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Our News - In Their Own Words - Waldmann Interview

Dr. Thomas Waldmann: 50 Years at the NIH

NOTE:  This interview is an excerpt from NIH Radio Podcast, Episode 12

Bill Schmalfeldt:
I’m sitting in a conference room.  I have no idea where I’m at other than the fact that I’m in Building 10 and the Clinical Center here on the campus of the National Institutes of Health.  And I’m talking with somebody who’s been here probably longer than this building has been here.

Dr. Thomas Waldman:
The Clinical Center was built in 1953.  And I came here in 1956.  I’ve been here 50 years.

Bill Schmalfeldt:
July 1, 1956, correct?

Dr. Thomas Waldman:
Indeed.

Bill Schmalfeldt:
Let’s put that in perspective, if you don’t mind.  Here are some of the news events from the days previous to your showing up at NCI: June 23, 1956, Gamal Abdel Nasser becomes the second president of Egypt; June 29th, Marilyn Monroe marries playwright Arthur Miller; June 29th, President Dwight David Eisenhower signs the Federal Aid Highway Act, creating the interstate highway system; and on July 1st, a young fellow named Dr. Thomas Waldman walks in through the doors of the National Cancer Institute.  What can you remember about your first day here?

Dr. Thomas Waldman:
I’ll return to that.  But let me give you my perspective of 1956.  In 1956 was the last polio epidemic.  I was an intern at the Massachusetts General Hospital --

Bill Schmalfeldt:
Mmmhmm.

Dr. Thomas Waldman:
-- and was immediately assigned to the polio ward.  We had 700 patients, 70 in respirators.  In this year, ’55-’56, before the first widespread use of the polio vaccine, I had in my textbook at that time, hematology, a discussion of my area of research at the moment.  And it said we have no idea what the role of the lymphocyte is.  If you think about it, what did we know then if AIDS had hit at that time?  It infects the T-lymphocyte, a cell that had not been discovered.  It’s caused by a retrovirus, HIV, a type of organism that had not been defined.  And it enters the cell through a receptor.  We knew no receptor whatsoever.  So indeed, much of the advance was contributed by patient-oriented research.  That is, research on patients such as in the Clinical Center where the doctor and the patient are in the room at the same time in a meaningful encounter.  So, when I came here, I came here as part of the doctors draft.  That is to say, between the Korean and Vietnam War, I came here for two years.

Bill Schmalfeldt:
I was going to ask about that.  You were supposed to be here for a two-year fellowship.  Was it the food in the cafeteria that kept you here or…

Dr. Thomas Waldman:
It was the ability in two ways to stay scientifically alive.  My total training in research was a $50, 5-0 dollar, grant to study arithropoda [spelled phonetically] in a little niche of the Harvard Medical School.  So, all the training that I had, and indeed, I soon became the equivalent of a tenured principal investigator, was through the contact in the corridors in the lunchroom, albeit not for the food, but for the science --

Bill Schmalfeldt:
[Laughs].

Dr. Thomas Waldman:
The ability to contact others and to learn.  And one has here a great number of people that will help you learn how to do -- they won’t do your research for you, but they will -- the other issue was the Clinical Center.  I cannot emphasize more the importance of the proximity of patients that you can attract from around the world with rare but instructive diseases that you can, for their benefit and for the benefit of those in science, study them as patients and their disease.  Taking insights from the patients, questions from the patient into the wet laboratory where you develop new insights that lead people like myself to make our own drugs: monoclonal antibodies.  These are uniform antibodies that we can then use first in animal models and then in patients to treat the patients with disease.

Bill Schmalfeldt:
The projects that you’re working on now, when you think back for 50 years, does it almost -- and I don’t want to oversimplify this, and you touched on it earlier -- does it almost seem like prehistory now?

Dr. Thomas Waldman:
Especially in fields like immunology that was not advanced.  Cardiology was advanced.  Endocrinology.  But immunology was at its infancy.  Questions that could not be asked 50 years ago have been answered definitively for the benefit of our patients.

Bill Schmalfeldt:
You didn’t even know the questions at that point.

Dr. Thomas Waldman:
Had no sense of the issues to address.  And this is not only not sensed by the public, but the new scientists that come here feel that anything that’s been known for at least three years came in with the pyramids.

Bill Schmalfeldt:
So, in the late ‘70s there’s this chance discovery that led to some very important breakthroughs in your research and for all of us, really.  What can you tell us about that?

Dr. Thomas Waldman:
A discovery that you might be referring to is the ability to make monoclonal antibodies by [unintelligible].  Using cells made by Michael Potter that could make, as a factory, a great number of antibodies that are each identical to the other which is what you need for a drug.

Bill Schmalfeldt:
Mmmhmm.

Dr. Thomas Waldman:
When they discovered this ability and within a few years, we used this approach to make an antibody to a growth factor receptor.  Cells need growth factors to go to receptors on their surface like a key in a lock --

Bill Schmalfeldt:
Right.

