Chapter 03: Research Innovation Leads to a New Ultrastructure Diagnostic Laboratory and Discovery of a Cytogenetic Marker

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Chapter 03: Research Innovation Leads to a New Ultrastructure Diagnostic Laboratory and Discovery of a Cytogenetic Marker

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Description

In this chapter, Dr. Ahearn sketches his main contributions to pathology and the institution. First he describes his development of a rapid histo-chemical technique for differentiating forms of leukemia. His technique required only 24 hours rather than the standard five days "“a "revolutionary" advantage, as he notes, for diagnosis and treatment. He describes the challenges of diagnosis at that time at MD Anderson and some of the institutional reorganization that took place as a result of MD Anderson's growth and commitment to new technologies. He also explains his view that work at MD Anderson was at the leading edge of innovation in the years when he first arrived.

Identifier

Ahearn,MJ_01_20110802_S03

Publication Date

8-2-2011

Publisher

The Historical Resources Center, The Research Medical Library, The University of Texas MD Anderson Cancer Center

City

Houston, Texas

Topics Covered

The Interview Subject's Story - Professional Path; The Researcher; Discovery and Success; Contributions; Overview; Devices, Drugs, Procedures; Overview; Definitions, Explanations, Translations; The Researcher; The Clinician; MD Anderson Culture; MD Anderson History

Disciplines

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

Transcript

Tacey Ann Rosolowski, PhD

Now, when you came to MD Anderson what roles did you serve?

Michael Ahearn, PhD

Well, I came as, in the Department of Clinical Pathology as an electron microscopist, and in those days the differentiation between myeloid and lymphoid leukemias were very unclear many times in the undifferentiated patients, and normally undifferentiated leukemias are only about 20%, but here the number is higher because so many patients were referred that could not be diagnosed outside the institution. And the therapy for the lymphoid and myeloid leukemias is different, and so there was a need to be able to differentiate them early on before you started treatment. And so we were doing ultrastructure histochemistry, which could differentiate early granule formation in the myeloid lines, and then within the myeloid lines there are variants. The M3 variant, which is a progranulocytic leukemia that has a hemorrhagic episode if you’re not aware when you start therapy to give some supportive therapy for that. So they were -- all the differentiations of the leukemias needed to be done, and we developed an ultrastructure diagnostic laboratory. And at that time, I guess, because there had never been any real need for speed in ultrastructure studies, it was about a five day process, because the tissue has to be cut very, very, very thin -- 600 angstroms -- and so it has to be infiltrated with plastic and then polymerized. But we developed a technique that allowed this process to take place in 24 hours, which was revolutionary at the time and rendered the diagnosis in a time that could be utilized by the clinicians to begin therapy. So we ran a 24 hour diagnostic service here for many, many, many years. And then, of course, molecular markers came along, and they allowed them to determine this in 15 minutes what had taken 24 hours in a really speeded up process, so it was...

Tacey Ann Rosolowski, PhD

Was there something about the spirit in the organization, resources at MD Anderson that enabled, that helped facilitate the speed with which you were able to make those discoveries?

Michael Ahearn, PhD

Well, I don’t think that there was anything particular about, it was just that the need was there from the human and the patients’ point of view, that we needed to be able to help the clinician determine, rather than having to start one therapy and if they didn’t respond switch, you know, midstream.

Tacey Ann Rosolowski, PhD

Well, I guess I’m trying to understand is how, you know, we have an institution that have this new like the electron microscope and they have this person who came in who knew how to turn it on, and so they’re setting in place everything to begin to do this kind of work. I guess what I’m trying to get at is how did MD Anderson as an organization, as an institution help support that kind of work?

Michael Ahearn, PhD

Well, I think MD Anderson has always tried to be on the cutting edge of anything regarding cancer, and I think that when the decision to acquire that microscope -- and those microscopes are very expensive; I mean, in today’s dollars perhaps not so much, but in those days $300,000 was a big investment, and that was just the instrument. The supporting laboratory that has to support that was a great deal more, because the corals have to have refrigeration in them and they have to have a unit. It has to be piped in, and the microscope has to be in an area that’s vibration free, so the compressing units for the [chilled water?]

has to be in a remote site. There’s a lot that goes on, so the development of that laboratory was a very expensive investment for the institution, but I think they realized the advantages that it could offer in the treatment and care of the cancer patient, and they were willing to make that expenditure in order to be offering cutting edge technology to the treatment of the hematopoietic malignancies.

Tacey Ann Rosolowski, PhD

So who was making the decisions to make those investments?

Michael Ahearn, PhD

Well, I think it came from the top down. It was the culture, you know. And certainly, my immediate superior was Dr. Bill Russell, which was Head of Pathology, but he had to get the funding from Dr. Clark, so it was...

