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Credit: Temtec Inc.
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Interview of David Haas by David Zierler on 2020 September 9,Niels Bohr Library & Archives, American Institute of Physics,College Park, MD USA,www.aip.org/history-programs/niels-bohr-library/oral-histories/XXXX
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In this interview, David Zierler, Oral Historian for AIP, interviews David J. Haas, President of the Tecco Corporation. Haas discusses his work as founder of Tempbadge and he recounts his childhood in Buffalo and then Texas. He describes his undergraduate education at the University of Buffalo, where biophysics was beginning to start as a distinct discipline. Haas explains his decision to remain at Buffalo for his graduate research, working under Fred Snell, and he describes his introduction to crystallography from David Harker at the Roswell Park Memorial Institute. He emphasizes the critical support provided by the National Institutes of Health (NIH), both to him as a graduate student and to biophysics generally at the time. Haas discusses his postdoctoral research in cryo-crystallography with David Phillips at the Royal Institute in London, and his brief work beforehand at the Naval Research Lab in Washington, DC. He describes his subsequent work at the Weizmann Institute in Israel where he continued his research in cryo-crystallography, and he describes the scene there during the Six Day War. Haas discusses his work at the Philips Corporation in New York, where he became involved with the X-ray research that would go into security scanners at airports and stadium venues. He explains his decision to go into business for himself with the launch of Temtec for which he created self-expiring visitor badges. At the end of the interview, Haas provides an overview for some of the major advances in biophysics over the course of his career, and he expresses optimism regarding the viability of antiviral therapies for Covid-19 by the end of the year.
This is David Zierler, oral historian for the American Institute of Physics. It is September 10th, 2020. I am so delighted to be here with David J. Haas. David, thank you so much for joining me today.
It's my pleasure. Thank you for inviting me to give this oral history.
Okay, so to start, would you please tell me your current title and institutional affiliation?
I don't use the "r" word, but I am retired. I have a private company called Tecco Corp, where I have put various patents over the years. So, I'm the president, general manager, and owner of Tecco Corp.
Now, is this a one-man operation, or there are more people in the company?
No, it's a one-man operation, but my wife Sandy is in charge, as always. For the past few years, I have been studying molecular and structural biology, trying to catch up from 1970 when I left basic science. Otherwise, I give Power Point presentations to a Life Long Learning group in Palm Desert, California. I have written several monographs anfd a number of scientific papers over the past fifteen years since we sold our business, Temtec Inc. Now I am planning for a Fellowship where I can research the evolutionary process of Airline Passenger Screening, called Electronic Security Screening, to other physical security applications, for buildings, sports events, public events, and many other locations. We all encounter Electronic Security Screening frequently today as it has migrated from airline passengers to physical access control all over the world. I was involved with the very first X-ray scanner, the SafeRay invented about 1970.
(laughs) Of course.
The females really run the world. Anyway. She was the vice president for TEMPbadge for 20 years, so I just let her have her position.
David, when did you start the company?
We started the company in 1981.
And can you talk a little bit about, how did it begin and what are its main objectives?
Well, I'd like to postpone talking about TEMPbadge for a few minutes. What I'd like to do, the most exciting thing in my life, I made a list of professional accomplishments. And the number one professional accomplishment of my life is the cryo-crystallography work. Not only did it prove to be very important, but 90% of all FDA approved pharmaceuticals designed in the past 10 years or more have used cryo-crystallography. It's just changed the world. In fact, the antivirals that are being designed for the COVID-19 today, all use structural biology, protein structures of the drug target, and use cryo-crystallography in the process. There was an article in this week's Science on the shape and the attachment of the binding site for the antibodies for the spike protein on the COVID virus. It had the three-dimensional structures of the antibody and the spike. The article had dozens and dozens of crystal structures from the synchrotrons and they were all frozen. It's just really mind-boggling. So, to a greater extent, this cryo-crystallography follows a phrase used by the Weizmann Institute: Science for the Benefit of Humanity.
And the Weizmann Institute, when I was there in the 60s, had the slogan which I always thought was fabulous, "Science for the benefit of humanity." And all of a sudden, in 2020, there's real science for the benefit of humanity. This cryo-crystallography has helped do that.
Oh, that's wonderful. Well, David, let's just back it up entirely, because we're going to talk about all of these things, and we'll do it in the structure of your life narrative. And so, a great place to start, of course, would be, let's start with your parents. Tell me a little bit about them and where they're from.
Okay. My father was born in Buffalo. His father had immigrated from Czechoslovakia in 1883. And he couldn't speak English, didn't know a soul in America. The story we were told is that he assaulted an Austrian soldier because of an antisemitic remark, and decided to scram out of Europe, and he did. He immediately took a ship and came to America. He didn't have any money, so he joined the Army immediately and was successful at that. My father was born in Buffalo in 1900. He went to school and graduated from medical school in 1928. Then he set up practice in Buffalo. So, he was a practicing physician, a GP and minor surgery, and he was well established in Buffalo. My mother was born in Newark, Ohio 1914. And her parents had come from Riga, Russia. She was a first generation American. They had a shoe store in Newark, Ohio. Then in 1930, when the Depression hit, so many businesses went out of business. So, the decision was made to move their store to Utica, Ohio where it ran successfully for the next 50 years. She went to Buffalo to live with a relative. So, my mother met my father in Buffalo, they got married in 1934. They had three boys, my oldest brother Gregory, who was a science managers at the Department of Energy for many years, and then my middle brother Johnathan. Johnathan went to the Merchant Marine Academy. He was in the Navy for many years. And then myself. I was born in 1939 we lived in Buffalo, and we had a very large house downtown. For whatever reason in 1942, my father decided to join the military, he joined the Army. He had a going practice and at 42, he just left it all behind. He was fully exempt, but something motivated his patriotic feelings.
David, did you know your father to be a patriotic man?
Yes, very much so. He used to talk about politics all the time. But I never, ever asked him-- You know, you always regret after people pass away, and you never ask them all the questions? I never asked him why he joined. But just recently there was a documentary on by the Public Broadcasting System, PBS, called G.I. Jews, and it talked about the Jewish participation in World War II. It was unbelievable. Half of all the eligible Jewish men in America joined the military. Half. So, there was obviously a patriotic movement, but also, he might have joined because of the stories of the Holocaust that were going on.
Which by 1942 were probably starting to trickle into American news outlets.
Oh, absolutely. So, we never understood why he joined the Army in the medical corp. He went to Guam, he served in Guam for the remainder of the war until 1945. Then my mother went back to live in Utica. She sold the house in Buffalo. We have concluded that he must have been with a group of soldiers from south Texas. It's the only thing we can imagine, because when he came back to America for discharge, he asked to be discharged in Harlingen, Texas. Now, you've never heard of Harlingen. It's down by Brownsville in South Texas, if you know where Brownsville is?
Brownsville I've heard of.
The very southern tip. It's right where the Rio Grande enters the Gulf. So, he was discharged in Harlingen, Texas in May or June of 1945. They were short of doctors in the Rio Grande Valley, as you might imagine, and he was offered a position in the new hospital they were building. He immediately bought a house in a town just six miles south of Harlingen called San Benito. He called my mother and he said, "Pack up the kids, bring them down, have all the furniture shipped." So, we moved into this new home for us. It was an older house, probably built about 1910 in San Benito. We even had a horse stabled in the front yard. You can just imagine. It was an agricultural town, about 10,000. 95% of the residents were Hispanic. And we went to school, and we grew up there. We graduated from the high school and each of us left San Benito for college.
So how old were you when you moved?
I was six years old.
Okay, so you don't really remember so much of Buffalo.
Nothing at all. We have quite a few photographs.
Well, you might not be able to comment on this from memory, but I wonder if you know from family stories, was your family Jewishly connected? Because in Buffalo, there was a significant Jewish community.
Oh yes. We were members of Beth Zion. Beth Zion was this enormous synagogue -- Beth Zion was built immediately after the Reform Movement was formed, about 1890, and it was the second or third largest synagogue in the United States. It was huge. But it burned down about 1962 or '63 while I was in Buffalo. But yes, my father went to Religious School and he graduated from Beth Zion. So, his family was part of the Jewish community. But in San Benito, we--
You must have been one of the only Jewish families.
Well, there was one other. A couple, the Yudesis. Miriam and Saul Yudesis, with their son Benjamin and daughter Anne, who I'm still close with. He's a judge there now, and I speak with him frequently. I saw his sister recently, she actually worked at the Los Alamos labs, and I met her at a meeting a year ago at Los Alamos. But yes, he was the only other Jewish family in town. Apparently, my father didn't really think much about that when he decided to move us there. But we basically had a reasonable upbringing. Surprisingly, my brother got his PhD in Electrical Engineering and taught physics at the University of Texas, he was very successful. Then he joined the Department of Energy. And my middle brother Johnathan was in the Merchant Marines, then was a senior officer in the Navy. And then myself. And I couldn't imagine how we could have been successful having been raised in San Benito. So at my 50th High School Class reunion from the high school in 2007, I had a group of friends, all sitting around this table at the banquet. I asked them, "Do you think that you got a good education here at San Benito?" A logical question. And what really surprised me was that we went around the room, and they said, "Just look at how many doctors and lawyers and scientists or technical people are in here." I replied, "Our class was only 75 people". There were a dozen or so sitting around. So, the class had a dozen or more professionals, so they all concluded, yes, San Benito schooling must have been satisfactory. Texas always had a very strong educational system, and I think we just benefited from it. I was quite surprised.
David, did you feel like you grew up in a science-oriented household? I mean, from an early age, did this feel like the trajectory that you were on?
No, not really. My father talked to us about medicine every once in a while. But we did have a workshop, and I made things. My brother, Gregory, became a ham radio operator, and was broadcasting on a long antenna strung from a two-story building. He talked all around the world. I wish I had paid more attention to what he was doing, because I would have learned a lot. And he got his bachelor’s in electrical engineering, and then his PhD in physics. I now realized how this paid off for him. And Johnathan, he was in the Merchant Marines engineering field. He fixed the engines and kept the ships operating. He was very successful as a technical person and officer. And myself, apparently, I did some of the same. In high school, I used to take motion pictures. Black and white with a wind-up camera, like a Bolex or a Keystone. And I used to sell news films to a local television station. So I would go out to an event, or I'd hear on the radio there'd been an accident or a fire, go out take pictures, take them back our house where I had a dark room. I'd develop the films myself, they were negatives, and then I'd drive them up to the television station. They would put them on the air. Because they used vidicons, they could reverse the image. So, they would run my negatives which would show positive on the screen. I took these news films for several years. I also built a 16 mm motion picture camera from scratch, it seems to have worked too. So, I could say yes. (laughs) All of us were technically inclined, all the way around.
With your father being a doctor, did you ever consider pursuing a career in medicine?
Oh, he wanted me to be a doctor. He wanted all of us to to be doctors.
He loved medicine. I used to ride with him when I was in high school, and he would make house calls all afternoon. So, I used to join him and ride around the farms, I'd take my books and sit in the car. Sometimes he'd be in the house for an hour or two. When he came out, he'd say, "Oh, I had to deliver the baby." And he always delivered them on the kitchen table with his cigar. When he passed away, the hospital did a count. He had delivered over 5,000 children.
He just loved delivering children. I mean just loved it. He said, bringing these human beings into the world is so wonderful and important.... And the hospital made a memorial to him, hanging his picture with a plaque after he passed away. He was a very successful doctor, a real country doctor. But he always wanted us to consider being a doctor too. But once I visited a friend at the University of Texas medical school and he took me through the medical school facilities, including the morgue. And I saw all these corpses - that convinced me that I did not want to be a doctor. (both laugh)
Not for you?
Not for me. I still have that image in my brain.
David, when did you start to realize that you had a special talent in the math and sciences?
I really didn't until I got into the University of Buffalo. So, I graduated from high school in 1957. I went to a junior college for a few semesters. Then I worked in a summer camp up in Wisconsin, and these people just knew more. When I came home, I told my father, "These Northerners, they just know more." I told him I wanted to go north. He said I could go to Buffalo, so I went to Buffalo where we had relatives, the next semester. And I got there in January 1959.
