An Interview with Howard Thames, PhD, FASTRO

By Naomi Schechter, MD and David Horowitz, MD

The following interview of Howard Thames, PhD, FASTRO, was conducted on June 11, 2020, by Naomi Schechter, MD and David Horowitz, MD.

Naomi Schechter:  It’s such a pleasure to have you for this interview today.

Howard Thames:  Thank you.

Naomi Schechter:  The first interview question that we have is about your background and where you were born.  I know that you let us know that you’re from Mississippi and Louisiana.  Is that correct?

Howard Thames:  Yeah.  Born in Monroe, Louisiana but my parents went back to Mississippi - both were from Mississippi - when I was a year old or something.  I spent the rest of my youth there, most of the time in Jackson, Mississippi.

Naomi Schechter:  What led you to your interest in chemistry and physical chemistry?

Howard Thames:  Well, that arose from a friendship with Billy Moore, whose father was a professor at Millsaps College in Jackson. But not of chemistry, he was a professor of history, his name as I remember: Ross Moore.  He got me interested in having a laboratory in the closet in our garage.  I exhibited in Science Fairs. Then when Billy and I came to the point in high school, in the 11th grade, of taking a course in chemistry, we realized that the person teaching it was the football coach.  So, that was an aspect of going to high school there and so his father got us accepted to Millsaps College even before we graduated from high school.  We did summer school, two summers in chemistry at Millsaps College.  After that (1959) was when I was accepted at Rice and went on via a chemistry major. 

Naomi Schechter:  Then, when you were in college, you were focused again on the physical chemistry?

Howard Thames:  And physics, yes.  Physics and physical chemistry.

Naomi Schechter:  You must have been good at math.

Howard Thames:  I was fairly good at math, yes.  I always enjoyed it.

Naomi Schechter:  And then you went on.

Howard Thames:  Well, after Rice, I had had a belly full of it and I decided to go into the army.  They found out that I could speak some German and French, and so they sent me to the intelligence-corps school in Baltimore.  I spent the next three years in Germany, in the Frankfurt vicinity.

Naomi Schechter:  How did you know German?

Howard Thames:  Oh, yes.  So here and there.  How did I know German?  Well, I took a couple of courses at Rice, but I was interested in it because of some books that I saw.  They were very famous and so forth.  I had a look at them in German and sort of started getting into it.  Then there was a friend there in my class who was German. I had some experience with it.  And something similar in French.  As a kid I had sort of an exposure to it through Dr. Fletcher who was French.  You probably wonder why he had the name that he had, if he were French.  I can explain all of that if you’re interested.

David Horowitz:  I would love to hear about that.

Naomi Schechter:  Please.

Howard Thames:  Okay.  Gilbert Fletcher's mother was French and his father was American.  He was born in Massachusetts, I believe in 1911, the same year my mother was born.  Several months after he was born his father died.  His mother pulled up stakes and moved back to Orléans in France and he grew up there.  I think he went to medical school in Paris and was a resident in Brussels when the World War II attack in 1940 began and the Germans were pouring in.  He was part of the famous huge retreat from Brussels to Paris that took place.  I don’t know if you’ve read about that - tens of thousands of people.  He went back to Paris.  But since he had an American passport, he was able in '43 or '44 just to get on a boat and cross over to the United States.

I’m going to get these years sort of mixed up, but he met my mother’s cousin Mary.  She was in a medical school in New York.  She was my mom’s first cousin, also grew up in northern Mississippi and was best friends with my mom.  She met Fletcher and they got married and everything.  Then he became sort of like a second father to me, and that was how I started learning French.

David Horowitz:  Tell me more about that. 

Howard Thames:  When I was young we would go over to see him and he would visit us.  My mother would tell me, "Now, when you pronounce his name, you know that girl down the street named Jill?  Jill Smith?"  Yeah.  "And you know what a bear is, right?"  I said, yeah.  "So what his name is, is Jill-Bear."  I’ll never forget that one.  Anyway, that’s just how it happened.

