Dogs Decoding the Mystery of Cancer
Dr. David Waters
“Cancer to be cured by 2015.” This was the challenge issued by the director of the National Cancer Institute several years ago. Though some fantastic advances have been made towards the realization of this goal, the gold ring is still eluding the medical profession.
In the past, lab rats have been given cancer, but the behavior of these artificially induced malignancies was not always the same as that seen in real life. Comparative oncologists, scientists who study cancer in people and animals have found a champion in the quest to eradicate this type of disease, the pet dog. Dogs have taken the lead in demonstrating ways in which we can improve detection, optimize treatment and ultimately prevent cancer in the future in dogs, other animals and people.
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Please, welcome your pet doctor host, veterinary media consultant and veterinarian, Dr. Bernadine Cruz.
Dr. Bernadine Cruz: If you ever hear anyone say, “Cancer will be cured by 2015”, you’ll probably think that they were crazy. But this was a challenge issued by the Director of the National Cancer Institute several years ago. There were some fantastic events have been made towards the realization of this goal. The goal ring still elude the medical profession. In the past, lab rats have been given cancer but the behavior of these artificially-induced malignancies was not always the same as that seen in real life.
Comparative oncologists, scientists who study cancer in people and animals have found a champion in the quest to eradicate this type of disease, the pet dog. Dogs have taken a lead in demonstrating ways which we can improve detection, optimized treatment, and ultimately prevent cancer in the future in dogs, other animals and people.
I'm very happy today that we have Dr. David Waters with us to talk about how to prevent cancer and how that we can live a very long life ourselves, and hopefully our pets, too. He's a professor of comparative oncology at Purdue University, Associate Director of the Purdue Center on Aging and the Life Course, and Executive Director of the Gerald P. Murphy Cancer Foundation in West Latvia, Indiana. He earned his Bachelor of Science and Doctor of Veterinary Medicine degrees at Cornell University and a Ph.D. in Veterinary Surgery at the University of Minnesota.
We’ll be right back with Dr. Waters.
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Welcome back to the pet doctor on Pet Life Radio with Dr. Bernadine Cruz. The doctor is in and will see you now.
Dr. Bernadine Cruz: Dr. Waters, thank you so much for being with us today. I really appreciate it, and I know so many people are concerned about cancer in their pets as well as in themselves.
Dr. David Waters: That’s certainly is true.
Dr. Bernadine Cruz: I also understand something that’s so near and dear to my heart now that I'm getting older is that you are also very interested in the biology of aging, but also very interested in studying aging in dogs. Why dogs?
Dr. David Waters: Well, we know that successful aging is a complex choreography of genes and lifestyle, and we believe that the lifestyle factors--and we're talking here about nutrition and things like physical activity--are really important determinants of healthy life span. If I ask you, Bernadine, what animal species are the most frequently used to study aging, what would you say?
Dr. Bernadine Cruz: Probably the fruit fly Drosophila, don’t they have a life span of day?
Dr. David Waters: Well, you're on the right track. It's worms and flies and yeast and mice, so really very simple organisms. Then you might say, “Well, mice, they're mammals” and maybe we're on the right track, but most of these aging studies studying mice that are kept under very rigorously controlled conditions, things like constant temperature, no exposure to viruses or bacteria, and the question becomes how exactly does that mimic the human situation?
So I'm here in Philadelphia and it's snowing and cold, three months ago it was 80° and who knows what bugs I was exposed to while I'm on my plane ride here. So we're interested in studying aging in dogs because people share their environment with the pet dogs, and we're testing a new idea and that idea is that some of the secrets to successful human aging can be found by better understanding aging in man’s best friend.
Dr. Bernadine Cruz: I know I've been a veterinarian now for over 20 years and I've seen in my own practice that pets are definitely living longer and we love to watch television and see the story about the person who’s now 103. Actually, I have a friend of the family, he's now 104 and he's still going strong. I keep looking at him and going, “Wow! What's he's secret of life?” What kinds of secrets have you found why people and pets seem to be living longer? What are we doing right?
