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National Cancer Institute H= istory Project
Interview with Dr. Ti = Li Loo
June 9, 1998
Interviewer: Gretchen Case<= /p>
History Associates, Inc., R= ockville, MD
GC: If you would just say your = name for the tape recorder.
TL: My name is Ti Li Loo.
GC: Okay. This is Gretche= n Case of HAI. I am interviewing Dr. Ti Li Loo. Today is June 9= , 1998, and it is about ten o'clock. Okay. Should I just start = by asking you questions?
TL: Sure, sure.
GC: Okay. I usually start= by asking about your education and how you came to the NCI, so where you s= tarted from and how you got to the NCI.
TL: Actually I went to, my coll= ege education was in China, at a university. The name was Tsing Hua U= niversity, which was located in Beijing. Tsing Hua was quite famous.&= nbsp; We had achieved three or four Nobel Laureates. The school was f= ounded by the Boxer Indemnity Fund. That is, in 1900, I think, there = was a war between eight powers, including the U.S., and the Chinese imperia= l government, and as a result of the war, China was compelled to pay indemn= ities to these eight powers. The U.S., under President Theodore Roose= velt, then decided to return the money to China and founded a university, c= alled the Tsing Hua University, which is reputed to be the Harvard of China= . And I went there.
I was trying to study medicine the first year. The War broke out a= fter the second year and we moved; we evacuated from Beijing and went to Ch= angsha and finally Kunming. Tsing Hua became associated with two othe= r universities and was called Southwestern Associated University. I graduat= ed from there in 1940. In 1942 I got a scholarship to study in Oxford, and = I went there in 1943, at Magdalen College of Oxford University. I spe= nt four years there to study chemistry and pharmacology. And then I w= ent over to the U.S. Initially it was to study medicine but it ended = up I was doing a postdoctoral fellowship. The first job was at the Un= iversity of Maryland, then I moved to Cincinnati and worked with Dr. L. H. = Schmidt, who was the Director of the Christ Hospital Medical Research Insti= tute.
After three or four years I was recruited by Dr. Gordon Zubrod to join t= he staff of the NCI. That was in 1955 after I became an American citi= zen=E2=80=94during the Korean War I had a rough time in this country, becau= se I wasn't allowed to go home and also I was not allowed to work, because = I wasn't a citizen. But through the influence of Senator Howard Taft = I was made an American citizen at the end of 1954, shortly after Christmas,= I remember. Then in 1955 I was recruited by Dr. Zubrod, who was an exceedi= ngly impressive, fine physician, scientist, and administrator. He wan= ted me to work on the pharmacology of anticancer drugs. At the time m= y colleagues included Dr. David Rall, Dr. Paul Condit, Dr. Jack Davids= on, and Dr. Marion Freeman. Later on Dr. Zubrod was made the Clinical= Director, in addition to being the Chief of the Medicine Branch, and the P= harmacology Laboratory was headed by Dr. David Rall. Then the clinica= l side of the medical branch was taken over by Dr. Emil Frei (who is called= Tom) and assisted by Dr. Emil Freireich (who was called J). The= y were the intellectual twins.
GC: Were they called the intell= ectual twins, or is that just how you looked at them?
TL: Yes, because constantly the= y were paged; you would hear Dr. Frei, Dr. Emil Frei, Dr. Freireich, D= r. Emil Freireich. [Laughs] They were the twins. I worked there until 1965,= when Dr. Frei decided to join the University of Texas M. D. Anderson Cance= r Center. He was recruited by another very famous and energetic leade= r, Dr. Lee Clark. So, Dr. Frei asked Dr. Freireich and a few others, = let me see now, Myron Karon, Dr. Myron Karon, Dr. Gerry Bodey, Dr. Ed = Gehan, and myself to move from the NCI to M. D. Anderson. And I worke= d there until 1965. I retired in 1965 and returned to the Washington area a= nd since that time I have been on the faculty of George Washington Universi= ty Medical Center Pharmacology Department. I officially retired a sec= ond time in 1993, but I am still, my name is still on the faculty list of t= he Pharmacology Department at GWU.
GC: Do you still teach or resea= rch down there at all?
TL: Not any more. No.&nbs= p; I had my last grant from the NIAID from 1990 to 1995, I think. All= the dates are iffy, because I can't remember the exact dates.
GC: Okay. Well, the dates= I can check up on. That's fine. How did you know Dr. Zubrod?&n= bsp; How did you come to know him?
TL: Well, he was a very close f= riend of Dr. Schmidt. When I was at the University of Maryland, my bo= ss was the late Dr. Drake, D-r-a-k-e, Nathan Drake, and he is a close frien= d with Zubrod and Schmidt, Dr. Schmidt. They all worked together on t= he malaria project during the war.
GC: Okay.
TL: And then Dr. Schmidt offere= d me a permanent job as a research associate at the Christ Hospital Medical= Institute. My wife expressed a desire to move back to Washington, be= cause she was brought up in the Washington area; her father was a diplomat,= a Chinese diplomat. And since I became a citizen, I could work for t= he U.S. government. So, I was interviewed by Dr. Zubrod, who was clos= ely associated with Schmidt. They were all very good friends. D= r. Shannon, of course, was the U.S. chief of the malaria research project.<= /p>
GC: &= nbsp; That was Dr. James Shannon?
TL: Yes. He died about tw= o years ago.
GC: That's right. Now, wh= en Dr. Zubrod asked you to come to the NCI, did he ask you to come for a sp= ecific project, or did he ask you just to come work for him and then .= . .
TL: Well, yes and no. Not a spe= cific project, but to work more or less in the area of cancer chemotherapy,= to study the pharmacology, which involved the disposition, the metabolism,= and the mechanism of action of anticancer agents. That's a broad, broad ar= ea. However, I'm allowed to choose whatever drug I wanted to study. H= e was a very broadly minded man.
GC: So, what was your first pro= ject? What did you choose to work on?
TL: First I worked on some thio= purines related to 6-mercaptopurine. Then the next one was on methotrexate,= which is a very important drug even today.
GC: Was that with Dr. Hertz?
TL: No. That's Dr. Li.&nb= sp; I was working on the basic science side. The clinic side was Dr. Li, Mi= n Chiu Li, who died, unfortunately, of a heart attack about twenty years ag= o.
GC: So who did you work most cl= osely with on these projects?
TL: Well, in the beginning I wa= s with Dr. Zubrod, who was the Chief of the Medicine Branch. Then later on = he was the Clinic director. The Pharmacology laboratory was taken over then= , first was Dr. Condit and then succeeded by Dr. David Rall.
GC: Did you work on your own, o= r would you have a staff of lab assistants?
TL: I had technicians, and late= r on I had two junior associates, recruited by me. One was Dr. O= liverio, Vince Oliverio.
GC: Oh. I am going to try= to interview him, too.
TL: Oh, yes. He is a = very intelligent fellow. The other one was Dick, Richard Adamson= . He is an amazing man. He got his Ph.D. when he was twenty-two= .
GC: Twenty-two?
TL: &= nbsp; Yes. He graduated from college at eighteen. He was one of the w= hiz kids.
GC: I guess so.
TL: Yes. We had quite a few whi= z kids during the time when I was there. There were two very importan= t things that fundamentally affected the NCI. One was=E2=80=94it was = during the Vietnam War era, in that era=E2=80=94so, a lot of the scientists= and physicians who didn't want to fight the War; they joined a uniformed s= ervice, the Public Health Service (PHS), and were commissioned PAs, officer= s with their own uniforms and ranks and so on. Some of these people w= ere extremely bright, for example, Frei, Freireich, Dave Rall, and Adamson.= They later on turned out to be great leaders in the area of biomedic= al research, particularly in cancer research. One important thing:&nb= sp; the time was right for these people to get together under the leadershi= p of Dr. Zubrod.
The second thing is the Cancer Act passed in Congress and all of a sudde= n we had a lot of money to spend. Dr. Zubrod took full advantage of t= his in developing the world-famous area of cancer chemotherapeutic research= . Although an unassuming man, the fact is that without him there was = no modern cancer chemotherapy. He was instrumental in integrating the= clinical with basic research in cancer chemotherapy and made chemotherapy = into a respectable modality of cancer treatment.
