, is no longer accepted, the archaea appear to be along the evolutionary lines of the eukaryotes, not the bacteria. They seem to be distinguishable from the bacteria. Because when you look at protein families, you’re dealing with families that have twenty different amino acids. In higher degrees of variability. When you look at RNA families, you’ve only got four characteristics to look at. So, you have a harder time creating an alignment based upon lining up just four pieces that appear again and again in a variety of arrangements.

So, the proteins were a better way to do alignment. And once enough proteins were available, people tried to use families of proteins to define evolution. People would look at all of the drosophila and all of the mammalian. But they never looked at a protein present in every living cellular species. Ribosomes are found in every cellular living species and every ribosome has numerous protein families on its surface. By creating a vector that aligns all members of each ribosomal protein family in the genebank (over 30,000 genomes) we can define an evolutionary tree for each family and examine the trees for consilience. We have aligned the twenty ribosomal proteins of the small subunit of the ribosome. In the families of each of the twenty ribosomal proteins we find positions in which glycine, proline, alanine or arginine are fully conserved in all 30,000 of the aligned proteins. On the output they look like long, black lines. And my students like it when I say, “Black is beautiful.” Because when we have those long, black lines, it means we’ve properly lined up 30,000 structures. And if there is a sequence in there that is wrong, it will show up as a white line running horizontally across those vertical black lines. And I call that “white trash.”

Zierler:

Black is beautiful and white trash, huh? (laughter)

Duax:

Yeah. And that has been appealing to my students of color. But only one of them has ever used that terminology in her presentation. And she is a wonderful, young woman who received the Martin Luther King award from her school upon graduation and has received other awards since. She’s a fine, young woman.

Zierler:

Bill, maybe this is an obvious question. But can you explain the value of taking an explicitly evolutionary approach to these inquiries?

Duax:

I’m happy to look for other data that supports or questions. This is a technique that we have developed that we feel is effective. So, that’s why we pursue this. I think that for one thing, I am very pleased to be teaching evolution to these students. I had a question from an audience once when we were making a presentation. And the student said, “But isn’t evolution just a theory?” And I said, “Well, we don’t address the question of whether it’s a theory. We just show how it works. We show the details of the evolutionary process.” When you can line up 30,000 structures from the earliest bacteria that extend over a three-billion-year time, then I think you are providing evidence of the evolution of everything. I don’t know that that answers your question. I can rephrase it.

Zierler:

Absolutely. It’s beautiful. No. It’s a beautiful, simple, and elegant response. Bill, I have another broad question. Can you reflect generally on some of the technological advancements that have been made in crystallography over the years? And how that’s improved both the research and the discovery?

Duax:

The process has been accelerating. The programs are stronger, are powerful. The computers run faster. The data collection is faster. My first data I collected on film and had to look at the film and say, “This spot is stronger than that spot.” You had to make a way to analyze all of those spots. And then the automatic, the Geiger counting techniques. When I was collecting a data set, I came to Buffalo. I was so delighted with this much more powerful technique. When I used the counting device in Baenziger’s laboratory- well, for carbon disulfide I collected every spot twenty or thirty times. And so, when I collected those twenty or thirty, I could average them. And when I averaged them, I could get an accurate standard deviation for every one of my measurements. That was all very important at the time if I was gonna talk about thermal motion in these crystals that I was growing. I had to learn how to grow them. I put the carbon disulfide in a capillary and my boss Baenziger had figured out how to take a source of liquid nitrogen and bring it on to the capillary. And the capillary would become filled with power crystallized. Then I would dial the cooling machine slowly back until there were only a few at the tip of the capillary. Then I’d dial it slowly on and a single crystal would form. So, that’s how I got the single crystals.

Actually, I tried for about three weeks. And I went into Baenziger’s office and I said to him, I was getting nowhere, I said, “Are you sure this can be done?” And he said, “Yes.” So, I figured, well it can be done. I’ve got to be able to do it. So, I went back in the lab. I figured this way out of getting the single crystals and then gathered the data. Then figured out I had to have cross data. I found out that depending upon the size of the capillary, the same crystal form would crystallize in different directions. It was influenced by the curvature of the capillary. So, I got the data. I was able to solve the structure. But I said to Baenziger, “When I asked you if it could be done, how did you know?” He said, “Well. I knew it could be done. I just didn’t know how long it would take you” (laughter). So, he just had confidence that somehow, I would figure it out.

