Elephants Rarely Get Cancer, Now We Know Why

By Janine Anderson | October 8, 2015 10:04 am
shutterstock_247834897

(Credit: mariait/Shutterstock)

Could a cure for cancer be hiding in the elephant’s genetic code?

The massive mammals have a much lower incidence of cancer than one would expect, given their size and long life span. It’s a phenomenon popularized by Oxford University epidemiologist Richard Peto, called Peto’s paradox, that larger animals have lower incidences of cancer, despite having exponentially more cells with the potential to mutate. Now, researchers believe they know why, and it could reap dividends for humans.

More is Less

“Elephants are 100 times the size of people,” says senior co-author Dr. Joshua Schiffman. “They should all be dropping dead of cancer and going extinct. But they have less cancer.”

Researchers at Huntsman Cancer Institute at the University of Utah and Arizona State University, with help from zoos and the circus, spent several years looking into what protections elephants have against developing the disease. Schiffman is a pediatric oncologist, professor of pediatrics at the University of Utah and an investigator at the university’s Huntsman Cancer Institute. He works with patients who have familial cancers, particularly those with Li-Fraumeni Syndrome.

Most people have two copies of a gene that codes for p53 – a protein Schiffman calls the “guardian of the genome.” People with Li-Fraumeni, a hereditary cancer predisposition syndrome, have only one working copy to code for the superhero protein that can jump in to repair damage or kill off a cell on its way to becoming cancerous. Without that genomic guardian swooping in to save the day, Schiffman said, people with Li-Fraumeni Syndrome have a nearly 100 percent risk of developing cancer in their lifetime.

Enter the Elephants

Elephants have 40 copies of the gene that makes p53: two normal ones, Schiffman said, and 38 with some variation that over millennia were inserted and remained in the animals’ DNA. He and senior co-author Carlo Maley, an evolutionary biologist at Arizona State University, theorized that elephants’ p53 would repair cells at a higher rate than in humans.

But that’s not what they found.

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Joshua Schiffman is a pediatric oncologist at the Huntsman Cancer Institute at the University of Utah. (Credit: University of Utah Health Sciences)

“We looked closely at our results,” says Schiffman “What we saw astounded us but made a lot of sense.”

The repair rate was similar, but in elephants, the genome guardian ramped up its other method of attack: cell death. For the elephant, Schiffman said, “it is so important that we don’t develop cancer that, instead of trying to fix it, where cells might go on to divide and turn into cancer, we need the ultimate protection – getting rid of the damaged cell completely.”

Schiffman and his team published their results Thursday in the Journal of the American Medical Association.

Across Species

The next step was to see if the p53 could help across species. Mouse cells given extra copies of the p53 gene seemed to develop some cancer resistance, he said. In the lab now, Schiffman said, they are taking elephant p53 and putting it into Li-Fraumeni cells to see what happens.

“We’re trying to be pioneers, to use these discoveries to do precision medicine,” says Schiffman.

He believes there could be a drug that could mimic the effect of p53, or a way to deliver these genes to people at risk of developing cancer, or who already have it to treat or cure the disease. He hopes to have a clinical trial within the next three to five years. The work has already given him a new tool when he talks with his patients.

“When I have a patient in front of me diagnosed with the syndrome, they will almost certainly get cancer,” he said. “But in that moment I’m able to tell them elephants don’t get cancer and we are working with the zoo and the circus to learn from elephants so one day you never have to get cancer.”

Then, he said, the children start smiling and laughing, and talking about how they want to go to the zoo.

“We’re putting all our efforts on this,” he said. “One child with cancer is one child too many.” 

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  • http://qpr.ca/blog alqpr

    This is a good news story that is mostly well written. So why undermine your credibility with that stupid reference to “exponentially more” cells in the elephant. If your are going to continue as a “science” writer, then please either learn some basic math or at least avoid using pseudo-mathematical jargon when you have no idea what it means.

    • francini

      An elephant being 100x larger than a person means at least 100x (or 10**2 times) as many cells as a human. Some estimates put the human body cell count at around 10e13 cells. Probably even more. So an elephant would have around 10e15 cells. Sounds ‘exponential’ to me.

      • http://qpr.ca/blog alqpr

        ANY positive number can be expressed as an exponential of any positive base, so with that interpretation ANY increase would count as “exponentially more”. But the mathematical definition of an exponential function is one in which the variable occurs as an exponent of a constant base (eg when the growth of population doubles every ten years then P(t)/P(0)=2^(t/10)). To use the phrase “exponentially more” in any other context is just pseudo-mathematical jargon intended to make the statement seem more important than it really is.

        • Maia

          Scientific terms often end up slipping into the ordinary lexicon where their meaning becomes loosened and metaphorical rather carrying on the “scientific term’s” exact meaning.That’s how language works. Always has. Why stress about it? Most of all, why throw around the word “stupid” and come off as rude while pointing out something in what might otherwise be a useful comment?

