Chapter 3: The Start of a Research Career on the Effects of Radiation on Normal Lung Tissue

Chapter 3: The Start of a Research Career on the Effects of Radiation on Normal Lung Tissue

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In this Chapter, Dr. Travis explains how her research career really began between 1976−1979, when she was a Research Scientist/Lecturer at the Gray Laboratory (Mount Vernon Hospital, Northwood, Middlesex, United Kingdom). She notes that “they took a chance on her,” as she had never been awarded a grant, but they saw potential and recognized that she had knowledge of lung pathology and radiation therapy. This was key, as the field of radiation therapy was starting to focus on the effects of radiation on normal tissue. Dr. Travis lists the researchers who were at the Gray lab at that time. She talks about the atmosphere and notes some lessons in mentoring she received from the laboratory head, Jack Fowler.

Next, Dr. Travis describes a collaborative project she undertook to develop a non-invasive assay of lung tissue after irradiation that involved measuring the breathing rates of mice as they developed lung damage from radiation therapy. She describes the rationale of the study as well as the challenges of measuring the breathing rate of mice. She describes the device she and her colleagues developed to measure breathing rates (see Figure One) and notes that this was the first time that anyone had measured breathing rates as animals developed lung damage from radiation.

Next she notes that it was very hard to get the field to accept the findings and describes how she and her colleagues addressed this by arranging for their measurements to be confirmed. With that evidence gathered, their paper was published (1977/78). Dr. Travis next describes one regret: that she didn’t patent this device and another (described below): both have been picked up by companies and are still being sold thirty years later.

Next Dr. Travis describes the “jig” she developed to immobilize non-anaesthetized mice for irradiation (see Figure 2). This was developed to simulate how patients are irradiated in the clinic and Dr. Travis explains how they were working with fractionated doses.

Dr. Travis goes on to describe more of her work at the Gray Laboratory and why it was such an ideal environment. She talks about the goals she had set to achieve in London and notes that at the end of her three years there, she had an independent research career.

Identifier

TravisEL_01_20140324_C03

Publication Date

3-24-2014

City

Houston, Texas

Topics Covered

The Interview Subject's Story - The ResearcherThe Researcher Professional Path Career and Accomplishment Discovery, Creativity and Innovation On Mentoring Professional Path Technology and R&D Discovery and Success

Transcript

Tacey Ann Rosolowski, PhD:

Now, I kind of feel like I need to ask for your guidance here, because we’re talking about your track, but we haven’t talked about your research. Do you want to kind of pick that up a little bit, and let’s talk about how your research evolved?

Elizabeth Travis, PhD:

Sure, yes.

Tacey Ann Rosolowski, PhD:

Okay. Let’s do that story, too, so we’ve kind of got both stories going at once.

Elizabeth Travis, PhD:

So this is where my research really evolved. I credit those three years, first of all, MUSC, for giving me an opportunity. I mean, they really did give me an opportunity to see what I could do.

Tacey Ann Rosolowski, PhD:

Now, when did your research career really start?

Elizabeth Travis, PhD:

At the Gray Lab in 1976. At the Gray Lab.

Tacey Ann Rosolowski, PhD:

But you were already working on—

Elizabeth Travis, PhD:

I was already working, and I had done some work and I had published some, but, you know, MUSC at the time didn’t have a lot of research going on. Rusty was a great mentor and taught me a lot, but it wasn’t well known in radiation, which was part of the reason why I needed to go somewhere else and develop myself even further if I was going to—I knew I needed that if I was ever going to have an independent research career. I knew that. I saw what I wanted, and I knew that I didn’t have even yet the right pieces to get me there. So I knew I had to get a really good postdoc. So they took a chance on me.

Tacey Ann Rosolowski, PhD:

The Gray Lab.

Elizabeth Travis, PhD:

The Gray Lab did. Like I said, I had met the head of the lab one time before then, so he remembered me, but they took a chance, because, you know, I didn’t come from an Ivy school. I came from a small state college. University of Pittsburgh was a good school. Medical University of South Carolina, nobody knew anything about in terms of radiation field. So they took a big chance on me.

Tacey Ann Rosolowski, PhD:

What do you think they saw in you?