So, a lot of credit must be given to Dr. Zubrod, who is, as I said, one = of the founding fathers of modern cancer chemotherapy. He is a scient= ist and physician and administrator, and a great leader. In the clini= cal side, of course, Frei and especially Freireich. In the basic scie= nces, Dr. Rall and Dr. Adamson and Dr. Oliverio. And then later on, t= he younger generation was Dr. Bruce Chabner and Dr.Vince DeVita. Dr. = Oliverio was Vince DeVita's mentor. He trained him in the laboratory.=
GC: Oh, I did not know that.&nb= sp; I have interviewed Dr. DeVita, too.
TL: Oh, yes. He was, late= r on, of course, the NCI Director. Also he is a graduate of GW Medica= l School, our medical school.
GC: Right. That's right.&= nbsp; You mentioned that Dr. Zubrod=E2=80=94you're right, he's very unassum= ing; he doesn't take as much credit as he should=E2=80=94that he really cha= nged the way chemotherapy was perceived as being a modality that was worth = something.
TL: Yes.
GC: How was it perceived before= NCI started working [on chemotherapy]? Or did it even exist?
TL: Before there was no scienti= fic basis. It has a haphazard kind of study. The first real stu= dy was by Dr. Gilman and Dr. Goodman, who noticed that people gassed by mus= tard gas had a tremendous leukopenia. Their white cells were wiped ou= t. So he thought maybe in that case it would be interesting to treat = leukemia patients with mustard gas. Of course, later on that develope= d into nitrogen mustard, which was a nitrogen analog of mustard gas.
GC: Yes. Actually, one of= my relatives was treated with that treatment.
TL: Oh.
GC: It's an older one. Th= ey don't use it any more, do they?
TL: They still use some sort of= mustard derivative, yes.
GC: Oh, they do? When did= you begin working with Dr. Frei and Dr. Freireich?
TL: &= nbsp; That's during the time when I was working with Dr. Zubrod. Yes.= I was in the basic science arm and they were in the clinical arm.&nb= sp; Another thing Dr. Zubrod did was to incorporate, to make the basic scie= ntists and the clinicians work together as a whole. MDs and PhDs trad= itionally have sort of a rivalry. The MDs think the basic scientists are ju= st =E2=80=9Cway out=E2=80=9D and know nothing about patients, and the scien= tists, the PhDs, think the MDs are just pill-pushers. But under Dr. Z= ubrod, he could make them integrate into a very harmonious entity. Th= ey worked together on the same problem. So, that's another thing:&nbs= p; You must give, people must give, a great deal of credit to Dr. Zubrod, w= here he can, as a leader, to make this working together as one unit: = A unified concept of cancer chemotherapy. That was really wonderful.<= /p>
GC: How did he do that? W= hat did he do that helped that?
TL: He is a physician, but he d= id pharmacology research with Dr. E. K. Marshall, who was the Department Ch= airman of Pharmacology at Hopkins. Dr. Marshall was also a marvelous = man. He started as a professor of physiology. He's a physician,= but spent a lot of time working in the laboratory. In the beginning = he was a physiologist and Hopkins decided to have a department of pharmacol= ogy and they started to recruit. And look who they recruited=E2=80=94= they recruited Dr. Marshall, who was a professor of physiology. And t= hen Dr. Zubrod had a keen interest in pharmacology studies, so he went= there and worked as a fellow with Dr. Marshall and learned the basic = lab techniques in the area of drugs. That's how Dr. Zubrod started to= incorporate basic science into clinical medicine.
GC: Because he had experience w= ith both sides of the work?
TL: Yes, yes.
GC: &= nbsp; On a daily basis did he do anything to kind of keep people working to= gether? Did he have meetings?
TL: He was working in the labor= atory, in addition to seeing patients at Hopkins. But he went to St. = Louis as a professor of medicine and pharmacology, I believe. You hav= e to ask him. He wrote a book. Have you seen the book?
GC: Yes.
TL: He gave you a copy?
GC: Yes. The Stairway of Surprise?
TL: Yes, yes.
GC: It's beautiful!
TL: Yes.
GC: It's really beautiful.
TL: So, you know a lot about hi= s career at NCI.
GC: When you were at NCI, did y= ou see patients as well as working in the lab?
TL: No. I'm not a physici= an. I'm a scientist.
GC: Okay. But you would n= ever accompany the physicians or anything?
TL: Yes, I did.
GC: Oh, you did?
TL: I made rounds with Dr. Zubr= od.
GC: Oh, you did?
TL: Yes. Even though I'm = not a physician. It was very confusing, because I am also introduced = as Dr. Loo, even though I'm not a physician. So, when I made rounds, = they [the patients] would think I was a physician but I was careful to say = I'm not a physician. I'm not clinically qualified. I'm a labora= tory scientist.
GC: But you would go on rounds = with Dr. Zubrod?
TL: Yes, yes.
GC: Did you get to know the pat= ients at all?
TL: Some of them, yes.
GC: Do any stand out in your me= mory as ones that you remember clearly?
TL: Yes. There was a comm= ander, a Navy commander called Commander White, I think. He had carci= noid tumor, I think. That is also a very interesting disease that is = sometimes responsive to chemotherapy, carcinoid tumor. He had it in t= he small intestine, I think. Under Dr. Zubrod's leadership, Dr. = Hertz and Dr. Li demonstrated the treatment of the trophoblastic tumors wit= h methotrexate. That was a major step in the history of cancer chemot= herapy, because before that the only thing was nitrogen mustard, and this s= hows that certain antimetabolites would work, too, even though in a limited= fashion.
GC: Now, you said you worked on= methotrexate as well?
TL: Yes.
GC: &= nbsp; But your project was totally separate from Dr. Hertz and Dr. Li?
TL: We used his patients' mater= ial, and also we used patients for the clinical pharmacology studies. = This was later done entirely under the direction of Dr. Oliverio and Dr. E= d Henderson.
GC: Ed Henderson. That's = not a name I've heard yet.
TL: Ed Henderson, I guess he re= tired. He's now with the FDA.
GC: The FDA?
TL: Yes. They published t= his, too. Oliverio and Henderson published the first definitive study= on the pharmacology of methotrexate in man.
GC: What was the Clinical Cente= r like when you got there? It just opened in 1953, and then you got t= here about two years later.
TL: Yes. It was very acti= ve. Of course, it was a new concept. The most important part wa= s the Heart Institute. They really worked very, very close together, = the clinicians and scientists. They had the world's most leading, the= most successful biochemical pharmacologists at the time under Dr. Brodie, = B-r-o-d-i-e, Brodie. They call him Steve, even though Steve was not h= is real name. Also Dr. Udenfriend and, of course, a Nobel Laureate, D= r. [Julius] Axelrod. Dr. Zubrod just wanted to start the same kind of= set-up as the Heart Institute, in having a group of scientists working clo= sely with the clinicians at NCI, and he succeeded beautifully. You ca= n say he was in the right place at the right time, because of the influx of= all these very bright scientists and physicians into the NIH, and also bec= ause of the Cancer Act, which was very much supported by a lady called Mrs.= Lasker.
GC: Mary Lasker?
TL: Yes.
GC: Sure. Did you ever me= et her, or did you know her?
TL: I met her once, but she cou= ld hardly remember me. She would come in and review our progress, and= Dr. Zubrod would make us present our major findings before her and before = other visitors. And also in the Congress, of course, Lister Hill, I t= hink, a senator, Senator Hill.
GC: &= nbsp; He's from Pennsylvania, I think? [editorial note: Lister Hill was a senator from Alabama]
TL: I forgot where he was from.= I remember very influential senators and congressmen, plus Mrs. Lask= er, helped a lot in pushing the enactment of the Cancer Act, which would al= so benefit us, after we left NCI, with Dr. Frei as the leader, at M. D. And= erson, because all our studies were supported by the NCI, through the contr= act or grant mechanism.
GC: Okay. Even when you w= ere at M. D. Anderson?
TL: Yes. We still were kn= own as affiliated with NCI, because we worked very closely with our past co= lleagues, Drs. Oliverio and Adamson, and later on Johns, David Johns. = You probably heard of him.
GC: Yes. So, you mentione= d that there was a lot of money. When you needed laboratory equipment= or resources or people or anything like that, was that easy to get or was = it hard to get?