Did you know what you wanted to study? Before you got there?
I had no idea whatsoever. And that in itself is an interesting story. I moved into the dorms. I had wonderful dorm mates. So, I went to registration a few days later, and I walk up to this instructor at a registration table. He asked, "Well, what are your courses this year?" My answer, "I have no idea what field I was going to study, so I certainly don't know what courses I'm taking." Well, he asked me a few questions, and I replied, "You know, I want some math and some science and chemistry." "Do you want to be an engineer? You could be an electrical engineer, mechanical engineer, chemical engineer...". "Or you can go into chemistry or physics." He went down the list. My reply was, "I always enjoyed physics in high school. I'll do physics." And that's it, I signed up and he put me in physics classes, and I took physics. I graduated from the University of Buffalo in physics. I am not sure, but I think this is the same person who taught some of my physics classes. His name was Harold Box. He was one of my instructors in the physics department. I was really lucky. My wife and I have often talked about just being in the right place at the right time.. And Harold Box was there for me at that time.
We've had at least a dozen experiences, and some of these inventions and patents have all occurred because of pure luck. I graduated in physics in 1961 and I immediately began graduate school at the University of Buffalo.
Now David, at this point, are you thinking about biology at all?
No. I actually took a summer school course in biology at the junior college back in Texas after the semester in Buffalo, the end of my sophomore year. I drove back to San Benito. You know, 1000 or 2000 miles, in those days we just jumped in a car and drove. During the summer of 1959, I took a class at the junior college in Brownsville in biology. I remember the teacher specifically saying, "This is a wonderful time to study biology. They have discovered this new molecule called DNA, and it actually holds the genes that make us living beings." I just thought that was precious, that they actually know the formulas that make humans - human. And so, when I returned to Buffalo, I didn't take any more biology but organic chemistry. Then my senior year, Harold Box spoke to us about the new Department of Biophysics. He said, "You students have to think about what you're going to do in the future, and whether you want to go to graduate school or not." He suggested that we could go over and talk to Department Head for the new Biophysics Department, a fellow by the name of Fred Snell. It was in the Medical School and I did just that!
So, David, the term "biophysics," that was part of your experience as an undergraduate? You came across this term "biophysics"?
Well yes, and it was a new term. The term biophysics, just like the term molecular biology had only been coined a few years before by Max Perutz. No one had ever spoken about molecular biology. But with the three-dimensional structures of proteins, molecular biology came in, biophysics came in, and these were entirely new fields. And we were very lucky. Fred Snell had one of the first biophysics departments in the country - he was a big advocate. He had NIH fellowships available and was very active in the field as well as the Biophysics Society. And I remember when I went to speak with him, he was just inspiring. I mean I just loved Fred Snell. Fred became very vehement against the Vietnam War, eventually was terminated from the University because he led the antiwar demonstrations. He had actually been on the 1945 Atomic Bomb Assessment Committee in Hiroshima. So, after World War II, he was one of the team that went to Hiroshima to assess the biological effects of atomic bombs on humans. He was certainly aware of war and civic rights.
David, within the sort of traditional physics curriculum that you had, as an undergraduate did you gravitate more towards the theory side of things or the experimentation side of things?
Oh, experimentation. I was strictly hands-on. I was never a theory person.
Right. Even as an undergraduate, you knew this about yourself.
Oh yes. I loved chemistry and the lab work. I was always strong in lab work.
And so, what were some of the more formative lab experiences you had as an undergraduate?
We put up a working display of an oscilloscope in the physics auditorium, there was a display cabinet, and we actually built an oscilloscope that operated in the display. So, they thought this would be exciting where people would walk in and see all the components of an oscilloscope. I mean, that was a big thing then. Remember, that was the 60s. Solid state electronics had just come in. So, I did this with several other students. Then we had some labs where we were plotting out the magnetic fields of magnets and other materials. But I just enjoyed the laboratories. I was always a hands-on person. In chemistry, I did very well and never had any problem with that.
David, when you want to contrast your not-standout status as a high school student in science against all that you were able to accomplish in college, what do you think made the difference? Was it simply your exposure to these topics at a higher level?
I think my dormitory mates and particularly my wife contributed to my success. Once we were married, she gave me good advice. I decided that she really is smart. She wouldn't say that, but I'm going to. I really mean this. At TEMPbadge, we ran our business from 1981 to 2002, for 21 years. And she was the vice president from day one! I told her she could be president any day. But she only wanted to be the vice president, and she took care of HR, took care of sales, telemarketing and any customer problems. I really found a gem for a partner. So, Sandy helped me tremendously, and that was very exciting. I think we talked about seeing the world and what we wanted to do and how everything was so exciting. We just really enjoyed that. But being exposed to University life, I think one of the reasons that I excelled, was because I was so impoverished coming from San Benito. I don't remember ever going to the library in San Benito. We hardly had television. There were no concerts, no plays, few outside activities. It was somewhat rural. All the farms grew cotton. My father loved the citrus trees. But I think it was because I was just so impoverished that in Buffalo - Sandy took me to Kleinhans Music Hall frequently, we went to plays, we went to parties. We really had a busy college life. She studied to be an occupational therapist. After graduating, she worked in occupational therapy for about ten years, even in Washington and England.
David, did you give any thought to leaving Buffalo to pursue graduate studies anywhere else? Or you were comfortable, and you just said full steam ahead, I'm already here?
I never thought about changing schools, I was very comfortable. Fred Snell said he'd give me a fellowship to study for my PhD and recommended that I go visit David Harker down at Roswell Park Memorial Institute. Harker was looking for graduate students, and Fred Snell said I could study crystallography. I had no idea what crystallography was.
Now, he was doing crystallography work at the time?
Yes, David Harker began the first protein crystallography in America.
There's a great story, if you look up the reference. I just reread the article the other day. It's an article written in 1998 by Alan Tulinsky. Alan Tulinsky wrote the history of what's called the Protein Structure Project. In 1949, David Harker was offers $1 million to perform whatever research he wanted to. Let me start at the beginning. In 1949, David Harker, worked at the GE Laboratories. He was a crystallographer, his advisor had been Linus Pauling. David Harker was an outstanding crystallographer, and never got the recognition he deserved. In 1946, he jointed the General Electric Laboratories in Schenectady, and his manager was Irving Langmuir. Langmuir had received the Nobel Prize and was just a marvelous person. In 1949, for whatever reason, Irving Langmuir came to David Harker and asked, "If you had $1 million for research, what would you do with it?" And David Harker responded instantly, "I'd solve the structure of a protein molecule."
Why was this, in your view, why was this single question so compelling to him?
I'm not sure. He must have become fascinated with biological macromolecules like proteins from Pauling. Just like Max Perutz who became fascinated with proteins. First of all, it's the biggest challenge in crystallography. Because these protein molecules have thousands and thousands of atoms. And so that was the challenge. Linus Pauling, remember, was his advisor, Linus Pauling had not discovered the alpha helix yet, but the structure of biological molecules were on their minds. He had Linus Pauling sitting over his shoulder. So obviously, Linus Pauling had a big influence on him.
And what years, just to complete the narrative, what years would he have been working with Pauling?
Something like 1934 through 1938, about that time. Pauling was so well-known, and he was a ball of fire, I'm sure. So, Irving Langmuir asked Harker if he had $1 million, Harker said, "Protein structure." A week later, Langmuir bumped into him again in the hall and said, "David, you have $1 million now. You can go and solve your protein structure." And he did. What happened is that Irving Langmuir had raised the money through several foundations, the Rockefeller Foundation and through the Langmuir Foundation.
And David, do you have a sense, what did that $1 million get him? Was it more about postdocs? Was it about instrumentation? Was it about building a lab?
Methods. Setting up a lab, methods, instrumentation. So, within a year, he had found a place to go. He went to Brooklyn Polytech. The well known crystallographer at Brooklyn Polytech who invited him. Isidore Fankuchen. And Ben Post was his graduate student there. He had worked with Perutz in Cambridge on proteins, so they knew protein crystallography. David Harker went to Brooklyn Polytech for ten years and ran the Protein Structure Project. He started working on ribonuclease but during those ten years, a number of things happened. First of all, he invented a new type of x-ray diffractometer to collect the data. Completely new. Previously all crystallography was done using photographic film. This was the first practical x-ray diffractometer where you could collect the intensities on a Geiger counter or a scintillation counter. I mean it was just revolutionary. The second thing that happened was in 1956, David Harker published a paper showing how to solve protein structures using the heavy atom method. Max Perutz had come up with the idea of using heavy atoms-- It's called isomorphous replacement. But Perutz had no mathematical solution for this and didn't know how to actually use the intensities from the crystals to solve the structure. David Harker worked it out. So, in 1956, he published his paper just as a sideline. The next nine proteins that were solved, lysozyme, hemoglobin, myoglobin, etc. the next nine all used David Harker's mathematics. So Max Perutz would not have received his Nobel Prize, John Kendrew would not have received his Nobel Prize, without Harker's mathematics. I believe that is the recognition that he never received.
Now, did he need to essentially invent a new branch of mathematics to make sense of this? Was this really, truly uncharted territory?
Oh, it was an extension of the current mathematics. It turns out that a few years before, he had published a paper with an associate named John Kasper. They had worked out how to solve crystal structures by using what are called inequalities between the intensities. They were based upon the fact that electrons are real and occupy space, whereas where there are no electrons, it's a void. It's a zero. These Harker-Kasper inequalities were published about 1950, and they were always in the background until the two scientists, Jerry Karle and Herb Hauptman used them to created what is called Direct Methods. During the late 60s, you could solve crystal structures without heavy atoms on just using the direct methods. Karle and Hauptman both received the Nobel Prize in about 1985. And they thought, of course, Harker should have received the prize too. And since he didn't, and that happens with the Nobel committee, when they went to receive their Nobel Prizes in Sweden, they invited Harker to be one of their guests. And I think that was one of the greatest thrills of his life. And he'd said afterwards, he guessed he just didn't do enough work, but he was pleased that Karle and Hauptman got it instead.
That's extraordinarily generous of him.
Oh, it was always just wonderful. I spoke to Hauptman before he passed away, and he said it was one of the best things he ever did, was invite Harker to come along. So, for ten years, the Protein Structure Project operated out of Brooklyn Polytech and they had many famous people visit, even Francis Crick went there for a year. And a number of other people. It was the beginning of protein crystallography in America. In 1960, his ten years were up. Brooklyn Poly wasn't going to extend his time, and he received an invitation to come to Buffalo to Roswell Park Memorial Institute. Roswell Park is a cancer institute. It's called the Roswell Park Memorial Institute. Harker had just moved there few years before my time, and Fred Snell knew him very well. So when I went down, Harker said, "I have no other graduate students. No problem, you can be my first graduate student and we can determine the atomic crystal structures with crystallography." I thought that was just so exciting. I mean, I didn't know anything about crystallography, of course, but it was an exciting field. And proteins I did know about, he showed me how he's worked on ribonuclease. We were going to solve the structure of a biological molecule with a thousand atoms in it. So, it was a big thing.
David, I wonder if you can talk a little bit about some of the administrative or institutional decisions that made pursuing a biophysics degree, you know, possible within the medical school and not within a biophysics department or a biology department or a physics department?
Well, first of all, we were exposed to all the medical school lectures and the whole medical school operation. And we were able to meet many of the medical people, and many of our instructors actually were from the medical school. The physiology instructors and the biochemistry instructors. They all were working in the medical school. So, this was all biology. It wasn't physics.
Now, did you consider an MD-PhD? Was that ever something you considered pursuing?
It was brought up, but I'll tell you this, after visiting the morgue in Dallas, I just decided it was not for me.
I didn't mean pursuing an MD to become a doctor, I meant getting an MD because it might have been academically useful to you.
Oh, it might have been, but still you have to dissect a cadaver, you know?
