Chapter 13: Building the Rodent Population and An Overview of MD Anderson’s Genetically Engineered Mice
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Description
In this chapter, Dr. Tinkey sketches the growth of the rodent facilities administered by the Department of Veterinary Medicine and Surgery and describes the genetically engineered rodents that many MD Anderson researchers use. Rodent facilities have grown in tandem with the growth of MD Anderson research.
She notes that the first significant expansion occurred in 2006 when the rodent facility was moved from its old location in the Jones Freeman Building to the new location in the Mitchell Research Building [BSRB]. Dr. Tinkey describes the “state of the art” caging systems that the Department invested in in order to reduce labor costs. She explains that the Department aims include identifying space to grow, sustaining the growth rate and achieving workforce efficiency. To demonstrate adherence to these aims, she talks about the roboticized cage washing system that has helped the Department maintain efficiency and control costs as the number of rodent cages has increased by twenty-five thousand between 2006 and 2016. She next sketches additional increases and some administrative changes in handling the rodent population. She notes that the Department is beginning a renovation to add another 8500 rodent cages.
Next, she talks about the genetically engineered mice that are important to MD Anderson research. She explains that “humanized mice” are “little avatars that grow a human tumor to generate a PDX or patient derived xenograft. She goes on to describe immune-deficient mice and nude mice, the latter being a “huge foundation” of cancer research that require a sterile environment with consequent special handling. She notes that the institution has invested over a billion dollars in animals for research, including genetically engineered mice that have been developed at MD Anderson.
Dr. Tinkey next talks about the Department’s emergency plans instituted to protect this investment. She recalls being at Baylor and the loss of thirty thousand animals during Tropical Storm Alison. MD Anderson keep animals in basements and protects animals with flood mitigation plans and on-call staff 24 hours a day, 365 days a year. She discusses the link between the Department’s Veterinary Emergency Plan and the institution’s Emergency Plan, noting the Department instituted a disaster plan as part of the accreditation process. She explains that MD Anderson’s plan is “very mature.”
Identifier
TinkeyPT_02_20160607_C13
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 University of Texas MD Anderson Cancer Center - Building the Institution; Discovery and Success; Overview; Definitions, Explanations, Translations; Healing, Hope, and the Promise of Research Care; On Care; Leadership; On Leadership; Institutional Process; The Business of Research
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:
I’d like to go back to a bit about the history of the department as it evolved, some of the things that you helped develop when you were chair, because I have a list of a whole bunch of things. Quarantines, and all these things that you’re responsible for overseeing. And as the institution has grown and grown you must have seen huge changes in the quantitative leaps in a sense of what you have to pay attention to. So can you take me through a little bit of that, how things began to evolve?
Peggy Tinkey, DVM:
The most obvious difference in the department is just size. And Dr. Gray really got us started on this, but this might be boring too, but we’re in good shape now because starting in about -- well, it was in 2006, so just as Dr. Gray was retiring and I was coming on. It was our first significant expansion of the rodent facility. We were moving from our old facility over there in the basement of the Jones Freeman Building, the Basic Research Building, into the BSRB. And at the same time the institution is great because it gives us tremendous amounts of money, but we invested in the most cutting-edge caging and watering systems that we could. So our caging system is really the modern standard in that it’s called an individually ventilated cage, which means it’s not just a cage of mice sitting there on the table with a lid on it. The cage fits onto a rack. And the cage itself has these two little pipes in the back. It’s like its own air-conditioning system. Air flows into the cage and is exhausted out of each cage. We did that for a couple of reasons. One reason was those racking systems at the time allowed us to house the highest number of cages per square foot of flooring. And we had space then, but we thought at some time if we continue to grow, space might be an issue. The second thing it did is that ventilation keeps the cage nice and dry. And so it allowed us to extend the interval between the times that we had to physically change the cage. And the highest cost in animal care is labor. And the highest time activity that our people is physically changing the mouse cages. Taking the mice and taking them from a dirty cage and putting them in a clean cage and then cleaning the cage. So that positioned us to be able to have the space to grow and be able to sustain a pretty significant growth rate with workforce efficiency. And the other thing we did is we went from water bottles to automated watering, which means we have a piping system on the wall where the pipes are attached to the rack, and each little cage now has little watering like I said in it. So it comes from the piping on the wall. We don’t have to put a water bottle on every cage. And processing water bottles is a huge time expense. So that means labor expense. And it’s also the highest rate of injuries in the animal facility because they’re heavy. You pick up a rack of water bottles and you twist and then you get a back injury or muscle sprain or something like that. So we did that and then we put in robots in our cage wash.
