The Mere Existence of Whales

By Carl Zimmer | February 28, 2011 4:23 pm

Strictly speaking, there should be no blue whales.

Blue whales can weigh over a thousand times more than a human being. That’s a lot of extra cells, and as those cells grow and divide, there’s a small chance that each one will mutate. A mutation can be harmless, or it can be the first step towards cancer. As the descendants of a precancerous cell continue to divide, they run a risk of taking a further step towards a full-blown tumor. To some extent, cancer is a lottery, and a 100-foot blue whale has a lot more tickets than we do.

Aleah Caulin of the University of Pennsylvania and Carlo Maley of the University of California, San Francisco, have done some calculations of the risk of cancer for blue whales thanks to their huge size. We don’t know a lot about cancer in blue whales, because blue whale oncology wards would be a wee bit awkward for everyone involved. So Caulin and Maley extrapolated up from humans.

About thirty percent of all people will get cancer by the end of their life. Scientists have been able to build good models for the odds of developing certain forms of the disease. For example, Peter Calabrese and Darryl Shibata of USC put one together last year for colorectal cancer. The colon is made up of a series of pockets called crypts. Inside of each crypt are a few stem cells that continually produce new cells that act as the lining for the colon.Calabrese and Shibata reasoned that the odds of getting colorectal cancer at a certain age depend on the odds of mutation at each cell division, the number of stem cell divisions a person has experienced, how many mutations are required to develop full blown cancer, the number of stem cells in each crypt, and the numuber of crypts in the colon.

Calabrese and Shibata found that their equation churns out results that are close to actual medical records. (Five percent of people get colon cancer by the time they’re ninety.) Their equation doesn’t just match the overall rise in colorectal cancer through life for the population as a whole. It also accurately predicts that tall women are more prone to colorectal cancer than short women–because they’ve got longer colons.

In a review in the journal Trends in Ecology and Evolution, Caulin and Maley took Calabrese and Shibata’s model and ramped it up to blue-whale scale. They found that the huge size of the animals means that by the age of fifty, about half of all blue whales should have colorectal cancer. By age 80, all of them should have it. It’s likely that blue whales should have far higher rates of other kinds of cancer, too.

Blue whales do get cancer, but it’s hard to believe that they get it at the rates that come out of Caulin and Maley’s calculations. Blue whales are known to live well over a century. Bowhead whales have reached at least 211 years. If blue whales really did get cancer as fast as the models would suggest, they ought to be extinct.

The failure of the model means that blue whales must have some secrets for fighting cancer. “The mere existence of whales suggests that is possible to suppress cancer many-fold better than is done in humans,” Caulin and Maley write.

The mere existence of whales is the most glaring example of what biologists call Peto’s Paradox. There seems to be no correlation between body size and cancer rates among animal species. We run a thirty percent risk of getting cancer over our life time. So do mice, despite the fact that they’re 1000 times smaller than we are. All animals studied so far have cancer rates in that ballpark. (And yes, sharks do get cancer.)

Caulin and Maley argue that when animals evolve to larger sizes, they must evolve a better way to fight against cancer. It’s possible that a blue whale simply has a souped-up version of our own defenses. We have proteins that monitor our cells for over-eager growth, for example; they can kill or zombify cells that on the road to cancer. When the genes for these gatekeeper proteins mutate, a cell becomes more likely to become cancerous. The opposite also seems to be true: Scientists have engineered mice to have extra copies of these gatekeeper genes, and they’ve found that the animals become more resistant to tumors.

Caulin and Maley suggest that nature has carried out this experiment as well. We have one copy of a gatekeeper gene called TP53, for example. Elephants–which are at a greater risk for cancer–have a dozen copies of the same gene.

Other defenses might include a more powerful immune system that can destroy new tumors. Big animals may have also lost some genes that make them particularly prone to developing cancer. And anatomy itself can offer a defense, Caulin and Maley point out. As the cells in each colon crypt divide, for example, the older ones get pushed up to the top and get sloughed off. As a result, there are few steps from stem cell to the final cell in a lineage. With fewer steps, we run a lower risk of developing cancer. Bigger animals may have evolved even more effective architectures.

It’s also conceivable that big animals enjoy defenses to cancer merely by being big. Big animals have a lower metabolic rate for their weight than smaller animals. With a lower metabolic rate, big animals produce fewer harmful byproducts that can cause mutations. One pretty wild benefit of being big has been proposed by John Nagy and his colleagues: big animals can kill cancer with cancer. Nagy’s idea is that tumors can develop “hypertumors”–cancer cells that parasitize their fellow cancer cells. Hypertumors would slow down their host tumors, making them less harmful to an animal. And since big animals can handle bigger tumors, their bodies would allow cancer enough time to develop hypertumors. It’s an interesting idea, but Caulin and Maley note that it has yet to be tested.

Then again, few of the other ideas they offer have been tested yet. But Caulin and Maley lay out a roadmap for doing so. Scientists could look at closely related species that span a big range of sizes, searching for telling differences in their cancer defences. Whales and dolphins would be a good pick, since blue whales are 2,000 times bigger than the petite Commerson’s dolpin.

But such an undertaking would have to overcome a lot of inertia in the world of cancer research. Cancer biologists don’t look to big animals as models to study–which is one reason there’s not a single fully-sequenced genome of a whale or a dolphin for scientists to look at. For most cancer researchers, mice are the animals of choice.

But if we want to find inspiration for cancer-fighting medicines, mice are the last animal we’d want to consider. It’s like learning how to play baseball from a bench-cooler at a Little League game, when Willie Mays is waiting to dispense his wisdom.

[Image: Photo by Ryan Somma]

[Update: various typos fixed, and a link to the paper added.]

CATEGORIZED UNDER: Evolution, Medicine, Top posts

Comments (88)

  1. What a great idea! I’d never heard of Peto’s Paradox but it makes sense that more cells should equal more cancer. I’d like to the face of people reviewing animal ethics applications asking for whales in their cancer research!

  2. This is a fantastic article. I’d be curious to hear from other scientists about the reasoning and mathematics that Caulin and Maley formulated. On the surface, it seems plausible to make a connection about the size of an organism and cancer rates. But I wonder if it’s too simplistic in a sense? The best way to find out would be to start studying bigger animals!

    “…which is one reason there’s not a single fully-sequenced genome of a whale or a dolphin for scientists to look at.”

    I can’t believe we’ve not sequenced the second most intelligent animal on the planet. What an oversight.

  3. That’s interesting. I have to say that the similar rates of cancer between species surprises me. Especially consider that we’re practically the only species that smokes cigarettes and eats junk food.

    Okay, seagulls eat junk food, but I hope you get my point.