There were some stray lines in the pattern. I figured out those were ice lines. That led me to have a better understanding of powder patterns. That helped me when I went to Abe Clearfield to work on the powder of these ion exchange things that were useful to him. But, I strayed, as usual. Your question was really about technological advances. So, we’d go from that stage of measuring the data off of film to right now, any structure up to 150 atoms could be solved in a day. Getting the crystal may take, may be the stumbling block. How do you get that crystal you need to put it on the diffractometer and then collect the data and put the data into the structure solution program? And now there are programs that will write your paper for you. I got to the point where each steroid structure could be followed by a certain pattern. And in my ribosomal protein work, each of the ribosomes will have its own paper. And there will be some things in common between them. But each ribosome has its own story to tell of the evolution of the ribosome. We can identify, almost certainly, that one particular ribosomal protein from the small subunit, S9, had to be one of the very first because it plays a critical role in the function of connecting the transfer RNA, the messenger RNA, and the ribosomal RNA, so that the new protein could grow.

So, I’ve told my students, “You’re all going to have to follow this motif, but you’ve got to find where your ribosomal protein shows itself for its specific function.” It’s been considered after the ribosomal structure was determined and it was discovered that the protein synthesis is taking place primarily around the ribosomal RNA, the transfer RNA, and the messenger RNA, is the point in which we really go over into the RNA world. Where people come to the conclusion that RNA was really there before DNA. And that the earliest proteins were produced without DNA. And it was an RNA world. I do not- our data does not confirm that, nor does it refute it. Our data does refute many things, such as the textbooks in high school and many textbooks still say that methionine is the first amino acid in all proteins. My students know, have proven to themselves, that that is not true. That at the earliest proteins in the actinobacteria, which go back and include tuberculosis bacteria- bacteria in single membrane proteins, the earliest proteins had only a single membrane. And in the course of evolution, after about a thousand years of there being nothing but proteins with a single membrane, we get proteins with a double membrane.

And that transition from single membrane to double membrane hasn’t been pinpointed exactly, which single membrane protein gave birth to the first double membrane. But we think that our analysis is a device that may help figure that out. At any rate, we then find that when we look at the very oldest of the single membrane proteins, which are the actinobacteria, and we look at the sequences of all of the ribosomal proteins in the actinobacteria, many of those ribosomal proteins do not begin with the methionine start code of ATG. We look at the sequence of the proteins and then we look at the sequence of its DNA. And we see that some of these proteins do not have the signal for methionine. Not only do they not have methionine ATG as their start code, they don’t have ATG anywhere in their sequence. So, they are without a methionine. Not only that, but if we look at the entire frame, you can read a piece of DNA six ways. Three ways on the coding strand and three ways on the anticoding strand. So, when we look at the coding strand of these early proteins that do not start with methionine, they don’t even have ATG in the coding strand. So, there is just no ATG yet. That codon has not entered into the repertoire when these earliest ribosomal proteins of actinobacteria first appeared. So, we can show the methionine was not always in the genetic code and we can determine whether it came in as a start code or if it came in as a member…just a residue in the sequence and later takes over the start code position. The start codes in the earliest are either GTG or CTG, which is valine or leucine. So, we are able to evaluate and determine how many of the earliest actinobacteria started with a valine, how many started with leucine, what was the real starting signal, and when methionine first appears. I see you’re smiling again so I think I’ve done that one.

Zierler:

Absolutely (laughter). No, no, no, no, no. It’s fascinating. No, no. Don’t read incorrectly into that (laughter). Bill, can you talk a little bit more about the development of the Cambridge Crystallographic Database? In what ways have you gotten, sort of, real satisfaction from the research abilities that this database has created?

Duax:

I haven’t used the Cambridge Database in years. But, when we did use it, it was very important to- it’s a little bit challenging in this case because most of my research has been steroids. And we’ve gathered all the same data for steroids. The Cambridge database has some programming, and that’s grown over time. Of different ways to analyze it, different ways to extract information out of the database. It isn’t a matter of just having a database. Helen says the same and the same is absolutely true of the Protein Databank. The databank is one thing. How to use it is another. Bioinformatics people have the skill to develop programs to analyze it, but they don’t have the knowledge of the structural information that’s in the database to figure out how to design those bioinformatic programs to use databases such as the Cambridge Database and a Protein Databank. Because we were doing mostly steroids, I didn’t have recourse to using the Cambridge programs. Plus, they’ve really grown in time as we evolved into doing the proteins. So, our use of databases for purposes of comparison or connection became stronger with the Protein Databank than it had ever been with the Cambridge Databank. But I know how valuable it is to the community. Part of my life has been to serve the community. So, we continue to receive copies and finally we said, “There’s nobody here to use it and we’re no longer in strong collaboration with anyone who is using it.” So, it’s probably been ten years since we’ve made real use of the Cambridge Database here. But that doesn’t in any way negate its value and importance to the community. And particularly to non-crystallographers who wouldn’t know what to do with the data. And hopefully the software that Helen has developed with her group, and Olga’s group have developed, has been very important to non-crystallographers being able to make use of the data. For drug design. Understanding function. Whatever.