TL: Oh, quite easy!
GC: Really?
TL: We were fully supported, fi= rst at the NCI. Dr. Zubrod would put his whole weight behind it, so w= e had no problem getting equipment and [chemical/biological] agents and per= sonnel. The only thing that was a problem was space, not enough space= .
GC: Oh, really?
TL: Yes.
GC: And was your laboratory in = the Clinical Center?
TL: Yes. In the first pla= ce, in the beginning, it was on the sixth floor, then we moved to the tenth= floor. Dr. Zubrod's office was also on the tenth floor, as well as t= he Cancer Ward was on the tenth floor.
GC: So, you were on the same fl= oor as the patients.
TL: Yes.
GC: And what about getting peop= le? Was that ever a problem, getting people?
TL: &= nbsp; Well, getting people, you have to go through the Civil Service, the u= sual government regulations. So, it was not as easy as when we moved = to Texas [M. D. Anderson]. The caliber of the junior scientists, the = technicians, if I may say so, was somewhat higher in Texas than at NIH.&nbs= p; The reason is at NIH all the technicians were protected by Civil Service= . It's impossible to fire them, if they're not competent. But y= ou don=E2=80=99t have to record that! Because I have high respect for= the NCI and my colleagues there. I just feel my technicians and the = research associates at M. D. Anderson were of somewhat higher caliber. = ; They were really wonderful people: very competent, worked very hard= . They virtually made me. Everything I have done is through the= ir help; without their help it is not possible.
GC: That's fine. Now, you= 've mentioned that you had a couple of associates working for you, Dr. Oliv= erio. Were you allowed to choose them, or were they assigned to you?<= /p>
TL: No. I recruited them.=
GC: You recruited them?
TL: Yes. Now, Dr. Adamson= was recruited by Dr. Rall, I think, and assigned to me. Let's see, w= ho else? Those are the two major ones.
GC: &= nbsp; What was the last name of that doctor?
TL: Well, Dr. Adamson and Dr. O= liverio.
GC: They were the only two.&nbs= p; Okay.
TL: I recruited people like Dr.= Kurt Kohn, who is also now a famous biochemical pharmacologist. He w= as most impressive. I hired him to work with me for half a year and I= exhausted all the things I could teach him.
GC: Really.
TL: He was so fast and so much = ahead of everyone. So I sent him to Harvard to do a Ph.D., and he ret= urned with the Ph.D., and M.D. A fantastic man! That's one of t= he people I remember most clearly.
GC: It sounds like you had some= amazing people to work with.
TL: Incredible! Incredibl= e! Such great leaders! I was so fortunate, because I also was a= t the right place at the right time with the right people.
GC: When Dr. Zubrod asked you t= o come to the NCI, did you know what kind of place it was? Had you he= ard of it before? Did you know that it had a reputation?
TL: Yes. Mostly because o= f the Heart Institute, because of Dr. Brodie, Dr. Udenfriend, those famous = people. Dr. Gillette, James, Jim Gillette. But when Dr. Zubrod = said he wanted to have the same set-up at NCI, I felt this is really a wond= erful opportunity. Who could possibly join the NIH and world-famous m= edical research institution and to be close to those leaders and be on the = ground floor to build up something in the cancer chemotherapy area. O= f course, in the beginning we were quite naive. We thought we could c= onquer cancer just like we could conquer malaria (today even malaria is res= urging as one of the major health problems) because nobody at the time coul= d realize the emergence of resistance. In this regard we must give a lot of= credit to Dr. L. H. Schmidt, who studied the chemotherapy of malaria and w= as also a world-famous man. He was one of the first to demonstrate th= e resistance of certain malaria bugs to chemotherapy. And then, of co= urse, now cancer is gradually yielding to the combined effort of chemothera= py and biotherapy. I think we have made major, really tremendous prog= ress=E2=80=94especially the current people, the young investigators. = They know so much. Compared with us they were so much well-trained an= d extremely intelligent and with such a broad vision. I think compare= d with them, I know they are just way ahead of our generation, in my view.<= /p>
GC: &= nbsp; But then the NCI was ahead of anything that had been done before, rig= ht?
TL: Oh, yes. The NCI=E2= =80=94another important thing is they spent most of their money in extramur= al research. So the money was equally, evenly, distributed among many= , many cancer centers, and where they had extraordinary talents, too, like = M. D. Anderson and Sloan-Kettering Institute and Roswell Park. But th= ey must not forget they were very generously and very intelligently support= ed by people sitting at NCI doing the administration: Dr. Zubrod, Dr. Olive= rio, and Dr. Vince DeVita. They did a very excellent job in distribut= ing the funds, to see that progress was made in every area. This is j= ust as important as laboratory research.
GC: And when you were on the ot= her end of that, when you went to M. D. Anderson and you were then receivin= g money from NCI, how was that? Did you still feel that connection to= NCI?
TL: Yes, because we had to subm= it proposals to the NCI and go through the peer review, and also review by = the NCI and, of course, by our former colleagues and supervisors. So,= intellectually and scientifically, we were just very close together.
GC: And, of course, you still k= new all the people that you had worked with for all those years?
TL: &= nbsp; Yes. We had to recruit de = novo, all anew, build a new set-up at M. D. Anderson. Under Dr. = Freireich, especially, it had become another international center of cancer= chemotherapy.
GC: Because basically your whol= e team, that whole team of people, went to M. D. Anderson, right?
TL: Part of them. Some of= the important people didn't leave, like Dr. Carbone, Paul Carbone, Dr. Hen= derson, Dr. Oliverio. They stayed behind.
GC: Was it a hard decision to m= ake, to leave the NCI?
TL: Yes. In some ways yes= and in some ways no. Of course, we had made friends. Our child= ren were reluctant to leave their friends and this area. My wife was = brought up in the Washington area, so she was reluctant to go. But it= was a tremendous adventure to go to Texas. To us it was a wild country, yo= u know, the Wild West. It turned out to be quite an adventure. And cr= edit must also be given to Dr. Clark, Dr. Lee Clark. He played a very= major part in the cancer research both nationally and internationally, and= nationally and locally at M. D. Anderson. He built M. D. Anderson Re= search Institute, the hospital institute. He made it into one of the = biggest and the most important ones in the world.
GC: &= nbsp; And it still is.
TL: Yes. He can be classi= fied as a benevolent autocratic director with a Texas mentality and persona= lity. Absolutely a lovable man. But his words go. He says= this and you must do it Or else!
GC: Sounds very different from = Dr. Zubrod.
TL: Ah, yes, yes. Dr. Zub= rod was democratic.
GC: So how would Dr. Zubrod man= age things on a day-to-day basis?
TL: He had to delegate his auth= orities. He had very capable help in the person of Dr. Nat, Nathaniel= Berlin.
GC: I interviewed him, too.
TL: Yes.
GC: He's wonderful.
TL: Yes. He's a physician= and a medical physicist with a Ph.D. And a lot of extraordinary tale= nts were helping Zubrod, like Dave Rall, Adamson, and Oliverio, DeVita, Geo= rge Canellos.
GC: Okay, I've heard that name.=
TL: Bruce Chabner.
GC: Now, can you tell me about = Grand Rounds, what were Grand Rounds?
TL: Oh, Grand Rounds were the i= mportant occasion for integrating science with clinical medicine, because w= e were all encouraged to attend them and we did attend. I learned cli= nical management of cancer mostly through attending the Grand Rounds, heade= d by Dr. Zubrod and Dr. Frei and Dr. Freireich. They would prese= nt different subjects. For example, they were talking about the troph= oblastic cancer and Dr. Li and Dr. Hertz would present, and the laboratory = scientists at the time were Condit and Marion Freeman, who would present th= eir studies of the disposition of methotrexate, how the blood levels, the C= SF [central nervous system] levels relate to the clinical response=E2=80=94= that kind of approach. And I would present what happened in the body,= how it was metabolized and so on.
GC: &= nbsp; So everybody got to hear the other side.
TL: Yes, yes.
GC: The other end of what was g= oing on.
TL: Yes, yes.
GC: And how often did Grand Rou= nds occur?
TL: Every week.
GC: Every week?