Tacey Ann Rosolowski, PhD

Who are some other people that you worked closely with at that time?

Michael Ahearn, PhD

Well, Dr. Jose Trujillo was a... He and I were both in clinical pathology. Dr. Trujillo eventually became Head of Clinical Pathology, which is now Laboratory Medicine, but he was a cytogeneticist, and in the treatment of certain cytogenetic abnormalities there were indicators of malignancy, and so by doing cytogenetic analysis you could tell when a patient went into remission and the abnormal cytogenetic clone disappeared from the hematopoietic system, and then when relapse came, impending relapse, the cytogenetic abnormality came back, and so it was used as an indicator of predicting relapse in hematopoietic malignancies. But the problem was that patients who were on maintenance therapy, cells did not divide properly, and so therefore you could not always get the mitotic figures that you needed to be able to determine whether the cytogenetic, abnormal cytogenetic clone had returned. But what we discovered early on, was that there was structure, ultrastructure bleb on the nucleus of the cells that had the cytogenetic abnormality. It was very closely associated with the cytogenetic abnormality, and that gave us an orthological marker that we could use to determine that this cell actually did have the abnormality in it, and it was interface cells, which did not depend on division, and so therefore they were present. So we were using the ultrastructure technique to also monitor patients that were under therapy to determine imminent relapse and return of their disease state.

Tacey Ann Rosolowski, PhD

I noticed that you coauthored a number of papers with Dr. Trujillo.

Michael Ahearn, PhD

Yes.

Tacey Ann Rosolowski, PhD

And how long did that collaboration last?

Michael Ahearn, PhD

A number of years. I don’t remember exactly, but it was a revolutionary thing at the time, to be able to take an orthological marker and associate it with a cytogenetic abnormality, and then to use it in a useful way in regard to the care of cancer patients.

Tacey Ann Rosolowski, PhD

Mm-hmm. So again, one of those -- for quickly seeing immediate results.

Michael Ahearn, PhD

Yes. And today, not necessary because we’ve gotten $$electrode markers?, but at the time all of these things were state of the art, so to speak.

Tacey Ann Rosolowski, PhD

I wanted to move on. We’ve kind of begun talking about your own research area, of course, but I was reading in a previously conducted interview with James Bowen, and he said something kind of interesting about the context of the historical moment of the 1950s and ’60s. He said it was really, as he called it -- let’s see if I can find his phrase -- he called it the golden age of cancer research, and he said that there were kind of three things coming together: there were discoveries from DNA and the whole, the way in which DNA was altered by cancer; and then the idea that viruses could transmit cancer; and then, of course, the electron microscope. And I’m wondering, since that was sort of the historical climate or, if you will, the history of science climate in which you were working, as well, how do you see the activities that were going on MD Anderson in that larger context? I mean, was MD Anderson more innovative? Was it kind of keeping up with others? What was that all about?

Michael Ahearn, PhD

I think it was perhaps more innovative. We had, as Jim had said, viruses were very much of interest at that time, and we had a virologist here, Dr. Leon Demokowski, and Dr. Demokowski got the second electron microscope to study viruses. His work was primarily research work, not involved in patient care. Our work, because of the intensity involved and the number of samples that we had to process daily, our application was more patient oriented than research, although certainly the observations that we made with Dr. Trujillo could be considered research observations. But they were primarily -- our work was involved with patient care. But Anderson was leading in the number of publications and everything in the field of cancer, even back in those days, in the ’50s and ’60s.

Tacey Ann Rosolowski, PhD

Well, and when you think about that time, were there any weaknesses in the system? I mean, we talked about, you know, the strengths, but were there things that you found frustrating dealing with the institution, things that needed improvement?

Michael Ahearn, PhD

No, I really do not think so. As I remember back, as much as we could think and dream, the resources were always there to pursue that, so I don’t remember any weaknesses at all in the institution. It was an experience -- everyone knew everyone else, and Dr. Clark, when he built the Anderson, he wanted the patient care and the research areas connected, because he said, “I want the clinicians to be able to talk with the research side of the house,” and that very much took place, because we were small. The area where the Clark building and the outkick from the original structure used to be a tree forested area out there, and they had round, concrete picnic tables, and the faculty on every day that it wasn’t raining -- we had no separate dining room -- we went through the patient cafeteria, which was a very small area and not sufficient for the staff, and we would go outside and sit at those round picnic tables out under the trees, and there was a lot of conversation and mixing of the research and the clinical staff at that time.

Tacey Ann Rosolowski, PhD

Dr. Clark very early had this commitment to teamwork and interdisciplinary --

Michael Ahearn, PhD

Very much so, very much so, and he promoted that in every occasion that he could.