Dr. David Waters: Well, it might be surprising to you how little we know about exceptionally longevity in dogs. We published the only scientific paper on exceptional longevity in dogs in a scientific journal called the Journal of Gerontology. This came out of work that we started in 1999, we launched a nationwide study and we intended to try to understand better what factors contributed to the cancer risk and longevity in Rottweilers. We studies Rottweilers because as cancer researchers, we knew that Rottweilers have a really high incidence of cancer especially osteosarcoma. As you know, osteosarcoma is the same bone cancer that teenagers .
We learned a lot about cancer from that study but importantly, we also got the first glimpse of exceptional longevity in dogs. This now has lead the Murphy Foundation to establish what we call “The Exceptional Longevity Database”, and this is where we are tracking the oldest bulldogs in the United States, and of course, we're starting with Rottweilers. Our goal is to find out more about these exceptional dogs, and in fact, we call the research study our lucky number 13 study because if Rottweilers lived to be 13, that’s equivalent to a person reaching 100 years.
So from this work, we've learned quite a few interesting things. When it comes to exceptional longevity, there's a strong advantage being female as you probably well know. Female dogs outnumber males in our study about three to one, and if you take a look at 100-year old people, that ratio is about five to one with the really, really strong female advantage.
The other thing that we know is that the scientist who study human centenarians, people who’ve reached 100 years of age, have shown that there's a tremendous heterogeneity among centenarians with regard to disease. For instance, Thomas Pearls who is the scientist who lead to the New England centenarians study divides centenarians into three groups and this really, really fascinating.
You see on TV centenarians and they all look the same, they look like the 102-year-old woman who was sitting around the table playing cards and so forth. But when it comes to disease resistance, there are three flavors of centenarians--the survivors, the delayers and the escapers. Survivors develop a major life threatening disease relatively early in life, say a heart attack at age 50 and then they survive through it to live to be 100.
Then you have the delayers, they're free of all major life threatening diseases until after the average age at death. For example, this would be a person who would develop cancer at age 85 but then still lives to be 100. Then the final category is the escapers, these are the real champions of disease resistance. They're free of all major diseases until after they reach 100 years of age.
So Bernadine, how do you think these three groups shake out? What percentages do you think for each of the three groups among human centenarians?
Dr. Bernadine Cruz: Wow! I'd probably say the escapers--since there's not a huge number of this anyway--might be in the line share of them?
Dr. David Waters: OK. So it comes out for people that it shakes out about 40% survivors, 40% delayers, and 20% escapers.
Dr. Bernadine Cruz: OK, I was wrong.
Dr. David Waters: So those people that have profound disease resistance are in the minority. So we did the same analysis in our centenarian Rottweilers, and what we found was this - 20% survivors, 20% delayers, and then a whooping 60% of the oldest Rottweilers were escapers. Now, the big question is, how should we interpret that data? One interpretation says, “Well, the numbers between dogs and people are different and dogs are simply a lousy model to tell very much about human aging.” Look at it differently, and we think that 60% escapers in Rottweilers reflects euthanasia within pet dogs.
For example, if a 12-year-old Rottweiler developed cancer and the owner elects to euthanize him, he never becomes a centenarian. We never get to study him as an oldest old dog. So the dogs who escaped all major diseases are the dogs that are overrepresented among the centenarian Rotts. The good news here for aging researchers is that if you believe disease resistance is central and essential determinant of exceptional longevity and we and others do believe that, then all these old pet dogs represent a population with extreme disease resistance.
Dr. Bernadine Cruz: Having this litter capability, are you able to see that there are genetic differences between animals in a litter? For instance, you have a litter of Rottweilers and followed them form birth to death, are you seeing that in that particular litter that most of them will become escapers, or is there a commonality that way?
Dr. David Waters: Yes, we haven’t been able to analyze that yet, but we are collecting the pedigree data on the oldest old, and just like in people, it seems that there is a familial clustering of centenarians. So centenarians seem to segregate in certain families, related dogs, just like those with related people. When you talk about the genetics of longevity, the data that comes from human twin studies suggest that the variation between how long you live and how long I live is about 25% genetics and 75% environment or lifestyle.
So I teach a biology of aging course to graduate students and I tell them, “When it comes to genetics and environment and how long you live, it's small g for genetics and big E for environment, that means lifestyle matters.
Dr. Bernadine Cruz: Since this is the “Pet Doctor” show, what can people do to try and have their pets--dogs, cats--live as long as possible? What lifestyle changes can they do for their pets?