TL: Every week would be present= ed some kind, some different subjects, different studies, ongoing studies, = and some major, major problems indicated in the laboratory and so on. = This tradition was carried on at M. D. Anderson.
GC: At M. D. Anderson?
TL: Yes. Especially under= Dr. Freireich, who was very effective in integrating science with medicine= .
GC: And that was something he h= ad learned at the NCI?
TL: Yes. He learned a lot= of things at NCI and did the same thing at M. D. Anderson. They recruited = fellows and they were required to first serve a year on the wards, and then= one year in the laboratory. So they know how laboratory research is = conducted. They pick their own mentor and spend a year or two in the = laboratory, in the same place, the same time. Dr. Freireich carried o= n the same tradition. So our physicians are different from the tradit= ional ones: They know something about basic research. Some of t= hem even spent time actually working in the laboratory.
GC: Just so they would have bot= h sides of that [work]?
TL: I had more than ten M.D.=E2= =80=99s in my laboratory, from various countries, at M. D. Anderson.
GC: So you said you had ten M.D= .=E2=80=99s in your laboratory.
TL: More than ten M.D.;s and, o= f course, several Ph.D.=E2=80=99s from all over the world, mostly from Chin= a, Japan, and Germany.
GC: Yes. Was that unusual= to have so many international people?
TL: No, no. It was quite = common at M. D. Anderson. Because Dr. Freireich was world famous, he = attracted many, many visitors and visiting scientists from all over the wor= ld, even today.
GC: Yes. Now, I've heard = a lot of different versions on how Dr. Frei and Dr. Freireich and your whol= e team, when the combination chemotherapy was started, the medical establis= hment at large was not sure this was a good idea, and there was some resist= ance at first.
TL: Yes.
GC: &= nbsp; Did you find that to be true?
TL: Very true. When I was inter= viewed by M. D. Anderson staff, I still remember what one of the leading ph= ysicians told me. He said, "You are wasting your time studying cancer= chemotherapy, because it just poisons and kills the patient and is not doi= ng any good," or something to that effect. That was in 1965. Dr= . Zubrod and Dr. Frei and Dr. Freireich showed cancer chemotherapy was effe= ctive in certain types of cancer, even though we realized it wasn't univers= ally successful in major types of cancer like lung cancer, breast cancer at= the time. Today, of course, it's different. Even lung cancer a= nd especially breast cancer in certain cases is treatable with chemotherapy= . So at the time the established physicians, even at M. D. Ander= son, were not, I wouldn't say hostile, but certainly were not very impresse= d by our approach that cancer chemotherapy plays a major part as a modality= of treatment.
GC: Did anyone ever question yo= ur work as a part of this?
TL: No, no, no. They were= very respectable. They respected the scientists more than they respe= cted the physicians, especially because there were conflicts of interest, b= ecause they think their approach was the traditional way, and these young g= uys from the NCI came in and wanted to do something new that in their view = was just a waste of time.
GC: &= nbsp; Did Dr. Zubrod have to, what was Dr. Zubrod's position on all that?&n= bsp; Did he just let them do whatever they wanted to do, or did he try to&n= bsp;. . .
TL: No, he was the leader of th= e cancer chemotherapists. Of course, he was also an extremely effecti= ve administrator and a total gentleman. He never offended anybody usi= ng abusive language. That's why people respected him and would accept= his judgment and his opinion. Dr. Freireich was=E2=80=94he is one of= the most innovative clinical scientists of this century and remains one of= the leaders in cancer chemotherapy, but he minces no words in expressing h= is opinion.
GC: That's true. And what= about Dr. Frei? What kind of person was he when you worked with him?=
TL: Dr. Frei is a marvelous man= in that he has a very good general concept of all branches of medicine and= of science. He is uniquely qualified in leading a group of scientist= s and physicians, because he makes you feel whatever you are doing is the m= ost important thing in the world.
GC: Oh, really.
TL: &= nbsp; He injects enthusiasm in every individual, so they are all loyal to h= im, especially Dr. Freireich, who was so loyal to Frei.
GC: They made quite a team.
TL: Freireich, of course, is th= e genius behind most of the innovative approaches to cancer chemotherapy.&n= bsp; He was an iconoclast. He would break all the existing rules and = concepts, for example, in leukopheresis, transfusion of platelets, and comb= ination chemotherapy. Yesterday I was watching PBS on cancer research= . They also talked about randomized clinical trial. He was, he = and Dr. Gehan, were the first ones to say in certain cases you do not need = randomization. In fact, randomization is unethical, because you know = this patient, this cancer patient is going to die if you don't treat him, a= nd you give him a placebo . . . Dr. Frei would say, "There's murder!"
GC: I can see that. I can= see him saying that.
TL: &= nbsp; He knows that normal randomization and historical control has a limit= . He knows very well. He is a genius. But he says evaluat= ing anticancer drugs is not like evaluating a drug for headache. You = do not have to go through so many red tapes and rules. You should exp= edite the approval of a drug for clinical trial; this concept was later pra= cticed by Dr. David Kessler, Dr. Kessler of the FDA, and nowadays the = approval of anticancer drugs is so much speedier than before. It was = also because Dr. Freireich was fighting for it.
GC: He didn't tell me about tha= t.
TL: Oh, he was majorly responsi= ble for the modern concept of the clinical trial, and the speedy approval b= y the FDA was entirely stimulated by him. He staked his career to fig= ht for his positions. And, you know, Dr. Freireich, he=E2=80= =99s a flamboyant man.
GC: He is?
TL: &= nbsp; We had a colleague, a junior colleague with me, an assistant professo= r under my supervision, who was diagnosed with cancer, with carcinoid, in f= act. He was home and his physician told him there's no hope: ju= st stay home and get ready for the inevitable. So, a friend of mine, = another colleague of this cancer patient, went to see him in Florida, and h= e found he was very sick. So this friend called Dr. Freireich and sai= d, "Dr. So and So is very sick and desperately needs help. His physic= ians say death is the immediate outcome." So Dr. Freireich flew there, gave= him an examination, ordered an ambulance, and ordered a private Lear jet t= o fly him from Florida back to M. D. Anderson, and paid with his American E= xpress card for the flight, of the several thousand dollars of airplane ren= tal and the ambulance. All the time he was afraid M. D. Anderson wasn= 't going to reimburse him, but to him the patient's life is far more import= ant than several thousand dollars, maybe tens of thousands of dollars. = ; That's Dr. Freireich. His patients were the most important, researc= h next. His patient's welfare is the most important thing in the worl= d, then his research.
GC: That's amazing.
TL: Yes. So, anybody who = says Dr. Freireich is hard to get along with and is difficult, I would say,= wait until you know him well. Just watch his patients and ask his pa= tients, "Is he a good doctor or not?" They would agree he is probably= one of the best doctors in the world.
GC: It sounds like you were ver= y loyal to him as well.
TL: &= nbsp; He is one of my dearest friends, because he is so honest, so caring, = so kind. It is probably to disguise his kindness, his gentleness, so = he has a rough front. He puts up a front that's to scare people. = ; But he is really nice. A = most broadly trained man, he knows so much. Are you a scientist, in a= ddition to being a writer and historian?
GC: Because I am a historian of= science, I know a lot about science, but I wouldn't say I am a scientist.&= nbsp; My father and my sister are both scientists, though, so I come out of= that. My father is a chemist and my sister is a botanist. So, = I grew up with science, but, no, I can't claim to have a degree in science.=
TL: Yes. It doesn't matte= r. If you know as much science, you are a scientist.
GC: That's a good way to put it= .
TL: So, science of history, tha= t=E2=80=99s very good. You know, my son-in-law is a scientist-writer.=
GC: Oh, really?
TL: He works for Business W= eek as a scientist. His name is John Carey.
GC: John Carey.
TL: &= nbsp; You may have read him.
GC: I am going to look for him.=
TL: He is a writer.
GC: Yes, it's very interesting.=
TL: A Yale graduate. He k= nows a lot of scientists, the science and also scientists, and he writes ve= ry well. He is an extremely intelligent fellow.
GC: It's amazing how much I've = learned from talking to people like you about cancer research and about sci= ence. I've learned so much doing these interviews.