  4. I understand why the paradox raises the question of why there are any 100-year-old blue whales or 200-year-old fin whales, but I don’t remotely understand the claim made in the article that the paradox argues for the whales’ extinction? That would only make sense if the predictive models suggest that whales should develop terminal cancer well before reaching reproductive age, which is in the 5-15 year range for the two species mentioned. I either think the author totally missed the point when arguing that whales ought to be extinct or he is making a point which I have myself totally missed.

    These numbers also don’t necessarily argue against old-aged whales either, only against a certain proportion of them in the population. There can be ONE 211-year-old fin whale given high cancer-risks; there just can’t be lots of them. I’m sure someone has already run the numbers on this, but it would be interesting to see a more rigorous analysis which compares animal size, animal mortality and the cancer-risks. Merely saying that large animals should die because they should get cancer early really isn’t specific enough a statement to say anything in my opinion.

    To put it differently, someone always wins the lottery.

    [CZ: Whales have very low reproductive rates, but they can have offspring into their eighties. If half of blue whales are dead by the time they're fifty, that's a huge drain on the population of potential reproducers. And that's just one type of cancer.]

  5. ” There seems to be no correlation between body size and cancer rates among animal species”

    So why extrapolate up from humans? It doesn’t make sense.
    Conversely why not look at mice, so small yet so cancerous? Also readily available. And cheap.

  6. Iain–We ought to have much higher rates of cancer than mice, but we don’t. And whales ought to have much higher rates of cancer than we do. But they don’t. That absence of high rates of cancer as you go to bigger animals indicates that they have more effective cancer-fighting traits than smaller ones.

  7. Argh. Willie Mays. Please.

    [CZ: Arg. Fixed]

  8. I think there are a couple of “ommitteds”, although I did enjoy the article.

    It was but briefly mentioned by one of the people commenting, but diet plays a major factor in cancer. Since moving away from healthy foods and inserting drugs into our systems and the food we eat, cancer in man has risen exponentially.

    Unfortunately, the drug and pharmaceutical companies profit on both sides. Europe, for example, will not buy USDA meat because of all the chemicals fed and injected into our cattle. The chemicals come from the drug companies. The result is that we are seeing far earlier menstruation cycles in children and an increased rate of cancer among our young. Then the drug and pharmaceutical companies provide the drugs to handle heart disease, etc.

    So I believe that whales have a longer life because they eat normal, healthy foods. I don’t think one has to be a brain surgeon to figure that out.

    And yes, “Willie Mays” is quite appropo…

  9. Thanks for noticing.

  10. Rob Knell

    Fascinating. Any chance of a link to the paper?

    Ta

    Rob

    [CZ: I thought I did link to it, but I guess I didn't. So I revised the post. Here's the link.]

  11. What about the water? Radiation and radio signals can’t travel that well through bodies of water and the whales are under more water than we’ll ever be their whole lives. So couldn’t that be protecting them from any cancer causing radiation?

    This of course assumes that radiation and electromagnetic waves cause cancer.

    [CZ: There's no evidence I know of that aquatic animals get less cancer than terrestrial ones.]

  12. Daniel

    I am rather naive in these topics but couldn’t this be due, in part, to natural selection?
    Lab mice have been bred for many generations, keeping all, including the weakest, alive and allowing them to breed further. Weaker genes, therefore a higher cancer rate.
    Humans have also bred for many generations and kept our weak alive and allowed them to breed.
    Whales on the other hand lead a harsh, natural life, the weak are weeded out, leaving only strong cancer free individuals?

    [CZ: Many wild animals also have cancer rates between about 20 and 40 percent]

  13. Michael

    Interesting article but it would help if someone proofread this first. Makes it very hard to read.

  14. Colugo

    The real question is, why is cancer a near-constant across body size? My guess: It has nothing to do with the awesome cancer-fighting ability of big mammals. Rather, it’s simple cellular selection. Cancer cells are competing with non-cancer cells. As their number scales up, so do non-cancer cells. Hence, a constant. Ta-dah.

    Aw, hell. I don’t know. Just putting that out there.

    [CZ: If mutation rates are the same in humans and whales, then the proportion of cancer cells to non-cancer cells will be the same. It's conceivable that large animals lower mutation rates with improved cell repair.]

  15. j1o1h1n

    “Why is cancer a near-constant across body size?” A rewarding looking question.

    Perhaps that 30% chance of cancer is needed for social stability among creatures with certain patterns of co-operation.

    Or perhaps there is a correlation between the rate of mutation in the gametes and the rate of cancer in the larger organism where the one leads to long term genetic success at the expense of the gene vectors.

    Naked mole rats don’t get cancer… what differences in their lifestyles can be used to develop these hypotheses?

    [CZ: No one knows yet. It may have to do with total isolation from predators.]

  16. John Silver

    Colugo raised a very interesting point. I would say a key point.
    Yes, ratio of normal to cancer cells very much does matter – because immune system (which works to monitor and eliminate tumor cells) also gets larger with body size.
    The logic behind Caulin & Maley’s or Nagy’s publications goes like so: cancer we observe comes from cancer cells which evade immune surveillance, and for those “invisible” ones number of normal cells no longer matters. Number of those cells is proportional to total cell number. Thus, we should expect more cancers with bigger body size.
    Is this expectation true? Comparing different species is not a very clean approach, because they are genetically predisposed to have different lifespans and tumor rates.
    But: if we can compare large and small adult animals of the same species, we can check if larger ones get more cancer despite having (nearly) the same genetic make-up. Yes, Calabrese and Shibata refer to higher rates of colon cancer in taller women. However, that’s just colon cancer in women. What about men, other species, and other cancer types? Among dog breeds, body sizes can differ drastically. Do we see higher cancer rates in larger dog breeds? *Not necessarily*. They do have higher rates of osteosarcoma. This is however expected (linked to more rapid bone growth in adolescence). But rates of other types of cancer do vary and are not necessarily higher in larger breeds (http://www.ncbi.nlm.nih.gov/pubmed/20453236). E.g., German Shepherds have lower-than-average tumor incidence rates and they still have normal lifespans.

    It leads to a question: is there a major flaw in logic of Cauley & Maley, Nagy and similar theoretical publications? Can tumor cell ever *completely* run away from immune system? Why do we have to invent hypertumors or hyperactive cancer resistance genes, when it can be something as simple as earlier aging of immune system in smaller species?

    [CZ: Immune cells may well scale up with body size, but so do total number of mutations, etc. The immune system would have to scale up to be hundreds of times more effective to account for the cancer. That's an interesting possibility, but it's not just an automatic result of increased body size.]

  17. Ferdinand

    Seems like the japanese have finally a legitimate reason to hunt the whale…

  18. Ashwin

    I think the reason humans are suffering such an outburst of cancer is because we have forced ourselves out of the natural sleep cycles. Before incandescent lamps, we slept right after sunset, woke up around midnight for about 2 hours, and then slept again until sunrise (this is still practiced in remote tribes with no access to electricity). Now, we force ourselves to stay awake for 16 hours and try to catch up with 8. Therein lies the problem.