Dr. David Waters: Well, that’s the end game for our researches, to try to understand what are the lifestyle factors and how they interact with the particular genetics to translate into successful aging. I think that there are certain factors that seem reasonable or intuitive like good nutrition and physical activity and maintaining a lean body weight. But were looking in these centenarian dogs a very, very detailed information throughout their life force. So we're collecting information on vaccination history, on medical history, on exposure to pesticides for example. That’s what we hope to get closer to finding out what are the key factors that determine successful aging?
Dr. Bernadine Cruz: Are scientists getting a handle on predicting how long we're going to live, what they can expect if all goes well that we could live it? Is there an end point, say 120 and the body just going to give out?
Dr. David Waters: Well, there are two wishes here to talk about and what you're talking about is, “Can we push maximum lifespan?” The goal of aging research is really not immortality, and pushing maximum lifespan very far. I believe that the goal of aging researches is to try to push healthy lifespan. Some scientist refer to compression of morbidity, in other words, can we live disease-free and free of major disabling diseases for as long as possible?
The other issue that comes to play is - are we very good at predicting who will age successful? I think the answer to that unfortunately is not very good at all. What we're seriously lacking are biomarkers and biomarkers are things, stuff if you will, that you can measure in blood or urine or toenails, or s skin biopsy, something noninvasives that would enable you to look at a group of dogs or a group of people and identify those individuals who are aging either fast or slow.
Scientists are working super hard to identify biomarkers and right now, dogs are helping with that. We're collecting biological samples--blood and urine and various tissues form these oldest old dogs. We want to create a national resource so we can find these biomarkers.
Dr. Bernadine Cruz: You mentioned previously dogs getting older and developing cancer, and that I know is the number one killer of older cats, number two being kidney disease. With these dogs that are getting older, what is the relationship of cancer and aging?
Dr. David Waters: Well, cancer and aging connection is a very interesting one. First, let me say that surprisingly, few scientists are crosstrained in both fields. I know that sounds weird, but in general, aging [++] cancer scientists don’t talk to each other, they essentially live in separate silos. We think this has to change, and because we think that the really fresh ideas in cancer prevention research are going to take place in these aging cancer intersection.
I would say that when you were young your mother probably warned you, “Now, Bernadine, don’t play in the intersection.” I know my mother did. What we jokingly say is, “Ignore your mother, play in the intersection because this is where the action is going to be.” As soon as we as cancer scientists turn our attention more toward prevention rather than just cancer treatment, then we're going to want to know what is it about old tissues--old prostates, old spleens, old livers that make them vulnerable to cancer? So we all need to play in this aging cancer intersection.
Dr. Bernadine Cruz: I had the opportunity, the pleasure of hearing you speak several months ago, and one of the things that you told this group of veterinarians, and it was extremely eye opening and it went against everything that I had learned when I have clients come in with a new puppies. I’ll say, “OK, you have a female, you're not going to breed it.” I try to convince them not to breed, “So, OK, what I want to do with you is to have you bring your female dog in about six, seven months of age, and it didn’t matter to me what breed they were. Let's go ahead, get them spade before it had its first heat cycle because all the research that I'd ever heard that you could decrease the chances of breast cancer by 98%.” You're data told me that I was incorrect, at least with regard to the larger breeds of dogs like Rottweilers.
What did you tell the group?
Dr. David Waters: As I said earlier, we conducted the study starting back in 1999, a nationwide study where we collected information from over 700 owners of Rottweilers. We were trying to look at factors that would predict who would get bone cancer and who would not. What we found was that early neutering or early spaying, and by that, I mean within the first 12 months of life, doubled or tripled the likelihood of the Rottweilers would get bone cancer.
Now, they developed bone cancer as adults, usually around eight or nine or 10 years of age, and this is a really great vivid example of how early life course events can affect adult health outcomes. Oftentimes, we think about aging research and we think about, “Well, that’s studying old worms or old flies or old dogs.” We really need to shake out of that and take on this life course perspective. So we shouldn’t be thinking about, “Let's wait until your dog is old to start thinking about how we can make your dog age more successfully.”
Dr. Bernadine Cruz: Now, this information that I have been giving to clients, it still holds true for the vast majority of smaller breeds [++], is that correct?