And I wasn't, I don't think, up to that -- just wasn't my forte. So, at the medical school, first of all, money was available. I was told, I've been told many times afterwards, that during the 60s, the NIH had a lot of money and there were very few students, so money was available. And I can just say, since this Back to the Future experience in 2015, I have looked at who actually sponsored my education. With Francis Collins being the director of the NIH today, I really have to thank them. The NIH really, really made my career happen. It would never have happened without the NIH. I had an NIH fellowship in biophysics for all my graduate work. The NIH fellowship I received to go to David Phillips at the Royal Institution, it was NIH also. And when I came back, Michael Rossmann's funding was NIH. So, I must say, I've come to be a believer in the national funding for biological sciences, and for medicine.
How much coursework did you have for graduate school? Or was it all in the labs and sort of working around the medical school?
No, actually, I started graduate school after graduating in Physics in May of 1961. So, September of 1961, I started graduate school in Biophysics. I took two years of courses, some physics courses, and biology courses, and biochemistry courses. So my first few years were very intense. At the same time my wife, Sandy, was studying occupational therapy, so she was at the same school, and received her degree in 1964. But I spent two years of intense coursework, and then the last year and a half was strictly crystal structure determination. I solved something like ten crystal structures of small organic molecules during my graduate work. I had access to two computers. The IBM 1620 was the computer of my generation. The 1620 was not a big mainframe. It was a small scientific computer. The engineering department at Buffalo had one also, and Roswell Park had one. And I solved all my crystal structures on that. The software for crystallography was all written by a fellow who I need to thank, Professor Ahmed in Ottawa, Canada. He'd written all the software for the 1620 - I used it extensively. I collected all the data on Harker's new manual X-ray diffractometer, what was called a Euclidian cradle, it was all collected by hand. You dialed in several numbers and you'd press start on the counter, count for ten seconds, and go to the next. I collected thousands and thousands of reflections. But in a year and a half basically, I solved ten crystal structures. Now, when I kept showing these to Harker, he was dumbfounded. Remember, I mean in his day, it took you a year or so to determine a crystal structure with hand calculations, and I had completed ten in a year and a half.
Now, what had changed, you know, experimentally or theoretically or technologically? What explains this rapid advance?
Well, it's very interesting, because I just read Tulinsky's article again. And Tulinsky points out in Harker's article describing the Euclidian cradle, which was built by General Electric, that all the x-ray data on protein crystals had previously been collected photographically. Typical it would take you six to 12 months to collect all the data photographically on a particular type of crystal. You'd have to the scan the photographs with a photo densitometer to measure the intensity of each spot. And then you had to make corrections, calculating the intensities by hand. It would take you on a standard crystal six months to a year to collect the data and maybe solve a small organic structure. With Harker at Buffalo, I used the Euclidian cradle and it says in Harker's article, it reduced the data collection down to a few weeks. I could collect all the data on a crystal in a few weeks, and then I would key punch the numbers into IBM cards. I did all my own work. I would key punch it in to punch cards, I'd put the cards in my car and drive them over to the computer center or to the University, put them through the IBM 1620, and I would solve the structure - you'd then print out the electron density maps. It was unbelievable. I could solve a whole structure of a small organic molecule crystal in about two weeks. it was just unbelievable. Harker was aghast. I remember at some time with him, he made me, as an exercise, calculate the structure using what are called Beevers–Lipson strips. Of course, you've never heard of them - nobody's ever heard of them. But back in the 30s & 40s, you didn't have computers, so how are you going to calculate a Fourier transform by hand? So Beevers and Lipson came up with these paper strips. They were about three feet long and they had numbers on them. Of course, it was analog. Analogous to the slide rule. Now what you would do is put them into a holder, you pull them along, and when you had them lined up with the right numbers, you would get an answer. You could add them up, then calculate each of your Fourier transforms with the Beevers-Lipson strips. I remember after doing that for a week, I just gave up, I said this is an unnecessary exercise. But Harker was just aghast that I could determine a crystal structure so easily. In preparing for this interview, I discovered that I had published ten papers in Nature and in Acta Crystallographica during my graduate work. Ten papers.
Now, was that the journal of record for crystallography?
Acta Cryst. It still is the primary journal. Acta Crystallographia. In fact, there are several new one, which I just published this article last year is called the IUCrJ Journal. International Union of Crystallography Journal. It's now the journal of record. What's interesting, I read in Science an article just a few weeks ago which intrigued me. It said that as a graduate student today, if you're lucky, you'll be able to publish three papers during your PhD work. And you should strive for three papers. And when I added up my graduate publications, I had published ten papers. I couldn't believe it, I mean really. But it was the new computing power I had. I was also very determined, and I had two 1620s available to me, so I almost never stopped work. I remember once at Roswell Park, I went in at night and on Sundays -- I always used the computer off-hours, because they used it for the medical work during the daytime. Once I went in on a Sunday, and the door was locked in the computing area. So I just climbed over the wall -- As I was using it, the police came. And they were ready to lock me up. Roswell had reported a break-in at the computer center. (laughs) And so they were ready to cart me off. I had them call somebody to tell them I'm an authorized user. But for my graduate work, I was very efficient. I actually spent only three and a half years working on my PhD. I'm really surprised now. But I worked every spare minute, it was very intense. Thankfully, Harker had provided me with the resources.
How did you go about developing your dissertation? In other words, with all of this lab work, what were some of the big questions that came together to make the dissertation?
I didn't have a lot to do with this topic. Harker had a chemical group, had two chemists, a husband and wife, the Bello's. Jake and Lanie Bello. And they were the chemists who prepared the protein crystals. They suggested that, why don't I just do crystals of protein denaturants. They've had a lot of their preparations crystallize out. So, they had crystals all over the place from these heavy atoms and from organics. And they said, "Many of these organics will denature proteins, so why don't you do a thesis on protein denaturants? Solve the structure so that we actually have the three-dimensional configuration of protein denaturants and then you will contribute something to protein crystallography because many of these organics denature the proteins." And that's exactly what I did. All ten of the crystals that I solved were protein denaturants. This included guanidinium chloride and acetanilide. For glaucarubin, a 32 atom natural organic molecule, some chemist had given it to one of the staff, Kartha. And it's a natural-occurring organic from plants. And it's also been used in cancer therapy over the years. But anyway, I had 32 atoms and they wanted to know the structure. So, Katha didn't want to work on it, so he gave it to me, and he said, "Why don't you just add this to your thesis?" It was a large molecule to solve, that's almost like vitamin B12. It was just phenomenal the way the structures could be determined. And it had a bromine as guanidinium bromide, so I had a heavy atom of bromine. I could use that to solve the structure. And I completed it easily, in just a matter of two weeks to a month.
And David, who was on your committee? Was it all professors in the medical school, or did you have people in the biology and physics department as well?
Oh no, I had the physics department too. Yes. It was Fred Snell from biophysics, a physiologist from the medical school, Harold Box from the physics department, and maybe somebody else. Harker, of course was on the committee. After I finished these ten structures, I remember Harker coming to me during the summer of 1964 saying, "I think you've done enough. You should be going on postdocs to other laboratories. Why don't you just write your thesis?" I was a very good typist (and probably the most important class I ever took in San Benito High School was typing). I have used typing all my life. I still thank my typing teacher for teaching me so well. I sat down that summer, and I typed out my own thesis, everything, did the drawings, did everything. One of the amazing things was that the Xerox copier, the 914, was just being installed in stores. Xerox had introduced the 914 photocopiers in 1962, and for the first time, I could type a single page without carbon paper for copies. The photocopier made all the difference. It was a big thing. Everybody said, all of a sudden you can go and make a copy. A real identical copy. Previously, before 1962, if you wanted to make a copy of a page, it was either a thermofax or photographic. The 914 was just a revolution. So, I typed my thesis and I ran down to the copy shop. I remember saying "this is what real technology is for". I made a half a dozen copies, gave one to Harker and the others. They all approved it, they made only a few changes. I graduated in February of 1965.
Now David, I want to ask you, particularly because you had already been well-published at this point, and so you were aware of some of the broader issues in the field. Where did you see your dissertation plugging into those bigger questions?
Oh, into protein chemistry. Everybody was talking about the three-dimensional structures of proteins, and this was 1965. Only two protein structures had been solved, myoglobin and hemoglobin. Nobody really knew how, but everyone thought these two structures were special. They're almost 100% alpha-helix. Enzymes can't work that way and bigger molecules either, so we don't know the full picture yet. But they did know that if you added the wrong organics, certain polar or non-polar organic, you would denature the protein. So, nobody really knew what all the protein structures were. And they felt the denaturants where one means by which protein structures were going to be deciphered. It's for that reason that Harker said in January, "All right, you need to find a postdoc laboratory for you, I suggest that you go to England. And I suggest you go to David Phillips."
Now David, I just want to interject here. Just to step back a little bit, because I want to ask you, 1965, thinking back to your father in 1942, obviously it's a very different war and a very different social situation. Was the draft or military service, was that sort of on your radar at all? Was this something that you had to contend with?
No, it wasn't actually. There were a number of demonstrations in Buffalo and at Purdue, and we saw them. Fred Snell was headlong into being one of the anti-war leaders. He led the parades down in Buffalo. I was well aware of it, but I had a student deferment, and I was never threatened by the draft. I just didn't think about that because I was so excited about being into protein structures and nothing to do with the war. You know, Max Perutz and John Kendrew had just received the Nobel Prize in 1962. So, proteins were in, DNA was in, they were just deciphering the genetic code. Molecular biology was in. And I thought that I was going to fit into the molecular biology. So, no. I thought the war was terrible. I didn't want to have anything to do with it. It never occurred to me that I could have gotten drafted. I don't think Sandy and I ever once discussed that I might have gotten drafted.
Right, because in 1965, it was really ramping up at that point.
Oh, it was terrible. Just terrible. I mean we saw all these terrible pictures on the news. But for whatever reason, I was just really busy doing my graduate work. I mean day and night. I guess that was just how I worked. That's all. Well, it showed, when I did the cryo-crystallography work at Purdue, I collected the cryo data with a diffractometer for three months straight, and I had to go in to the lab day, night to fill the Dewar’s with liquid nitrogen. I mean, I just was there day and night.
Now David, in terms of pursuing a postdoc in England, right? What was going on in England that was either more relevant or above and beyond what you might have been able to accomplish in the States?
Oh well, England was where the action on protein structure was, so Harker insisted that I should go to England. He knew all the crystallographers, Perutz and everyone. He said that's where the protein structures are being solved. Max Perutz and Kendrew had already done it.
But the question is, what exactly was happening in England that was not happening in the United States?
I'm not sure exactly what. The prestigious individuals were all in England. He said I would get to hear some of them speak. Max Perutz, by the way, came to visit Harker a number of times. I met Max during my graduate work. The only American who was known worldwide in protein structures was Linus Pauling. The leaders were obviously the British, so this is where most of the postdocs went from the American laboratories. In 1965, you have Max Perutz, Francis Crick, Watson, and you have Sir Lawrence Bragg and David Phillips. You had a whole host of Britishers, and very few Americans who were at the pinnacle or the forefront of structural biology. So, Harker said, "You might as well go where the action is." This was January 1965. And I did. Interesting thing, David Phillips got right back to Harker and said, "No problem, but I can't take him until September." So, we agreed, "Fine, I'll come in September." Harker told me "You can't waste six months here." He had contacted Jerry Karle, remember Karle and Hauptman, and Jerry Karle and Hauptman both were using his direct methods at the Naval Research Lab in Washington. So, Harker told me, "I contacted them, they said come on down and solve a few structures using direct methods." In February of 1965, Sandy had already graduated, Sandy and I drove to Washington. We spent six months in Washington at the Karle's Laboratory, the Naval Research Laboratory. One of the most wonderful experiences we have ever had. A story about Jerry Karle and Isabella Karle, when they gave the Nobel Prize to Jerry and Herb Hauptman, there was a third Prize available. And it was Isabella Karle, who was a crystallographer, who had done all of the work to prove the direct methods. Both Jerry and Herb told the committee, "We would not have gotten the Prize without Isabella." The Committee still did not change their mind. There's a book called, "Famous Women Scientists Who Were Passed Over." Like Madam Curie and a few others. Isabella Karle was one of the people-- And Kathleen Lonsdale and there's a few others. This book on women who, extremely successful in the sciences, but did not get the Nobel Prize because of the feminine attitudes. And Isabella Karle was one of them. Anyway, we spent six months there and while in Washington, we saw every government building, museum and everything. Every Smithsonian building. And we spent a wonderful six months in Washington.