TL: Well, I'm sure you didn't l= earn much from me, but I'm sure you were impressed by Dr. Zubrod and F= reireich, Frei. Frei is also very flamboyant.
GC: Is he?
TL: He=E2=80=99s very broad [br= oadly trained]. He's a very friendly man.
GC: &= nbsp; He's up in Boston now.
TL: Yes. Even though he's= retired, he still works very hard.
GC: Yes. He still goes in= to his office?
TL: Freireich is not retired.&n= bsp; Neither officially or unofficially. He is still working.
GC: You mentioned at one point = that Mary Lasker and some of the senators were very supportive of the Cance= r Act and the Cancer Institute and all that. Did you ever feel like t= hat was, I know some people expressed concern that politics were getting in= volved with science. Was that ever a concern?
TL: No, no, no, no. If th= ere is any kind of interaction with politics with cancer research, it is al= l for the good.
GC: All for the good.
TL: &= nbsp; Yes. Occasionally there are some politicians that push their pe= t project and pet drug, but through the convincing arguments of Dr. Zubrod,= Dr. Freireich, Dr. DeVita, they would change their mind. Like they w= ould push for Laetrile, antineoplastin, and things like that. Quack m= edicine. They were shot down by scientists and physicians in the most= effective, gentle manner. Otherwise a lot of money would be wasted i= n the wrong direction.
GC: Mary Lasker, did she ever c= ome down to the lab? You said you would present for her?
TL: No. They were in a di= fferent building, in a conference room like this, they would sit in there a= nd Dr. Zubrod would say, =E2=80=9CTi Li Loo will now present what we have f= ound,=E2=80=9D and I would make a short ten- to fifteen-minute presentation= of what we were doing and what's the purpose of doing it.
GC: So it was a very formal kin= d of presentation.
TL: I would say more informal t= han formal.
GC: Oh, okay.
TL: Because we had to tone down= , making the presentation intelligible to these great supporters of ours.&n= bsp; They never interfered. Never. They always give you tremend= ous support and encouragement. Never say to you, "Ti Li Loo, why don'= t you study Laetrile?"
GC: That's good.
TL: Yes.
GC: Did you ever go down to Con= gress? Did you ever go down to testify?
TL: No, no, never. No, I = don't rank, I don't rate. That's for people like Zubrod, DeVita, and = Dave Rall.
GC: Now, you must have worked u= nder Dr. [John R.] Heller and Dr. [Kenneth M.] Endicott as directors. = Is that right?
TL: Yes. They were way ab= ove me. They were the directors, yes.
GC: Did you have any contact wi= th them, or did you know them at all?
TL: Yes. Dr. Heller, Dr. = Endicott called me to their office, to talk about something. I've for= gotten. It was a long time ago. Yes, just a short five or ten m= inutes talk. They wanted me to go there and ask me some questions.&nb= sp; Impressive people, very good.
GC: What was Dr. Heller like?= p>
TL: &= nbsp; Oh, I can't remember. It's so long ago. Also there was a Stu Sessoms.=
GC: And who was he?
TL: He was somewhat of a boss f= or a while, but I'm not really sure about it now. At the time I was l= ow down on the totem pole and people above, I'm not sure who they are and w= hat they do and who is whose bosses. Only later, gradually, we realiz= ed the hierarchy.
GC: Yes. Did your divisio= n or did the NCI get a lot bigger during the time you were there? You= were there ten years. Did it grow a lot while you were there?
TL: Yes. Oh, there was a = tremendous growth. New divisions were forming, reorganization, reallo= cation. Everything was going on. It was a very fast expansion; = so many hired, so many personnel. Unbelievable.
GC: And was that good changes o= r did it affect your research in any way?
TL: Well, I think it was inevit= able. When you have so much money to spend to expand the scope of you= r research, you have to increase the personnel. But when you increase= the personnel, the politics become so complex.
GC: &= nbsp; Oh, you mean interoffice politics?
TL: Yes. The internal pol= itics becomes so complex. So I would much prefer to go to a small pla= ce, or a smaller place, like M. D. Anderson. That was one of the indu= cements to go to Texas.
GC: That was one of your reason= s to go?
TL: Yes. Of course, Dr. F= rei was very persuasive.
GC: Was he?
TL: Yes.
GC: How so?
TL: Well, he thinks it's a trem= endous opportunity. He is the big boss. He will be in charge of= all the chemical research over there, and Dr. Freireich would be his right= -hand man. That's really a big attraction, you know. People who= were recruited from NCI to go there were all first-caliber, I mean, the le= ading expert in their field: Myron Karon, Gerry Bodey, Evan Hersh, Ed= Gehan. That's the people I remember. There were some others.= p>
GC: &= nbsp; Was there a lot of work between the Institutes? Did the Cancer = Institute collaborate with the Heart Institute, or NIAID, or any of the oth= ers while you were there?
TL: Some. Not as much as = I would have hoped. For example, at the time the best cancer research= done at NIH was by the Heart Institute.
GC: Oh, really?
TL: Because of the carcinoid tu= mor and the biochemical and pharmacology involved. Of course, I conte= sted, because later on our group was making some major contributions. = But at the time we joined the NIH, it was true, because they were studying= carcinoids. Carcinoid produces certain cardiovascular problems, as y= ou know. Tricuspid insufficiency, the flush in the face, and so on.&n= bsp; So, also the patients excreted 5-hydroxy indolacetic acid. There= is a very strange kind of biochemistry going on in the patients.
GC: I noticed, I was looking at= , you started in the OADR at NCI? Do you remember what that was?
TL: NODR?
GC: OADR. I was looking i= n the old directories.
TL: &= nbsp; Oh, yes, yes, yes. Office of the Associate Director of Research= , Dr. [G. Burroughs] Mider.
GC: Oh, you worked with Dr. Mid= er?TL: &nbs= p; Dr. Mider was Dr. Zubrod's boss, and this Sessoms was Mider'= s boss and colleague or something. NCI is constantly changing. = Even today. You never knew who your boss was going to be.
GC: Really?
TL: Dr. Mider recruited Dr. Zub= rod.
GC: Right.
TL: Because Dr. Shannon recomme= nded Dr. Mider to give these young physicians research experience, because = Dr. Zubrod studied malaria with Dr. Marshall, and in that group was Dr. Sha= nnon, Dr. Brodie, and all those people.
GC: Yes. Okay. So t= hat's what that was. But you were doing research at that time, right?=
TL: &= nbsp; Yes.
GC: Because I noticed you went = from OADR to the medical branch of the Clinical Pharmacology and Expe= rimental Therapeutics Section, and then Laboratory of Chemical Pharmacology= . And I didn't know if that was just that the names of the sections w= ere changing or if you were actually moving offices?
TL: No. Just the names changing= .
GC: Okay, okay.
TL: I moved my lab twice, from = the sixth floor to the tenth floor, but nothing else.
GC: Nothing else really changed= .
TL: No. No. The sam= e, well, there were different bosses rotating.
GC: So that was just the reorga= nization.
TL: Yes, yes.
GC: &= nbsp; That's interesting.
TL: Yes. So long ago.&nbs= p; I have to think about it. I think mostly that is correct.
GC: Okay. When you would = get a new boss or a new reorganization or something like that, did that aff= ect the work you were doing, or was that just kind of outside . . = ;.
TL: Oh, some, yes, because you = have to consider the supervisor's personality and their approach. Not= everybody is Dr. Zubrod, who is easy, understanding, sympathetic, en= couraging. Dr. Freireich for about twenty years was my boss and he wa= s different from Dr. Zubrod. Nonetheless, I enjoyed the opportunity t= o work with him. But an entirely different approach.
GC: Right. When did you, = now, you didn't do any cancer research before you came to the Cancer Instit= ute. Is that right?
TL: Yes. I was doing mala= ria research, first when I was in graduate school in Oxford, and then at th= e University of Maryland, and then in Christ Hospital with Dr. Schmidt.&nbs= p; It was all malaria research. At the time malaria was a very import= ant problem when we were fighting in Southeast Asia, New Guinea and the Phi= lippines, and various places. Malaria was so debilitating and sometim= es fatal.
GC: &= nbsp; So, when Dr. Zubrod called you and said, "I want you to come do cance= r research," what did you think about that shift in research? What di= d you think about cancer research? Or what did you think about cancer= ?