Tacey Ann Rosolowski, PhD

And it sounds like at that time the small scale of the institution --

Tacey Ann Rosolowski, PhD

Absolutely. I wanted to pick up like one little detail, because one of the things I’ve noticed is that the names of departments change amazingly in this institution. Now, I think it said you were hired in the Department of Laboratory Medicine. Is that what it was called when you...?

Michael Ahearn, PhD

No, no, no.

Tacey Ann Rosolowski, PhD

OK.

Michael Ahearn, PhD

It is now Laboratory Medicine. It was Clinical Pathology.

Tacey Ann Rosolowski, PhD

OK, so that was the original name in ’65.

Michael Ahearn, PhD

Well, it really started out as Department of Pathology, but right after I arrived they decided to split Pathology into Anatomical and Clinical Pathology.

Tacey Ann Rosolowski, PhD

Why was that done?

Michael Ahearn, PhD

Because of the size, the growing needs, and the differences in the needs to support those two areas, distinctly different.

Tacey Ann Rosolowski, PhD

OK, and so it went to those two, and then what happened?

Michael Ahearn, PhD

Well, years later I think that they figured that the term Laboratory Medicine was better than Clinical Pathology in describing the scope and function the department had evolved into.

Tacey Ann Rosolowski, PhD

OK, so the name change at that point was just a descriptive term and not -- it didn’t represent any structural change.

Michael Ahearn, PhD

No.

Tacey Ann Rosolowski, PhD

OK, OK. Now, I think I read in one of your CVs that you directed the Diagnostic Ultrastructure Hematology Laboratory --

Michael Ahearn, PhD

Yes.

Tacey Ann Rosolowski, PhD

-- for 23 years, and when did you take on that role?

Michael Ahearn, PhD

Well, when I came.

Tacey Ann Rosolowski, PhD

When you came. OK, OK, so that was --

Michael Ahearn, PhD

1965.

Tacey Ann Rosolowski, PhD

OK, so that was right away. OK, and what was your mission when you took on...? Did you have a sense that there were things you wanted to develop or to change?

Michael Ahearn, PhD

Well, first of all, I never anticipated that I would stay 23 years in that area, but there was always an excitement and a challenge there, and so I never felt that the call left, and here I’m winding up 46 years at the same institution, so...

Tacey Ann Rosolowski, PhD

Was there anything in particular that you instituted in the running of that laboratory that...?

Michael Ahearn, PhD

Well, as I said, the development of the 24 hour diagnostic service part of it was revolutionary at that time. No one else was able to do that the way we were doing it, so...

Tacey Ann Rosolowski, PhD

And how were you able to do it?

Michael Ahearn, PhD

Well, by incorporating and looking at the techniques involved. The penetration of the plastic -- we instituted a high vacuum processing, and then we just speeded up every part of the process by different alterations in the techniques, in the infiltration of the plastic and in the polymerization, and ultimately the sectioning and examining it. And then, too, some of the staining, the histochemical staining process, we altered that, too, (inaudible) detect early peroxidase in forming granules.

Tacey Ann Rosolowski, PhD

Would you... Directing that laboratory for 23 years, and you’ve noted any number of times that, well, things are really different now, how would you describe some of the important changes that took place in your field during that period, in terms of the research, the knowledge?

Michael Ahearn, PhD

Well, I think that we saw that there were better treatment offered for the patients in the institution, those with hematological malignancies. Ultimately, Anatomical Pathology got another scope for their work. Ultrastructure offered a lot of advantages in those days, and as I said, particularly in the area where I worked of hematological malignancies, but no one is using an electron microscope today to determine the difference between myeloid and lymphoid leukemias, because we have much faster, much better, more accurate methods with molecular markers. But in those days it was a constant challenge to work out new techniques and to be able to refine the techniques that we had, and then just the day to day service activity, which was...

Tacey Ann Rosolowski, PhD

Mm-hmm. What was the size of the department at that time?

Michael Ahearn, PhD

Relatively small. I think when I came Dr. Trujillo and myself and Dr. Merrick, which was a biochemist, and Dr. Roman Rienta was a microbiologist, and Dr. Shively. That was about the extent, I think, of the people that I worked directly with in those days.

Tacey Ann Rosolowski, PhD

And then support staff? Did you have other support staff?

Michael Ahearn, PhD

Yes, we had support staff in the laboratories. Yes.

Tacey Ann Rosolowski, PhD

And what was the size? Do you remember about how big it was, what your personnel was like?

Michael Ahearn, PhD

I think I had two technologists and a secretary.

Tacey Ann Rosolowski, PhD

Oh, so it’s still a relatively small --

Michael Ahearn, PhD

Yes.

Chapter 03: Research Innovation Leads to a New Ultrastructure Diagnostic Laboratory and Discovery of a Cytogenetic Marker

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