  19. This seems to tie in with your recent article on aging. Larger body size = less predators = less chance of dying young. So, the larger animals get, the more natural selection would favor those animals than can extend their reproductive years, as long as they don’t sacrifice too much of their fitness in their younger years. Of course, this doesn’t speak to the mechanisms, but it does speak to the selection pressures.

  20. Steve

    1000 times as many cells only needs about 10 extra cell divisions. So in a lifetime, perhaps a whale’s cells might divide 60 or so times versus a human’s 50ish. In those terms, whales don’t seem quite so impossible. So, you might expect whale’s to have a 20% greater risk of cancer during their life. Now, the fact that they don’t seem to have a significantly different rate of cancer is interesting – but could be a facet of the statistics used to measure the incidence of cancer in animals.

    [CZ: It's not so simple as that. For example, colon cells keep dividing our whole life. So there will be a vast number of divisions in colon cells. That's one reason why colon cancer is one of the most common types.]

  21. JC

    Fascinating post.

    CZ: I’m quite intrigued by your figure of certain wild animals having cancer rates around 20-40%. Searching on Google a while ago, most of the articles seemed to indicate that high(ish) cancer rates in wild animals are generally attributable to environmental toxins (such as PCBs) and virally transmitted cancers.

    Are there examples of wild animals with cancer rates around 20-40% that are strongly linked to viruses or (human-made) environmental toxins?

    [CZ: The paper I cite has a list of references for more information.]

  22. jld

    @Fatboy
    Yes, it’s almost tautological if we can see the big beasts, evolution has given them defenses against cancer.
    Ultimately shouldn’t this be correlated to life duration rather than directly size?

  23. JC

    Argh. My comment above should say “Are there examples of wild animals with cancer rates around 20-40% that are NOT strongly linked to viruses or (human-made) environmental toxins?”

  24. JS

    Extrapolating from humans is a ridiculous idea, especially Western humans, who get cancer at much higher rates than other people BECAUSE THEY EAT A CANCER-PROMOTING DIET. DUH.

    [CZ: Differences in cancer rates between different cultures exist, but they are very small compared to the theoretical difference between our cancer rates and those of whales]

  25. ofisher

    Isn’t the problem that people nowadays just get too old for their size?
    People in “primitive/natural” society can expect to die under 40. A small minority gets cancer under 40.
    In modern society, 80 is no longer special.
    Maybe our size and cancer resistance are just tuned for a 40 year lifespan. Successful procreation is perfectly possible within that lifespan. So there was never an evolutionary pressure against cancer resistance.

  26. ofisher

    Small correction: So there was never an evolutionary pressure for cancer resistance.

    [CZ: Actually, there was. And continues to be. It's just that it is focused on resistance during youth. See my recent post for details.]

  27. Laura Houston

    an excellent example of Survival of the fittest…very powerfull in nature!

  28. whaler

    Survival of the fittest, unlike humans or rodents, whales don’t mass reproduce or find ways of prolonging their life. What is the cancer rate with Elephants? I imagine it is fairly low as well. I would speculate the faster the metabolism the greater the risk, as cells die faster and need replacing. I haven’t googled the Blue whales migration pattern but if they are anything like Humpbacks, they don’t eat 6 months out of the year. If there were only a few 100,000 humans living a nomadic lifestyle, only breeding after reaching their 30′s I’m sure our cancer rates would be relatively low as well, those genes would be breed out to a certain degree. Interesting article overall, I just don’t think it’s asking the right questions.

    [CZ: Actually, mutations that lead to cancer later in life would spread in a population of people who only lived to their thirties, because they would have no effect on reproductive success.]

  29. Sam Sinclair

    Something worth noting is that blue whales are not being exposed to the same level of electromagnetic fields and distortions to their food sources that modern humans are. Humans are living in a frequency soup of harmful electromagnetic radiation, the effects of which are only starting to be understood. Our food supply has likewise been adulterated by chemicals, pesticides, genetic manipulation, additives, etc.

  30. Fros

    JS is correct in saying that extrapolating information about cancer in humans to cancer in whales is a foolhardy endeavor, for many reasons. Furthermore, what constitutes cancer for the purposes of this study? Since there are more cells in a whale and larger organs, is it not possible that cancer occurs at high rates and is just not observed? Are these whale cancer rates determined by simple observation of carcasses or is there an element of genetic testing? I understand this article is largely for lay persons but these questions should have been addressed.

    [CZ: Strictly based on body size, blue whales should have cancer rates hundreds of times higher than us. This is not the sort of thing that would go unnoticed in studies on whale carcasses.]

  31. amphiox

    Very interesting. Of course trying to study cancer in animals that live in water and are bigger and live longer than the researcher is going to present certain difficulties. And the ethics of cancer research on animals arguably smarter than chimps is also going to be an issue.

    Cancer is studied in mice precisely because they are small (so you can study lots of them at once easily), they have short lives (so you can get results quickly), and because most people find it acceptable to deliberately give them fatal diseases, and kill them arbitrarily in large numbers.

  32. Neil

    First timer (h/t Marginal Revolution). Really enjoy the blog.

    In ofisher’s defense, he obviously meant there’s no evolutionary pressure against cancer in its current form though all these statements seem to myself to end up rather tautological in logic (why doesn’t (erm, evolution make) X do Y? Evolution.)

    Everything amphiox says is true. I work with mice and feel a twinge of guilt every day that I add to the scores of what feels an already genocidal tally, but I’d certainly feel, uh, much worse killing a goddamn whale a day, though one wonders whether that would be a fallacious preference. This is to ignore for a moment the obvious logistical impossibility of the task.

    [CZ: The authors of the study propose some ways to study cetaceans without killing them. Genomes are a great place to start.]

  33. rcorrino

    Did these scientists consider that the cancer gene in these animals have already been selected out? Blue whales are ancient animals, older than humans. If these scientists’ theory is correct, those blue whales that have the pre-cancer gene have already been weeded out by natural selection….. the same thing that natural selection would have done with humans if we were not “smart” enough to develop medicines and cures for our other afflictions.

    [CZ: Blue whales are a few millions old; our ancestors split off from chimpanzees about seven million years ago. So there's no a priori reason to think they've simply had more time to lose oncogenes. But natural selection might have favored mutations that got rid of them, to compensate for an increase in body size.]

  34. Brian Too

    Erm, there’s a giant unspoken assumption in this article. Are cells in different species of roughly the same size?

    If the blue whale has more cells than a mouse, in proportion to it’s increased (mass? volume?) then the article makes sense. If the increased body size is made up of, not increased numbers of cells, but increased average cell size, then the premise starts to fall apart.