David Horowitz:  It sounds like you’ve really spent a lot of time with him growing up.

Howard Thames:  Oh, not when I was young -- once or twice a year, I think, they would visit each other.  Then his kids -- let me see, Walter was born in 1950 and Thomas was born in 1954.  Something like that.  But they lived in Houston because, after he and Mary got married in the late '40s, he became – just as MD Anderson was forming - the first radiation professor.  Sorry.  The first head of the radiation oncology department at MD Anderson in 1948.  So then he was in Houston and came back to Jackson occasionally.  Then in 1959 I came as a freshman to Rice and I would spend weekends at their house, and everything.  In that Word document I sent in, I explained how he is the one who really is responsible for connecting me up with cancer therapy and MD Anderson.

David Horowitz:  Yes.  So you said that you had an offer to go to Baltimore, to Johns Hopkins.

Howard Thames:  Right.

David Horowitz:  But he was able to get you in at MD Anderson.

Howard Thames:  Yeah.  I married in 1966 and entered grad school at Rice. Son was born 1967, daughter 1970 just before I finished my PhD thesis (“Spin Orbitals for the Helium-2 Wavefunction”).  Hopkins offered me $6,000 a year.  I didn’t see how that was going to work in Baltimore, which was where I received training for the intelligence corps.  So he talked to the head of biostatistics (Stuart Zimmerman) into taking me on for a year or so to do a postdoc there, to learn some statistics and all.  Things worked very well and I stayed on for -- on the first of June it’s 50 years since I started working there.  I’m still on as part-time having retired in 2005.

Naomi Schechter:  You mentioned you also knew Rodney Withers.

Howard Thames:  Oh, yes.  Well, after I got going there about two years or so, I was over at the Fletcher’s house for a weekend.  He and Mary were over there with the kids and all.  He said why don’t I come and meet Rod and see if I found his research interesting, and I said okay.  So I went and met Withers, I don’t know, about '74 or '75.  He immediately got me interested because he had sort of a quantitative approach to radiation biology.  He asked me how I would approach the problem of doing this and the other, and we began working together for many years until he left Anderson in 1980 to move to UCLA.  But we kept up the correspondence after that.  That was how it happened, Fletcher did it.

Naomi Schechter:  What I remember most about you is that you're so clinically oriented and collaborative.  So I imagine that a lot of those early works were kind of brainstorms between you and these other leaders.  Do you want to talk about some of your early work in radiation oncology, some of the projects you worked on?

Howard Thames:  Let me see.  That was a long time ago.

Naomi Schechter: Like the alpha/beta work.

Howard Thames:  Yeah.  The first alpha/beta paper was published by Douglas and Fowler in I think '76 or something like that.  That was about the same time that I was fitting all of that data from Rod and his associates.  You know Lester Peters was there at the time.  I’m trying to look through this list of papers to see sort of what we were working on.  We had all these models of the cell cycle and then we had a model for cobalt-60 dose distributions.  All of this old stuff, method for estimating dose-modifying factors.

But the main thing that got my attention was radio sensitivity, and so I was really interested in the alpha/beta ratio when it came out.  Then we showed that you could actually characterize fractionation effects in terms of the alpha/beta model: “Changes in early and late radiation response with altered dose fractionation: implications for dose-survival curves”.  That was in Red Journal 8:219-226, 1982.  So we sort of took off along those directions. During those years I had a close collaboration with Jolyon Hendry at the Paterson Inst., Christie Hospital in Manchester, that culminated in our book “Fractionation in Radiotherapy” (Taylor and Francis 1987).

I finally retired in 2005, after having done many, many things as you know.  You can look at the CV and tell.  Then they put me into this thing that Anderson has to keep their fingers on you, which is called a research professorship.  So they keep you on for half or third time and then you establish sort of what you were doing there and continue it or work with someone else.