Elizabeth Travis, PhD:

I think they saw that I had knowledge of something that they wanted. I had knowledge that they wanted. I knew about lung. I knew lung pathology. That’s what I was trained in. And I had some radiation background, and that’s when the field was just beginning to focus more on the side effects of radiation than only on the tumor, which was most of the focus. So I had pathology, and none of them were really pathologists, and that’s what I brought to the lab. And that was just a remarkable both professional and personal experience, being in that. I mean, that is where my research career really developed.

Tacey Ann Rosolowski, PhD:

So tell me about that blossoming. How did that take place?

Elizabeth Travis, PhD:

It was an exciting environment surrounded by some of the best minds in the field at the time, Jack Fowler, Julie Denekamp, I mean just the most respected people in the field. You couldn’t help but learn. There were other postdocs there and we just all worked together. It was a small lab; it wasn’t big. There were always people there from the States. We met a lot of people. They introduced us. I mean, the head of the lab, one of the things I learned from him about mentoring is when the big names in the field come to the lab to visit, they didn’t visit with the staff, the faculty there; they visited with the postdocs and the graduate students, because it was an opportunity for them to meet us and for us to talk about our work with them, and so you get your name—the work you were doing, you got to talk with these people about it, which then helps you get a job later on. But there was a guy who was an engineer and another fellow who was another postdoc, and he knew a lot about the vasculature, and the three of us, we wanted to develop a noninvasive assay for lung damage, which was what I wanted to do, because the only assays we had at that time for lung was when the animal died. So you radiated them, you count the dead bodies, basically, and there was a little bit done about the pathology. One of the things that I lacked was my quantitative training because I was a pathologist. I was trained at looking at images, recognizing patterns, and how to quantify that is one of the things we did at the lab as well. But we developed—in fact, where’s the picture of it? Where’s my breathing machine? I still have the original somewhere. This is a jig that’s to jig animals. That’s another thing we developed. Where’s my breathing machine? Can’t find it. How can that be? So anyway, the model was what you used to measure pulmonary function in people, a plethysmograph. Here it is. Here it is. I have a picture.

Tacey Ann Rosolowski, PhD:

Great. Wow. Do you have that scanned at all?

Elizabeth Travis, PhD:

No, but we could.

Tacey Ann Rosolowski, PhD:

That would be great, because if you scan that and the other, I actually can put it right in your interview.

Elizabeth Travis, PhD:

Oh, perfect. I’ll do that.

Tacey Ann Rosolowski, PhD:

Yes, that will be lovely.

Elizabeth Travis, PhD:

Yes, I’ll do that.

Tacey Ann Rosolowski, PhD:

Terrific.

Elizabeth Travis, PhD:

Yes, so we developed this little plethysmograph, and so you can see—

Tacey Ann Rosolowski, PhD:

I’m sorry, what is that called?

Elizabeth Travis, PhD:

A pleth—it measures breathing rate, and the way it measures breathing rate is it’s a sealed chamber. The animal can only be in there for a certain period of time. It has a little pressure inducer in the end. It was a microphone that the engineer modified to measure very small pressure changes in the chamber as a mouse breathed. You closed it up and you left, and we recorded it. At that time, we recorded it out on paper.

Tacey Ann Rosolowski, PhD:

The old days.

Elizabeth Travis, PhD:

The old days. Then I would look at it and I would analyze these rolls and rolls and rolls of graph paper with all these little blips going up and down and measure the breathing rate. We standardized how to do that, and this was the first, the very first time that anybody could measure breathing rates. And why it was so important is it measured changes in their breathing rate, because what happened is the animal developed the damage as their lung gets filled up with fluid and cells, and they switch to rapid shallow breathing patterns, but it happens gradually. So we were able to measure changes in lung function in mice that had had both lungs irradiated, long before, and at doses that were sub lethal and long before the animal—we had to sacrifice the animal because he was in pulmonary distress. So it was a real breakthrough. It was really hard to get the field to accept it.

Tacey Ann Rosolowski, PhD:

Why?

Elizabeth Travis, PhD:

Because the mice were breathing very fast, and nobody thought they breathed that fast. So we wrote the paper. We couldn’t get the paper published. So what we did, we filmed slow-motion, filmed an animal in the breathing chamber, such that we then put it up on a screen, and we got a whole bunch of people to sit in the library at the lab. We said, “Okay, we want you to count how many times the thorax of that animal moves.” And everybody did it, and indeed the numbers were right. Our numbers were right.