TL: =E2=80=9CI have to learn!= =E2=80=9D I had to learn from the ground floor. I had a teacher= , Dr. Zubrod is my teacher, my mentor. So I learned everything about = cancer from him and cancer as a disease. Actually cancer is more than= a hundred diseases, and the treatment and chemotherapy, it was all taught = informally by Dr. Zubrod, through the rounds and through his papers, very e= ffective man.
GC: Did other people coming in = to the Institute have that same kind of experience, where they didn't have = the previous experience with cancer and then they came to the Institute and= learned it?
TL: Most of them never had any = experience. Dave Rall never had any experience with cancer research.&= nbsp; Paul Condit was not in cancer research, even though he was a physicia= n. Jack Davidson was the only one with experience in cancer research,= in biochemistry of cancer drugs. You know him, don't you?
GC: Jack Davidson?
TL: &= nbsp; Yes.
GC: I was hoping to interview h= im. He is not very well, though. He wasn't able to do an interv= iew with me.
TL: No. If you talk to Dr= . Oliverio, you've covered talking with Dr. Davidson. His work is ver= y familiar to Dr. Oliverio.
GC: Oh, good. That's good= to hear. Yes, I hope to catch him.
TL: I have high respect for Dr.= Davidson.
GC: He did some very good resea= rch.
TL: Very, very good, v= ery good. An amazing man. He is also highly specialized in radi= ochemistry.
GC: What was the best thing abo= ut working, about doing research, at the National Cancer Institute?
TL: &= nbsp; The first was the colleagues. The caliber of your colleagues wa= s so impressive, and you can really learn a lot from your colleagues. = The second is that the resources are quite ample, other than the space.&nb= sp; You are not limited by equipment, by drugs, animals, and you had plenty= of supplies. Third is the reputation of the NIH as a major internati= onal biomedical research center. So, the place, the personnel, and th= e resources. There was a time when I was there you would never have to worr= y about your budget. Nowadays you have to, because you have external = review. In my time the review was there but very informal. Ther= e was no site visit. The reviewers would come and you would just give= a ten- or fifteen-minute presentation. Not as serious as at M. D. An= derson, which sometimes consumed two or three days, where you have to take = care of site visitors. We had to rehearse internally and then, of cou= rse, above all you have to work terribly hard; otherwise, you don=E2=80=99t= get your papers published and you have no grants.
GC: Was it easy to get publishe= d, being from the NCI?
TL: No, no, no, no.
GC: No? It didn't make an= y difference?
TL: &= nbsp; No, no. It was totally impartial peer review. If you don'= t have anything, nobody is going to accept it, whether you are from the NCI= or from M. D. Anderson. It will be rejected outright. Sometime= s even a very good paper would be rejected.
GC: Not what they wanted.
TL: No.
GC: How did the reputation help= you? You said you really enjoyed the reputation of the Institute.
TL: Oh, yes, yes. Because= when you go out for your meeting, you say you are from the NCI, the reacti= on from the audience is entirely different.
GC: Really.
TL: They show their respect.&nb= sp; The same at M. D. Anderson.
GC: You said that all the resou= rces were ample, except for space. Why was space such a problem?
TL: &= nbsp; Well, as you can see, the clinical center was just built and we had o= ne module, every senior investigator has one module that is about twice as = big as this room. When you get going with the equipment and the techn= icians, it is very crowded. And usually you get involved in more than= one project and you wish you had more than one module.
GC: So a module was maybe 25 fe= et by 35 feet? Something like that?
TL: Yes, something. The w= alls are moveable. You can tear down and remodel very easily. B= ut the place is expanding, all the people are coming in. There consta= ntly is a shortage of space. That's why later on they moved the admin= istrative, extramural staff, away from the laboratories.
GC: Just so they could have&nbs= p;. . .
TL: Now they're farmed out all = over the place.
GC: Yes, they are in all differ= ent buildings now.
TL: Yes.
GC: &= nbsp; Was there anything you did not like about working at the NCI? W= ere there any problems inherent to that place?
TL: Not really. The only thing = is, when you get bigger, there is more internal politics and personalities = to deal with, which I wished I didn't have to. Just concentrate on doing my= work and not trying to make my boss happy and that sort of thing.
GC: I think that happens a lot = of places.
TL: It's inevitable. When= you have more than two people, there is politics because you always want t= o win the third man to you. That idea of constantly working harmoniou= sly and no difference in your opinion, that's impossible.
GC: That's great. What wa= s a typical day like for you? What time would you come in to work and= what kind of activities would you do? Then when would you leave?&nbs= p; How long would you be there?
TL: Oh. When I was workin= g very hard, no problems bother me. I come in frequently about seven = o'clock [a.m.]. First is getting things started. Second, at the= time there was no reserve parking, so I could park in the front. And= I seldom would leave before six o'clock [p.m.].
GC: That's a long day.
TL: Yes. This I carried t= o M. D. Anderson. I got there even earlier, I got in initially at six= o'clock [a.m.] and worked until after six o'clock [p.m.], because it was v= ery competitive for the department money at NCI. You don't get work d= one, you have nothing to publish and nothing to present, you have no record= , and you get no grants, and you can't do your research. You know, the publ= ish or perish principle.
GC: Oh, yes. It's the sam= e in history.
TL: It's true today and was tru= e and it will be true, because there is nothing else you can do. Rese= arch is not economical. It doesn't produce anything tangible that wil= l be economically productive. A lot of research may not even help the= patient directly. Some of it, we hope, will. Very often the re= search turns out to be a failure. I studied more than fifty drugs.&nb= sp; Probably most of them weren=E2=80=99t active in the clinic. Usele= ss. No more than five or ten drugs I studied turned out to be good.&n= bsp; A couple of them are good today. Methotrexate is one. We s= pent a lot of time wasted. But who can tell? You cannot predict= just from your animal studies, preclinical studies that this drug is going= to be useful or useless clinically. You can't predict.
GC: &= nbsp; Right. Did you feel like there was a good balance between basic= research and clinical research?
TL: Yes.
GC: Or applied research?
TL: Yes, yes. Yes, I thin= k under the leadership of Dr. Zubrod and Dr. Freireich, yes. We had v= ery good balance and good support. We made a lot of progress that can= be used in the clinical direction immediately.
GC: You have answered my questi= ons so well. I just wanted to check and make sure I didn't miss anyth= ing. What was the atmosphere like in your laboratory? What was = the general atmosphere? How did people work together?
TL: &= nbsp; Very well, very easy. There were no, except in very few cases, = no strong personalities. The technicians, most of them were very comp= etent, worked hard, except I feel that they were not as dedicated as at M. = D. Anderson, because they are more or less bureaucrats protected by the Civ= il Service system. Come in 8 [a.m.] to 5 [p.m.], 8 to 5. If you= ask them to stay late or come in early, they usually agree reluctantly and= , of course, they would take comp time later. Not as devoted as at M.= D. Anderson. You asked them to do something, they used to do the job= as necessary, to stay late or to come in early and do it. And they w= ould not count the pennies and say, =E2=80=9CI took a half an hour off now = because I was in a half an hour early some time.=E2=80=9D But on the = whole they were dedicated. Most of them were competent and not very m= any strange personalities to deal with.
GC: That's good. Were the= re teams of people working on certain projects, or did people kind of move = between projects in and out?
TL: Usually the senior investig= ator will pick several projects. When I was working on, for example, = methotrexate, I also worked on thiopurines, and also I worked on some other= drugs at the same time. When you were stuck on one area, you g= o and jump in another one. You put your emphasis on that. You c= an't always count on that your work on this one is going to be a success.&n= bsp; Sometimes you get stuck and you may not have anything to publish for s= everal years. This philosophy I learned in America. When I was in Bri= tain, it's not so critical, that publish or perish. Later on, of cour= se, you learn quite a bit in the system and you gradually become Americaniz= ed. Nowadays in Oxford, Cambridge, it=E2=80=99s the same thing=E2=80= =94if you don't publish, you don't survive. Well, there's no record!&= nbsp; You have to think about what other record do you have? You say,= =E2=80=9CThis man is very productive, made a lot of progress.=E2=80=9D&nbs= p; But it=E2=80=99s all in his head! That's no good. You can't = present it. That is, you have to get it in print and everybody agrees= that this is a good piece of work. So, publish or perish is necessar= y, but this should not be pushed too far and say, unless you publish one pa= per a year you will never be promoted. That kind of attitude should n= ot be adopted. On the other hand, Dr. Schmidt, in his later years he = didn't publish much.