Zierler:

Bill, I’d like you talk a little bit about your involvement with the ACA over the years. You know, first as a member of the field and then in your ever-growing official capacity.

Duax:

I went to ACA meetings very early on. I can remember being…one of the people who so impressed me at ACA meetings is Isabella Karle. Who worked at applying the methods that Herb and Jerry developed and Jerry continued to develop. And she would give wonderful talks. Someone in South Africa would send a sample of a frog toxin. I remember one of the talks that I heard her give was about this toxin off of a- she showed a picture of the ugly frog and then she purified the toxin, got the crystal, solved the structure, and talked about what this toxin looked like. And she probably compared it to whatever- there weren’t that many toxins known at the time. I was blown away with her delivery. She had used direct methods to solve the structure. She was very, very- Jerry and Isabella used something called symbolic addition to solve structures. And she taught a lot of people how to use symbolic addition. She would sit in front of her television half watching the television and half doing symbolic addition. She was a great- she spoke beautifully, and she taught well. And she taught the community how to use symbolic addition.

Michael Wolfson and company wrote programs to automate structure solutions that was called MULTAN. And at the time the Nobel Prize was awarded to Herb and Jerry, there was a lot of controversy as to whether Isabella should share, or whether Michael should share. But the Nobel Prize can only be given to a maximum of three people. I have written editorials criticizing that as saying that that’s a divisive thing. That it should not have been limited to three people. It should be whatever is the appropriate number of people to acknowledge for what was done. Because in the case, Jerry and Herb were identified as the people who were responsible for the theory. But even when you identify the people involved in the theory, there’s a third person who developed the tangent formula. And that was David Sayre. David Sayre was in England. He developed the tangent formula. He also was one of the developers of FORTRAN when he was working in the U.S. And David Sayre’s contributions were critical to Herb’s ability to evolve the theory of structure determination. And Sayre always called it the tangent formula; he never called it the Sayre equation. The rest of the world called it the Sayre equation. But he was hurt when the prize went to Herb and Jerry. And Isabella was hurt. And Michael Wolfson was hurt. And their supporters and followers were all very much, it damaged their relationship among all of those people.

Zierler:

What was so serious about this? What do you think exactly caused all of these feelings?

Duax:

The fact that Herb and Jerry were given this award which seemed to give them full credit for direct methods and seemed to ignore the contribution of others who made critical contributions was recognized by the community at large.

Zierler:

Do you think the way that the award was accepted, that the recipients might have done more to emphasize that the collaboration was in fact, much larger than the recognition?

Duax:

That would have been a good idea. But that isn’t the way things went until Ada Yonath got the Nobel Prize for the ribosome structure.

Zierler:

Yeah.

Duax:

She was in competition with two other people. They acknowledged how wonderful…each of them said how wonderful they were having done this. Ada Yonath brought her entire team together behind her and said, “These are the people who did this.” She very graciously acknowledged the support of all of her team of people that worked with her. Ada is a wonderful example of a Nobel Laureate. When Ada grew the crystals for the ribosome, there were a lot people trying to grow the crystals. Ada grew the crystals. She let it be known how she grew the crystals, and everybody jumped into the game and the other two were Venkatesan, who was an Indian working in Cambridge, and the third person was in the U.S. supported by Howard Hughes. And Cambridge and Howard Hughes put plenty of money into catching up with Ada. And one of the MD-PhDs that I admire, Paul Sigler, was very concerned that Ada was gonna lose out. But the British gave their annual award to Ada in recognition of her growing the first crystal. And so, the race was on. And fortunately, Ada was able to solve the structure as well as Venkatesan. Venkatesan went on to be the first Indian to be the president of the Royal Society, which is a very good thing.

Zierler:

Right.