It was a good experience in D.C., for you and your wife?
Jerry Karle and Isabella, every month or so, they'd have picnics in their back yard in Washington. The entire laboratory was invited. Talk about marvelous lab managers and personalities. They ran the most wonderful laboratory. We just really loved being with them, and in fact, when we sold our business in 2002, we decided to thank our mentors. "Let's just go back and thank all the people who made our life possible." We invited Jerry and Isabella to dinner at their favorite restaurant in Washington on the Potomac and we had a wonderful dinner with them. I told them, "Just thank you for being who you are." They were just wonderful people.
Now, do you know that six months was a fixed time in D.C., or was the plan to stay there longer?
Oh no, no. Six months or less as I was filling the time interval before going in September to the Royal Institution in London. So now I know why David Phillips said he would not be ready for me until September. They were just finishing the structure of lysozyme in March. And they had to write the scientific paper when the structure was finished. He published the paper and then David Phillips gave a formal lecture at the Royal Institution in March of 1965 on the three-dimensional structure of an enzyme. Sir Lawrence Bragg was so proud of this accomplishment. It was the first enzyme structure, and David Phillips spoke about how he saw enzymes working on a molecular level. And then after that, he wrote the article for Scientific American. At the same time, he was preparing to disband the laboratory and the lysozyme group, basically, in 1966. Sir Lawrence Bragg, who was the director of the laboratory, had to retire at the end of 1966 or 1967, so David Phillips couldn't stay on at the Royal Institution anyway. He was hired for a position at Oxford, and therefore, the whole laboratory had to close at that time. My time there was just perfect, it was good for David Phillips to set me up for the radiation damage project and good for me with a project that I could continue on my own. Everyone in the lysozyme group was trying to find their new positions. Louise Johnson, Tony North and the others. They were all looking for positions. Because an entire laboratory was disbanding, you needed to find positions for about ten crystallographers.
David, I wonder if you can talk a little bit about some of the cultural differences, both in and out of the lab during your time in England?
Well, Sandy and I have concluded that we've really had good fortune during our lives. We has just been in the right place at the right time. David Phillips, by offering us that position of the postdoc got us going. So, my salary was from an NIH fellowship, from America, and I was getting $3000 at the time. David Phillips told me that I was the third-highest paid person at the Royal Institution. British salaries were really low and the cost of living in London was even lower. It was unbelievable. We had enough money -- I mean, in England, you cannot believe how bad the economy was. We actually were able to buy a brand-new car, for $1500. Certainly one of our best decisions ever. We drove it for the next ten years! But that's how different it was. So, Sandy and I never were short of money, and now we had a car. We could drive everywhere, we drove all around Britain and the continent. We'd made some wonderful friends.
Let me tell you how unique the Royal Institution was. First of all, it was not a university. In fact, it wasn't even a commercial laboratory. David Phillips had suggested this project and I worked on my own the whole time. There were no seminars, there were no lectures, there were no students or anything like that. The Royal Institution had many formal lectures and events during the week and every Friday night they would have a formal lecture in the Faraday Lecture Theatre. The lectures were begun by Michael Faraday in 1821. So, Sandy and I found ourselves basically in an environment of 150 years earlier. In order to go to the Friday evening lectures, you had to wear a black suit, and she had to have on a long, dark dress. The lectures were a formal event for everyone.
We went to the lectures almost every week. The lectures have operated the same way for the last 150 years. The speaker is invited in, the doors open. The clock in the Faraday Lecture theatre, a very famous lecture theatre, would chime. They opened the doors, the lecturer walks in. He gives his presentation. The clock chimes one hour later, and if he doesn't walk out at the chime, meaning he continues talking, it's considered rude and embarrassing. And if he walks out before the one-hour clock chime, it's considered that he doesn't have enough to say. They still do the same thing, more or less. It's a very famous theatre, another story. But anyway, Sandy and I attended the lectures regularly and met many different people. I worked there for a year and a half on this project, which ended up as cryo-crystallography. We also attended a number of other events there. During the work week, they always had tea and Sir Lawrence Bragg attended teatime, every day at four o'clock. Sir Lawrence's father, William Bragg, had started tea in 1934, when he was also director of the Royal Institution. Every day at four o'clock, everybody congregated in the library for tea. So, I saw Sir Lawrence and David Phillips every day. It's the only time I actually got to talk to anybody, because I never saw them anyplace else. Sandy and I were basically Victorians and we did everything we could in Victorian London. We saw every place in London that was of interest.
The laboratory where I worked, in the basement, had hardly changed since 1900. When they gave me a desk in an third floor room, I am sure the dust on that desk and chair was the same dust that was on Michael Faraday’s desk when he was there about 1810 and 1860. Everything was original, it hadn't changed a bit. And the elevator I used to go to the third floor was a hydraulic elevator. Definitely 1880 vintage, maybe even an original Otis. Now, it was run by pressurized water from the Thames. You would get in the elevator, and there was a rope in the corner which ran through a hole in the floor, and the rope was attached to the water valve in the basement. You would pull the rope, open the valve, the elevator would go up. And of course, the elevator was moving, but the rope was stationary. You never held onto the rope! Otherwise you'd get injured. And then when you got to your floor, you held the rope and pulled it to close the valve. It hadn't changed a bit since it was installed. The other thing I can tell you is that Sir Lawrence invited Sandy and myself to lunch. He always invited all the new employees to lunch. When we were at lunch with Sir Lawrence and Lady Bragg, Sandy and I, of course were nervous wrecks because we were very young and just didn't know what to say. We must have looked like - we were very young Americans. So naive and undereducated. It's embarrassing to think about how they thought of us. But anyway, we survived and had a nice lunch that we have always remembered.
David, I want to ask you, as an NIH fellow, did you have any contact with the NIH? Did you feel in any way that you were a bit of an ambassador to England as an NIH scientist?
Actually we felt we were representing America to all our friends and acquiesces. I received some mailings from the NIH. But that is about all. The American embassy had a contest which I entered. They asked, "We would like to have a short essay on how the British could become more knowledgeable about the Americans or vice versa." Whatever it was. And I actually wrote the essay and sent it in. Never heard from them, but it was interesting that they wanted us to improve relations between the two countries. I know they had enough Americans in the UK during World War II. So, we never had any major problems during our time in London. We had a little bit of trouble with the language, and of course the coins were impossible. This was the time with 12 pennies to the shilling, and it was just terrible. I got ripped off a number of times, not counting my coins at the Underground stations. But we managed otherwise. We made a number of friends, we drove all over Europe with them. And since we had a car, we drove all over England too. It was the highlight of our lives.
And David, would you say that your research, how much did it change from the things that you were doing in graduate school?
Oh, the work at the Royal Institution was completely different from anything I had done in graduate school. Completely different. Let me tell you this is a good point in 1965, 1966 to talk about cryo-crystallography.
Right, right. Please.
I made a list of accomplishments, professional accomplishments, and the number one was creating what is now called macromolecular cryo-crystallography.
But this term was not in use circa 1965?
Oh, absolutely not.
In fact, I always called it "freezing." Everything was freezing. Elspeth Garman, who is the leading expert in radiation damage to protein crystals, every time I'm with her and I use the word "freezing", she corrects me. It's "cryocooling" it's not freezing. The difference is not really important here. But many words have changed. Cryocooling, macromolecular was hardly used, and cryo-crystallography was only developed in the 1980s. So, I arrived at the Royal Institution, we got there in September of 1965, and David Phillips took me around and introduced me to e+verybody. I met the whole group. A week later, we went to a local pub for lunch and discussed projects. He suggested that I work on lysozyme crystals as he had a large supply, and the project was to see if I could reduce the radiation damage to the protein crystal while the data was being collected. The purpose of the project was to be able to collect all the X-ray data from a single protein crystal which would remain undamaged by the X-rays. I never actually knew at the time why he suggested it, but now I do. Two years before, with Colin Blake, he had performed work on myoglobin and had demonstrated the changes from X-ray damage to the protein crystals. The protein crystals start deteriorating immediately, and the x-ray diffraction pattern weakens. And not only does it weaken, but it weakens at different rates. The reflections at very high resolutions weaken faster than the ones at low resolutions. So, he suggested this project and I thought it would be important and interesting. I already knew that it would benefit protein crystallography in general.
I knew radiation damage was a problem. Harker had the same issue with ribonuclease, and really every protein crystallographer had the same problem. It is universal. All protein crystals deteriorate from X-rays at room temperature. And typically, after 10 or 20 hours of exposure, you have to put a new crystal on the diffractometer. So, for example, myoglobin and hemoglobin, they used hundreds of crystals to collect the data. David Phillips, to solve the three-dimensional structure of lysozyme, probably used 100 crystals. And that causes a tremendous data problem. I mean you have to scale between the different crystals of different sizes, the different shapes, different orientations. So I was aware of this from Harker.
David, just to zoom out for a second, what were some of the experimental or theoretical advances that sort of got this whole new endeavor started for you?
Oh. David Phillips had written this paper on the damage of protein crystals with X-rays. And the reason that he did the work with Colin Blake is that they had invented, at the Royal Institution the first automated x-ray diffractometer. David Phillips and William Arndt had invented what's called the linear diffractometer, so you could put a crystal on it, and it would move from position to position to collect the X-ray diffraction data automatically using punch cards or paper tape. It would collect all the data and most of the actual data from lysozyme was collected on the prototype linear diffractometer. There was only one built at the Royal Institution, it was their prototype. They used it for all of their data collection. No film. However, after operating the unit for about a day or two, they had to replace the lysozyme crystal because the x-ray intensities would change due to the x-ray damage.
David Phillips had built this linear diffractometer to collect their data but probably did not expect this particular problem. They had to frequently change the crystal due to the X-rays damaged, a serious nuisance. He wrote a paper, along with Colin Blake, on radiation damage - it was the first serious study on the subject. So when I arrived, and it surely continued to bothered David, he simply suggested that it would be a good project, to see if I could stop radiation damage using lysozyme crystals. And of course, Harker's ribonuclease and lysozyme had the same radiation damage problem. In fact, as I said, all protein crystallographers experienced radiation damage with all protein crystals. I simply replied, "That sounds good to me. That would be interesting and useful.
Not only that, it would have real significance -- "Can you imagine?" David said again, "Collecting all your data on one crystal, on a single crystal." Yes, even Harker had talked about that. That's the goal. David said that Fred Richards at Yale, had cross linked the lysines in the protein molecules using bi-reactant glutaraldehyde. Using this four-carbon molecule that cross links the proteins together, if you simply add glutaraldehyde to the solution, it binds to the lysines on the surface of each protein molecule, making the crystal stronger and rigid. It would turn a protein crystal of individual protein molecules into a crystal of one molecule composing the whole crystal. So, it's a single, huge polymer. He suggested that "This would make the crystals mechanically hard, and it might stop the radiation damage." I felt that was a great start, and that's how I did start by cross-linking lysozyme crystals.
All the x-ray equipment was in the basement of the Royal Institution. It was all film equipment except for the one linear diffractometer. I am sure the film equipment had been in the basement for 50 years. It may have been the same film equipment that was used by William Bragg. In fact, it's the same laboratory where James Dewar did his work back in 1890. The same laboratory where James Dewar invented the Dewar flask - The Thermos Bottle. James Dewar succeeded in liquifying hydrogen in that same laboratory.