Dr. David Waters: Is this the data about the early neutering?
Dr. Bernadine Cruz: Correct.
Dr. David Waters: Is that what you were referring to? And breast cancer protection you mean?
Dr. Bernadine Cruz: Correct.
Dr. David Waters: Yes, so when I'm asked what do we say, “What about my dog?” I'm very, very quick to say, this was a study on Rottweiler dogs and it's a little bit dangerous to extrapolate this to other breeds of dogs. For example, miniature poodles get hardly any bone cancer but they have a high risk for breast cancer. So there's a trade off, and I wouldn’t be recommending that owners of miniature poodles keep their female miniature poodles intact because they're trying to protect them against getting bone cancer. That’s not really advisable. But in the breed such as the Rottweiler where breast cancer risk is very low and bone cancer risk is very high, our results suggest that you don’t want to do the early neutering or spaying because you actually increase the risk for bone cancer.
Dr. Bernadine Cruz: Well, we've been speaking with Dr. David Waters. He's been giving us some fantastic information about longevity in people, longevity in pets and cancer. We’ll be right back with Dr. Waters right after this short break.
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Announcer: Welcome back to the pet doctor on Pet Life Radio with Dr. Bernadine Cruz. The doctor is in and will see you now.
Dr. Bernadine Cruz: Dr. Waters, one of the things that I find very interesting is that there are so many similarities between cancers that people get and cancers that dogs spontaneously get. What are some of the similar cancers that both species are prone to?
Dr. David Waters: Well, there are several. Osteosarcoma is the most common bone cancer of large and giant breed dogs, it's very very similar to the osteosarcomas that affect teenagers. That’s the number one cancer that affects teenagers. Bladder cancer is a cancer that often affects dogs particularly Scottish terriers and that mimics the aggressive or invasive form of bladder cancer in people. We know that dogs and men are the only two species that get prostate cancer naturally with any appreciable frequency. It's not zebras, it's not mice or even gorillas and so that’s a very, very interesting observation. In fact, when you talk about comparative aspects of cancer, it turns out that dogs and people are the two species that are more likely to get hormone-sensitive cancers like prostate and breast cancer. Nonhuman primates don’t get those tumors very often at all.
Dr. Bernadine Cruz: Amazing! I was reading something where you are the Executive Director, the Gerald P. Murphy Cancer Foundation talking about selenium and prostate disease that you just mentioned. I think this really highlights what can be so frustrating sometimes, you're listening to the news and “Oh, everyone should take Vitamin E. Vitamin E is great for everyone.” Then a couple of years later after you've bee taking your megadoses of Vitamin E, they're saying, “Oh no, Vitamin E is not good for you to take, it causes more problems than it helps.”
Now, you've been doing some interesting studies on using selenium and prostate health. Could you go into that a little bit?
Dr. David Waters: Yes, I think the frustrating thing that you're describing is that there's an overly simplistic view to health and that is all we have to do is find the “good things” and then we’ll be all set. So whether that good thing is Vitamin E or Vitamin Dr. Bernadine Cruz: or selenium or whatever your favorite good thing is, and our approach was to take a closer look and explore this idea that those really matters. So we have to find the good things, but the good things are only good things if they are in the right dose. So in other words, couldn't it be that when it comes to a trace mineral like selenium and cancer prevention, too much of the good thing is not necessarily a good thing.
So we conducted a study where we were able to feed elderly dogs different levels of selenium. Selenium is a trace mineral, it's an essential nutrient because it's part of your and your dog’s antioxidant defense mechanisms. And, we fed different amounts of selenium and then we were able to measure the amount of DNA damage in the prostate. What we found where there was intriguing is that the dose responses of U-shaped, the dogs with the highest DNA damage were those that had low or high selenium levels. In other words, you wanted to be in the middle, that was where the optimal dose of selenium was.
The interesting thing was then we were able to take data published on human studies on selenium and prostate cancer risk in men, and we were able to show that those results paralleled our dog curve. So in other words, we could predict that those of selenium that lowered the risk for prostate cancer in men. So the important issue here is we've got to find the good things but those matters.