GC: He didn't.
TL: He has loads, loads, tons of data, but never published! Later, through the gentle persu= asion of Dr. Zubrod and Dr. Marshall, he had several thick volumes publishe= d in the Cancer Chemotherapy Reports, which you can find in the library.&nb= sp; But a lot of things are buried, because his work got so much ahead of h= is publications, he couldn't ever catch up. That's one of the mistake= s he made.
GC: So he just never was able t= o analyze all that data.
TL: He did his analysis. = He didn't publish. If you ask him, he would give you the data, but th= at is not in print, so nobody can refer to it.
GC: Wow. So, if you had s= everal projects going on at one time, your technicians would also shift, ac= cording to what you were stressing at that time?
TL: &= nbsp; Yes, yes. Depends on my own strategy at the time, =E2=80=9CLet= =E2=80=99s all work on this . . .=E2=80=9D and so on.
GC: This is tape two, with Gret= chen Case interviewing Dr. Loo on June 9, 1998. Do you know=E2=80=94t= his is a question I asked Dr. Rall, too, and he wasn't sure=E2=80=94do you = know if the Laboratory of Pharmacology came out of one of the, the NCI was = formed from a division of NIH downtown that was called the Laboratory of Ph= armacology and then the Office of Cancer Investigations at Harvard, and tho= se two labs came together to form the NCI in the late 1930s, in 1939. = Do you know if the Laboratory of Pharmacology that you worked in was part = of one of those original divisions, or if it was created later?
TL: No, no. It was create= d entirely by Dr. Zubrod, de novo from the beginning. It rec= ruited the staff in certain directions. It was entirely Dr. Zubrod.= p>
GC: Okay.
TL: Before that there was no La= boratory of Pharmacology as such.
GC: &= nbsp; Okay.
TL: There were people studying = experimental cancer chemotherapy in laboratory animals, mostly mice and rat= s, for example, Dr. Abe Goldin, who died of cancer fifteen years ago. = He was one of the major scientists who contributed from the basic science = point of view to clinical cancer research. Unfortunately, you will no= t be able to interview him. He was a very important player in the fie= ld.
GC: Yes. His name has com= e up quite a bit.
TL: Yes. And then there w= as a doctor, I can't remember his name. Well, so many individuals who= later took on major responsibility at the NCI. I'm stuck with names.
GC: That's okay. Most of = them I can look up, so don't worry about names or dates or anything. = This is a kind of tangential question, but when you worked, you used, I ass= ume, rats and mice and different animals. Did you have, did each lab = have, their own supply of animals, or was there a central animal room or an= imal facility?
TL: &= nbsp; At NIH there was a central animal supply, away from Building 10. = ; They were in a very fine building. It was very well managed. = We had plenty of, at that time, of course, the animal rights people were no= t so active, so we had monkeys, dogs, rats, and mice. This research w= as mostly done with mice and then rats, then dogs, I think, and monkeys.
GC: But if you needed animals, = you didn't have to order out to a supplier?
TL: No, no, no. We would = just go to the animal quarters. Of course, you had to give them notic= e, on a certain day, at a certain time you need this kind of animal, and so= on. They were housed, however, the rodents were housed in Building 1= 0. The dogs and the monkeys were housed separately, entirely separate= , and the stock animals, the rodents mostly were housed separate.
GC: Yes. That's probably = good.
TL: Yes. Nowadays I think= they moved away.
GC: What was your favorite proj= ect, or the way that you feel you contributed the most to the NCI, what do = you remember most about being at the Institute?
TL: At NCI, the thing I remembe= r most is methotrexate.
GC: Methotrexate?
TL: Yes. The other thing = is I was also trying to show that, at the time they had a drug called methy= l-GAG.
GC: Methyl-GAG?
TL: Yes. Methyl-GAG, G-A-= G=E2=80=94what G-A-G stands for I can't remember=E2=80=94methyl-GAG, which = was used in leukemia and very effective. But it has very, very strong= side effects so it is not used any more. And then there was a gentle= man who published a paper that said, hydroxy-methyl-GAG, which is a certain= experimental cancer agent which he said is better than methyl-GAG. T= his is a negative study, because I proved his hydroxy-methyl-GAG was methyl= -GAG itself with a molecule of water.
GC: Oh, really.
TL: And then I made methyl-GAG = myself and proved that the new methyl-GAG was no better than methyl-GAG.&nb= sp; Let me correct it. I made the real hydroxy-methyl-GAG, which turn= ed out to be no better than methyl-GAG. But I spent a long time, six = months or so, and made it. The other study I initiated was the metabolism o= f cyclophosphamate, cyclophosphamate. I had a theory it was oxidation= , at the time people were suspecting the drug was hydrolyzed in vivo to give you nitrogen mustard, and I said it isn't. I didn't have t= he solid experimental evidence, but based on my theory, I said it can't pos= sibly be a hydrolytic process but an oxidative process. And then I tr= ied to make the metabolite to prove I was right; that=E2=80=99s the end of = the study=E2=80=94I never made it and never proved it. It was up to s= omebody else in the laboratory to prove it was an oxidative process. = But I was the first one to propose it was oxidation rather than hydrolysis.=
GC: So even though you were the= first one to propose it, no one ever acknowledged that.
TL: Yes. Because I just w= ent to meetings and said, =E2=80=9CI think this is an oxidation.=E2=80=9D&n= bsp; First, you publish nothing and second you have no evidence, laboratory= evidence of this, that's no study. I agree, that's no study.
GC: Now, with the hydroxy-methy= l-GAG, when you disproved, when you proved that it was just methyl-GAG with= a molecule of water of hydration, as you said, was that, did that, I don't= know what the right word to use is, did that cause an upset or a .&nb= sp;. .
TL: Yes, yes.
GC: Can you tell me about that?=
TL: &= nbsp; Yes. There was a Szent-Gy=C3=B6rgyi. Do you know Szent-Gy=C3=B6= rgyi? He was a Nobel Laureate. He said=E2=80=94I can't remember= exactly what he said=E2=80=94he said something like, =E2=80=9CCancer is ca= used by something that could also cure cancer at the same time if the molec= ules were switched around.=E2=80=9D He had that theory, that cancer d= rugs and carcinogenic compounds could be one and the same. With littl= e structural modification, they become anticancer drugs, with little struct= ural modification, become carcinogenic compounds. Which is interestin= g, but there is no proof. Then he cited, he said, for example, =E2=80= =9CMethyl-GAG cures cancer and hydroxy.=E2=80=9D No, he said, he said= something like =E2=80=9CMethyl-GAG . . .=E2=80=9D
GC: Causes cancer?
TL: =E2=80=9CCauses leukopenia;= hydroxy-methyl-GAG doesn't.=E2=80=9D Something like that. Agai= n, you'll have to go to check.
GC: Okay. I'll check that= .
TL: So I said, =E2=80=9CThat's = nonsense, because you didn=E2=80=99t make hydroxymethyl-GAG. I've mad= e it.=E2=80=9D So that was an argument with a Nobel Laureate. I= said, =E2=80=9CHe cannot cite the story of methyl-GAG as an example, becau= se hydroxymethyl-GAG has never been made until I made it.=E2=80=9D
GC: &= nbsp; Now, was this an argument in print, or was this an argument, in fact,= in person? Did you ever speak to . . . ?
TL: Yes, it was in Science<= /em>. There was a letter to the editor.
GC: Oh. Wow.
TL: He published some kind of c= omment, =E2=80=9CEven though your theory may be right, I don't believe it= =E2=80=99s right.=E2=80=9D But to cite methyl-GAG and hydroxy-methyl-GAG as= supporting vidence of your theories is wrong, because nobody had hydroxy-m= ethyl-GAG until I made it.
GC: That's quite a feat, to hav= e an argument with a Nobel Laureate.
TL: Yes. Later on he had = his final say, he said maybe I [Dr. Loo] never made it either. But I = didn't want to keep on, because I had better training in synthetic chemistr= y, and I know I made it. I have the physical chemical evidence.