It was really a crude place, unpainted and very dingy. It had all these unused high-voltage cables running along the ceiling just like Frankenstein's laboratory. And I was instructed never touch any of the these wires as they might have live voltage on them. So I began the radiation damage project with crosslinked lysozyme crystals as the first test for radiation reduction. I worked on this project by myself in the basement for 15 months. You cross-link the crystals, then take a precession photograph to obtain the x-ray image at time zero. The crystal stays in the X-ray beam for two days, and once again, take a second precession photograph. The two day exposure would cause the X-ray intensities to change in a specific pattern. So, I crosslinked many crystals and repeated that experiment several times. Every crystal showed the same radiation damage pattern. The conclusion was obvious, no reduction in radiation damage. The conclusion was that crosslinking by itself did not stop radiation damage. I told David Phillips, he was somewhat disappointed, but my plan was, "Well, what I'm going to do is take these crosslinked crystals which do not dissolve and add chemicals like organics and salts to determine if they will protect the proteins. All kinds of molecular scavengers that may pick up or block the free radicals. Basically, we knew why the protein crystals are being damaged. The X-rays are entering the crystal, they're very energetic, they hit electrons, they eject the electrons from the atoms, the electrons move and cause a reaction somewhere which breaks down or changes the protein molecules, causing the crystal to deteriorate. So, if I added scavengers, that may stop that from happening. David felt that was a good idea, basically the only idea. Over the next 10 months or so, I did this work. I put in literally dozens and dozens of organics and inorganics. And nothing changed. After two days of x-ray exposure, every sample that I set up had no reduction in radiation damage. So that took me through 1965 and then into late 1966. During the summer of 1966, David Phillips had accepted the position in Oxford and everyone's departure was set.
David Phillips accepted a position in Oxford while all the other lysozyme people were looking for positions. So, he spoke to me during the summer, saying that I will have to find a new laboratory to continue my project. And he suggested the Weizmann Institute, that he know the crystallographers at the Weizmann. He'd been there a number of times and knew a number of the people. After contacting them, they responded right back to David. The manager of the crystallography lab was Wolfie Traub. Wolfie said that space is available, come anytime.
By the end of 1966, everybody had departed and the Royal Institution was basically empty of the lysozyme group. So, what happened is that Sandy and I decided we were going to leave London in December. We also had our first child Stuart. He was born in September in London. We packed everything into our car, with Stuart and in December we all drove to Dover, took a ferry to France, drove to Marseille for a ferry to Israel. We were young and daring, I'll say that we were not concerned about going to Israel. We got on an Israeli ferry and in a few hours, we landed in Haifa.
Haifa is near the Weizmann Institute?
It's 60 miles south of Haifa. It's in Rehovot. We had everything in our car. Almost. We left a large steamer trunk with items that we never used at the Royal Institution since it would not fit into the car. I just left it in the coat closet in the lobby. And it was still there when I returned six months later for the return trip to America.
Anyway, we arrived at the Weizmann Institute. I went to the administration building and they immediately took care of us. Wolfie had arranged for the Fellowship, and they also provided an apartment for us. We were directed to the apartment complex, we moved in, and it was pure heaven. Pure heaven. Sandy loved it.
And David, how well-developed were the labs at the Weizmann Institute that were going to be relevant for your research?
In those days, the Weizmann Institute was built originally in an orange grove. Each morning I walked from our apartment through the orange grove to the laboratory.
The Weizmann Laboratories were state of the art. The Weizmann was formed in 1934, has always been a state-of-the-art research institution. Its moto is Science for the Benefit of Humanity. They also talk about being curiosity driven. And the science language of the Weizmann is English. There were so many Americans there that English was normal, even though many could speak Hebrew. The labs were pristine. When it was originally set up by Chaim Weizmann, he said, "What scientists need is support. Just give the scientists their head and let them create their science - we just provide the support." And the Weizmann has some of the most unbelievable support, equipment, facilities, maintenance support. Anything you need. So, from day one, I landed on my feet. I took all of my supplies with me from the Royal Institution, because I was continuing the radiation damage project. Wolfie agreed with me and said just to continue right here. The X-ray equipment was almost identical to that of the Royal Institution.
The X-ray generators, Philips generators, as it turned out with precession camera and photographic supplies. It was like a no-brainer, so I just continued where I had left off at the Royal Institution.
We made friends right away. They have lectures and seminars every week in English. The campus is lovely, very green. The cafeteria was nearby, and everyone congregated there at lunchtime. Sandy found a nearby grocery store with a manager who spoke English. So she had no problem with setting up the living accommodations. We found the Weizmann really is a unique facility. For three months, I continued adding all these organics and salts to crystals for testing, but nothing reduced the radiation damage. So, after about three months, and this was March of 1967, I made a list of other means that might stop the radiation damage. I chatted with Wolfie several times. This list of alternatives is published in the History of Science paper earlier this year, in the March 2020 paper in the IUCrJ journal, the International Union of Crystallography Journal. One items in this alternative plan was to freeze the crystals, to use liquid nitrogen. I chatted with Wolfie about that, and he said, well, I'm really in luck. He had built a cryocooling apparatus that was sitting right there in the laboratory on one of the x-ray generators and I could use it. The laboratory technician could trained me on how it operated. That was basically the end of March 1967. From my previous work at the Royal Institution, I knew exactly what to do, and surprisingly it appears that I followed the correct procedures. I took a supply of lysozyme crystals, added what we now call a cryoprotectant, in my day, we called it an antifreeze to eliminate ice formation in the crystals. It's a cryoprotectant. I froze the crystals, using glycerol on the first ones, sugar on the remainder, as the cryoprotectant. I first cryocooled crystal showed a perfect x-ray pattern. Two days of X-ray exposure, no change. A week, no change. And after a week of exposure, I thought, " This looks like it's real. Looks like cryocooling the protein crystal, making all the water in the crystal turn into an amorphous glass, really does stop the radiation damage." So, then I cryocooled a second group of lysozymes crystals with sucrose, same thing - no apparent radiation damage. These experiments are explained in detail in the IUCrJ 2020 paper. This was in April. It turned out that on May 5th, there was a great deal of war hysteria going on. If you recall, this was the run-up to the Six-Day War which started June 5th. But if you listened to the radio, there was a great deal of war hysteria coming from the Voice of America and the BBC. Also on television. Sandy's mother called almost every day from America, telling us to "Send my daughter and grandson out of Israel." You can just imagine; it was really hysterical. Everybody in America was scare. And so, every day her mother called--
David, so what happened?
So finally, I told her, "As soon as the American embassy announces for Americans to leave, we will take a boat back to England."
When you got to Israel, did you have any idea what the security situation was like?
Not at all. In England, we had heard very little news. None at all. And in fact, after we had arrived in Israel, somebody asked, "Aren't you worried about a war?" I hadn't even heard of it. But this changed at the end of April. There are now a number of history books on the Six Day War, and the chronology of what happened. But by the end of April, Sandy's mother was really getting angry, and I continued to tell her, "As soon as the American embassy suggests that we leave." So on May 5th, the American embassy put out an announcement, "All Americans should leave." And what we did is load up the car with a suitcase and our son, and I drove them to the airport, to Ben Gurion Airport, we got her on a plane, and they flew back to London. So, we just bought a ticket at the airport and they got on the next plane. And she flew back to England. She said, she was sick most of the trip, the gentleman next to her held Stuart the whole trip. (laughs) She got to England. And we actually had called our English friends, and they said they'll put Sandy up as long as needed. So, we had a secure place in England while I just continued at the Weizmann Institute. We were very lucky. I mean, if we hadn't had the friends, if she hadn't gotten on a plane, and if the war had been different. Throughout May and June, I was all by myself, very busy doing these cryo-cooling experiments, which were very exciting.
Cryo-crystals were just an unbelievable experience. You could actually collect all your data on a single crystal without any noticeable radiation damage. So, with the precession photographs, there was no indication of any radiation damage. I thought the crystal would last forever. This was really a high point in my life experience.
David, I want to ask - can you talk a little bit about being in Israel as an American Jew during this time? Did you feel Zionistic at all? Did you feel a sense of pride in Israel? Did you ever consider, once the war finished and Israel was secure, did you ever consider making Aliyah?
Oh, no, not at all. We was very Zionistic, my wife and I. Sandy and I both had read quite a bit about Israel and know the history. I had worked at a Zionist camp in Wisconsin for several summers, so we both knew about the country. And when David Phillips suggested that I go to the Weizmann, I could not have wished for a better place. I had never expected to be at the Weizmann Institute, but now I would get to Israel. Even Europe had been more than we expected. That was almost Israel. But to get to Israel was just phenomenal. Neither Sandy nor I had any hesitation. With our American friends at the Weizmann, two couples who were very close with us, we drove everyplace with them in Israel during the few months we were there. We went to see Herzl's grave and all the sights. The War of Independence sites. We went to Tel Aviv and Jerusalem. We just did everything on the weekends. And in fact, I think it was the 5th or the 6th of May, the Weizmann made an announce that "Anyone who wants to, can get on the bus at five o'clock so they can go to the Israeli Independence Celebration." The government had decided, in order to make Israel look like it's not going to war, it's going to have its normal Israel Independence Celebration in Jerusalem. So, they held it in one of the football stadiums in Jerusalem, and it was packed. They wanted as many people there as possible, but of course, everybody was in the army. So, they went around rounding up people like us, I decided it was no problem, and at five o'clock we got on the bus, drove to Jerusalem, and I still remember being in the stadium hearing the speakers and the band playing. It was a real experience, and then two weeks later, the war began.
Even though Sandy and I were fairly knowledgeable about Israel, the Weizmann really surprised us for being so entrepreneurial, for being so exciting. Not only that, the campus was beautiful, and the laboratories were so well-equipped. Sandy and I still speak of the experience. By the way, I can say that after the war, I received a book from the Weizmann President thanking me for remaining at the Weizmann during the war. I am sure all the non-Israeli visitors who stayed received one also. But almost everybody in the Institute had departed before the war, either going home or on vacation. The Weizmann Institute was completely disserted before the war, in May.
So, what happened is that, it was Monday morning, June 5th. I went to the laboratory and all of a sudden, everyone was saying the war has begun. Some Weizmann official came around and they told us, each of us had to do some type of a safety task. I was assigned to protecting the Stone Building, which is the administration building. I was supposed to put out the fires if the building gets bombed. They showed me where the fire hoses were, and said, "You're on watch here. You're in charge." I slept on the steps of the Stone Building for three nights, waiting for the bombs. And every time I go back to the Weizmann, I go back to my spot. It's really touching. The war was a challenge, I had absolutely no idea how to put out a building on fire. I mean (laughs) it's just amazing that, you know, in those days, you did what you were asked to do.
You must have felt that your life was in danger.
That was very interesting. Many people said, "Aren't you afraid?" Remember, we were going to be driven into the sea.
The Israelis were going to be driven into the sea. I didn't think that. I guess I was just too young. What I did see were tanks being carried along the roads every day. The roads were full of tanks going north, south. But I had no fear. I just didn't have any fear. And I think I was pretty much naive. Just young, innocent. Young people think they are invincible. You see what is going on right now with this pandemic. Everybody who's under 30 is invincible. And so I took care of the Stone Building. I would have put out the fire if there had been one. After the war ended in six days, the Six Day War, there were very few people around but some of the staff I spoke to told me, "There's not going to be any resumption of science for another few months or maybe six months." All the soldiers are going to be occupying this territory and therefore no one's going to come back to work. All the people in the lab, Wolfie, the lab technicians, all the students were in the army. So, there was nobody there. I actually called or telegraphed Michael Rossmann at Purdue about the position he had offered me when he answered back the year before, when I had inquiring for postdocs from the Royal Institution. Michael knew David Phillips very well. When I contacted Michael after the war from the Weizmann, he told me to "Come to Purdue at any time. We'll be available for you at Purdue." It was sometime like June 15th, I just packed up everything in the car, left a message for Wolfie and I drove back to Haifa. I took the next ship, another ferry, arrived in France, and then drove back to London. After a few days in England, Sandy & I packed up and boarded the next steamer back to America. We came back on the S.S. Bremen. We arrived home in July of 1967. So, the one thing that I did have, though, I had all my precession X-ray photographs from the Weizmann laboratory. They proved to be invaluable for Michael. If I hadn't gone to the Weizmann, two things would not have happened: cryo-crystallography would have been delayed, probably ten years, not performing the work then, and the 1996 HIV therapy would probably have been delayed by years. I was told in October, 2017 at the Cold Springs Harbor X-ray Methods Course that nobody would have considered doing cryocooling for many more years. Cryocooling had already been shown to have negative effects on protein crystals. This work at the Weizmann certainly was important, the Weizmann experiments probably advanced structural biology by ten years. And not only that, as you will see if you read that review articles on the HIV pandemic, the effect on the HIV infected individuals was unending . The 1996 antiviral therapy saved hundreds of thousands of lives.