    Of course now I’m not accounting for the longevity of the species. Nor am I factoring in that there are different DNA loads in the cells of different species. And at that point I start to realize that I’m out of my depth on this topic!

    [CZ: Yes, cells in whales are about the same size as in humans and mice.]

  35. Speaking of oncogenes, what sorts of viruses infect whales? Are they subject to viral introduction of genetic material in all the wrong places, as we are with HPV, etc.? You see that you’re now the official cetacean expert here.

    [CZ: Dolphins do get cancers from papillomaviruses]

  36. Thank you, Carl. Fascinating essay. This is one more reason, as if they weren’t enough, to repeat Carl Sagan’s conclusion in his book “Cosmos” that the killing of any whales by any humans for any reason is insane.

  37. No offense, but there are some flawed assumptions underlying this article.

    One of the big reasons humans get colorectal cancer is that WE EAT A DIET THAT IS EVOLUTIONARILY UNSUITED TO US. Our digestive systems these days are compromised by antibiotics, antibacterial soap, processed foods, and all sorts of nasties. And we were probably not even designed to eat grains or other things that ferment and rot in our gut.

    Whales, on the other hand, eat what they were designed to eat.

    I suspect that cancer rates are proportionally high in humans, for our size.

    So yes, the whales have a “secret” for fighting cancer: Eat properly!

    [CZ: Human cancer rates are 30%, which is comparable to other animals, both smaller and larger.]

  38. Markus9000

    With organisms that are in an environment full of toxins, it is known that cancer rates can be higher.

    Are there any studies of cancer that can provide correlation with cancer rates vs. the rate of introduction of new toxins in the environment?

    When did humans first start getting cancer? Has the rate and type of cancer increased over generations? Anecdotally one could easily say yes. One can also demonstrably say that since the Industrial Revolution the amount of environmental toxins for humans (and other species) has increased dramatically. The environment has changed in a short period of time, in terms of toxins. How does that correlate to cancer rates? How does that correlate to any species’ ability to defend against cancerous cell mutations? Over time?

    One hypothesis could be that increased rates of cancer could correlate to increased rates of toxins in the environment. The antitheses is then that with a low rate of new toxins, low rates of cancer would follow.

    The environment of whales has certainly changed with the onset of humans. How have the cancer rates changed? If there are relatively no new toxins introduced to the environment, could the evolutionary process reduce the rates of cancer? Could immune systems that are more evolved over time fight the cancer more effectively? As the rate of new toxins changes for organisms, how do the cancer rates change?

    Off the cuff I’d say that whales have longer life spans, slower generational cycles and have also had an environment that introduced new toxins more slowly than the humans’ environment. Subsequently, their immune systems have eliminated mutations more effectively over time.

    Thank you for a thought-provoking article.

  39. zackoz

    A fascinating and thought-provoking article, Carl. Thank you.

    I notice you’re giving many more responses to comments than usual (with terrific patience, I may say).

    Is it just the topic, or is there a change in policy?

  40. Patrik

    It’s simple evolution guys! There are a large number of humans with a mutation rate that is far lower than the norm, when it comes to cell devision. That means they’re less likely to get cancer. Blue whales would equally have some whales with a lower mutation rate. Only the whales with a lower mutation rate survive, to produce offspring. It’s an evolutionary pressure on the survival of the species.

    [CZ: Mutation rates are, indeed, subject to natural selection. But natural selection can also select against mutation rates that are too low, because species become less evolvable. So there's no reason to assume, a priori, that blue whales have evolved lower mutation rates. But it is certainly a hypothesis worth looking into. (I don't know where you got the information about some people having low mutation rates. You'll have to point me to a source.)]

  41. scott duncan

    Given that all the different sizes and species of animals have different risks of cancer and conversely have developed their own unique ability to fight back at these cancers it is interesting to me that they seem to have developed a similar success/failure rate for fighting cancer across species. It is almost if there are optimal rates for survival driven by some external factor outside of the animal and cancer themselves. That might be something to look at.

    Scott

  42. Paul Orwin

    Really interesting article Carl, and I think there’s no question that looking at chronic disease in diverse animals (along with many other things!) can have real, direct benefits in medicine. This is another reason why basic research in biology is so important (I’m looking at you, gov’t budget cutters!). You’ve done a nice job answering a lot of questions in comments, but I’ve got one more – I wonder if the basic assumption in your title (animals with cancer die) is correct, or rather, scales in a linear way. In other words, can a blue whale simply tolerate a 50lb tumor, while a human obviously has more difficulty. I am not a cancer biologist, but my relatively lay understanding is that tumors can be tolerated, and the real danger of cancer to any organism is metastasis of tumor cells into vital organs, and the formation of tumors in places that end up disrupting organ function. So maybe a blue whale, by virtue of its immensity, can simply tolerate a lot of tumors in a lot of places, and getting fairly large, without dying? I wonder if we have enough data on cancer in whales (in particular, what are the limits of detection – would scientists find a 5cm mass in a 20m whale carcass?) Of course, the ethics of this sort or research is very dicey indeed, but certainly whales that die naturally and are recovered could be dissected and analyzed thoroughly.
    On another note, I’m not sure there is any good reason to invoke a selection argument here, since the divergence of whales is relatively recent, and the generation times are very long.

  43. Colugo

    Evolvability: Aren’t K strategy, long generation time, small litter (generally also large and long-living) species inherently handicapped in terms of evolvability? If cancer is a cost of evolvability, then wouldn’t whales have higher cancer if their evolvability handicap were compensated genetically? Is there selection in larger lineages to reduce the cost of evolvability by reducing somatic mutation rate while maintaining germline mutation rate? Or do K species forgo evolvability in exchange for higher survivorship of individuals?

    The big question is whether the constant cancer rates across species are due to intracellular processes, in which case they are genetic and likely due to antagonistic pleiotropy or some other life history selection, or if they are mostly the result of inter-cellular processes, in which case they are scaling phenomena. (Mathematics of networks? Fractal properties of surfaces and branching? Scaling of regulatory networks? Somatic selection? High mean metabolic activity of cells in smaller species resulting in more somatic mutation?)

    The outlier (low or zero) cancer rate of naked mole rats suggests genetic and life history selection. However, we should consider scaling effects as well. (Of course size is related to extrinsic mortality, which relates to life history selection, but I mean scaling in cellular community and other organismic processes.)