T. A. Rosolowski, PhD:
What does that mean?
Peggy Tinkey, DVM:
We have robots that actually pick up the cages and dump them and stuff and put them on the conveyor belt that goes into the washing machine.
T. A. Rosolowski, PhD:
For the record, my jaw just dropped. That’s so cool.
Peggy Tinkey, DVM:
I think we’ve got some video if you want. I could take you in there if you want to see the robot.
T. A. Rosolowski, PhD:
Oh my gosh, totally.
Peggy Tinkey, DVM:
So we roboticized about maybe five years ago. But we’ve done these things because the rate of growth -- I have to go back and look and see. I can’t even remember. I know we’ve grown at about a 12% annual rate, which is a lot. So I’ll say our cage census in 2006 was maybe, I don’t know, 10,000 cages, and today we’re 35,000. Yeah, so that’s the most obvious thing. In 1993 our department, I don’t know, maybe we had 3,000 cages then, I don’t know. But we were over in the basement of the Bates Freeman Building over there. In 1999 the large animals moved from that area into the basement of the Clinical Research Building over in the Tan Zone. So that was our first expansion. The rodents were still over there but the large animals moved over here, and we got new experimental surgery suites. It was awesome.
T. A. Rosolowski, PhD:
I’m sorry. That was in --
Peggy Tinkey, DVM:
Nineteen ninety-nine. In 2004 the animal facility at South Campus all up to that time was not Veterinary Medicine. It was a research-run satellite by Josh Fidler [oral history interview] and Margaret Kripke [oral history interview]. And in 2004 Josh was wanting to step down. He was planning to step down as chair. Anyway he wanted Veterinary Medicine to take over the animal facility. So that was the second I guess significant expansion of the department. We took over that facility at South Campus.
T. A. Rosolowski, PhD:
I’m sorry. The year again for that?
Peggy Tinkey, DVM:
Two thousand four. And that facility I think at that time was running about 3,500 cages or something. And in 2006 the rodent facility moved over here, and then things went crazy. So in 2008 we renovated the South Campus animal facility and expanded our capacity to 12,000 cages. That’s the capacity we expanded. And then we renovated again over there and expanded in 2013. And we’re just in the very beginning phases of another renovation over here which will add another 8,500-cage capacity. So we could easily be running 45,000 or 50,000 cages in a few more years. That’s a lot.
T. A. Rosolowski, PhD:
Wow. Now obviously this increase is tracking along with the increased emphasis on research here.
Peggy Tinkey, DVM:
And recruitment.
T. A. Rosolowski, PhD:
And recruitment. OK. Anything else that it’s reflecting? Or those are the biggies?
Peggy Tinkey, DVM:
Those are the biggies. And the fact that 99% of our animals are mice I think just reflects that 25 years ago people discovered you could genetically engineer the mouse. And so that and the fact that now there’s these really sophisticated animals where their immune system is deficient but then they’ve been reconstituted with a human immune system and now we’re taking direct patient samples. We’re taking tumor samples directly from patients and implanting them in these humanized mice. So basically the mice are a little avatar. They’re growing the human tumor along with the human. And right now the timeline, the tumors don’t grow fast enough in the mice for it really to be able to inform the therapy for the patient. But what they’re doing is they’re profiling tumors so that if you get a tumor and it has the same genetic profile as one we’ve already got in our bank, we can already tell you what therapies will work and won’t work on you. And so that’s called PDX, patient-derived xenograft model. And so that’s a really up-and-coming thing too.
T. A. Rosolowski, PhD:
So with these genetically engineered animals are there additional things that you have to take into account?
Peggy Tinkey, DVM:
Yeah, they’re weird.
T. A. Rosolowski, PhD:
OK, well, tell me how. What kinds of challenges come with those little guys?
Peggy Tinkey, DVM:
So before we talk about the genetically engineered, let’s just talk about the immunodeficient. The immunodeficient mouse was just a huge turning point in cancer modeling. And the nude mouse, he’s immunodeficient, he doesn’t have a thymus, so he doesn’t have T cells, so he can’t reject tumors. The nude mouse was initially discovered like in 1960, 1969 let’s say I think was the first publication. So by the mid ’80s early ’90s it was really taking off. People were discovering hey, you can implant a human tumor cell line in a nude mouse, and now you’ve got a human tumor. This is really great. So the use of immunodeficient mice in cancer research is just like one of the huge foundations of cancer research right now. But they’re immunodeficient. So they need a sterile environment. In fact I hired a new person today, and she was coming just out of a veterinary practice. And she said something about an autoclave, like a sterilizer. And she said, “Someone told me you had an autoclave as big as this table.” And I laughed, and I said, “We’ve got an autoclave as big as this room.” And she said, “Oh my gosh, I’ve never seen an autoclave bigger than a microwave.” Yeah, so in this facility we have like eight walk-in autoclaves. They’re not as big as this room. I’d say they’re as big as half of this room.