Coming back to the history, so we got back to America, we went to Buffalo. We reorganized ourselves. Picked up our clothes and everything, and we drove to Purdue. At Purdue, Michael was wonderful. Michael Rossmann has been one of the outstanding crystallographers. I'm sure that he's been nominated for a Nobel Prize. He passed away about a year ago, sadly. But he was just really outstanding as an individual. And he has many accomplishments. Michael asked me what I wanted to work on and I told him, "I want to provide absolute 100% proof, that the cryocooling of protein crystals in liquid nitrogen stops radiation damage." He initially thought it was all BS and that cryo-cooling would never work - he really was unconvinced. I had my precession photographs from the Weizmann and I told him "Look, I can show you it does work." I just kept waving them. There were a number of people in the laboratory, his grad students and postdocs, who all sat in on the my discussions with Michael, but no one was convinced. I mean nobody was convinced. They all knew that freezing causes ice to form. When ice forms, it expands. When ice expands, it breaks up the crystals. Finally after a few weeks, Michael decided, "Fine, I agree, you may do the tests, and I will loan you one of my x-ray diffractometers and that part of the lab for three months, and not a day more." He added, "You've got three months to do it." He gave me a several thousand dollars for supplies and added, "But you have to do all the work myself and you have to build the equipment." So, Purdue was absolutely wonderful with is glass blowing and machine shops. This was September, 1967. I built an exact duplicate of the of the cryocooling apparatus that I had at the Weizmann. Michael loaned me his diffractometer. About March or April 1968, I started collecting the data. One other item that Michael insisted on is that instead of using lysozyme, I had to use lactate dehydrogenase crystals, which is the protein that he was working on. He said he had enough crystals and as it turned out, I only needed a half a dozen because the cryocooling preserved them during the X-ray data collection. Once you froze a crystal, you used the same crystal continuously. So, Michael thought, if it was successful, it would be good. But he had very little confidence that it was going to be successful. Michael told me to "Just go and do your work. Let me know what happens." So, I did, and during the summer of 1968, I collected all the data, the cryo-cooling was successful, the equipment worked successfully. I wrote up the first draft of the paper and gave it to Michael. He processed his end of the data and he submitted the paper in July of 1969 to Acta Crystallographica. It was published in April 1970. That is the primary cryo-cooling paper, a substantial paper, which has a graph that shows that radiation damage in Lactate Dehydrogenase at cryo temperatures is reduced by more than ten times. This was clear proof positive that cryocooling does reduce radiation damage. Michael was thrilled at that, but he never did anything with cryo-cooling himself. Nor did anyone else for more than twenty years.
And what's the significance at this time? I mean, if we look back 30, 40 years, right? It's so obvious how fundamental this is now, but does this realization sort of play out over a longer period?
Oh. It played out over a much longer period of time. During 1969, 1970, I interviewed for a dozen jobs at academic institutions and pharmaceutical companies. Some of the same pharmaceutical companies that have very large crystallography groups today - Merck and Pfizer are right here in New Jersey. Every one of them told me it was worthless work and had no practical application. And in early 1970, I had become so discouraged, I abandoned any thoughts about cryocooling. I totally forgot about it. For 30 years, I can't believe how completely I kept it out of my mind.
I decided to take a position in industry. I decided I'm much better at making things and inventing things, so I joined Philips Electronic Instruments in Mt Vernon NY. I never heard a word about cryo-cooling between 1970 and 1999.
A caveat to that story is in 1999, it's 30 years from 1970. I was in Indiana in 1999, and I decided, "Well, maybe I should just go back and say hello to Michael. I really enjoyed my time there." I drove to Purdue and we had lunch. Michael did not stop talking about cryocooling and freezing and protein structures the whole lunch. He told me, "It's all based upon the 1970 paper." I absolutely couldn't remember a thing about cryocooling or writing the 1970 paper. I had put it so far out of my mind. I asked, "Michael, did we even publish that paper?" I couldn't even remember that. He made me a copy. It's the first time I actually saw it. Cryocooling protein crystallography had come back into my mind after 30 years. I couldn't even remember what I had done. And it still didn't excite me. I had no idea how big of a technique it had become. So 1999 passed without any interest, I went through 2010, another 10 years. Only in 2015 did I finally grasp the significance of cryo-cooling. I have had no close friends in crystallography until 2010 when Sandy and I started spending the winters in Palm Desert, California. Alex McPherson, Michael's graduate student in 1970 was a professor now at University of California Irvine. He's done marvelous work on how to crystallize protein crystals, it's really unbelievable. He started coming to Palm Desert with his wife Fran, also a crystallographer, to have lunch with us. He kept talking about how cryocooling and protein crystallography and structural biology-- used all these words I had never heard before. I never really understood the significance of cryo-cooling, I just couldn't grasp it. I was also very busy doing other things and never looked into it.
Let me digress back to 1970 and wrap up the Purdue story, I took this Philips position in February and in April 1970 we went to Philips Electronic Instruments in New York from Purdue. That was the last time I worked in crystallography. Sandy and I were in industry for the next 30 years. I never looked at a crystallography paper, never talked to a crystallographer for 30 years. It was so foreign to me. I was really burned out when I left Purdue, I had been so discouraged. I thought David Phillips would think it was the greatest thing, it accomplished his goal. But I never heard from anybody. Not a soul. And in fact, I am sad to say that I never even spoke to David Phillips about the subject ever again. I never even spoke to David Phillips again, before he passed away in 1999.
But you never stopped believing? You always knew that there was going to be some value here?
I'm not sure of that. I was so discouraged. I remember giving one of my best seminars at a pharmaceutical company someplace here in New Jersey. I'd come for an interview. They just said, "We'll get back to you, you know, we're surely not going to do anything with this freezing business." As I said in my article, it was just another piece of science that goes into a dusty journal. It may be real science, but it has no practical value. That's what I really thought. When Michael started talking to me in 1999, I was shocked, like what is this about. He just kept talking about what a wonderful job I'd done (laughs) and the paper was fantastic, and cryo-cooling is being used all around the world. I had no idea what he was talking about.
David, can you talk a little bit about your time in industry? What, you know, you had been in an academic environment up until this point. What were some of the things that were different immediately, not obviously about the day-to-day, because it's a very different environment, but in terms of the research and the kinds of questions that you were after.
Okay. I will come back to the cryocooling at the end.
Let's talk about industry. So, It was April 1970. I went to work for Philips Electronic Instruments. It was very well-known company. This Philips division was in a very old, dumpy building in Mount Vernon, New York just north of the Bronx in New York City. It's in an old part of the town and the building dates from 1935. This is where people like William Parrish had worked. A very famous crystallographers. They made all the x-ray instruments and the x-ray generators there. The Philips X-ray generators are used everywhere, painted black or green. They're still being used, even the very old units. The same ones I had at the Royal Institution and the Weizmann Institute. Philips Electronic Instruments, when I got there, was completely different, a different world. They had regular business meetings and I was in the engineering department. I was the principle scientist for X-rays. So the first thing they did was assign me to be the radiation safety officer. Now, if you want to have a curse ever put on anybody, you make them into the radiation safety officer. Not only did I have to learn all the rules and the regulations, but you have to enforce them. And if a radiation accident occurs, you must deal with the Federal and State Governments. Anyway, I was the radiation safety officer. And then they put me on an exciting project - "You're in charge of this project. It's called the Automatic Powder Diffractometer, the APD." You take an x-ray pattern of small powder particles, they make a series of rings, and the position of these rings are unique to that crystal structure. With a database of all of these rings, today there's something like 900,000 powder samples, so you can uniquely identify what your powder sample is. You take any material, grind it up, and you match these X-ray rings to a database - positively identifying what the powder is made of. It's widely used in industry and analytical chemical laboratories. You want to be sure that the iron mineral or the iron ore that you're bringing out of the ground is the right percentage and consistency, so the way you tested it is by making a powder diffraction sample. I worked on this APD for two years. I now think it was probably the very first, completely computer-controlled X-ray instrument. Completely automatic. It would change 35 different samples, and it used what was called then, an industrial controller. They still use them now for numerical control of automatic machines. Philips manufactured these numerical controllers, it had 4K of memory. 4000 bytes. And yet it ran the whole program in a production plant, or in a mine. You could put all your samples in it in the evening, and overnight it would run automatically, all 35 samples, and in the morning, you'd be able to have your complete quality control samples analyzed. It was a big success from Philips. Then, what happened was that serious airline hijackings had begun, remember, 1968, with the Cuban hijackings. Nobody had a solution on how to stop the airline passenger hijacking problem.
Two engineers, at Philips Government Systems, which happened to be also in Mahwah, New Jersey, in the same town as Philips Electronic Instruments. They invented the first x-ray machine for airline passenger screening, called the SafeRay. That was the very first low-dose x-ray scanner suitable for airline passenger screening. They demonstrated it to the Federal Government on September 25th, 1970, to 30 or 50 Federal Government Law Enforcement agents in a hangar at National Airport. Everybody was there. The FBI, the Secret Service, the White House, the Pentagon, all the government officials. They looked at this TV image of the contents of their briefcases and bags. They couldn't believe that you could put your briefcase on this little stand without any lead shielding around it, and it would show you the contents. And of course, it would show a perfect silhouette of a gun. In those days, they were always big guns. It turned out, the hijackers always used big guns. Because the hijackers wanted you to see it. This convinced the FAA and the Federal Government Agencies that a solution to the airplane passenger hijacking problem had been found. As it turned out, Philips Government Systems was being closed down, and they were moving the division to Eindhoven, Netherlands. The Government Systems was actually part of the Philips Broadcasting Group. During the 1960, these two engineers and their group had actually perfected what's called the Starscope. During the Vietnam War, this was the invention of having a telescopic lens that would amplify at night. Night vision telescopic lens. They could be given to snipers. This became a serious weapon, terrorized the North Vietnamese. These engineers are the ones who actually perfected the Starscope, which was the first night vision equipment. It used a light amplifier in it. That's how they invented the SafeRay, by amplifying the very dim X-ray image from a fluorescent screen with the Starscope light amplifiers. However, it turned out the SafeRay project was being transferred to Philips Electronic Instruments where I was. They needed somebody to be in charge of airport security and airport passenger screening. And with that - they pointed to me. I mean, I didn't really have a choice. They said, "You're in charge of it." And what happened is that we took a couple orders for the SafeRay. You may remember, January 5th, 1973, is when the Federal Government, the FAA, instituted the law for mandatory passenger screening. 100% mandatory. After January 5th, 1973, everybody had to be physically searched when they boarded an airplane, either a hand search or by an X-ray scanner. Of course, it was all done originally by hand. But then the x-ray machines came in. The passenger walked through a metal detector and their luggage passed through the x-ray machines - it became so obvious and better. Philips Electronic Instruments made a couple of these SafeRay units, and then I started designing its own brand new machines. The first ones, before I became involved where really awful designs. And only a few were sold. But in 1974 I designed what was called the Dynafluor VI. Which was a very low design and it had a conveyor on the floor that crossed through the cabinet X-ray unit. At that time, there were a couple other companies making airport x-ray machines, but they were very clumsy, poorly designed and not X-ray safe. The Dynafluor VI was very successful, and we sold about 300 units around the country. And not only that, I would give lectures at the security meetings on how to use them. We basically became the leaders in the field by 1975. I went on to designed three or four other machines, and by then, all my work at Philips was always airline passenger screening. I just looked at my publications and found that I had published 17 papers and articles during that period of time. They were all technical and public relations papers on the benefits and how to use a low dose x-ray system for security - explaining how Electronic Security Screening is good? Where else would security screening be used, not at airports? And it became a major application.