Duax:

Because in the U.S., we had strong support from the Indian postdocs in the ACA, but they were never given a leadership role until Rao, our treasurer, and later CFO, became treasurer. That was the first time an Indian scientist was given a significant role in the management of the ACA. Prior to that, when I became president, I asked one of the leading Indian scientists, Sundaralingam, who was a collaborator with Helen Berman, if he would be the chairman of a committee to choose a prize winner. And Sundar was ecstatic to be asked to be on the committee to choose a winner. If he had won the prize, he would have really been ecstatic. But he was just pleased that as president, I for the first time asked a member of the Indian community to take responsibility for chairing an awards committee. That I gathered photographs, even before I became president, I would take a camera to ACA meetings and I took pictures of everybody. Husbands, wives, children, everybody. And I would take upwards of seventy to one hundred pictures each year. I would have them developed and the next year I would bring those pictures back and give them to the people in the pictures. So, I got a reputation as a guy who will give you pictures. Paul Sigler said that all the best pictures he had from ACA meetings came from me. I did the same thing all my life with other gatherings.

So, my involvement with the ACA, I started out going to the meetings, enjoying the presentations. I went to sessions in which I saw Hauptman and Karle being badgered and ridiculed by David Harker and others until the Nobel Prize turned that all around and people who wouldn’t pay any attention to his research wanted to learn how to do it and the schools for direct methods started. But that was later. At the ACA, when I ran for president and won, I immediately, I was at HWI. I looked into what was going on. The ACA headquarters was at the AIP in New York, near the United Nations. And I went down to see what was going on. We had our headquarters there. We paid for an office and maybe a little storage space for five days a week, monthly payments. We had a secretary who came in for a half a day and changed her shoes and then changed them again and went home. On her desk there was a stack of correspondence that had to be at least a foot and a half tall.

As soon as I was president, I started a membership drive. Six months later, nobody had applied for membership and I couldn’t understand it. So, on the desk of our secretary at the AIP, on the top was a letter from someone complaining that they had applied for membership two months earlier and hadn’t heard anything. Well, further down in the pile, I came across that application. So, all applications for members, etc., just accumulated on the stack. The woman who was running the office would come in. She’d look at a few pieces of correspondence on the top and begin to work her way down, but her one day wasn’t enough time to deal with all this correspondence, which wasn’t even sorted. It was merely stacked. But if she had an application, she could put the application in this corner of her desk, and someone would come and take it away. But the stack accumulated.

The next time I went down to New York at the AIP, I tossed everything into suitcases, brought it back to Buffalo, hired a halftime secretary, and we went through the correspondence. And very shortly, I persuaded the membership that we did not need to have an office in New York. People in New York said, “How can you run an office in Buffalo? Out there in the sticks? It’s much better to run it in Washington, D.C. or New York, where we know how to do things.” Another constant message. I’d been at a meeting where I’m giving a talk. International invited meeting. One of the speakers says, “Why are you in Buffalo?” And I said, “Well, I have a wonderful opportunity in Buffalo. It’s great. I can do research…” “Yes, but why are you in Buffalo?” It was like denying Christ three times. Three times the guy- then I realized he’d meant, if I’m any good, why the hell am I in Buffalo?

Zierler:

Right.

Duax:

Baloney. So, I brought the office to Buffalo. And we have worked it out to where we can have a full-time secretary. Before we had a full-time secretary- what did happen in New York was the newsletter got prepared. So, we started doing the preparation of the ACA newsletter in Buffalo. We still used some of the facilities of the AIP. They were very good at helping us with production. Putting together the product. And working on the distribution. But they were not good at raising income. They didn’t know our advertisers. Our advertisers didn’t know them. Actually, they never did any of that for the ACA. What I just described they did for the IUCR. For the IUCR newsletter. For the ACA, we just transferred the newsletter preparation into Buffalo.

We eventually had two people working. The other thing about having a secretary in Buffalo…prior to that, annual meetings and ACA business were all handled by the counsel. Which met twice a year. There had to be two meetings a year, so that the counsel could meet twice a year. I was the person who first suggested we go to one meeting a year because we need to have opportunities to go out to the community and should not have to spend two meetings a year doing nothing but crystallography. We would benefit by having one meeting where most of the members would attend. We’d do the business. But the counsel was unhappy because that meant they would only be able to meet once a year and not twice a year. Crazy. Eventually, they figured that out. And it was about four years later after I made the first proposal that Philip Coppens, again, as president, made this proposal and we went to one meeting a year. But the reason they had to meet, it was they had to do all the planning for the meeting, anything that the ACA was doing required them to make decisions. Cause there was no executive officer, there was no secretary. There was nobody above them. And their composition changed from year to year. So, there was no continuity. Many things had to be reinvented every year or every two years as there were changes. So, by getting a full-time secretary, that secretary at my direction was able to take on all of these planning exercises. Where we should hold the meeting and we began to have long range plans for the organization, the meeting site, etc. Marcia Vair was the first full time secretary and she was fabulous.