After seven years’ participation in various research projects, starting in 2012 the CROR (Committee on Radiation Oncology Research) offered to start funding me.  It’s been going on 8 years now.  I worked with this person and that.  Nanoparticles was I think with Krishnan, wasn't it?  Anyway, that was some four or five years ago.  I can’t remember exactly.  Sunil Krishnan.

What I’ve been doing in the last three years or so is working in the brachytherapy research group run by Steven Frank.  He has assembled a retrospective, seven-institution dataset with about 14,200 patients.  The patients were treated either by isotope only, or by isotope plus androgen deprivation therapy, ADT, or plus external-beam treatment or both.

We had all of the baseline data on the patients and on each patient we had the sequence of PSA  measurements made post-treatment.  So we looked at it in several different ways.  One of them was, what is the best predictor of a coming clinical failure from the changes in the PSA profile?  As you know, way back 20 years ago we showed that PSA > nadir plus 2 was the best predictor of clinical failure after external beam therapy, using techniques called ROC analysis.  Then nadir+2 has continued in use, and so one question is should they use nadir+2 for brachytherapy?  I think that’s going to appear in the Red Journal.  And the answer is yes.  It is as good as some other things we tried.

The second one is, what is a good success definition, not a failure definition, in patients who have been followed sufficiently that the PSA bounces get passed.  We showed that something like the surgical failure definition of PSA two-tenths or greater, is sort of the borderline between absolutely cured, when it’s less than that; then two-tenths to five-tenths, about 90 percent of them, and so forth.

The other thing I’ve worked on is looking at risk groups.  In other words, how to decide whether a patient should receive ADT or not, or how aggressive the treatment should be, which isotope should be used and so forth?  Can you use the risk groups defined for external beam therapy 20 or 30 years ago?  I’m not sure.  And that’s what you see in the literature.  If you read brachytherapy papers, they are using the risk groups that were defined for external beam.  So I’ve been applying a method known as CART, acronym for Classification and Regression Trees, to separate those four different treatment groupings into statistically different outcome groups to try to piece together what are the risk groups.

In fact, we’re finding that T stage really doesn’t make a big difference.  That makes sense because brachytherapy is an ablative treatment and so you wouldn’t care too much how big the original tumor was.  That may be a factor if your endpoint is distant failure.  Then we’ve also found that Gleason score is very important and that the 3 plus 4 versus 4 plus 3 is important.  You shouldn’t try to just lock them into a Gleason score of 7 as you see in some of the data and other things.  So I’ve spent a lot of time on that.  That’s been in the last two or three years, I suppose, and I think they signed me up for another year.

David Horowitz:  It sounds like that’s been a very fruitful collaboration.

Howard Thames:  I hope that they've benefited from it.

Naomi Schechter:  You mentioned that sometimes the collaborations go in directions that are unexpected.

Howard Thames:  Yeah.

Naomi Schechter:  Can you comment further?

Howard Thames:  I really don’t want to mention any names, but I think you know what I’m talking about.

Naomi Schechter:  Are you coming from a biostatistical perspective that you’re recommending a conclusion, and that they want to go into a different conclusion?  Or are you saying that the research goes in a different direction?

Howard Thames:  I think research or treatments go in a different -- well, for example, in the 1990s there was a series of randomized Phase III trials to look at hyperfractionation for head and neck and for whatever.  There’s a fairly uniform finding that it was a treatment superior to conventional fractionation.  Then it was tried against other things like acceleration and so forth.  Subsequently I’d say that I don’t know why if it is because of health insurance limitations i.e. how much it costs to go treat for seven or eight weeks versus four or five weeks, and is probably not favored by the patient, but the tendency is to move away from that toward hypofractionation.  That’s just sort of then something I’ve not really come to grips with.

I just saw and I corresponded with Jens Overgaard about this paper they published in the Lancet in 2017.  I looked again at this meta-analysis they did of hyperfractionation versus other different fractionation schemes.  But at least with MD Anderson and most centers I think across the United States, things have drifted away from hyperfractionation.  That’s one of the things that I found surprising.

Naomi Schechter:  Like the high dose per fraction for hypofractionation, vs high total dose for hyperfractionation?

