Chapter 12:The Impact of Successful and Unsuccessful Research Studies
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In this chapter, Dr. Tinkey talks about the impact two research studies, one successful and one unsuccessful.
She first discusses Kian Ang’s radiobiology study that she participated in when she was first hired. She explains that the study was designed to determine of the maximum dosage for radiation delivered to the spinal cord was valid. Dr. Ang determined that it was not, allowing for higher doses and new lifesaving procedures for patients. Dr. Tinkey talks about her role on this study as clinical veterinarian and explains that this result has an impact on her commitment to animal research.
Next, she talks about a plastic surgeon’s attempts to test an artificial trachea in dogs. This study failed because a proper biomaterial was not available. She explains that the failure of the tracheas created serious post-surgical complication in the dogs, forcing the PI to abandon the study. She also notes that the complications were very upsetting: one technician wanted to bring in IACOOC and a controversy broke out in the department over the value of this kind of experimentation. She talks about the value of having conversations about the humanity of animal research.
Identifier
TinkeyPT_02_20160607_C12
Publication Date
6-7-2016
Publisher
The Making Cancer History® Voices Oral History Collection, The University of Texas MD Anderson Cancer Center
City
Houston, Texas
Interview Session
Topics Covered
The Interview Subject's Story - The Researcher; Overview; Definitions, Explanations, Translations; Professional Values, Ethics, Purpose; Inspirations to Practice Science/Medicine; Influences from People and Life Experiences; Discovery and Success; Healing, Hope, and the Promise of Research Human Stories; Offering Care, Compassion, Help; Patients; Patients, Treatment, Survivors; Cancer and Disease; Controversy; Care; On Care; On Research and Researchers; Leadership; On Leadership; Controversies; Ethics
Creative Commons 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
T. A. Rosolowski, PhD:
Tell me about some of the most challenging research studies that you’ve collaborated on.
Peggy Tinkey, DVM:
Challenging.
T. A. Rosolowski, PhD:
Or memorable or however. Things that really show what the Veterinary Department can bring.
Peggy Tinkey, DVM:
Well, the very first one that was ongoing when I was hired, the radiobiology study. I’m probably relaying it much too simplistically because there was probably a tremendous amount more that Kian Ang derived from that study than what I’m going to tell you. This is part of why I think I elected to stay in animal research. So the reason that study was being done was because at the time the maximum dose that the spinal cord could be given of radiation was 45 Gray. So if a young man got Hodgkin’s lymphoma and they had to irradiate the mediastinum, the middle of his chest, there really is no way to totally block the spinal cord. Or for certain lung tumors. There were certain cancers where you can’t eliminate the spinal cord out of the field because anatomically there’s just no way to do it. And so let’s go back to the Hodgkin’s lymphoma example. So if the young man was given Hodgkin’s lymphoma and the spinal cord received 45 Gray when the kid was 20 years old and he got cured of his Hodgkin’s and everybody’s happy, but then 20 years later when the guy is 40 years old he gets another tumor, and let’s say he gets a lung tumor. And the lung tumor might be pretty easily cured if it could be removed surgically and irradiated. But the spinal cord already got 45 Gray when the kid was 20. So the radiation oncologist would not give radiation. Would not give it. Because over 45 Gray the risk of paralysis is super high. So people might die because they can’t get the radiation that might have cured them, because the practicing standard at the time was it was malpractice to give spinal cord radiation over 45 Gray because you’re going to paralyze. So people are in this dilemma. So should I get paralyzed? Well, it wasn’t even a choice for the patient because the physician won’t do it. They just won’t do it. So Kian Ang wondered is that a standard set in stone. Could you give more radiation to the spinal cord and not see paralysis? If you gave the spinal cord a sufficient time to heal? Or perhaps it was the way you gave radiation? What if you fractionated the radiation dose and gave small doses but more frequently? Would that make a difference? So that was the study that was going on. They were going to irradiate the cervical spinal cord of animals in different ways to see could the spinal cord tolerate more than 45 Gray. And the answer is yes, it can, and now that’s what they do. It seems like such a simple question. But prior to the time of the study it was just like no, 45 Gray, you’re done. Doesn’t matter if you need radiation to save your life or not, you’re not getting it. And that always made a huge impact on me, because again, I’m a simplistic person. I can understand that. I can understand the dilemma of being a 40-year-old person who needs radiation who can’t get radiation. And now I’m either going to die of my cancer or I’m going to risk getting paralyzed. Which one do I want? What a horrible dilemma. So the lifesaving research that Kian Ang did made a huge impact on people’s lives because now we know that the spinal cord under certain conditions can tolerate more than 45 Gray.
T. A. Rosolowski, PhD:
And was this the study that involved all the rhesus monkeys?
Peggy Tinkey, DVM:
Yes.