She took on more and more responsibility. Her salary was compensated appropriately, even though she didn’t go to college. And some of the council members were upset that she was getting a higher salary than their secretaries. I had to make it clear exactly how innovative she was and exactly why she earned the salary and they always supported the salary increase. But they resented it. So, you learn how to deal with people and how they express themselves.

Zierler:

Yeah.

Duax:

So, Marcia Vair took over the office. At times we had more than one person in the office and we’re now back to two full time we went to having two most of the time. There was a third person for a while, but we’re now to two. And with the pandemic, we’ve just gone through the first distance program. First, what we’re on right now. Zoom meeting. And it was successful. Just as my Zoom summer school was successful. Because, whereas previously, I only had students coming physically from the immediate area, except for one person from Toronto who talked her father into taking a room at a local hotel and he lived in a hotel for three weeks so she could come to the summer school at HWI. Now she wouldn’t have to do that by Zoom. We had two students from California, one from Oregon, and two from Boston. So, we have an international program in evolution of proteins.

So, the ACA now has evolved to where it’s going to hold Zoom meetings as long as necessary. After, we were successfully based in Buffalo and were recognized as the center for crystallography, headquartered in Buffalo. Which is a major center for crystallography itself. The next step was I was approached to edit a newsletter for the International Union of Crystallography. And this is the first time the union would have a newsletter. The staff of the International Union of Crystallography has a substantial staff in England that is responsible for all of the publication of its journals. And many other things. They did not feel they could take on this newsletter. So, I was pleased to have the offer to run the newsletter out of Buffalo. Andre Authier, the then president of the IUCR called me one morning and I had just gotten out of bed. And he asked if I could do this. And after consideration, we had an exchange of correspondence and came to the conclusion that I would undertake this with the assistance of the AIP.

He had wanted to use a publisher such as Springer. But AIP, from my association with the AIP, growing out of my ACA position, I knew that Springer was not the partner I wanted to work with. I trusted the AIP. I had been going to AIP meetings for years as an official representative of the ACA. Even before I was president. I was on the committee that selected the site for the AIP headquarters outside of Washington. Which was initially, I thought, a good location. But it hasn’t prospered as well in its location as it might have, had it been located more approximate to downtown Washington. Some of the people who originally shared offices in the AIP building have moved into other quarters in downtown.

So, the ACA affiliation offered me the opportunity to learn the benefits and the power of the AIP. And the AIP was the right choice to help me get the International Union of Crystallography’s newsletter publication up and running. Eventually, as I started to say earlier, they weren’t particularly good at raising advertising funds. What they were charging for the advertising was so much that it didn’t leave much profit to the IUCR itself. So, I felt we could probably do the advertising out of Buffalo. We continued to do the production and mailing for another year, and then with their help, made contact with the people that they use for printing and distribution and began to use them from Buffalo. The advertising turned out to be a smart move because we were sending the newsletter to all the crystallographers in the world. This is the International Union of Crystallography newsletter going to all crystallographers in the world. Not only those who were in the world directory that the International Union provided, but we were going to all the meetings that crystallographers were likely to attend. And we took those attendance lists. And we created a huge list of addresses of people worldwide. I went to a lot of meetings in Europe and brought back address lists for crystallographic meetings in Europe. So, we had this huge list that encompassed probably eighty-five percent of all the crystallographers in the world. So, anyone who is trying to sell a diffractometer is going to reach all of their potential buyers by putting an ad in the IUCR newsletter. It was much cheaper to advertise in the IUCR newsletter and you would reach your entire audience, than C&EN News and Science and Nature and everyplace else at a much higher cost. So that worked out very well to the success of the income to the IUCR newsletter. And eventually, the IUCR newsletter might have become self-sustaining. But eventually, these advertisers also knew how to contact everybody directly and advertise on the world wide web or other sites and avoid having to use hard copy advertising in principle journals or highly regarded journals.