          • d-dectiri

            Heaven forbid anyone should ‘complain’ while everyone else is jumping in unison… no, no that would be so incorrect and seriously unfriendly… silence!

        • Tomek Brzezinski

          i think the main point is that volume increases exponentially (^3), while the size of the cells that fill in the volume does not, they have a limit. That is where the “exponential growth” comes in. We refer to an increase in size typically as 5m tall vs 10m tall is “twice as tall” while we could of course say “4 times as voluminous” but we don’t.

          You’re right it’s a meanignless semantic distinction, but it’s based on our precedent of how we refer to bigger things, and the fact they’re filled in with volume-limited objects (cells)

        • Theresa Rose Anna Cousineau

          just like your post. lolol

    • http://ja9anderson.wix.com/byjanineanderson Janine Anderson

      I’m going to plead editor’s choice on that one. That wasn’t my turn of phrase, though I’m going to go with francini on the ultimate justification there.

      • http://qpr.ca/blog alqpr

        If you don’t have the guts to stand up to an editor who wants to make you say something that you don’t fully stand behind, then you shouldn’t be a journalist of any kind – let alone a “science” one.

        And if you continue to “go with francini” on the idea that any number which can be expressed as a positive power deserves to be advertised as “exponential” then I don’t think you will be much missed if you choose to leave the field of “science” reporting – even though, aside from that aspect, I found your article quite well written and interesting.

        Please reconsider, because if you ARE capable of recognizing the importance of NOT using pseuo-mathematical jargon to spice up your delivery, then I think your future contributions WOULD be missed.

        P.S. To any higher-ups at Discover who may be reading this: Whatever “editor” who insisted on the insertion of that word “exponential” in this story should probably be fired!

        • Anthroariel

          Alqpr: Interesting that none of your comments address the substance of the article, just the choice of descriptive wording. You make a fuss over nothing-we all understood the author’s point even without the use of “showoff” phraseology like you suggest. Could it be that you are, in fact, nothing more than a snob? Or perhaps just a mediocre troll?

          • http://qpr.ca/blog alqpr

            My only top-level comment started with a favourable overall response to the story. The rest have been in response to challenges to my objection to the use of “‘showoff’ phraeseology” – which I think is something that should be avoided in science journalism (especially when technically not correct).

          • Prof

            I must point out that the phraseology IS technically correct. If the article was a discussion of mathematics, then the term “exponentially more” would be incorrect. However, in normal usage, the term “exponential” is defined as ‘very fast or increasingly rapid’. Therefore, describing the increasingly larger number of cells that make up a larger animal, the phrase “exponentially more” would be grammatically correct and would constitute correct English phraseology.

        • Kengi

          If you don’t have the guts to mention Nazis in your post then you shouldn’t be a troll of any kind – let alone a “math” one.

          The only thing THAT prevented your post from earning a FAILING troll grade WAS the random CAPITALIZATION of words.

          • Eliot

            …which I point out is juvenile and grammatically incorrect, so maybe he shouldn’t be posting at all, not being an expert at it.

          • Angus Gordon-Farleigh

            Sorry Eliot & Kengi… Cannot go with that, in fairness. If the writing field fails to allow expression modifiers like bold/italic/underline/colour, then the writer is ONLY left with capitalisation! See what I did there?

            Nevertheless, modifiers should only be used in moderation ~ they tend to distracting untidiness as disjecta membra throughout a text.

            FWIW, I’m in agreement with alqpr with respect to his assertions about the ‘exponential’ word usage.
            In the author’s text, the word is being used within a scientific/mathematical descriptive framework, despite being ‘presented to the layman’.
            In being so presented to an assumedly non-science-versed readership, there is then an incumbency upon the writer to precisely ‘say what’s meant & mean what’s said’ without using possibly confusing scienc-y terminologies.
            He must write either/or non/scientifically or suffer a pratfall between two chairs. Which is precisely what’s happened here, rendering his usage almost a malapropism. It’s quite lazy, or if you prefer, laconic journalism.

            While this usage did cause me pause and a raised eyebrow as I initially encountered it, I was humourously struck more by the malappropriacy (I made that word up, btw) of its insertion, rather than guttural indignation for its presence.

            I do think it was worth noting however, that scientific discussion should be conducted as precisely as possible, even toward audiences of laypersons, lest incorrect impressions are unwittingly fostered. That’s just commonsense and manners.

    • Eliot

      Some people just can’t pass up the opportunity to show how smart they are. Usually the ones with massive inferiority complexes. In case you haven’t noticed, Discover Magazine is for lay people. It is not a scientific journal. So, it speaks to its audience. That you may have some specialized training does not make the lay person an idiot.