T. A. Rosolowski, PhD:
OK, so what were you doing to help manage all of this population?
Peggy Tinkey, DVM:
I was the clinical veterinarian for all the rhesus monkeys. So for the research protocol itself monkeys are like two-year-old kids. You can’t just put them in an irradiator and say, “Now hold still.” So all the animals had to be anesthetized. So we were anesthetizing animals. We were blocking the field of radiation. We were doing all the X-rays to plan the dose field. Kian actually did the radiation, but we did just about everything else with the animal. And then we took care of the animals daily. So again monkeys, every quarter all our animals had a physical exam. They got body weights, and they had their teeth cleaned. Then of course, monkeys being monkeys, I told you that the emphasis on enrichment and psychological enrichment has really come to the forefront over the last 10 or 20 years. So this was about the first time. Prior to that, research monkeys sat in a cage by themselves. But now we were beginning to realize that the absolute best enrichment for a monkey is another monkey. So we tried to pair-house everybody. And most of the time it works. But monkeys being monkeys, they had a tendency on Friday afternoon to get in a huge fight, beat each other up, and then need to be sewn up because they’d bit each other and lacerated each other. So I repaired lacerations. I treated diarrhea. I was the veterinarian for the monkeys.
T. A. Rosolowski, PhD:
Did they really choose to do that kind of thing on Friday afternoon?
Peggy Tinkey, DVM:
Oh, most inevitably. Not always. But yeah, like guys, you want to decide to have a big screaming hissy fit at 4:00 p.m.? And now somebody bit somebody’s hand and now I have to sew it up.
T. A. Rosolowski, PhD:
Natch. Cancel those dinner plans.
Peggy Tinkey, DVM:
Exactly. But that’s just the life of a clinical veterinarian. It’s just the way it is. It was that way in practice too. I could guarantee you the C-section was going to come in either as the last appointment on Friday or Saturday, always. It’s inevitable.
T. A. Rosolowski, PhD:
So tell me about another study.
Peggy Tinkey, DVM:
I’ll tell you one. And this is one that we might want to recuse out of the record. So I told you the one about Kian Ang because it was successful, and it was so obvious to me the human welfare impact that some of these studies have. The next one I’ll tell you about was not successful. It’s still not successful. It was a good study, not successful, but it illustrates the role of the veterinarian, but it also I think illustrates some of the emotional rigor perhaps. So the other one I’ll tell you about is we had one of the plastic surgeons who really wanted to develop an artificial trachea. I don’t study a lot of tracheal physiology. But apparently the trachea is an incredibly hard organ to replace. But if somebody has a big head and neck cancer, and resecting the cancer means that you have to resect part of the trachea, that’s a real big problem for individuals. The trachea doesn’t sew together very well. There really is no replacement trachea. [Redacted] And so he’d done some preliminary work in rats and it had been OK. But he wanted to scale up. Sometimes the selection of an animal model comes down to something as simple as you’ve got to have an animal of relevant size. Sometimes it’s just a size thing really. And so he’d done some preliminary work in rats. He’d had some pretty good success. Now he needed to go to an animal of relevant size. We were either going to use a dog or a pig. We elected to use a dog because either animal would have worked, but the reality is pigs are really hard to handle. They’re nice animals. But the minute you touch them they go wiggy and the scream and they run around and they’re hard to restrain and everything. And dogs are much easier. And we knew this was going to be a very hands-on-intensive study. Because it was model development and it was surgical. And we anticipated that we were probably going to be doing a lot of nursing care on the animal. And so pigs would have been really hard to put in an oxygen cage and restrain and examine 10 times a day and all of that. So we did it with dogs. Long story short, we could not develop a biomaterial structure that met the criteria. Either the structure was too weak and it collapsed, after a couple of days it would just get too soft and collapse, or it was too rigid, and when the animal moved his neck it would break apart the suture line, or it was reactive. And it was pilot, so I think we only used probably about six or seven animals for this. But the reality, like I said, it was very nursing-intensive, they were hound dogs, very good dogs, big lovable dogs, and when the postsurgical complications occurred they were strenuous on the dog. It would result in a lot of respiratory stridor, respiratory distress. We were up here day and night. Sometimes the animal would go into respiratory distress within a 30-minute period. It was a rough study. And we had veterinarians crying, we had technicians crying. When Dr. Yu decided to stop the study, he still had a lot of ideas, but I think he was just like, “I can’t handle this anymore.”
T. A. Rosolowski, PhD:
What were some of the lessons learned from it? I know that people are often reluctant to talk about the so-called failures, but often it’s only through those, and failures can sometimes be very instructive, they have to happen. Was there anything big that came out of this?
Peggy Tinkey, DVM:
The biggest one is we don’t have the right material at this time. That’s why he put it on permanent hold. The deal is he got these good results in rats because their trachea is that big.