So, we again were part of a trend, seeing things change. Watching the evolution of advertising, the evolution of marketing, and tried to stay abreast of what was going to be productive and keep the ACA solvent and alive. And the ACA’s endowment, when I took on the presidency, the endowment was about $250,000. Due to having successful meetings, a hard-working office, and a treasurer who’s financially brilliant (Rao). Our endowment is now over a million dollars. Which is still only a million dollars, but it’s better than $250,000 and gives us a certain level of more security. And the meetings, which were attracting about 200 people in the year I was elected president are now routinely attracting 600 people. And this Zoom meeting did have 600 people. And what’s been done is you don’t have to pay meeting registrations if you’re a student or an alumnus because if you’re paying membership, that’s fine. We keep our membership. We don’t lose our membership numbers. But we don’t have to be making charges that are only part of having a physical meeting.

So, that I think is going to be the next step in the evolution of the finances in the planning by the committee as to how will they go forward. A lot of people are saying, it’s unlikely we would go back to a physical meeting. That the Zoom meetings have so much advantage. You avoid high expense. You avoid use of gas. You avoid airfare. You avoid things that are not helpful to the economy or the climate or the environment. So, Zoom meetings are environmentally friendly, I believe. And are the way to go. You just have to figure out how to do them more effectively and more appealingly. I think that the Zoom Democratic Convention had several elements in it that were brilliant. The opening scene where all of these children from across all fifty states finally Zoom in to just faces in red, white, and blue on stars was one of the finest pieces of that. Also, the roll call where we saw the people in their setting of their background. In fields, in factories was a brilliant presentation of the scope of our democratic society. Okay.

Zierler:

Bill, given both all of your work at the national level at the ACA and at the international level with crystallography, in what ways does having both that national and the international perspectives sort of advance crystallography, generally?

Duax:

Crystallography’s been international right from its beginning. Very early on, it was not too long before there were forty members. Forty member countries. Over the course of my career, I’ve visited most of the forty countries. In particular, when I was president, I made a trip to South America because I specifically wanted to touch base with all of the members in South America. And the ACA had already begun a South American outreach program where we were trying to help South America to become in addition to the individual countries, the forty countries that are membered, members of the International Union of Crystallography. There is an ACA country membership and a European group membership, and we helped the South Americans to develop a group so that they have a South American association affiliated with the IUCR.

So, there are different ways that the IUCR is able to bring in people from all different countries and all different backgrounds into their commissions, into their committees, into their regional affiliates. And we hope there will be an African regional affiliate. There was a meeting of the African crystallographers that I attended a few years ago. I am pretty much reluctant to go to any more meetings, anywhere. Not just because of the pandemic, but because of my age and because of things that I still want to accomplish. But I would be interested to return to the African gathering if there is another it’s been postponed now, but I really felt that that’s an important place to be. When I was president, I gave a talk saying that the future of crystallography was going to be in Latin America and Asia. And Africa. And I believe that that is the case.

Crystallography allows you to maintain intellectual property rights to things in your country. Each country has its own ensemble of plants, insects, bacteria, all these things. When people came out of the United States and went into Mexico to gather material, steroid basic compounds that could be used as the basis for creating antiestrogens and progestins for birth control pills. They went into Mexico. They used Mexican yams to extract materials, steroid related compounds. Then they came back into the U.S., went to Eli Lilly and made the synthetic compounds that were used for birth control pills. If that technology had been retained and available in Mexico, birth control pills could have been developed in Mexico. Which would have been beneficial to the population problem in Mexico as well as the economy of Mexico as well as retaining their intellectual property rights to what they have. And when I went to the South American countries as president, that was one of the strongest messages I tried to bring them. Build up your crystallography. Preserve your intellectual property rights on everything that you can study and learn about.

So, the International Union continues, that’s its philosophy. It has all these commissions. And I as president of the International Union, was urging them to make sure they had gender equality in the membership of their commissions. Japan is still most likely to have all of its connections with the International Union via male representatives. Other countries have changed that. Portugal is one of the finest at having perhaps even a higher ratio of women representatives to the IUCR. Setting that aside, there is this effort to keep in touch with all the world community through its crystallographers. When I was setting the program for the Seattle conference of the International Union, I went into the council meeting and told them that my program committee was going to have gender equitable representation. The committee there, all men, told me that that was a mistake. That it should only be the brightest. You should only decide who’s on the program committee based upon who is the best crystallographer. So, I assured them that all the women that I would put on that committee were as bright as or brighter than any of the men that I would have on the committee. They would be good crystallographers. And that is how I behaved from then on. When I became president of ACA, I took the action of running two women for president the next year because at that point, I felt that women were underrepresented in leadership positions in ACA. So, I ran Helen Berman against Ann Kerr, who had been a former treasurer. And Helen won the election. And we continued to be friends and staunch advocates of crystallography ever since with occasional disagreements of opinion.