  44. jld @ 24,

    I don’t think my comment was tautological. Maybe I didn’t explain it very thoroughly, but that’s because Carl has just written an entry explaining the concept in detail, and I wouldn’t pretend to be anywhere near as versed or as articulate on the subject as Carl. But, I’ll try to explain a little more clearly. If the concepts laid out in this article were correct, then if whales devoted the same resources to fighting cancer as humans, they would have higher cancer rates, and would die younger. As long as they still survived long enough to reproduce, then they would keep on existing as species. But whales don’t have that high of cancer rates, and in fact have very long life spans. Why? What type of selection pressure would favor whales to live not just into their 30s or 40s, but over a century? Why would they devote more resources into fighting cancer than other animals? Per Carl’s prior article, if an organism has a high risk of dying young, it will tend to have traits that optimize its fitness in youth, even if those traits cause it to age faster, because most organisms will be killed before those negative effects of aging have much effect. The less chance an organism has of dying young, the more natural selection will soften the effects of aging, so as to extend the organism’s reproductive years. Species find compromises between the extremes of living fast & dying young vs. living slow and steady. My original point was that whales have so few predators, that they have a low risk of being killed, and so this type of selection will favor whales that can extend their reproductive years.

    Go read Carl’s Darwin Day entry for a much better explanation of this.

  45. Peter Macauley

    I don’t want to die.

  46. John R

    Interesting article, but the findings are not terribly surprising, especially given your recent entries regarding the balance between traits benefiting the young and those benefiting the old. More cells increases the risk of cancer but commensurately increases the selective pressure on cancer prevention and surveillance mechanisms. It seems possible that this sweet spot of cancer rates that’s consistent throughout species of various size could be the result of equilibrium reached between pressure to sustain cancer-fighting mechanisms and the costs (energetic, metabolic and other) of doing so.

  47. sean

    Blue Whales eat a LOT of Krill.
    Krill is a major source of Omega-3′s
    Coincidence ?

    [CZ: Sperm whales don't eat krill. And they don't have astronomical cancer rates you'd expect from body size alone, either.]

  48. OcanAmat

    Nice exposition of the argument, but from reading it I also get the misleading idea that “blue whales must have some secrets for fighting cancer.” I think given the amount of efforts put into cancer research we much rather come up with complicated mechanisms for the lower cancer rates than accept the much more probable hypothesis that one of the other variables is accounting for the decrease in odds while increasing body size.
    “… the odds of getting colorectal cancer at a certain age depend on the odds of mutation at each cell division, the number of stem cell divisions a person has experienced, how many mutations are required to develop full blown cancer, the number of stem cells in each crypt, and the number of crypts in the colon.”
    So why not going into those rather than postulating mechanisms that we might “port” to human cancer research? It might be as simple as slower metabolism, without having to go to the improbables of hypertumors.
    It would be nice to know how cancer odds change according different body sizes in the same species correlate to those same odds calculated for similar body size dispersions in a different species. That could probably tell a lot more than just blindly expecting bigger animals -> higher odds.

  49. Auntiegrav

    I think the article was very good. Covered the basics. The question of cancer is not the ratio of cancer to non-cancer cells, however. It is the physical effectiveness of the immune cells/system vs. the effectiveness of cancer cells. This ratio should not change much with size except for variations in diet and environment, which favor one or the other. As for the blue whale, I think it is probably an effect of the age of reproduction. Since older whales are reproducing, then the robustness of their immune cells in combination with lower metabolism allows for longer life in the face of the cancer threat. This longer life allows more time for individuals to develop habits or proteins or symbiosis with gut bacteria/skin flora which increases the whales random attempts to change vs. cancer’s random attempts at occupying the same life-space. Life is anti-entropy, cancer is pro-entropy. All life is basically in this battle, with life’s random mutations vs. entropy’s random threats(cancer should be considered an accelerated environmental change within the body, as far as the body’s individual cell adaptation process is concerned).
    I hope that is clear as mud.

  50. Joy

    This would be an even stronger article if the author had mentioned that some of the expected cancer breakthroughs, based on mice, have not worked in humans….and the apparent reason is that humans already naturally have evolved genes that do more or less the same thing that the cancer-suppressing treatments do in mice. The most obvious example would be the angiogenesis inhibitors, which prevent blood cells from forming fast, in response to tumor signals, to grow more blood vessels / bring more nutrients to the “greedy” tumor cells. This, in turn, tends to starve out the most aggressive (“greediest”) cells in the tumor, which are generally also unable to downregulate their division. Lovely breakthrough… in mice. The results in humans have been underwhelming (a bit helpful in some specific tumor types, but not earthshattering) because in humans, there already are some blocks to runaway angiogenesis. Either because the sorts of aggressive tumors that drive angiogenesis most intensely are also those that strike early, and cut into the reproductive years (creating an evolutionary bonus for angiogenesis suppressors)…or because slower growing, longer living organisms tend to give up the tendency to more, unregulated growth in all tissues. We don’t regrow parts and limbs as well as simpler organisms, but we also don’t grow out of control body parts (blood vessels or otherwise) at anywhere near those rates.

    In addition, we (humans) are still a little ways above the theoretical absolute baseline for spontaneous mutation in cell division. That baseline is determined by the likelihood of a specific DNA base shifting its flexible molecular conformation into an energetically unfavored state, just as it happens to be read for DNA replication. (It’s like someone taking a picture of you, randomly, in the one instant that you fall headfirst on ice while holding a bicycle in each hand, leading a computer scoring algorithm to believe that you are actually a car, based on being horizontal, with 4 wheels and no obvious head.) Could be that whales are even closer to that baseline. Or more provocatively, they could have some additional DNA-marking or mutation sensing mechanism that would help them detect and repair the mis-copied base. (Our bodies can tell there’s a mismatch of the old and new strand, but it’s pretty close to a coin toss, as far as the cell deciding which half of the mismatch should be fixed.) Rather than studying whales, per se, tissue culture of whale cells would be very cool…might be as simple as checking how much harder it is to induce enough mutations to “immortalize” them, or whether that’s even possible.

    On the other hand, some people assert that the figures for whale lifespan are considerably overblown (so to speak).

  51. Joy

    And for Fatboy–tell people to look up r strategist and K strategist. Good exposition, BTW.

  52. sean

    Sperm whales eat a lot of squid which has the same EPA/DHA as shrimp……
    They are still getting a lot of omega-3

    But truth be told , the metabolic rates of the animals makes a lot sense too…

  53. Since the populations of whales in the wild are not substantially documented as to their cancer rates, it may be impossible to extrapolate meaningful correlations with humans. That having been said, the study obviously serves to provoke some interesting arguments regarding cancer.

  54. David

    Yep, plenty of omega-3, not to mention exercise. I have a good friend who’s a blue whale, and he goes swimming every day!

  55. OMCTC

    Or maybe it’s because they eat a zero carb diet.

  56. direwolfc

    How does one exhaustively search for tumors in a 200 ton animal? What if the size a tumor would need to be to be lethal for a blue whale body is massively larger than a lethal tumor in a human body? Maybe tumors have difficulty growing beyond a certain size to approach that larger lethal size for angiogenic or cell-signalling reasons?