Dr. Thomas Waldman:
-- in order for the cell to divide and mature.  And we made an antibody to one of these growth factors.  It happens to have a name IL2, the IL2 receptor.  And what was so important in the intervening years is the resting normal cells of our body do not have this receptor and do not react with our antibody.  But abnormal T-cells involved in leukemia, involved in autoimmune disease, that is, diseases where T-cells attack our body: rheumatoid arthritis, multiple sclerosis, and a blinding disease called UVitis.  They have this receptor on the surface of the cells, as do T-cells involved in rejecting grafts.  So, we reasoned that we could use our antibody to eliminate cells we wanted to get rid of in these diseases without toxicity to the patients.  And this, indeed, turned out to be true.

Bill Schmalfeldt:
Okay, here we are 50 years and one month and several days into your career here at the NCI.  Now you are certainly somebody, Dr. Thomas Waldman, who could rest on your many laurels.  What gets you motivated to get up in the morning, get dressed, fight the rush-hour traffic in the Washington, D.C. area and come to the campus?

Dr. Thomas Waldman:
I mean, it is the most exciting part of life, more so than even the Redskins winning [laughs].

Bill Schmalfeldt:
[Laughs].

Dr. Thomas Waldman:
And I was a Redskin fan when Sammy Baugh came [laughs].

Bill Schmalfeldt:
Slingin’ Sammy Baugh [laughs].

Dr. Thomas Waldman:
To have a problem and resolve it and, especially, then to translate that into something that has an impact on human disease.  And, so, initially, our antibody was used to treat – to prevent the rejection of grafted organs, the kidney, and was approved by the FDA for this purpose.  But then we saw that we might treat with collaborators in the Clinical Center.  And I want to emphasize the enormous value of other groups in the Clinical Center for these studies. 

So, we used this anti-tact or diclisomad, its official name, to treat patients with multiple sclerosis and reduced new episodes of disease by 78 percent, new attacks on their brain without any toxicity.  UVitis, a blinding disease we’ve studied in collaboration with Bob Nussenblatt of the Eye Institute.  And we’re able, with administration every three weeks indefinitely, to prevent any progression of this disease that patients could come off all other drug therapy.  And so these aspects, using the antibody in new ways for patients with T-cell malignancy, leukemias and lymphomas.  We arm the antibody with a radioisotope and can put a proportion of the patients into long-lasting remission.  This includes patients with Hodgkin’s Disease that have failed all other therapy, where 75 percent of the patients enter a partial or complete remission with this approach.

And there are always the opportunities of seeing things from the Clinic you cannot explain.  You cannot explain with the prevailing paradigms or ways of thinking.  And, so, with that, as we treated with our antibody, we had such a confusion.  And in resolving that confusion, we discovered a new growth factor called IL15.

Bill Schmalfeldt:
You sound to me like somebody who’s still very excited about science.

Dr. Thomas Waldman:
Again, science at the interface, science at the translational level, science where one has basic insights, you make new agents and apply them to the Clinic is unbelievably exciting.

Bill Schmalfeldt:
So, what would you say to that young scientist walking through the door today for his or her first day at the NCI?

Dr. Thomas Waldman:
Think in innovative ways.  Break the paradigm.  But do it.  Get in there and get your hands dirty.  And -- but collaborate with others.  Learn from others.  Don’t be remote.  One of the great things about the NIH is the enormity and the richness of the number of people here.  There are 16,000 people at the NIH, which means that there is someone interested in virtually everything in biomedicine and you can go to them.  And with the Web, with the meetings, you will have a chance to talk to them.  And, again, I found, having been at Harvard and elsewhere, that the doors are more open here than anywhere to conversation.

Bill Schmalfeldt:
So, nearly three months after you began here at the NCI, we look at a date.  September 25, 1956.  That was the date that the underwater transatlantic telephone cable was finally opened up for public use.  You think of all the science, all the discovery, all the things that we didn’t know that are now common knowledge to people, not just in the scientific community, but to folks like me who are laymen and are interested in this topic.  It’s an honor to sit here with you, Dr. Thomas Waldman, somebody who’s had such a large part to play in all this science.  Any plans to hang up the lab coat any time soon?

Dr. Thomas Waldman:
No.  I view science and its contributions like a river.  That is, with tributaries, but always moving forward, always building on what is developed in the past so it gets bigger and bigger.  There may be eddies when things are found to be perhaps not the way one perceived it, but it’s constantly building.  I wish that peace and other things had an inevitable progress.  But I think a listing of what we have learned in 50 years is bewildering.  And I have had a chance to go back to the World’s Fair of New York where people predicted.  And, amazingly enough, people do not predict paradigm shifts or they wouldn’t be that.  That much of what we are most excited about was not predicted.  A few events, going to the moon, Jules Verne may have envisioned.

But so many things are undefined.  And there’re so many opportunities.  As I say, vaccines, since Jenner, have been unbelievably successful in preventing self-limited diseases like measles or polio where you have a disease and then are forever okay.  The challenge for us immunologists is to get vaccines so that they work for the chronic diseases that escape it: cancer, AIDS.  And I feel that these will not be solved in my lifetime so there will always be questions.  And I’m not going to hang it up.

Bill Schmalfeldt:
Dr. Thomas Waldman, thank you, again, so much for your contributions to everything and for your time with us today.

Dr. Thomas Waldman:
Thank you.

[end of transcript]

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