Zierler:

Bill, that’s a great segue. You mentioned, you know, there’s still things that you’re working on currently. Just to bring the narrative up to the current date, what are some of those projects that you’re working on and you have been working on in recent years?

Duax:

I’m very much a strong supporter of the Black Lives Matter program. I do not feel that I have ever been as successful with the development of minority leadership in the ACA or the IUCR as I was with women. Gender leadership. Equity. Because my wife and I have four children- our fourth child is an adopted Black child. At the time, it was an action that was not well thought out, but an action that has turned out to be very beneficial in the long run. Because it has sensitized me to what it is really like to grow up Black in America. I’m wearing this button about racism. I’ve been wearing this button for about three years now. My son gave me the first one that I wore and then I bought 200 and I’ve given away a couple hundred already. When people see me wearing this in a store or on the subway, they complement me and ask me what it’s about. I ask if they want one and if they say yes, they get one. One person thought that instead of “racist” it said- come on- on my forehead. Maybe I should wear it on my forehead.

Zierler:

I think that’s a little extreme.

Duax:

They thought it said “radish.” And that I was an anti-vegan. At any rate. I’m in two different speaking groups in Buffalo that have a forty- and fifty-year history. One of them still has only white, male members. It does not allow women or any minorities. There are no bylaws that say that; it’s just a fact. The other group had been all men, but they eventually began to allow women. They wanted the women to come because they wanted the women to listen to them. So, for a few years, the women didn’t speak. But now the women are speaking and they’re doing very well. So, at the all men only program, about two years ago, one of the speakers gave a talk and shortly after the Sandy Hook murder of children, the speaker decided it would be good to have a demonstration of weaponry. And brought about twenty guns into the room where we were gonna have the talk, including copies of the AK rifle that was used to kill the children. And thought that this was a perfectly fine presentation.

Subsequently another person gave a presentation defending why we needed Donald Trump’s wall. And I had to sit through that hour presentation. Afterwards, since I was already identified as the flaming liberal in the group, they turned and said, “Well, don’t you have any comments, Bill?” They were just baiting me wondering what I would say. I did make some comments and then I left the room. That was in a January. I spoke the next month. And I talked about my personal Black history. And described how I had grown up. How I was brought up to be prejudiced. To be a white supremist. And how my life experiences caused me to change and turn away from it. How by the time I got to college, I was determined. And after my wife and I married, that we really shouldn’t have children. We should adopt children because there were too many unwanted children in the world. And she cried and said, “Oh, you don’t want to have children with me.” But after she had three, she decided that adopting was not a bad idea because she was morning sick every day of the pregnancies. By that time, I thought, “Well, I’m having enough trouble raising three kids on my salary.” But she persevered and we adopted my son, Stephen.

Every step of the way has been a learning process. Finding out that people who did want to adopt a Black child, there were a portion of them who would only adopt a Black girl because a boy would carry the family name. So, who are these people who will raise a Black child, but don’t want their name to be born by Blacks? Those are the good people! (laughter) So, I’ve sent you a copy of my Black history thing. It goes into all of the integration of Blacks. The good Blacks were Aunt Jemima, who cooked you pancakes in the morning and Uncle Ben, who made your rice for you. And all of the servants. So, it’s a been a policy of white supremacy allowing for a few good Black servants if they behave themselves. So, I’m so happy with the Black Lives movement. And have gone carefully to a couple of demos. And I am quite pleased with…I’m one of these people who wasn’t really ecstatic about Biden. But I’m deciding I should pretend that I was because I don’t want in any way to jeopardize this ticket. I think Kamala Harris is terrific. So, that’s my political point of view. And I don’t know what I started on and then drifted.

Zierler:

(Laughter) Well, you’ve certainly gotten excited about sociological and cultural issues over the past few years. Bill, I think for my last question, I want to ask a forward-looking question. And that is, sort of, one that combines all of the many things we’ve talked about over the course of our discussion today. And that is, what are you most personally excited about in the field of crystallography looking to the future? And what are you most optimistic about regarding this historical moment that we find ourselves in with Black Lives Matter and including and increasing diversity and inclusivity in the field of science, generally? What are you most optimistic and excited about looking ahead in both of these realms?