    Still, in that case, all else being equal, blue whales would have lots of smaller (relative to the blue whale) non-lethal tumors in their body by some advanced age, which does not seem to to be the case. Fascinating article.

  57. Interesting article and great outside the box thinking. It would be interesting to study the genetic differences, the differences in nutrition and environmental factors. Maybe one reason researchers prefer mice is they pose less logistical problems?

  58. Trond Engen

    A couple of years ago I read an article quoting an old study of dead roedeers on a Norwegian island. I was surprised to see that a great portion died from (or with) cancer, given their short lives and slim bodies. But then I thought it made sense; I imagined it to be a simple trade-off between cancer-risk and recovery from injuries, and that animals that reproduce sufficiently in six or ten years can afford a sharper regeneration tool (I can’t remember now if the article also mentioned the ability to recover or if that was a conjecture of my own based on how they had survived wounds. I’ll see if I can find the original study, but I doubt it’s online). Anyway, the mole rats with no predators might suffer fewer injuries and afford a dull tool, the blue whale has both few natural enemies and exceptionally little body surface per volume, so that too might afford a dull tool. My speculation is purely superficial, though, since I don’t know anything about what their respective diets do to their intestines.

    (Sorry if I’ve overlooked the same point being made in the comments.)

  59. Trond Engen

    That long and winding comment would have been much shorter if I’d read the Darwin lecture first.

  60. tim rowledge

    “Since moving away from healthy foods and inserting drugs into our systems and the food we eat, cancer in man has risen exponentially.”

    So you’d suggest eating like the the 1500′s and not using any medicine dating from that sort of period? Do you perhaps see some mechanism that might prevent the average lifespan returning to the 30-ish years that appears to have been the typical back then? Maybe modern medicine and all those nasty drugs have some value.

    And do you by any chance have some sort of backup for claiming the cancer rate has risen ‘exponentially’? Are you claiming it has risen from say 3% to 30% since ‘moving away from healthy foods’?

  61. Excellent article!

    With the article and with all the comments and CZ’s responses to the comments, you would think that eating healthy has a comparatively little effect on cancer rates for humans. But still there are other diseases that still give humans good reason to eat healthy and excercise

  62. Mischa Goss

    Whales live under water. If water acts to moderate incoming radiation, whales as a group may be subject to fewer mutations than land creatures. Are mountain goats subject to greater cancer rates than creatures living nearer to sea level?

    The correlation may vary with altitutde, with lower rates for those living below sea level.

  63. A very nice reading, but perhaps written around an obvious question? Different animal species are not simple collections of the same cells following a different pattern. Only from a very simplistic view of animal evolution as the result of building bodies by putting together more or less units of the same mutation-prone cells you would end up thinking that a large animal should be suffering a higher risk of developing cancer.
    This view is obviously wrong, every animal species developed to be as it is after reaching an exquisite equilibrium. From the cellular point of view, this includes reaching equilibrium between proliferation and function, and excess proliferation leads to cancer.
    It is true that by looking at large animals we can learn a lot on how these species managed a high number of cell divisions while avoiding cancer, but wouldn´t we learn more from an animal that shows an extraordinary cancer defense for its small size, such as the naked-mole rat? This goes without mentioning the clear practical benefits of studying smaller animals in the lab.
    Also, when you mention that “Scientists have engineered mice to have extra copies of these gatekeeper genes, and they’ve found that the animals become more resistant to tumors”, it would be worth mentioning that this might also be the case for some humans that unnoticingly carry extra copies of tumor suppressor genes, or more effective gene variants, and are more protected against cancer. But it would be also worth thinking about why evolution would have favored the current genetic make up, with the number of tumor suppressor genes that we have. Perhaps increasing tumor suppressor activity above a certain threshold might have some detrimental side-effect, such as aging.

  64. Willem

    Thank you for this great article. I never thought about whales in such a way. I find it mindblowing and very interesting. Thank you for this little treasure of knowledge.

  65. Kim

    Very very interesting post. Caulin and Maley suggest comparison between dolphins and whales, but couldn’t good data come from comparison between cats and lions? Felines are very similar to each other, and there can be 100 times of difference in weight between them. It is one order of magnitude less, but it is easier to get a lion than a blue whale into the lab.

  66. As the authors of this paper, Aleah and I have wanted to weigh in but haven’t had a chance until now. CZ has done an excellent job responding to the posts. We couldn’t have said it better ourselves. We’ve only managed to process the first part of the comments and hope to continue to respond to the others later, but we wanted to weigh in now without waiting for a full response, so here are a few additional thoughts:

    Chris Lindsay, we don’t have great mathematical models of carcinogenesis. The one we used didn’t include out-growths of pre-malignant cells (“clonal expansions”), which clearly changes the probabilities of the next mutation occurring in that population.

    There is partially sequenced dolphin genome, and people are actively working on sequencing other cetaceans, but nothing is available yet.

    Keith Wiley, (I hope this is the Keith who was a friend from my time at UNM) since we don’t have great models of carcinogenesis, it is hard to be precise about the expectation of the relationship between cell number and expected age of cancer onset. As CZ pointed out, one of the current best models would estimate a huge mortality and affect on reproductively active whales from just one type of cancer. Of course, cancer mortality is a sort of race condition between all the types of cancer to see which one you get first. So, although we can’t be precise, the 1000X more cells in a whale would certainly cause massive cancer mortality in reproductive, and probably pre-reproductive whales, if they had the same biology as humans. Obviously they don’t. We don’t have great data on whale lifespan and cancer rates, but the data we do have shows they don’t even get 10X more cancer than humans. There has been selection to suppress cancer in large long-lived organisms and we’d like to understand how that is achieved.

    Thewhalepeople.com, there are clearly a lot of ways that humans have perturbed their cancer rates through changes in diet and our modern environment. However, the argument can equally be made by comparing mice and whales with 1,000,000X more cells. So we can leave humans out of the discussion (until we get to implementing cancer prevention).

    Daniel, if you take wild (outbred) mice and raise them in the lab, protecting them from predation, ~50% will die of cancer, so this isn’t an issue of inbred mice.

    Colugo, I don’t think the paradox is solved by cellular selection. In fact, a central result of population genetics is that the larger the population, the more efficient selection is. In other words, with a large set of cells, a carcinogenic mutation with only a small selective benefit would tend to sweep through the cell population of the tissue.

    John Silver, the data on immune surveillance is mixed. If you suppress the immune system, you don’t get a lot of new cancers and those that do show up are the ones that are initiated by an infectious agent. We are finding that in most tumors, they recruit macrophages and other immune cells to do some of their dirty work (e.g., stimulate growth of new blood vessels, provide proliferative signals to the cancer cells etc.). On the contrary, in a few cases, inflammation in the tumor is associated with a better prognosis (e.g. in colorectal cancer). As CZ says, better immune surveillance is a potential solution to Peto’s paradox, but it is not clear to me that the scale of the immune system makes the paradox go away.