Tacey Ann Rosolowski, PhD:

Wow.

Elizabeth Travis, PhD:

So then we got the paper published. And this was actually repeated by some very well-known names in the field of pulmonary physiology, and they did the same thing and then they said, “Yes, she’s right. This is correct. We’ve produced these data.” One of the things I regret, because at that time you never thought of this when you were a scientist. This has, since then, been—[ ] picked up by a company and they are selling them. I was at a meeting about a year or so ago, radiation research meeting, and these two things were both sitting out there, and I went over to the company and I said, “Interesting.” They’ve revised it, and we revised it, too, but this was the original. And I said, “Well, I’m glad to see that.” And they said, “Yes.” They said, “So-and-so developed that.” I said, “Oh, no, no, no, no, no, no. He did not develop that.” I said, “You’re speaking to the individual here. I will send you the original paper if you don’t know it.” So this is like thirty years later, and this is still making money for people. Frustrating. Very frustrating. (laughs) And the same with this. So the other thing—

Tacey Ann Rosolowski, PhD:

And that other—

Elizabeth Travis, PhD:

So this is a jig to irradiate mice, because the only way people were irradiating mice was to anesthetize them, and so I wanted to get rid of the [anesthesia] —particularly because I wanted to do experiments where I wanted to simulate what we did in a clinic, which was to give a little bit of radiation every day. It’s really hard to anesthetize animals over long periods of time without killing them. They become intolerant to it, and you either don’t get them anesthetized and they squirm around, which you don’t want because you’ll miss the lung. You have to make sure, just like you do with a patient, you have to make sure that the radiation is going where you want it. So we developed this so that we could irradiate a mouse without anesthetizing him. I have one of these somewhere, too, my original jig. And there was a young man in the lab who was my technician at the time, who now has his PhD, and he helped do this. It had a slight tilt on it. It was like at an angle. The top of it was at an angle. So what you would do, we did that because mice, they’re small in the thorax, so you want their thorax right in between these two little posts.

Tacey Ann Rosolowski, PhD:

We’re looking at the image, and there are two pieces of Plexiglas kind of at an angle, and I guess that kind of wedges the animal in?

Elizabeth Travis, PhD:

This is flat, and then the top of this is slanted. It has a little nose thing that you can adjust, and the lung basically fits into these posts. I mean the thorax fits into those posts.

Tacey Ann Rosolowski, PhD:

Between those two angles of Plexiglas.

Elizabeth Travis, PhD:

Yes, and what you do is, they like to run into small spaces, so we would pick them up, and you’d get the mouse’s nose going in the opening there, and I would stick my thumb up behind him or her, and they would run in.

Tacey Ann Rosolowski, PhD:

“Come on in.”

Elizabeth Travis, PhD:

They would just run right in. It did not—and then you’d pull their feet out in front of this. You can’t see it here, but you’d pull the feet out in front of it, and the legs would be here, and you would just swivel these in, and they couldn’t move. You would just hold the thorax.

Tacey Ann Rosolowski, PhD:

Right. So they were completely stable for irradiation.

Elizabeth Travis, PhD:

They were completely stable. In fact, we did experiments out at Berkeley on neon ions, and that is a horizontal beam, so the animals had to be vertical, and they were on this little track that went along. They had to be, and only one of I don’t know how many hundreds we irradiated, because we did, again, a lot of—it’s called fractionated radiation. We did fractionated doses, and I think hardly any of them fell out of this jig. So these are the two things I did at the Gray Lab, and then all of the work I did there centered around radiation effects on the lung. It was such an environment because it gave you the opportunity, first of all, you didn’t have to write grants, and it gave you the opportunity—took us a year to develop this chamber, to get it developed, refine it, and get the data out. And I think the first paper was published in 1976, ’77, ’78, maybe, probably ’78.

Tacey Ann Rosolowski, PhD:

That actually seems pretty quick, if you got there in ’76.

Elizabeth Travis, PhD:

Oh, yes, but we were, I mean, laser-focused, laser-focused.

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Chapter 3: The Start of a Research Career on the Effects of Radiation on Normal Lung Tissue

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