Howard Thames:  Right, going toward high doses per fraction, right, not low dose per fraction.  But my guess is that the physics and imaging have changed quite a bit in the last 20 years.  So it could be that I'm really not fully in line with all of those developments.  I don’t know really all the developments that have occurred there.

David Horowitz:  I wanted to take a step back to your collaborations with Dr. Withers.  The two of you had such a fruitful and long-lasting collaboration.  I saw that you also were instrumental in publishing his archives and making those publicly available.

Howard Thames:  Yes.

David Horowitz:  Would you be able to talk a little bit more about that?

Howard Thames:  Yes.  Well, Kathy Mason and Nancy Hunter were the main technical leaders in his experimental group and responsible for amassing all of that data from those experiments.  We talked about it.  That Rod had died of Parkinson’s disease about four years ago, I can’t remember exactly, and that it would be a shame that some of those things were relevant for a research that was going on in radiation oncology.  And it would be ridiculous for someone to try to start those experimental techniques up in mice again and so forth when it's already been done.

So we decided to put together all of that data, classified into different categories, and put it in the computer so that anyone who wanted to use the data could get access to it.  What I did was to convince Sunil Krishnan and his little group at CROR to make  all that available online using one of the systems there, so they could respond to incoming emails.  There have not been that many but some have asked for access to the archives, and so that’s why we did it.  To make it known, we put it in two or three of the radiation oncology journals – in the Red Journal and the Green Journal and so on.  That was it.

David Horowitz:  I think it’s a tremendous service and, again, honoring all of the work that you and he did to continue to make that available to the radio oncology community.

Howard Thames:  It’s really the work that he did.  Not that I did.  I didn’t do any of that.

Naomi Schechter:  Let’s talk about your long-time collaboration with Michael Baumann?

Howard Thames:  Yeah.  I went up to Mass General in the late '80s.  Herman Suit invited me to come and give a course in some kind of numerical stuff that I was doing in analyzing data and so forth, to the residents and grad students.  I went up there I think once or twice a year for several years.  Then, I think it was 1989, I met Baumann who was a resident there and who had come from Hamburg.  He’s a German, and it’s always fun to find someone who speaks German and everything.  He went back to Hamburg in 1991 as I remember.  Is that right?  1992, maybe.  And he was on the rad onc faculty there.  He then began to organize this annual meeting aimed at the residents—to bring them sort of up to date with things.  It was a student -- what do you call a one-day meeting -- where papers are presented and the students get a chance to present papers?

Naomi Schechter:  Journal class?

Howard Thames:  Something like that, yeah.  I can’t remember the name that he gave to it.  I’m struggling with that.  So he invited me to come and give the opening talk for several years in Hamburg.  Then I moved on more from that into collaborating with his grad students in analyzing newer data and so forth.  I would go over there twice a year maybe.  That lasted until 1995 or '96, or something like that.

After the Berlin Wall came down in 1990 he took a job in Dresden in 1996 or ’97 and moved the entire thing over there.  He wasn’t the department head there until 2002 or '03 or something.  About eight or ten years he was on the staff there and a guy named Prof. Thomas Hermann was the department head.  So I just continued what I’d been doing in Hamburg, but in Dresden.  The meeting continued in Hamburg a couple of years, so we would go between Hamburg and Dresden, but then it moved to Dresden, continued year after year.

Another thing I always went to was the annual ESTRO ski meeting in France.  I think I attended the first one in 1986 in Chamonix.  I would meet Baumann at this ski meeting after the mid-90s.  That continued on and on.  Then finally I think everything came to an end when he was hired to be the head of DKFZ in Heidelberg.  That was the end of the Dresden thing.  So, he is sort of head of the NCI kind of guy now.

But I did see him again when we organized a biannual meeting of the Gilbert Fletcher Society.  I became president of the Gilbert Fletcher Society in 2016.  They had a meeting in Houston and then in alternate years they had meetings overseas.  In 2017 I chose Dresden to have the meeting in, I spent the time to put the meeting in Dresden together in collaboration with the woman who became chair when he left.  Her name is Mechthild Krause.