  67. I found this searching for an answer to a different question. I got some very good insight, but it seems like my original question is relevant to the topic and unaddressed.

    What about background environmental ionizing radiation? Large animals completely shield against a large number of particles of radiation incident from the general atmosphere, and the effect gets bigger the bigger the animal is. A blue whale, on the other hand, is shielded by the ocean as well! The center of a blue whale is getting almost no radiation dose aside from what is contained in its own materials (internal dose).

    The effects of low-dose radiation are not clear to us at all generally. Some people think that a sustained higher dose could, in fact, help prevent cancer, but this view would be problematic looking at the blue whale. How would an organism manage cancer risks in a nearly sterile radiological environment?

  68. Jld, you are right that lifespan is an important factor. Cancer risk should be related to the product of both size and lifespan, which is why we were careful to say “large, long-lived animals”

    JS, Sam Sinclair, vince and Alex, there are 100-fold differences in rates of different types of cancers in different parts of the world. Some, if not much of that is likely due to diet (as well as other exposures). So I agree that is important, but Peto’s paradox can be posed based on the differences between mice and whales, so explanations that focus on something special about humans doesn’t solve the problem.

    Ofisher, the “average” lifespan of ~40 years in our ancestors is misleading because it is the average of a lot of infant and childhood mortality with adults that lived well past 40. In any case, we are interested in how evolution has tuned cancer rates to preserve fertility in these large, long-lived organisms.

    Whaler, we agree with you that metabolism is likely an important factor, and our current favorite research path to solve Peto’s paradox. The paradox applies equally to elephants and so we are studying them too.

    Fros and Fuente de la Eterna Juventud, Peto’s paradox is essentially a reductio ad absurdum argument, so we agree that in essence the extrapolation from humans is foolhardy – that’s really the point. There is some significant difference in the biology of whales and elelphants compared to humans (and mice) that makes the extrapolation absurd. In any case, when cancers reach full malignancy, they grow exponentially, so a large body size couldn’t hide them for long (unless John Nagy is right about the evolution of hypertumors). It will be interesting to find out if there is natural copy variation in the number of tumor suppressor genes in humans. I agree that naked mole rats are an important animal to study for similar reasons.

    Amphiox and Neil, you are right that whales are not a good laboratory organism. We get our fair share of ribbing about that. However, they can be studied by taking dart biopsies from their skin with minimal harm to the animal, and that is what our collaborators do.

    Rcorrino, CZ is right that it is inaccurate to say that Blue whale are more ancient than us, but your point still holds. We are interested in whether evolution has weeded out cancer susceptibility in whales, or build in extra redundant checks on cancer. That’s one reasone we’d like to sequence some cetacean genomes.

    Markus9000, there is a small field of paleo-oncology that has tried to determine if cancer rates have changed over time. Studies from ancient Egypt, medival Germany and modern English graveyards suggest that they haven’t (Nerlich et al. Oncol Rep 16, 197-202 (2006))., but a recent review article (http://www.nature.com/nrc/journal/v10/n10/abs/nrc2914.html) argued that cancer (adjusted for age) was rare in ancient times. So the answer remains unclear.

    Patrik and CZ, there are measurements showing that humans have different capacities to repair DNA damage. We published one such study: Chao et al. Cancer Epidemiol Biomarkers Prev 15, 1935-1940 (2006). And yes, we agree with your insight that lower mutation rates is one reasonable hypothesis for solving Peto’s paradox.

    Scott Duncan, I think life history theory would suggest that there is some optimal level of suppressing cancer, but it is hard to get a good grip on all the trade-offs. That is, I agree with John R.

    Paul Orwin, as I argued above, malignant tumors tend to grow exponentially, so a big body can’t buy you much time. However, you bring up an intriguing point. In general we don’t know how cancer kills us in the end. It isn’t usually the case that it consumes a vital organ. There are some “warm autopsy” studies that have looked at this: sometimes your immune system collapses (for unclear reasons) and you die of infection. Sometimes, you die of a starvation response (“cachexia”). Sometimes the hormone signals in the body get disregulated in what is called a “cytokine storm” and for some reason that I don’t understand, that causes death. One purely clinical observation is that most people die when their (malignant) tumor gets to be about 1kg. So this remains an interesting, and important clinical question. John Pepper asks, what if we intervened in the immediate cause of death rather than attacking the cancer? Can we turn cancer into a chronic disease (and improve quality of life in cancer patients at the same time)?

    Colugo, the evolution of evolvability (and mutation rate) is a complicated field because we are talking about indirect selection – not selection on survival and reproduction of individuals but upon a trait that affects the probability of changes in survival and reproduction in a lineage. As we said in response to Keith Wiley’s comments, we don’t have a great grip on how cancer rates should scale with number of cells, but the size differences are so big, that it is pretty clear something interesting is going on.

    Fatboy, we agree with you that the low rates of extrinsic mortality in large long-lived organisms probably lies behind the evolution of both the long lifespans (e.g., mole rats) and the large body size (though of course, large body size helps reduce predation, so there may have been some positive feedback such that larger body size led to less predation, which allowed longer lifespan, etc.)

    OcanAmat, we agree with you that the models of cancer risk already point to parameters for lowering cancer risk. In fact, many of the hypotheses for solving Peto’s Paradox flow from those models. However, it isn’t always clear how we could implement changes in those parameters, and so we are interested to see how evolution did it (and which parameters were the ones that got tweaked). In other work in our lab, we are trying to measure the parameters of somatic evolution so that we can find cancer prevention strategies that modify those parameters.

    Auntiegrav, we agree with you that improved immune system surveillance might be a mechanism for solving the Paradox. But it would have to be more than proportional (if X% of human cells escape immune surveillance to generate cancers, then X% of a whale with 1000 times more cells would lead to 1000 times more cancers).

    Joy, one thing we’d like to do is some mutation rate measures in freshly biopsied whale cells. There is a whale cell line (showing you can immortalize them), but cell lines are often more like cancers than they are like normal tissues. We’d also love to have been able to mention some expected breakthroughs, but we are just starting this project and so should probably be more humble about our promises.

    High Point, we agree there isn’t good data on cancer rates in whales (some in beluga whales), but I’m pretty sure it isn’t 10 times the human (or mouse) rate, let alone 1,000 times.

    direwolfc, I agree with you.

    Kim, yes, cats and lions would be another interesting and potentially fruitful comparison. Ideally, we’d collect a lot of closely related species that differ in size (or lifespan) by orders of magnitude. Did evolution light on the same solution over and over, or are there different mechanisms for cancer suppression across the tree of life?