And the biggest event was that in 1976, the Secret Service rented x-ray machines from Philips, the Dynafluor VI. For the Democratic and the Republican Conventions of 1976. So everybody going into the convention would have their purse or their bags x-rayed and the attendees would walk through a metal detector. This event was very successful, but more than that, the news media who was at the convention of course, showed these x-ray machines being used someplace other than an airport. And they commented, "Look what it can do. People walk through so fast, and not only that, they can see guns and food and everything else". After 1976, the low dose x-ray machines began to be used, rented and sold, for many types of applications, and from what I see today, at major sports event, entertainment events, etc., I am told that everybody who goes in gets their carried items x-rayed, particularly looking for food, liquor and weapons. So, it's become a major success, and it has changed American society. It's changed the world's society.
And David, where is the origins of Temtec in this? Is this a gradual development on your part? Or at some point do you say specifically, "I'm branching off on my own"?
I'm branching off on my own. That's exactly what happened. It was around 1976, '77, '78, Philips Electronic Instruments was sort of floundering, and I was unhappy with the company’s performance. I just wanted to do something else. I decided about 1978 to invent something new and start my own business. I had even taken a business correspondence course the year before, and in those days, it was by mail. No internet. On business management. So, I took this correspondences course from a company in Chicago on Business Management. I even filled out all the exams, sent them back by mail, they'd give you a grade, and then you'd go on to the next part of the course. I was looking for something to do, a business, and I was very unhappy with my position. I went to the HR manager at Philips a number of times. They suggested that I just go and find another job or do something else. They had no suggestions on what I could do because I was a scientist. What else could I do except science? Then in 1979, I became involved in a couple of simple adventures that I dropped. Several years before, I had an idea for a color change visitor badge which could only be used once. I had no idea how to make such a product, but l decided it would be a great product if made as a paper visitor badge that changes color. By the way, you worked at the State Department for some time. The State Department was one of our early customers for using what's called a Self-Expiring Visitor Badge. Were you ever given a visitor badge that changed color? Well, that was our invention.
Oh yes. Yes.
Some of them turn blue, some of them turn brown. Some of them turn red. The State Department had the one-day time badge, for visitors, temporary use. This is 1979. I spoke to Sandy that I'm going to do something new, I don't know if she thought I was crazy. I was working in our basement and I set up a small chemistry lab to solve this problem, to invent a color-changing visitor badge. So, let me tell you how I had the idea.
I had the idea in 1976 in Kansas City. I flew into Kansas City for the Democratic Convention, because I was assigned to set-up the x-ray machines, not actually operate them, but set them up for the staff. If they break, I was supposed to fix them too. And I was assigned to train all the operators. That's my job. I loved doing this operational work. That was really fun. Everyone received a contractor badge or credential in order to protect all the bigwigs and whatever. So the first thing you had to do when you got to the convention center is to go to the Secret Service Office, and they have to make you a badge. Instead of going to my hotel, I went directly to the convention center to get my badge. Walking in, and I thought to myself, "This is going to be something - this is the Secret Service, you know. They're going to give me some fancy badge so that I'm really controlled." I walked in, they sit me down on this stool, and had their Polaroid Camera standing there. On the back wall is a cloth that has "Secret Service" written on it. That is a background pattern for ID protection, to make the ID tamper resistant. They took this picture of me, laminated it, and gave me the badge. That was the process. The dates on the badge showed it was good for the whole week. I remembered commenting, "This is terrible, I'm only going to be here for two days. I could use this badge all week. But if I lose it, somebody else could pick it up and use it for the remainder of the time." At that moment, sitting on this stool, I thought what they should have is a self-destructing badge. They should have a high-tech self-destructing badge so that as soon as I left the facility or after a specific date, the badge would be no good. And I just kept that idea in my mind for several years. Talk about a eureka moment. I still remember sitting on that stool. In 1979, when I was looking for a product or business, I started asking security directors about their visitor control badges. Since I helped sell the x-ray machines and I went to all the security and law enforcement trade shows, asking the security managers from TWA, Eastern, Delta, all the other security managers I knew, "Do you have problems with visitor badges?" And to the last one, they all said, "It's a nightmare." (laughs) "Visitor badges are the worst. You give them out, you can never get them back. People reuse them. But the worst people that reuse them are salesmen. After you give them a badge, they come back again because then they can go make another sales call." So, I knew going into this badge business would be OK. It turned out some of these security managers, actually, were the first to use our TEMPbadge badges.
And just to step back also for a second David, can you talk about coming from Philips, were there any intellectual property considerations that you had to think about as you were venturing off on your own?
Intellectual properties were not so important in those days. Philips in the United States only files a few patents. We made a list of all the improvements that I had made to the low-dose x-ray machines, the Dynafluors and the other products. We had created new x-ray tubes and made many other improvements to the X-ray scanners. You can still see some of these improvements in today's scanners. I obtained only a few patents on those. Philips applied for very few patents. What surprised me was that Philips, none of the Philips people, who invented the SafeRay were able to convince the Philips Corporation to protect this product, they never got a single patent on the SafeRay. Philips could have owned the entire low-dose x-ray machine business. But they never got a single patent on it. The same is true for Philips Electronics. They were very careless; they just didn't care. In particular, the self-expiring badges had nothing to do with them, and I did not worry about that. So, intellectual property, no. I could tell you a related story, I was designing an ultraviolet printer for TEMPbadge. I had no idea how to make an ultraviolet lamp circuit. I called General Electric in Schenectady and asked the operator, "Can you connect me to one of the ultraviolet lamps engineers?" And I got an engineer on the line, I talked to him for more than an hour and he designed the whole circuit for me on the phone. It was unbelievable, I mean it was worth a million dollars. I just built the circuit that way. So, what we did, I designed a working self-expiring badge. We showed it to some of our security friends. They loved it. They said, "Boy, it's a one-day badge. You give it to visitors and then you don't have to worry about it." In those days, but even worse later on, if you have a Department of Defense contract, or similar, they require very strict visitor control. If you lose any of your visitor badges, you have to locate them because they can compromise your entire visitor control program. Nowadays, with electronic badges, that's not as big a problem. But back then, they were all visual badges. If you lost one, somebody could just come in and wave it to receive admission. Nobody ever reads the text on badges. You just waved your badge and walk in. In 1981, I decided we were going to start TEMPbadge, which manufactured, printed and sold self-expiring visitor badges, one day badges. It would solve the visitor badge problem for companies that maintained some level of security. By the way, the self-expiring visitor badges are still widely used, hundreds of millions of them are still used every year around the world. When we sold the business in 2002, self-expiring badges like the ones you used at the State Department are widely used, 20 or 25% of all the visitor badge business in America are Tempbadges. We were supplying about a 100 million badges each year. It was just a wonderful business. What a successful product. We started in our basement. We went to our first trade show, the first trade show was in Atlanta. It's called the American Society for Industrial Security. And this is where all the professional security alarms and cameras and x-ray machines and metal detectors-- they're all displayed there. And I had arranged with one of the salesmen from Philips to help us. Customers began buying right away, including the State Department. Everybody had a visitor control problem. Particularly government buildings, they always had problems with visitor badges walking away. Self-expiring badge sales began in 1981. Every year sales increased. We never had a single year for 21 years where sales decreased. We were selling initially a light-sensitive badge that used ultraviolet light. Then in 1987, after working out of our basement for seven years, we moved to rented space. I was trying to perfect a chemical time badge. I didn't want an electronic badge. Everyone would say, "Just put a chip in it, make it electronic. But that's not what I wanted. We wanted a 10-cent badge so that we can compete with regular paper badges which are purchase by the millions. I did all the chemistry in our basement and we had a working product, a one-day timed, self-expiring badge by 1987. This is the product that the security managers wanted - one day. Everybody wanted a visitor badge with guaranteed self-expiration. Then we moved out of our house into a rented facility and purchased our own printing presses - TEMPbadge began for real. So, the short story of TEMPbadge is that we operated it for 21 years, Sandy was the vice president who ran the company - Sandy was marvelous. She swore from day one she would never work for our business with me, but she did a marvelous job from day one. We had more than 8000 customers and we were shipping 50-100 million badges a year. That's a lot of badges - about 20-30% of all the visitor badges used in the United States. Particularly for high security facilities like the military, Government Buildings, the Secret Service. The White House, the United States Capitol, thousands of locations were using them. And they're still being used today. We had 35 absolutely wonderful employees - it was a very successful and fun business - just like a big family. We had more than 50 patents to protect us, as I came to realize that if we can keep competitors out of the business, with patents, we would avoid having price discounts when selling through distributors . So, we had dozens of patents, many of them were just defensive patents. We had such a dominating patent portfolio, which also was purposely very confusion, that anybody who looked at us would be afraid of infringement. And when we sold the business in 2002, we still had 40 active patents. There were no competitors when we sold the business, so of course the business value was a premium in 2002. The World Trade Center was actually our largest customer. By 2001, they were using 200,000-300,000 visitor badges a year. And I could speak of the World Trade Center, Douglas Karpiloff was the security manager who died in 9/11. He had been the security manager for the World Trade Center for a decade. In fact, he was probably right up on the top floor of the first tower when it collapsed because he cared so much for the people working there. He was also a good friend. The badges products performed very well. Sandy wanted to retire and that's how we decided to sell the business. We sold Tempbadge right after 9/11 as all security business became more valuable then. Fortunately, Sandy and I have been very busy ever since.
Let's come back to cryo.
(laughs) Okay, so 2002, we sold the business. Sandy retired because she is a sewer, buys sewing machines, makes quilts and does not have a spare minute. If you have not gone into a sewing store lately, you will be surprised by the 21st century computer controlled sewing machine, which you have never seen before. These new sewing machines are not only computer controlled, but they have cameras, Bluetooth, etc. A top of the line home sewing machine today sells for $20,000. It's like a car and probably more complicated.
I wasn't interested in retiring. I write a book in 2007 on personal identification, the history of driver’s licenses, passports, all type of personal identification. Why you are required to have identification documents today, and who invented the photo ID with your picture on it. Before 1900, nobody had any ID documents. But personal identification has become important, for the primarily reason that people are dealing with you at a distance over telephones, over the internet, remotely. They must be sure that you are who you say you are. At the same time, I joined a US National Committee with ANSI, American National Standards Institute. This group wrote procedures on proofing and establishing an identification profile for a person. It's generally not easy. Immigrants who come to America or refugees, they have absolutely no papers or documents whatsoever. How do you find out who they are, that what they say is true? It's difficult and it's usually only from what they say. You also do not have fingerprints or any other biometrics. I've been on that committee, it's been very productive and this is now a National ANSI Standard for the United States. Then I wrote a monograph about the two engineers and the origin of the original low-dose x-ray machine - The SafeRay. I've also traveled on a few archaeological digs, on a number of dinosaurs digs and field trips like that. That's a sideline. Coming back to cryo and 2015, Alex McPherson, Michael Rossmann's graduate student, and his wife Fran, would come to have lunch with us in Palm Desert. In February 2015, Alex mentioned, "The American Crystallographic Association meeting is going to be in Philadelphia this year. Since it's so very near me, just drive down and join us. Why don't you come down and attend the show?" This is the annual meeting of the American Crystallographic Association which has been around since 1946. It's one of the mainstays in terms of basic science associations. Harker and most crystallographers belonged to it. I agreed, "Okay, it sounds like fun." In July, I drove down for one day to the American Crystallographic Association meeting in Philadelphia. I'm standing at the door and Alex comes in with a group of other people, and he starts introducing me to everyone. Many of them are very senior crystallographers. He continued, "This is David Haas. He invented cryo-crystallography." At the time, I didn't make much of it. But then one of the fellows, Jim Pflugrath, showed me this cryo paper his wrote, it shows that cryocooling has been used to determine the 3D atomic structures on over 100,000 protein crystals. It just blew my mind. 100,000? I mean, when I'd finished crystallography in 1970, there were about seven protein structures known. 100,000. He says, "Yes, and they're being submitted at a rate of 10,000 a year now." They're all cryo-cooled. He said, "Every synchrotron has cryo-cooling apparatus. They're all cryo-cooled to reduce the radiation damage." So, I was just amazed. After the day at the meeting, I went home to find out more. I kept thinking to myself that, "This must be more important than I think it is". Jim also told me about the protein databank, the PDB. At home, I went online, and discovered that the PDB is the database for all protein structures worldwide. Today, 2020, they have 155,000 protein crystals structures. When I wrote the paper for the 2020 IUCrJ Journal, Elspeth Garman, who was gracious enough to do a search of the PDB to find out just how many of all of the crystals used for these protein structures were cryo-cooled. Her chart showed that more than 90% of these 3D protein structures were determined at temperatures around 100K. Something like 150,000 protein structures were determined using the cryo-cooling technique. In fact, every synchrotron in the world has cryo liquid nitrogen cooling systems with robotic control. After some time on the internet, I decided that I couldn't even read the papers because the language was so new to me. Fifty years out of the scientific field can make a difference!