      • http://qpr.ca/blog alqpr

        Yes, Discover Magazine is *for* lay people. But if it is to be a reliable source of information on scientific issues, then I think it would be best for it not to be written and edited *by* lay people.

        I am sorry if my criticism of the wording was seen as insulting to the readers who saw nothing wrong with the wording in the article, and maybe it was a bit too harshly phrased even for the author and editor. But the number of respondents who defend the phrase “exponentially more” as actually appropriate in that context is indicative of a failure in the educational system – which is unfortunately compounded by sloppy writing in the popular science literature.

        Many issues that voters in the modern world have to deal with require a much higher level of numeracy than may have been the case in the past – in particular, for example, an understanding of the difference between exponential and power relations (for those who want to know, the difference is in whether the independent variable is ‘upstairs’ or ‘downstairs’ ). I believe that magazines like Discover have an important role to play in preparing us to deal with such issues and so I’m afraid I do get a bit (too) angry when they fail to set a good example.

        • Chad

          I would just like to try and translate for alqpr here, as I would casually define myself as a bit of an angry nerd myself. I think what he is trying to say, and I’m merely paraphrasing here: Worst…episode…ever.

          Do the rest of you get it now?

    • Jefecaminador

      He didn’t say elephants, he said larger animals have exponentially more cells than smaller animals. Which is factually correct, given the standard when comparing sizes of animals is usually length.

    • Constantinos C

      Make your point but don’t disrespect and undermine others because that undermines your credibility as a person, not a professional. For all your apparent knowledge and intelligence, your manners are quite poor.

  • Ivar Ivarson

    It would be interesting to see if other big mammals like whales and rhinos have developed similar genetic strategies.

  • Tosin Otitoju

    toooo cooool!

  • Kathleen Sisco

    Actually, you wonder why we dont have that adaptation. It would appear we used up our protein with the big brain.

  • Lady Bird

    Very interesting post!

  • Me

    Great article Janine. Ignore the troll. :)

  • Suzanne Sadedin

    Upregulated p53 activity in humans is implicated in Huntington’s disease. Which makes sense, since the symptoms involve early death of brain cells. So this isn’t a panacea in itself. But as we learn more of the gene regulatory networks involved, we may be able to develop something much more fine-tuned that has the benefits without the costs.

    • JohnBoy

      How does this tie in with the observed mutation of the Huntingtin gene?

  • Carl M Anglesea

    Learning how P53 activates cancer-specific apoptosis would be the holy grail of cancer research. Do I see a Nobel Prize in the making for Joshua Schiffman?

  • http://davidarnoldaofascandal.com/david-arnold-of-aofaq-and-the-dominatrix/ davidarnold597

    David Arnold as the main director of AoFAQ, has until recently enjoyed
    the cosy and lucrative position of administrating the issuing of
    regulated certificates in several areas including health and safety and
    first aid. Claire (Dita_Von_W_Lash) gained a pass on the course and gave it a high
    score on the evaluation sheets provided. Following the course she then
    placed several internet posts up including setting up a blog site
    discrediting the training company, its director and claiming there was a
    complaint lodged to AoFAQ about the course.

  • Chuck Meyer

    What I don’t understand is why some would believe the larger the animal, the more likely the chance for cancer? Isn’t the question how efficient is the body is at removing cells at a pre-cancerous state? Wouldn’t that efficiency be independent of the size of an animal? That is like saying that I have a greater chance of cancer because I am overweight, compared to my former thinner self. While that may be true because obesity may be linked to certain cancers, it is not true just because I have more cells. Peto’s paradox seems logically flawed.

    • Eliot

      Cancer is a gene mutation. The more cells, the greater number to be affected/replaced by mutated ones.

    • Tomek Brzezinski

      Most overweight people do not have remarkably more cells, they simply have larger lipid cells. Your lipid cells change over a great range in size.

      other people have responded the probability bit, about the size of the elephant having more cells and therefore more cancer chances. I’m not sure how well that stands up to stats analysis though, but its presumably an established concept for the elephant researchers to weigh heavily on it.

      • http://qpr.ca/blog alqpr

        “elephant researchers…weigh heavily” nicely done!!

    • http://qpr.ca/blog alqpr

      To amplify on Eliot’s response:
      If the cancer-removal efficiency is independent of the size of the animal (let’s say 99.9999%) then a fixed proportion (one in a million in our example) of all cancer cells will proceed to become noticeable cancers. If one in a billion cells turns cancerous (or has a cancerous offspring) each year, then the number of cancers arising each year will be one per million billion cells (ie one in 10^15). Since there are between 10^13 and 10^14 cells in the human body the chance of cancer is a bit more than one in a hundred years but less than one in ten years – which seems about right. (Of course I just picked the numbers to make it come out like that.)