T. A. Rosolowski, PhD:
So we’re talking like 7, 8 by 10.
Peggy Tinkey, DVM:
Put it this way. We do tons of safety training because you do not want to get locked in the autoclave, because that would be bad.
T. A. Rosolowski, PhD:
So what do you sterilize in there?
Peggy Tinkey, DVM:
Cages, bedding. When we do occasionally use water bottles, water bottles. Now we used to sterilize all our rodent diet, but we went to sterilized irradiated diet several years ago because although it’s more expensive we recoup the expense back in labor savings because we can use a different workflow process with setting up the cages. But we have this huge industrial materials management flow to produce -- everything that goes into that facility that touches the animal is sterile. Everything. Like I said, the cage, the lid, the top, the bedding. We put them under a HEPA-filtered hood. We have all protective clothing on and gloves when we change them out. So yeah, it’s really highly technical. It’s not just like oh, here’s a bunch of mice, I’m going to dump them in another cage. We go to a ton of length to keep the animals in sterile environment, in sterile air, highly protected. Like I told you, we’re running these herd health surveillance programs all the time to make sure we don’t have anything in there undetected.
T. A. Rosolowski, PhD:
So what’s the investment in a population of genetically engineered mice like this?
Peggy Tinkey, DVM:
Stacy told me the other day. We have a poster downstairs that we published about maybe five or six years ago that said we had over $1 billion in our estimated cost in the animals. So we’re probably over $1 billion. Now how she arrived at that I don’t know. But there’s some costs that are intangible because we also have here genetically engineered mice that have been developed here. So if you’ve invested five years to knock out a gene, some of the mice are very sophisticated. Like mouse with gene A knocked out has been crossbred to gene B so you’ve got an AB that was crossbred to C, now you’ve got an ABC that was crossbred to D. And that might have taken you four years to get there. So if you for some reason have a fire and lose all the mice in the room that were ABCD, you’ve got to go back and repeat four years of work potentially. We have disaster plans to keep you from having to do that, but yeah, we’ve got really billions of dollars’ worth of investment sitting in our animal facilities right now.
T. A. Rosolowski, PhD:
So obviously there’s the health of the animal, which is implicitly protecting these populations and protecting the institution’s investment. And you have an emergency plan. I assume you need to worry about these little guys escaping and all of that. So what are some of the other considerations you have to stay up nights worrying about?
Peggy Tinkey, DVM:
I was at Baylor when Tropical Storm Allison came, and Anderson was lucky because they did not sustain any really flood losses, but Baylor was not lucky. And that was really a terrible experience I don’t want to have to repeat again. But the reality is I think that storm came on June 8th, 2001, it was a Friday night, so on Saturday morning half my animal facility was flooded. We had four feet of water in our animal facility. I have some really horrible video. But if I had rooms where racks had eight shelves of mice, the first four shelves were under water. The top four shelves had live mice in it. And so Baylor was devastated. We lost 30,000 animals overnight that night when Tropical Storm Allison came. So from that experience clearly we have animals in the basement here. And we have a great physical plant crew. We have people on site 24 hours. We have a really in tune facilities staff. They drill with floodgates. We have great flood mitigation. But still I worry because I’ve done time and motion study on trying to pull 20,000 cages out of a facility to even move them up to the fourth floor, and the reality is it would take I think we calculated like five days. So you’re not going to be able to. We’re a defend-in-place organization. So that is constantly on my mind. And because of that we do hurricane ride-out training, we do flood drills. We do all these. Yes, we have a very well written disaster plan and an animal evacuation plan, even though that’s probably not practical. And that’s always on our mind. We had a fire in an unoccupied animal room about 10 years ago. And that really shook me up. So we’re tuned into that too. Sometimes people lose animals through flooding not because it’s raining outside but because their sprinkler system goes off. So we have an on-call supervisor, an on-call vet, 24 hours a day 365 days a year, because things happen. But yeah, we have a super well written disaster plan, and like I said, the institution manages their emergency response through a national workflow called the Incident Command System. They’ve done that now for, I don’t know, the last six or seven years. So the cool thing is that every time there’s -- like we had some inclement weather, some really heavy rain and flooding, not this past couple of weeks, but when the institution was actually at level three, like we canceled some patient appointments. When was that? Was that about six weeks ago?
