Chapter 04: Early Research on Stem Cells and Erythropoietin

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Chapter 04: Early Research on Stem Cells and Erythropoietin

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Dr. Alexanian explains how he came to MD Anderson in 1964, then then talks about the evolution of his research, beginning with his experiences working on stem-cell kinetics while working with Dr. Laszlo Lajtha when he was on fellowship in Manchester, England. This focus enabled him to make the move to his second research fellowship in Seattle, where he worked with Dr. Clement Finch, a specialist in red cells, who taught him to focus on disease from a clinical perspective. Dr. Alexanian explains the skills he learned from these two mentors. He also notes that his experience enabled him to apply for grants for his own projects, and initiated work on erythropoietin. He describes his research and notes that he was the first person to measure normal levels of this hormone in human urine.

Identifier

Alexanian_R_01_20140415_S04

Publication Date

4-15-2014

Publisher

The University of Texas MD Anderson Cancer Center

City

Houston, Texas

Topics Covered

The Interview Subject's Story - The Researcher; Discovery and Success; Definitions, Explanations, Translations; Influences from People and Life Experiences; Professional Path; Career and Accomplishments; Joining MD Anderson

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

Disciplines

History of Science, Technology, and Medicine | Oncology | Oral History

Transcript

Raymond Alexanian, MD:

So can I ask, I'm sure many of these itineraries are similar to what-you've heard others like this?

Tacey A. Rosolowski, Ph.D:

You know, it's amazing, some people are incredibly focused, "I'm going to do this. This is what-."

Raymond Alexanian, MD:

Do this in one place.

Tacey A. Rosolowski, Ph.D:

And others are more, you know, open to opportunities and things that fall very organically. It's all about what opportunities and mentors come your way.

Raymond Alexanian, MD:

Right. That's right.

Tacey A. Rosolowski, Ph.D:

So the stories can be very, very different.

Raymond Alexanian, MD:

I'm sort of in the latter category.

Tacey A. Rosolowski, Ph.D:

Yeah. Well, it's very interesting. So tell me how did the cancer focus start. Tell me about that.

Raymond Alexanian, MD:

When I was in Manchester, it's obvious that I had no job after that, so my previous mentor, Dr. Finch, F-i-n-c-h, in Seattle said, "When you're finished in Manchester, you're welcome to come back here, and we'll get started on a program for you." So that was my intention until Dr. Lajtha, my Manchester mentor, who was often a visiting lecturer throughout the world and had given a lecture and was invited at a program at MD Anderson Hospital in 1963, came back and said, "Ray, I've got a job for you." I said, "What do you mean, Dr. Lajtha?" He said, "Well, they're looking for somebody like you down at Houston." I said, "Well, that's interesting, because I don't have a job unless I go back to Seattle." So I sent in my resume, which was virtually nonexistent, just my school program, and I had a couple of papers in Manchester, but it was very-and so had an interview here in transit back to Seattle.

Tacey A. Rosolowski, Ph.D:

Who did you interview with?

Raymond Alexanian, MD:

In transit back, my wife and daughter went on to Seattle, and I detoured for an interview with Dr.- [interruption]

Raymond Alexanian, MD:

So, Dr. Bergsagel, B-e-r-g-s-a-g-e-l, Bergsagel, I had an interview here, and that was followed by-let's see. That was in July of 196-

Tacey A. Rosolowski, Ph.D:

Let's see. It must have been 1963?

Raymond Alexanian, MD:

Sixty-three. Followed by a second interview in December of 1963 at a hematology meeting where I presented a paper and-

Tacey A. Rosolowski, Ph.D:

Now, when Dr. Lajtha said, "They're looking for somebody like you," what did he mean? I mean, what were you doing at the time?

Raymond Alexanian, MD:

I had finished the two years in hematology and was finishing-no, two years in hematology, one more year of research in Seattle and one more year with him.

Tacey A. Rosolowski, Ph.D:

What was the research that you were doing?

Raymond Alexanian, MD:

With Dr. Lajtha?

Tacey A. Rosolowski, Ph.D:

Mm-hmm.