Dr. Bernadine Cruz: On the same study, I found it fascinating that I think you know that typically you need to go on and have a blood test done or have something that’s moderately invasive to figure out how much do I have in my body or how much do I need? What are you using or what is the Gerald P. Murphy Cancer Foundation using to determine, at least in humans, the amount of selenium that somebody needs?
Dr. David Waters: Right. We've established a toenail test called selenium health, and it enables us to not invasively as you said measure selenium status, and this is with toenails. It turns out that you can measure trace minerals in toenails, selenium is one of them. By measuring toenail level of selenium, it gives you a pretty good integrated look at the amount of selenium you've been getting in diet or supplements over the last three months. The idea here is if it is this U-shaped world, in other words more is not better, then we should not be indiscriminately supplementing with selenium because more of that good thing could be detrimental. So this test allows man to measure the toenail levels of selenium and then adjust their intake of selenium, they can lower their risk for prostate cancer.
So the keyword there is, and you used it, noninvasive. We need these windows to our physiology and how our body is working and they have to be noninvasive like blood or toenails or urine.
Dr. Bernadine Cruz: So hopefully, we're working towards a point for our pets as well as for people where we can have a very personalized cancer prevention program. Is that what scientists, comparative oncologists are really working towards right now? Is that the goal?
Dr. David Waters: Yes, you know this idea of personalized medicine really came in vogue with the advent of human genome project. You probably bet as soon as that came on the scene, you heard lots of people talking about personalized medicine, and it turns out that the whole idea of cancer prevention is relatively slowed to take hold in the scientific community. So it's no mystery that when we talk about personalized medicine and cancer, usually most people are thinking are once you developed cancer, can we personalized your treatment to your particular cancer?
We on the other hand, are championing this idea of personalized cancer prevention. In other words, we want to stop giving advice that is designed for the average person because who is the average person? I'm not sure that I've met he or she, but if we can tailor the strategy to meet your own cancer risk and what is going to be best for you in terms of those, in terms of timing. In other words, it may be that certain nutrients can be beneficial at a particular part of your life like when you're in your thirties or forties, but not so beneficial in your fifties or sixties.
Duration is also an issue. There was a clinical trial that was done looking at dietary fat and whether or not dietary fat influence breast cancer risk in women, and it turned out in that study it wasn't. But that was in women who were 65 years of age and the intervention was only for seven years. So, we could sit and ask the question, “Does dietary fat matter in terms of breast cancer risk?” Well, maybe when a woman is in her thirties.
So one of the terrific things and advantages of the comparative work in dogs is dogs have a compressed lifespan compared to people, so that if we do an intervention trial, say a five-year intervention study in dogs, that would be equivalent to changing the lifestyle of a person for 40 years, and that’s really unprecedented.
Dr. Bernadine Cruz: So I as a veterinarian wanting to give good advice to my client that comes in with a puppy, that comes in with a kitten and you've been so much into nutrition to have us realize this longevity. What recommendations should I give to my new pet owner to have this pet live as long a good quality of life as possible?
Dr. David Waters: Well, I think that common sense things in terms of balanced diet and good amount of physical activity, proper vaccination schedule to protect against infectious disease and then stay tune because what we're hoping to accomplish is to get better and more complete recommendations that would be more tailored to the individual pet. As you might expect, this is probably going to mean that we need to do some test, maybe a blood test for example to determine whether your dog was susceptible to oxidative stress or relatively resistant. Then based upon that, our recommendations would follow based upon the results of your pet.
Dr. Bernadine Cruz: Well, I love the idea of personalized medicine, I especially love the idea of preventing cancer versus trying to treat it once it's been there because it is such a horrid disease for people as well as pets.
Dr. Waters, thank you so much for being with us. You've given us great information for the pet owner as well as for the pet itself.
If you want to learn more about the Gerald P. Murphy Cancer Foundation, Dr. Waters, where should people go? What's the website?
Dr. David Waters: It's www.GPMCF.org, and that’s for General P. Murphy Cancer Foundation.
Dr. Bernadine Cruz: Well, I wish you the best of luck because I know you’ll be saving lots of people’s lives and lots of animals’ lives.
Thank you very much for listening to us today. If you have any questions about cancer or what's best for your pet, the best thing to always do, see your own veterinarian, take your pet in twice a year for wellness exam because it's so much better to prevent a disease than to try and treat it.
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