Duax:

I think within the crystallographic community, electron microscopy is the wave of the current future. The ability to look at smaller and smaller crystals. To look at aggregates of where three or four molecules come together in order to have a function. That wasn’t possible until the last couple of years where we’re beginning to make inroads to that. So, I think that electron microscopy and smaller crystals, larger crystals, being able to follow reactions in the crystal. It’s been possible to do that for a while. But, to get better and better at being able to assemble things and then trigger a reaction and watch the reaction happen. So that we learn more and more about the dynamic properties. I don’t in general favor dynamic publications. But when it’s talked about as a truly dynamic reaction observable with crystallographic and electron diffraction evidence, I think that that’s exciting and will remain exciting. And will continue to open up, expand our understanding of how the world works. I guess my goal has always been to understand an explanation for the underlying reality around us. As I said, I think that Zoom meetings are a way of the future, being more concerned about the environment, our use of resources, our use of energy. All of that, I think, is where the future must carry us if we’re to survive.

Other points- I did not send you my philosophy page. And I have often made the comment that God and religion are evolutionary concepts that appeared after evolution of primitive man. Evolution went on for a couple billion years before man appeared, and it was a couple billion years of evolution before the concept of a god or multi gods ever appeared. And it has evolved. Afterlife is a fantasy that becomes appealing at the time of death to those who die. And to those who love and don’t know how to survive the loss. I’m currently in the process of surviving the loss of my wife and daughter. So, I feel very sensitive to this issue. The U.S. was founded on the basis of white supremacy with Blacks being identified as two-thirds of a human white. The earliest men’s clubs excluded women and non-whites from membership. And were white, male supremacist bastions. Obama’s election was welcomed as evidence of change. Didn’t change. We had the backlash of the white supremist march in Charlotte. Trumps “good people. Minorities are still excluded from membership in many men’s clubs, discouraged from joining, or not welcomed in ways that would welcome them. That is not just the problem of the white community it’s a problem of the white-Black community. We don’t know how to relate to each other. We don’t appreciate each other, and we think differently in many ways and feel differently. And we have to learn how the other thinks and feels if we’re going to survive. Oh, this is a nasty…but why don’t people who love dogs and cats oppose hunters who shoot harmless deer? I think the anti-gun crowd ought to get aligned with the Prevention of Cruelty to Animals. And, that’s enough. I think I’ve covered it (laughter). Thank you very much for this opportunity.

Zierler:

Bill, it’s been an absolute pleasure speaking with you. It’s very heartening and reaffirming to hear how your passion over the years has reverberated in so many different areas. In research, in service, in socioeconomic, and cultural issues. And I’m so glad that we connected, and I want to wish you a lot of luck in your future endeavors.

Duax:

Thank you very much.

[End of Recording]

Postscript:

Buffalo

My wife and I have been very active in civic projects in Buffalo.

In 1979, my wife Caroline graduated from Daemen College, where she majored in performance piano. The Concord Trio that she formed had local performances including fund raising events for a local dance company in which our daughter Sarah was the youngest dancer.

Caroline received a master’s degree from the School of Social Work of SUNY Buffalo (1989) and worked for Catholic Charities from 1989 to 1995. She was on the Family Selection Committee for Habitat for Humanity from 2000 to 2010. We were co-chairs of the Buffalo chapter of American Field Service for two years after our oldest daughter Julia spent 6 months in Tunis. We organized and prepared annual fund-raising dinners for 100 people.

In 2002 Caroline collected 700 signatures to preserve the Historic Gate house of the Hedstrom Mansion in Amherst. In 2006 we purchased the property to preserve the gatehouse, barn and stable, half an acre of woods and the stonewall surrounding the property. In 2012 the gatehouse was designated as a landmark by the Historic Preservation Commission and we were awarded the Rehabilitation /Adaptive Reuse Award from the Preservation Buffalo Niagara Society. Caroline served on the Amherst Historic Preservation Commission from 2010 to 2017.

The Saturn Club of Buffalo was founded in 1885 and has had the longest running annual variety show of any club in the United States. The 100th Saturn Chairing Show will be celebrated next year. I have sung and danced in 27 shows and was the principle librettist for 20 of them satisfying my high school ambitions to be an actor and a writer.