T. A. Rosolowski, PhD:
And it could stand up to the stresses.
Peggy Tinkey, DVM:
But it couldn’t do it like this.
T. A. Rosolowski, PhD:
What was the material that was being used?
Peggy Tinkey, DVM:
I can’t remember. And so there just was not a biomaterial available at the time. It was like you got to wait for some time in the future. But the other thing that you might be interested in is we started the study, and about the third or so dog in, one of the technicians said, “I don’t think this study ought to go on. I’m going to ask the IACUC to come and take a look at it.” And that was an interesting time too because even in the Veterinary Department there were very strong and very opposite opinions about that. It’s never bad to have the IACUC come and take a look at it. But still the feel that it had from the investigator felt betrayed I guess a little. Like oh, I’ve got this. And it was a technician. But I was working closely with another veterinarian. Actually she and I were on opposite sides of it. I was on the side of there are people dying because they don’t have a trachea and yeah, this is a very rigorous study but I think we need to continue to try. And she was of the opinion it’s not ready, don’t try. And part of the reason I was of the opinion I was was I really went home several nights thinking maybe we just shouldn’t be doing this, and Dr. Gray, was he retired by that time? No, he wasn’t, because I was still in Surgery. But I don’t think he was intensely involved in the study. He was administrating stuff. But I went to see him one day and said, “I’m really troubled by this. I’m the attending veterinarian of the institution and I don’t know if I’m doing the right thing for the animals.” And one of the stories he relayed -- and this is why I believe that some of the early studies being done here by R. Lee Clark were bone marrow transplantation, because one of the stories he relayed is he said, “Peg, I had a similar experience when we were doing all these bone marrow dogs.” He said, “We probably failed.” I don’t know the number. “In 50 or 60 dogs before we got that first success. We were getting pretty darn discouraged. But if we hadn’t persevered.” Now bone marrow transplantation is standard therapy. If you’ve got certain kinds of leukemia or myelodysplastic diseases, you’re going to get a bone marrow transplant. And what if we had just after dog 20 said, “Oh, this is not going to work,” and just given up? So I think that’s why I was on the side. But it created a lot of tension even in the Veterinary Department with people saying, “This is inhumane, we shouldn’t be doing it,” and other people saying, “Look, this is the history of research. We’re going to do everything we can to make sure the dog doesn’t experience pain or distress, but just because we’re failing doesn’t mean it isn’t work that should go on.” So that was a learning experience for me too because that was probably one of the most rigorous things I had to deal with, with veterinarians disagreeing with each other. Disagreeing like yelling at each other in the hallway disagreeing.
T. A. Rosolowski, PhD:
I know that yelling isn’t always the most effective thing, but I’m wondering if those ongoing conversation -- because I imagine they come up. They can’t not come up. What’s the value of those conversations do you think in the long run? Have you seen productive things come out of it? Do you think it just stops the work?
Peggy Tinkey, DVM:
Oh, no, no, it’s almost always productive. Maybe I’ll say it’s always productive. It’s productive because nobody knows everything. There’s always value in a diversity of opinions. And when I say yelling, that’s only a reflection of how deeply people feel. And so there’s never a downside to people feeling really engaged and passionate about stuff. The downside would be if it stopped the conversation. So the good thing is it forces people. I might say publicly, “I’m 100% sure this study should go on,” but privately I’m thinking about it. And I’m thinking about what somebody else has said, and I’m considering and reconsidering. And maybe it prompts me to either do a little more reading or call a couple more people or something like that. Because you have to be willing to question yourself. It sounds counterintuitive but I think that’s the biggest value of conflict. It makes you question yourself.
T. A. Rosolowski, PhD:
It’s that passionate encounter between different perspectives. And hopefully people instead of entrenching themselves, they’ll open up just a little bit like you said and consider a different point of view.
Peggy Tinkey, DVM:
And I think 90% of the people do. I think there’s that 10% you just can’t get. But they might not admit it right there in front of you, but they go home and think about it. And that’s the other cool thing about veterinarians too. Like I said, we may have just a go to the mat contest about something, but it’s for the animal. That’s what brings us together at the end. I might think A and you might think B and we might really be at odds with each other because we’re so passionate. But we’re both passionate because we think it’s the right thing for the animal. And at the end we’ll come together on it.
T. A. Rosolowski, PhD:
Well, I’m really glad you shared that story because I think it really demonstrates just that emotional human ethical part of what you do. It’s part of what you do every day.
Peggy Tinkey, DVM:
Yeah, it is.
Recommended Citation
Tinkey, Peggy T. DVM and Rosolowski, Tacey A. PhD, "Chapter 12:The Impact of Successful and Unsuccessful Research Studies" (2016). Interview Chapters. 1232.
https://openworks.mdanderson.org/mchv_interviewchapters/1232
Conditions Governing Access
Redacted