    Alan, ionizing radiation might be important. It might be more helpful in that case to think about elephants and skin cancer, as a potential counter example, but maybe an elephant’s internal organs are better shielded enough to account for their cancer suppression. Could be.

    Thanks to you all for your interest and engaging questions!

  69. Carlo Maley:

    It really is important to consider Elephants! Not only that, but large dinosaurs too, although I may be going too far there. Dinosaurs may have lived in an age with a much thicker atmosphere and we might over-extrapolate, but at the same time, natural radiation is higher the further you go back in history (same applies for tectonic movements for the same root cause).

    I think elephants are sufficiently large to shield against high energy gammas, but natural radiation contains more low energy gammas anyway. But then again, cosmic radiation is of an entirely different sort that you almost need a mountain to shield against, but Blue Whales practically have that – a mountain-sized mass for shielding.

    The question of external radiation (in the case of whales) seems kind of unimportant to me, because the whale itself contains radioactive materials. The only relevant question then, is the heterogeneity between the elements in the water and the whale. It could be that the whale is more radioactive than the water. Nonetheless, cosmic radiation is gone, expect for coming up to the surface. Each organ in the whale could have a very different lifetime profile of radiation throughout its lifetime than what we typically deal with on land.

    Natural radiation is likely to be critical to the appearance and evolution of life on Earth, but it could also be a major hindrance to life developing on the universe. Some forms of mushrooms can actually use ionizing radiation for useful purposes. It’s interesting to think that other organisms could live off radiation, but it’s hard to build a house out of mud when the mud is constantly destroying the blueprints! Then again, if the mud never harmed the blueprints, we might not have ever had certain kinds of mutations that were critical to making the blueprints in the first place.

  70. As a veterinary oncologist (www.oncovet.com) I found this article and the discussions that follow fascinating. One insight that I can offer is that in the world of dogs, the smaller the dog, the lower the rate of cancer.

    We also know that the dog is the species with the largest intra-species variation in size. In other words, the difference in size between a chihuahua and a Great Dane is greater than the difference in size between any two individuals of another species. This size differential is thought to be due to one gene – the insulin-like growth factor gene (Science. 2007 April 6; 316(5821): 112–115).

    In the dog world size seems to “work backwards.” Large dogs tend to live shorter lives while small dogs enjoy greater lifespans. This paradox is the antithesis of what is observed if you compare the life span of a blue whale with a mouse.

    It may be that the genetic reasons for why small dogs live longer is the reason why they have less risk for developing cancer.

    Comparative oncology, the study of cancer in other animals as a model for cancer’s biologic behavior in people, is a wonderful and fascinating field. As veterinary oncologists, we truly believe that by studying the behavior of cancer in dogs and cats, we can learn not only how to treat people’s pets more effectively, but we can glean valuable insights into how to better treat and perhaps even cure cancer in people (and maybe blue whales).

    (More information about comparative oncology can be found at http://www.acfoundation.org)

    CZ: Gerry, thanks for your comment. Here’s a passage from the paper you may find interesting:

    “Interestingly, within a species, size is associated with an increased cancer risk. In humans, 3–4 mm above the aver- age leg length results in an 80% higher risk of nonsmoking- related cancers [22]. Also, children with bone cancers tend to be taller, and osteosarcomas occur in large dogs 200 times more frequently than in small- and medium-sized breeds [23]. There has probably not been enough time to evolve additional mechanisms to protect large dogs from this in- creased risk and counteract the extreme artificial selection for size. This suggests that animals that evolved to be larger as a species developed mechanisms to offset this increased cancer risk, whereas above-average individuals do not have additional defenses compared with smaller organisms with- in their species and, therefore, fall victim to cancer with greater probability. This divergent trend within versus between species is an example of Simpson’s paradox.”

  71. Braithwaite

    I bumped into this article while researching for my monograph on the same subject i.e. the subject of cancer genesis. There are something like 10 x 17th cell divisions during the life of an individual human so the potential for entirely spontaneous mutations–and cancer–are endless. On the other hand, since the very beginning of life, cells have had a vested ‘interest’ in genomic integrity and precise replication. They have developed multiple genomic mechanisms to attend to the problem. This is obviously true because, otherwise, the very first cell would have produced two bizarre, non-viable daughter cells and the experiment in life would have been over before it started.

    As life forms achieved greater complexity, the possibility for genomic error increased. Mechanisms for thwarting such errors must have increased–probably by natural selection mechanism–in parallel. Presently about 40% of human genes are–directly or indirectly–involved with the preservation of genomic integrity. This gives some idea how vitally important this function is to the cell and the human organism.

    In terms of mammalian life, humans are large, long-lived animals. Our genomic defense mechanisms need to be especially potent. In those few species–like the great whales–that have cell numbers that exceed human adult cell numbers by a factor of 1,000…and…given that some of these animals live well over a hundred years, it follows that their genomic defense mechanisms are more robust than that of humans and certainly more robust than that of small, short-lived mammals. If this weren’t true…numerically and theoretically…a adult male blue whale living twice as long as a human…should have 2 x 10 3rd more cancers, which would mean that most blue whales would develop multiple cancers at early ages which would clearly be non-selecive. All great whales [which would never have evolved in the first place] would have gone extinct long ago.

    On the other hand, much the same is true of humans. Relatively speaking our cancer rates, in comparison to tiny, short lived animals, is far less than it ‘should’, theoretically be. Nature must have hyped up our genomic defenses over our short-lived relatives. Proof of this theory will be long in coming but I think it is coming.

    In my opinion, genes [in the general sense of 'gene'] that code for genomic integrity will increase in number and potency even as a particular organism increases in cellular number, age, and especially genomic complexity.

  72. Pallbearer

    A question about cancer rates in blue whales. I read a book published in the 70′s – the hey day of factory whaling – and it commented that cancers in blue whales were rare – or non- existent. This data was derived from biologists examining the carcasses of blue whales as they were processed. This would certainly give a cross section of cancer rates, ages and types. Recognizing that the “processing” of the whale was not very scientific – but the study “size” would have been very appropriate… Could you comment or source what cancers have been found in blue whales? With the recent treatment of leukemia with immune-modulated cells – having a model of a creature that potentially has a “hyper-immune” system might prove interesting – but also potentially devastating to a species under pressure.

  73. Fascinating. so much is happening so fast in cancer research that one dares to hope that in a few years there will be methods and cures we can barely imagine!
    I have cancer.
    martin
    thousandfeathers.com

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The Loom

A blog about life, past and future. Written by DISCOVER contributing editor and columnist Carl Zimmer.

About Carl Zimmer

Carl Zimmer writes about science regularly for The New York Times and magazines such as DISCOVER, which also hosts his blog, The LoomHe is the author of 12 books, the most recent of which is Science Ink: Tattoos of the Science Obsessed.

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