T. A. Rosolowski, PhD:
Yeah, about six weeks ago.
Peggy Tinkey, DVM:
And we activated the Incident Command Center. And so I was here overnight and stuff going to the Incident Command meetings. But it’s cool because it’s everybody from patient care and nursing and the cafeteria. Everybody’s together giving a report. So if I needed resources, like if I felt like I had to evacuate animals, I could ask for volunteers. I’m sure I’d get them from all over the hospital.
T. A. Rosolowski, PhD:
So your emergency plan dovetails with the institution’s.
Peggy Tinkey, DVM:
It exactly does, yes.
T. A. Rosolowski, PhD:
Amazing. So who is involved in creating the veterinary emergency plan?
Peggy Tinkey, DVM:
So it’s really matured a lot over the years. Like I said, the institution went to the Incident Command System response after 9/11. The National Incident Command response developed after the 9/11 disaster in 2001 because I think people recognized that there was a disconnect between local, state, and federal resources. Nobody knew what was going on anywhere.
T. A. Rosolowski, PhD:
I interviewed Bill Daigneau[oral history interview] actually who was involved in putting that all together.
Peggy Tinkey, DVM:
OK, yeah. And like I said it wasn’t even developed nationally until after 2001. So I can’t remember when Anderson went to it. But I’m going to say maybe it was 2007 or ’08, something like that. That wasn’t my decision. That was the institution’s decision. But I think that was a really good decision because when we first put our disaster plan together in the department we put it together because our accreditation standards say you have to have a disaster plan. But it was pretty infantile. It was like well, let’s see. Well, fire might be a disaster. Yeah, flooding might be. We were doing it on our own. But then there were several nationwide things. When was Hurricane Andrew in Florida?
T. A. Rosolowski, PhD:
Don’t remember.
Peggy Tinkey, DVM:
So Hurricane Andrew in Florida, there was huge impacts to some of the animal care programs. Remember they had all those monkeys running around? Right. So programs have had disasters over the years and the lab animal community is a pretty small community. So over the years I’ve attended a number of seminars about disasterproof organizations and writing well thought out thoughtful disaster plans for animal care programs. So we matured. And then when the institution went with the ICS, I’m not sure I would have thought about the Incident Command System on my own, but when they did that, they forced all of us to take the Incident Command training. This is another one I’m like, “I got to do this?” But it was really good. So I would say MD Anderson is probably -- I’m affiliated with the accrediting organization. So I actually go and do site visits to a lot of organizations. And we have a very mature disaster plan compared to a lot of places. So it’s probably about as good as it can be really for an academic research organization. I suppose the army has a better one or something like that. But we’re pretty good.
T. A. Rosolowski, PhD:
Cool. We’re almost at five o’clock.
Peggy Tinkey, DVM:
Oh, are we? OK.
T. A. Rosolowski, PhD:
Yeah, we are.
Peggy Tinkey, DVM:
Have we covered everything we needed to cover you think?
T. A. Rosolowski, PhD:
Well, I have a few more. Would you mind doing another hour at some point? Would that work?
Peggy Tinkey, DVM:
That’ll work just fine. I’m out of the institution for the next three days but then I’m back for two weeks. I have to do a site visit actually. The last week in June I’m actually doing a site visit at two other institutions. But I’m here all July.
T. A. Rosolowski, PhD:
OK, that’ll be no problem. We can figure out a time. Well, listen, this has been a very interesting conversation today.
Peggy Tinkey, DVM:
OK, I hope you’re getting something good. I don’t know. My life seems so ordinary to me. So I’m thinking like oh, this is going to be so boring.
T. A. Rosolowski, PhD:
Not at all. Well, let me just say for the record I’m turning off the recorder at four minutes of 5:00 and thank you very much again for your time today.
Peggy Tinkey, DVM:
Yeah, absolutely.
Recommended Citation
Tinkey, Peggy T. DVM and Rosolowski, Tacey A. PhD, "Chapter 13: Building the Rodent Population and An Overview of MD Anderson’s Genetically Engineered Mice" (2016). Interview Chapters. 1233.
https://openworks.mdanderson.org/mchv_interviewchapters/1233
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