      But for an elephant, which is about 4 or 5 times the linear “size” of a human the volume, and so the number of cells, is greater by the cube of that factor, ie about 100 times greater. So over a comparable lifetime it should end up with 100 times as many cancers in its body. If cancers were all of limited size then none of them might be fatal, but of course the bad ones are exactly the opposite of “limited”, and once they get off to a good start they are certain to be eventually fatal. In the elephant (IF the defense mechanism was only as effective as ours) the first such cancer would be quite likely to occur in the first year of life.

      If the cancer grew at the same rate as the animal then the elephant might just end up at the end of 20 years with 20 or so small cancers in its body, but here is where “exponential” growth really does come in. An aggressive cancer grows by doubling its size over approximately equal intervals and so grows exponentially fast, whereas the hosting body typically stops growing at maturity. So even a small cancer acquired in the first year of life would kill the elephant quite quickly.

  • L Cavendish

    Good thing we discovered this before making elephants another extinct creature…

  • Scorpion_J

    Interesting research, but it has a long long way to go before it can be applied to humans in general, that is if it works.

  • Glenn Jones

    Thanks for the ‘good news’ story

  • dondehoff

    Most of these comments are just the result of the very contagious, off-subject game of “mental masturbation”—and “fiddling while Rome burns” I like “Ivar’s” short but meaningful contribution.

  • Brian Prewett

    I’ve chainsmoked tobacco and Cannabis for over 30 years, guess I have a couple copies of P53… Or, maybe the medical community isn’t ready to accept an actual cure for cancer that they can’t regulate, control, patent, and capitalize… just yet.

  • Brian Kyung Byon

    I did some research and published some theories. So do whales, which can live 213 years, have veins larger than elephants and people combined. It seems that psychosis/psychology is also involved in this. Some animals have inability to break down food, so they digest it without discrete (poop), and they become violent. The fact that large veins have advantage than small veins is that these particles don’t get clogged (as same reasoning as how large pipe is required in cities to pump big masses to avoid clogs and explosions). Small veins, for some cases, are known to get easily clogged leading to stroke. However, large veins don’t get strokes. If people somehow find ways to completely remove 0% of junks (small particles, metal particles, particles, and others), so as the effect of large veins as almost, I think we’re good. Right? Bible says people can live well over 900 years. Imagine, baby being born without a single harmful particle at the atomic size (small), and living to the fullest. Let’s not clog our veins – Amen. Sorry for messy syntax, but many of you should still be able to get it. This is a miracle discovery. Also sorry I do not have solid evidence to support my theory…

    • davidstrail

      You’re an idiot.

    • Roll Robin

      People like him evolve ideas and make the tech world spin. I do admit he did phrase it a little weird, but he did something no predecessors ever did: sharing. I’d call him a science revolutionary who’s not offensive and shows mere positiveness. Not some obese elderly man watching younger generation by sitting on a sofa eating chips 24/7 to call him an idiot.

  • Avi Roni

    And the subterranean blind mole rat, the size of a small rat that can live >20 years (X4-5 than rat), a hypoxia-tolerant rodent has a p53 that is more effective in inducing the transcription of Cell Cycle Arrest/DNA-repair genes than apoptotic genes. And…. it is resistant to cancer

  • https://twitter.com/Mr_Roshan Mr Roshan

    So, we just have to genetically engineer all humans for a limited benefit – or we could invest energies in all the environmental nonsense known to cause cancer (as in avoiding it) – high carbohydrate and processed foods, physical inactivity, cleaning compounds at home, fire retardants at home, regular usage of mobile phone devices, likely regular WiFi exposure, fluoride etc.

  • Iftikhar Qayum

    No doubt this is a plausible mechanism and a possible therapeutic route, but remember that it is the native or ‘wild’ type of p53 we are talking here. In cancer cells, the p53 is mutated so that it no longer functions as an efficient tumor suppressor or apoptosis inducing mechanism. This gives transformed cells protection and allows them to remain and divide instead of being killed. So it’s not a simple case of reactivating the mutated p53 or inserting normal p53, both of which methods have been tried experimentally. Currently Crispr Cas9 offers an alternate method to repair the damaged p53 genes.

    • Maia

      If you read up on Crispr techniques you will see that they are not nearly as precise and accurate as presented. The degree of precision required to repair mutated p53 or insert the normal version…? Well, let’s just say, from what I can tell, we aren’t there yet. Inaccurate “repairs” would cause more or worse damage.

      • Iftikhar Qayum

        Maia, the latest modification of crispr is almost error free. Moreover just recently four new proteins have been isolated from bacteria that can block crispr editing at specific or unwanted sites. Together, these innovations hold great promise for the therapeutic use of crispr.
        Insertion of normal genes into cells is an old technique using viral vectors and libraries and is successful too. However crispr would become the main technique in future.

  • petergkinnon

    How does the instance of the Naked Mole Rat, which reputedly has zero cancer incidence, and is by no means large, fit into this scenario?

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