We had a very interesting meeting there.  We hired this tour group to take us around the very interesting places close to Dresden.  I even got some grandkids to come over there with their parents.  But that was the end of my association.  I email with him sometimes, but he’s a very busy guy now.  So that was my association with Michael Baumann.

Naomi Schechter:  You were also in the army intelligence corps in Germany.

Howard Thames:  Yes, I was.  Yeah, '63 to '66. 

Naomi Schechter:  Can you tell us anything about that?

Howard Thames:  Not really.  I can tell you what I was doing.  I worked at training the spies from the East to communicate by short-wave radio with the West.  The communists in East Germany were doing the same thing, in reverse direction.  They had a shortwave radio transmitter in East Berlin and we had ours in Dachau outside of Munich, where the Nazis had that concentration camp.

What happens is that back in those days you had a woman who would speak on the radio in terms of groups of numbers.  Each group had five numbers in it.  She would repeat the group of numbers once and then move on.  It sounded something like this in German: eins, fünf, acht, neun, Sieben and so forth.  She and her replacements just went on and on 24 hours a day.  The agent would compare these numbers with certain text in a book we gave him, to derive our message. My job was going to different places in Germany, France, and Italy where I could get in contact with these guys from the East, to teach them how to use this book to convert those numbers into text so they can understand the message.  If you know what I mean.

David Horowitz:  Uh-huh.

Howard Thames:  This is called a one-time-pad system.  What we had for each of those guys would be a system of using the date and time of day and so forth.  Then he would get a copy of this book such as War and Peace.  It would be exactly the edition that we had back in Frankfurt.  What they would then do is on the right day, at the right time, they would put together the message, then his agent handler would go and say I want to tell him to do this and any other way.  They say, okay.  So then they would translate that into numbers from the text.  Like you would open to page 650 (depending on date and time of day) in War and Peace, paragraph two, and then you start reading the words.  You see what I’m talking about?  It was an encryption method.  That’s what Howard spent his time in Germany doing.  So I traveled around a lot and got in trouble sometimes.

David Horowitz:  What sort of trouble, if you can say?

Howard Thames:  Well, for example, once I had to teach them how to use the shortwave receiver and transmitter so they could transmit back.  I’ll never forget there was this hotel in Konstanz, on the Bodensee at south border of Germany and Switzerland. I would always get the hotel room on the top floor to try to get away from all the guys drinking beer at the bar on the first floor, and everything.  But the one thing that happened was that when we actually hit the key and sent stuff out, the TV set down in the bar went blah, like that, and just everything blurred.  Then they found out who was doing this and I was forbidden to do that anymore in that hotel.

Then there was a time that I was bringing one of those transmitters to this Polish guy who I was going to meet in Paris.  I took the train down there.  I don’t know how they knew this but somehow the police stopped me when I got off the train at the Gare de l’Est (East Station) in Paris and said they wanted to see what I had in my bag.  They took it.  I had a German passport, so they brought in a guy speaking German. After about 1 minute, he told them I wasn’t a German, I was an American. So, I got arrested, had an overnight in the police station.  But then they contacted the American Embassy and all.  They came and got me out.  So things like that did happen.

David Horowitz:  It certainly sounds like your French and your German served you well.

Howard Thames:  Here and there, yeah.  I just wish I could still do it.  I’m losing it as time goes by, but I can give you some French or German if you really need it.  Maybe at another time.

Naomi Schechter:  How did you manage the balance between your career and your family life?

Howard Thames:  Yes, of course.  There still had to be camping trips.  There had to be trying to get my daughter interested in music because I always loved to play the piano and everything.  I don’t know.  It’s hard to remember.  It was a long, long time ago. The son was born in '67.  The daughter in '70.  So they’re in their 50s now.

Naomi Schechter:  You mentioned that your words of wisdom would be focus, focus, focus.  Do you want to elaborate?