I spent the next year or so taking some biochemistry courses and watching biology, structural biology lectures, just trying to learn this material. And 3D macromolecular structures are even a new field, called Structural Biology. I had never even heard that name before. Molecular biology, structural biology, all these new terms. And of course, the names of all the thousands of proteins are completely new. It took me many months to even become sufficiently fluent to read the papers. In 2016, we saw Alex and Fran several more times. and continued to have lunch together. Alex suggested "Why don't you see if you can attend the Cold Springs Harbor X-ray Methods course?" To my surprise, Alex was one of the two founders of the X-ray course 30 years ago, beginning it as an x-ray teaching course workshop. It is the primer X-ray workshop, still running ever year, 16 days at Cold Springs Harbor Laboratory on Long Island in October, a world-renowned laboratory. The Laboratory runs many courses, but the X-ray Methods course was the first, for 30 years. The formation and the development of structural biology has come out of this X-ray Methods Course at Cold Springs Harbor Laboratory. I called the Laboratory in February 2017, the responded a few days later with "You're invited to attend the 2017 Course, it's in October 2017. The Laboratory will provide dormitory, tuition, food everything's at no charge. 16 days." So, I attended, I can tell you, the most intense 16 days I have ever experience. They had classes from eight in the morning until eight every night, including laboratory work. And it was a full class of sixteen student plus about ten staff. What a fabulous experience, but it's unfortunate that they can only take 16 students. There's a substantial waiting list because of the limited amount of equipment for the hands-on workshops. So during the first week, we were given lysozyme to grow crystals. The crystals grew within a few days, lysozyme crystals, and then on Friday, individual crystals were scooped up in a loop and dipped into liquid nitrogen, cryo-cooling the crystal to 100K. The crystals were mounted onto a holder and put in a liquid nitrogen Dewar for transport by FedEx to the Brookhaven Laboratory synchrotron where the X-ray data will be collected. The next day, Saturday, we all traveled to the synchrotron and our crystals would be mounted by a robot into the X-ray beam. A complete set of X-ray data would be collected on a single crystal, one crystal in only one minute. Synchrotrons are very high-powered x-ray machines. The synchrotron x-ray beam is about 10 million times more intense than conventional vacuum x-ray tubes. What I saw was exactly what David Phillips had hoped for in 1965 - to be able to collect all the X-ray data from a single crystal. Absolutely mind boggling. Basically, I saw the realization of the five years work, 1965-1970, developing Macromolecular Cryo-crystallography. This event was like a Back-to-the-Future experience. I was transported back to the 1960s after seeing the practical application of the technique I developed and proved would work.
In 2018, I was attending the annual American Crystallographic Meeting in Toronto where I met Stephen Burley, the Director of the Protein Data Bank. He invited me to give a seminar at Rutgers on how cryo-crystallography was developed. I thought this was quite exciting, so we set the date for April 24th, 2019. He says, "We'd love to hear your presentation and how your work contributed to the success of protein crystallography." It was the first time that I actually had assembled all of the material that I needed to talk about the history - it happened 50 years ago.
The presentation at Rutgers University went well. I guess it impressive them because Stephen Burley suggested at lunch afterword, "You've just got to write this up as a paper." My response was that, "I'm not sure I can do that. To make it into a scientific paper, you need all the details, all the references, drawings." I thought that it was far-fetched but sure enough, the next day, the editor for the IUCrJ Journal emails me from the International Union of Crystallography - Edward Baker. He wrote that, "We'd like to have you write a paper. Here are the guidelines, blah, blah, blah. If you need any help, let me know." So, I spent the entire summer of 2019 locating as much cryo history and documentation as I could. I spoke to a number of people because all my personal materials (I mean everything) had been lost some years before. I wrote the paper and I submitted it in November 2019. It was quite a challenge. Elspeth Garman did the statistics on the number of cryo-cooled crystals deposited in the Protein Data Bank - more than 90%. I was able to round up all the other pictures, and I asked Ed Baker to read my first draft and comment. He thought it was a well-written paper and very interesting. So, after submitting it, he gave it to the referees for peer review, and the referees came back with positive recommendations. It was December of 2019, that's almost a year ago. The paper was published in March 2020. Several things proved interesting. One of the referees just praised the work and congratulated me on an important contribution to biology and medicine. He said, "This is really quiet a remarkable feat - and you did a nice job in presenting it. You actually presented a step-by-step History of Science paper of what you actually did." Discoveries just don’t come out of the air. How did this happen, the cryocooling idea? How did you come up with using cryoprotectants? I'm very pleased that I was able to write it in a professional manner. The second referee suggested that my example of the Lazarus Effect during the HIV epidemic as a benefit of this science was important. A true example of "Science for the Benefit of Humanity". By the way, did you get a chance to read the 2020 paper?
Oh, I've had to read it three or four times just to appreciate all these new detail. I'm really pleased how well it reads. It is a first-hand History of Science paper. That's how I wrote it. When I discovered the HIV Lazarus Effect, it made me proud to be a scientist! I used as the example of the success of cryo-crystallography the Lazarus effect for HIV in 1996. The Lazarus Effect decreased the death rate from 96% down to about 10%. Hundreds of thousands of HIV infected people are living normal lives. And this is a direct result of being lucky at the Weizmann Institute of Science.
So the second referee said , "I can see how Haas picked this as an example, but he has no idea what cryo-cooling and structural biology have done for medicine and science." I was just surprised. He's probably right since I still have had little exposure to the impact of structural biology to the sciences. As an example of that, just last week (September 2020) with the pandemic, I was in my car in the park here, I started reading Science Magazine. And on page 1119, this scientist, Ian Wilson, had published the structure of the COVID-19 antibodies. He had the structure of the spike protein from the COVID virus printed right there, on the page, and a second picture showed the structure of an antibody that was binding to it. He was explaining the RBD - the binding domain on the spike protein where the antibody atoms attach to the spike protein atoms. In the Binding Domain. I looked at it and said to myself, "This is really unbelievable. All this, all this structural biology was performed in just a few months." The COVID-19 virus is going to be handled quickly because of all of these coincidences that made structural biology happen. It just was really surprised. So, the referee was right. He said I could not even imagine the worth of my work fifty years later.
Sandy and my life have been really exciting. We've really been very lucky to have been a team-- she's the vice president as she wishes, of course. We have traveled through our life’s with vision, hope and work. Since we retired, I have prepared the Timeline for our lives. As part of this ANSI ID Committee, we learned about LifePrints. So, I prepared our family LifePrint. From our LifePrint, Sandy and I concluded that during our life, twenty-two of our life decisions were good, purchasing houses, accepting jobs, etc. We won. We found that seven decisions were bad, not so good. We really made mistakes and bad things happened. But what was surprising is that there were thirteen decisions, voluntary and involuntary events that happened to us, like going to David Phillips at the Royal Institution, that happened just by pure luck. So, thirteen of our life events happened because of pure luck, just being in the right place at the right time. This is really surprising, and probably a good example for others.
Well, David, now that we have worked up to the present day, we have traveled decades, we've traveled the world, we've traveled between labs and academia and industry. I want to ask, you know, for my last question, a forward-looking question because we're still right in the middle of this pandemic, what have your experiences in cryocooling and macromolecular crystallography and molecular structural biology. How do we get out of where we are now? What have you learned over all of your years in academia and industry that might serve as a blueprint for how we can get out of our current pandemic?
Well, I can tell you, it's already happening. If you look at the HIV pandemic, there is a graph from the CDC in one of my papers that shows between 1980 and 1996, hundreds of thousands of people became infected with HIV and died. In America, 700,000 Americans died from HIV between 1980 and 2015. And it took scientist ten years to start making antivirals that worked to manage the disease. Because the HIV protease enzyme was only identified in 1986, and it was the three-dimensional structure of this proteases that accelerated the drug design in 1989 that produced the successful antivirals several years later, in 1996. This was the HART cocktail of three drugs, FDA approved in 1995 and widely distributed the next year. Ten to fifteen years for HIV antivirals to be developed. This year, basically starting in January, scientists already had crystals of the COVID-19 spike protein and several other proteases. By March the structures had been determined, and the pharmaceutical drug designers were busy at work. It's called Structure-Based Drug Design. Whereas several potential antivirals were identified from existing drugs by the various pharmaceutical companies, specific targeted drugs were being worked on by March 2020. Antiviral and vaccine development against the COVID-19 virus was well underway in basically three months. It took ten years for the HIV structure-based drug design to begin, and sixteen years to bring them to the public. Molecular biology, structural biology have already made a difference. At the recent August American Crystallographic Association Meeting, which was held on Zoom, scientists were showing the structures of the COVID-19 virus and the structures of its proteins.
The scientists are actually doing their work. Medicine is doing its thing. "Science for the Benefit of Humanity" is already working against this pandemic. And before the end of the year, there certainly will be antivirals available. New antivirals. The vaccines, after they go through their testing. It is reported that there are 130 vaccine candidates, I'm sure that many of them will be successful. So just let science do its thing. Keep politics out of it.
That's such an important point. You know, right now, while we're in the middle of it, it could seem like this is lasting forever, but it's such a fundamentally important point to look at where we were with HIV research and to recognize that things actually now are happening at a lightning pace.
Oh absolutely. Remember that during the 1980s, if you became infected with the HIV virus, you had only a 4% change of living for more than 2 to 4 years. There was a 96% death rate for HIV. I was just amazed during the recent Crystallographic Meeting on Zoom, they were showing all these structures after just a few months. It's just mind-boggling. The scientists have got a handle on this pandemic. You just don't hear them talking because it's all in the scientific Journals and Meetings. They're just doing their thing.
Well, that is a much-needed dose of optimism and hope that makes all of the reasons why I was so excited to speak to you today even that more amplified, so that we can get this message out as soon as possible. Because, you know, it's always important for people to understand that physics and physicists are part of these stories as well. That it's actually fundamental to this whole story of how we get out of where we are. So, David, it's been an absolute delight speaking with you today. It's been so interesting to hear about the fundamental role of serendipity, a non-scientific concept of serendipity and how that's played a role in all of your adventures. The importance of having fun and pursuing your passions and not being so concerned about career decisions, and all that you've accomplished. So, it's been a delight and an honor to speak to you, and I'm so glad we were able to do this.
I'm also pleased. By the way, I basically told this HIV story in a very succinct way with a video I made for iBiology in December 2019. This has truly been a real Back-to-the-Future experience for me. Did you get a chance to watch the iBiology video?
I did. I did.
Well that's what the oral history is for. You have a lot more time to flesh everything out.
Good, well it was a pleasure speaking to you.
It's a pleasure.