Raymond Alexanian, MD:

Well, it's an area called stem cell kinetics. It has to do with the primordial cells in the bone marrow that lead to other cells, normal cells. What are the normal-is there some grandfather cell that accounts for all the different red cells, white cells, and platelets? It's called the stem cell, and it had to do with that primordial cell that he had an interest in and that if they could understand that cell, that might eventually lead to an understanding of leukemia and other diseases like that.

Tacey A. Rosolowski, Ph.D:

What did you find most intriguing about that research? Because you stuck with it.

Raymond Alexanian, MD:

Well, first of all, with Dr. Finch, who was also a research scientist of some renown in red-cell disorders, like anemias and conditions like that, had been a very good teacher in terms of approaching research problems related to red cells and how to understand anemias and the processes and causes and diagnoses and so on. All of these areas were in their different phases of evolution. So he was a very good person to teach his students how to approach these diseases from not only a clinical way but a research way. Then with my time in Manchester, this was a similar process of where one can-I worked with hundreds of experimental mice, literally hundreds of mice, and where one could apply techniques of transfusion into mice, believe it or not, exposing them to low oxygen and injecting animals and radiating mice and work out answers to certain questions related to stem cells. So with those two consecutive years added to the clinical hematology, I was prepared to work this out and also have the qualifications, with help from Dr. Finch, to apply for a research grant so that I would be developing my own projects, at first with his supervision and then with my own. And that's, as you can imagine, a fairly intense one-on-one, "What are you doing this week?" And, "Report to me what's the progress, and are you writing this up? Are you presenting this, or what are you doing?"

Tacey A. Rosolowski, Ph.D:

It's like really intense mentoring.

Raymond Alexanian, MD:

And then when you write something, he said, "Well, send me a draft of what you're writing." So I would write something, which I thought I was good at writing, but I was not really as good as he was, of course, and so he would edit everything I wrote in great detail. He was a terrific, superb editor of science-writing. He says, "Are you saying something that's clear here? That's not clear to me."

Tacey A. Rosolowski, Ph.D:

Is this Dr. Lajtha?

Raymond Alexanian, MD:

Dr. Finch first, and then Dr. Lajtha, the same thing, a double-barreled sequence. And he said, "Well, if you can't write clearly, then you can't think clearly." So I didn't quite agree with that, but still you can think up to a point but maybe expressing it is different, so I was drilled heavily for two years on this.

Tacey A. Rosolowski, Ph.D:

So with both problem solving and kind of basic knowledge and-yeah.

Raymond Alexanian, MD:

So I was in a good position to come here, and so I had my own research project here.

Tacey A. Rosolowski, Ph.D:

And what was that?

Raymond Alexanian, MD:

Well, at that time, I carried the program I had begun in Seattle. You see, there was another year in Seattle in '63, as I was-

Tacey A. Rosolowski, Ph.D:

So you began your own research project during that year?

Raymond Alexanian, MD:

During that year with Dr.-that dealt with the hormone called erythropoietin. It's sort of spelled out in the writing. And this substance is, as you know, widely used now for treating anemia and-

Tacey A. Rosolowski, Ph.D:

And what was the project? What were you working on with it?

Raymond Alexanian, MD:

Well, it's hard to believe, but I was the first one to detect or measure normal levels in human beings, which everyone knew that it was there, but no one could quantify it, so I was able to quantify it in human urine. So my project dealt with large twenty-four-hour collections of urine from patients and normal people, and we would take the urine and concentrate it into a tiny amount by essentially drying it up, dry up the urine by allowing the water to flow through a cellophane filter over a period of time, and you're left with a small amount, say a cupful, that represents a twenty-four-hour collection, or even less. And you can take those small amounts and inject it into mice and measure their erythropoietin. There's more to it than that, but that's essentially the process.

Tacey A. Rosolowski, Ph.D:

Now, what does erythropoietin do in the body?

Raymond Alexanian, MD:

As human beings become more anemic due to blood loss or due to disease, they build up a normal response with high levels of erythropoietin, which is a hormone, to make more red cells. It's a compensating feature for anemia, and it's also a compensating feature for people at high altitude, so as you get low in oxygen, it helps you adjust. It's part of a normal adaptation, I guess similar to many other hormones like insulin. When the sugar levels are high, we make more of our insulin to bring it down. And other hormones.

Chapter 04: Early Research on Stem Cells and Erythropoietin

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