Howard Thames:  I think what I was trying to say is that in my experience, as you pick out something, a direction to go in, you might as well keep your eyes on that direction until it shows that it’s not going to be a success.  Leave your eyes off of other possible directions.  Don’t be constantly diverting, if you understand what I’m saying, and moving this way and that.  Stay focused on what you’re doing now.  If you have to change, then change.  That’s what I meant.

Naomi Schechter:  Is there an example that you wish to share from your life experience?

Howard Thames:  Yeah.  For example, I got closely working with Rod Withers.  This would have been the late '70s, early '80s.  There was some pressure to interest me perhaps into moving into a more biostatistics-oriented direction for example, in planning clinical trials and in setting up - you know what I’m talking about - the numbers of patients required and all of this kind of thing.  It was an interesting thing to do but my decision was that, as long as you’re on track and having some success in a given direction, you'd be best advised to stay with that.  Stay focused on it.  Don’t try now to start spending a couple of hours a day learning how to play basketball or something.  Does that make sense?

David Horowitz:  Absolutely.

Naomi Schechter:  I think it’s good advice.

Howard Thames:  That’s what I did.

Naomi Schechter:  How would you describe your greatest accomplishments?

Howard Thames: I don’t want to seem too overly satisfied.  I’d say that the success stems from application of techniques that you learned in chemical physics and things like that to problems that arise in interpreting radio biological experimentation.  That’s where I think I succeeded best.

Naomi Schechter:  What would you want to make sure you’re remembered for?

Howard Thames:  I have to be careful here.  I have to be careful.  I’m very happy with all of it.  The early successes were with interpreting Rod Withers’ technique.  Let’s see.  From there, we moved on to looking at -- I don’t know.  I'm trying to think.  It’s going back so far.  It’s hard for me actually to cook it all up.  I can talk to you about the last three or four years but --

Naomi Schechter:  Well, if I look at it, it was in dose response and fractionation.

Howard Thames:  Yeah.

Naomi Schechter:  And dose response relationship.

Howard Thames:  Dose response relationships, fractionation, sensitivities, how does this change with oxygenation versus lack, you know, the cells are lacking in oxygen and so on if they become radioresistant, and how does this all fit together in trying to piece together the results of a fractionated treatment?

Naomi Schechter:  Your career really spanned the physical chemistry, and the biology, and the statistics.  So you have such deep insights into all fields.

Howard Thames:  Oh, that's nice of you to say that.

Naomi Schechter:  That’s why we wanted to honor you.  We appreciate it.

Howard Thames:  Nice of you to say that.

Naomi Schechter:  And you're very humble.

Howard Thames:  Thank you.  Thank you.  I’m very honored by this call.  I can’t tell you. Naomi Schechter and Horowitz, yeah, I have to remember you guys.

David Horowitz:  Thank you.

Naomi Schechter:  We’re honored to be on this phone call with you honestly.  So thank you so much for taking the time to tell us more about your life.

Howard Thames:  Thank you for calling.  Well, I hope that I cleared things up for you.  I don’t know if it was mysterious or not.

Naomi Schechter:  Well, we learned more about you and about your friends and family who are also leaders in our field.  You live the dream of many.  So thank you for sharing your stories with us.

Howard Thames:  I was very lucky to have Gilbert (Jill-bear) Fletcher as a second father.  I'd say none of these things would have happened otherwise.

Naomi Schechter:  But I want to tell you we really so much appreciate you taking the time to share with us.

Howard Thames:  And I appreciate it.  Thank you very much.  Thank you.

Naomi Schechter:  You’re welcome.  As being on the head and neck service and I worked with Dr. Kian Ang and others there, so I know it was like a lively group.

Howard Thames:  So you knew a lot of the people I worked with, yeah.

Naomi Schechter:  Yeah, yeah.  I think that your accomplishments speak for themselves.  We’re really just so grateful for your contributions to the field of radiation oncology.  Thank you.

Howard Thames:  Thank you very much.

David Horowitz:  Thank you so much.