GC: Can you think of who else I= should talk to from the NCI? I can tell you I talked to Dr. Frei and= Dr. Freireich and Dr. Zubrod, and Dr. Rall and Dr. Berlin.
TL: &= nbsp; Yes. And Oliverio, you're going to talk to.
GC: I will talk to Oliverio.
TL: And the other guy is Shepar= tz. Saul Shepartz.
GC: Saul Shepartz?
TL: Yes.
GC: Is he still, do you know wh= ere he is?
TL: No. He's retired, but= he, in fact, he has a long history associated with the NCI, especially wit= h the Division of Cancer Treatment. A very famous man, so you can, so= there=E2=80=99s no chance you can miss him. Because he knows so many= people, because he has spent so many years with the NCI.
GC: So he is one I should defin= itely talk to?
TL: &= nbsp; Yes. As a basic scientist and administrator, not as a physician= . [Jack] Davidson, if available, is very interesting to talk to, but = [laughs] he might not even remember as much as I do.
GC: Okay. Yes, I told him= I would check back with him after a while, so I'll do that.
TL: Dave Rall. Richard Ad= amson.
GC: Okay.
TL: He's in town.
GC: He's in town?
TL: Yes. He lives in Poto= mac. His telephone is probably in the book, I think.
GC: Okay, good. And he wa= s one of your associates, right? Your clinical associates that worked= for you?
TL: &= nbsp; In the beginning he was an associate, but his star rose so fast. = ; He became the Associate Director for Cancer Etiology and was acting as th= e NCI Director for several months, I think, when DeVita left.
GC: Is that right?! I was= wondering who that was, because DeVita left and then someone didn't, Brode= r didn't come in right away.
TL: Yes.
GC: So that's who was in there?=
TL: Yes.
GC: Okay.
TL: Richard Adamson.
GC: That's very interesting.
TL: The guy who got his Ph.D. a= t twenty-two, graduated from college at eighteen.
GC: &= nbsp; Unbelievable.
TL: Yes.
GC: Unbelievable.
TL: We had a Ph.D., another Ph.= D., at the time, also a whiz kid. I forgot his name, unfortunately.&n= bsp; There's another one. And there were a lot of physicians that wer= e there. Like Dr. Freireich, he got his M.D. at twenty-two.
GC: Dr. Freireich did, too?
TL: Didn't you know that?
GC: Well, I guess I never = . . .
TL: He went to medical school a= t eighteen.
GC: I did know that. I di= d know that! You're right. Because we talked about that, being = away from home at eighteen, for medical school. Oh, my goodness, I ca= n't imagine.
TL: &= nbsp; You didn't know he was such a genius.
GC: I did know. Everyone = told me he was a genius, and then when I met him I figured it out. He's qui= te interesting.
TL: I have written a chapter on= cancer chemotherapy with him. It was published two years ago. = The data is probably . . . it is five years outdated. I will send you= a copy of the book, the whole book.
GC: I would like that.
TL: It's called Principles = of Pharmacology. The chapter on cancer chemotherapy was written = by Freireich and me and dedicated to Zubrod. I will bring it to you o= ne day as a souvenir.
GC: I would like that. I = would love that. Have I missed anything?
TL: It=E2=80=99s up to you.
GC: Okay. You've answered= so many of my questions. I think I've gotten, had the virus cancer p= rogram started when you were there?
TL: &= nbsp; Yes.
GC: Did you have any involvemen= t in that?
TL: No, no.
GC: That was pretty separate, w= asn't it?
TL: Yes. And the person w= ho was famous there was Dick Rauscher.
GC: Right, right.
TL: And he became the only Ph.D= . to head NCI.
GC: Right.
TL: He was very, very good.
GC: So you knew him?
TL: &= nbsp; I knew him by casual acquaintance, not well. Dr. Zubrod and he = worked together, of course, and Vince DeVita.
GC: Did it make a difference wh= en the directors of NCI changed? Like when Heller left and Endicott c= ame?
TL: No. Nothing to do wit= h us.
GC: Nothing to do with you?
TL: No. Not from the divi= sion chief [levels of administration] down. Nothing to do with us.&nb= sp; Only with the associate directors, division chiefs, and the big-shots.<= /p>
GC: Yes. Okay. Were= you at M. D. Anderson in the 1970s, when the National Cancer Act, the War = on Cancer, was declared?
TL: Yes, yes, yes.
GC: What did you think about al= l that?
TL: &= nbsp; Oh, I think it was a great idea, except people wrongly put too much h= ope on it. They think if you put a lot of money in, the cancer proble= m will be solved. It isn't as easy as that. Dr. Zubrod explaine= d very clearly that cancer is more than a hundred diseases. We don't = even know what really causes cancer. There are so many factors, etiol= ogical factors. They all cause cancer, but which one has caused this = particular cancer in this particular patient? And we don't know the g= enetic defect at the time. So, people should be patient. The pr= ogress we are making today is just as predicted. That was a very majo= r advance in the politics of cancer research, to give the scientists and ph= ysicians the money to push for it, even though at times the progress is so = slow that the people become disheartened and start to criticize. Some= of the criticism is really unjustifiable.
GC: Yes. I know when the = Act was passed in 1971, and the War on Cancer was declared, and they said b= y 1976 we want to have cancer cured. What did scientists think of tha= t at the time?
TL: &= nbsp; I think it was overly optimistic. To set a time is wrong. = Progress is made, especially in basic science, molecular biology, by leaps= and bounds. All of this eventually will have a major impact on clini= cal cancer treatment. You don't know at this time how important a cer= tain discovery really is, as the progress in immunology and molecular biolo= gy recently realized, you can see maybe that cancer is going to be cured in= five years. Who knows?! Maybe we really have the magic bullet.= It's hard to say. Nobody can, in his sane mind, predict, altho= ugh I am very optimistic.
GC: And you're still very optim= istic?
TL: Yes. Absolutely. = ; I can't put a, give you a time, but I say there will be a cure for the di= sease. Just like AIDS.
GC: Really?
TL: Yes. In the beginning= , when I was in AIDS research five years ago=E2=80=94I had a grant from the= NIAID=E2=80=94I thought this will be no serious problem, that one virus ca= uses the one disease. I didn't know the virus was so smart and change= s so fast. It was the first time, not the first time, in fact, that I= made a major mistake. I gave up major research because I think my kn= owledge of molecular biology is so rudimentary, I can never come up with a = real major advance in the chemotherapy of AIDS. But it will be solved= . The young people are so smart.
GC: Well, they've done so much = already with the new . . .
TL: Unbelievable. They ha= ve a vaccine now.
GC: Yes.
TL: In clinical trial.
GC: Yes. It really is unb= elievable.
TL: Any other questions?
GC: I think we mostly got it.&n= bsp; Did you work, you talked a little bit about you worked from like 7:00 = a.m. to 6:00 p.m. Did you work weekends sometimes, too, if you needed= to?
TL: I worked much harder at M. = D. Anderson, and at NIH the last few years I worked very hard. In the= beginning my children were young, so I had to spend a lot of time, spare t= ime, with them.
GC: Right.
TL: &= nbsp; Which was absolutely necessary and really very enjoyable. Later= on, when they were in high school, I could let them stay home by themselve= s, and with Dr. Freireich=E2=80=94he worked very hard, too, you know=E2=80= =94we worked on Saturdays, yes, at least a half-day.
GC: On Saturdays.
TL: Yes. Dr. Freireich wa= s a very inspiring man.
GC: It sounds like it.
TL: Oh, he's a delight to work = with. Dr. Zubrod, of course, was an old-fashioned gentleman-scientist= . Very just, very right, very polite. Most impressive.
GC: I was very impressed by him= . I really enjoyed meeting him.
TL: Anything else?
GC: I think that's all. D= o you have anything you'd like to add before I turn off the tape recorder?<= /p>
TL: Now, if you have questions,= you can always ask me over the phone again.
GC: &= nbsp; Okay. Let me stop the tape.
TL: You have my phone number?= p>
GC: Yes.
TL: Which is unlisted. Bu= t you have it.
GC: I got it from the [alumni] = directory.
TL: Yes. In the book.
End of transcript