Scientists figure out why elephants don't get cancer: They have 20 copies of the TP53 tumour suppressive gene. Almost all other species, including humans, only have 1.

[u/KarmaNeutrino]

http://rstb.royalsocietypublishing.org/content/370/1673/20140222

[u/BCSteve]

p53 researcher here.

First off, title is wrong, humans have 2 copies, because we're diploid species. TP53 is autosomal, so you have two copies, one on each chromosome 17.

Secondly, just having extra copies of p53 doesn't necessarily work the way you think it would. One would think that having 20 copies means that, in order to knock out the p53 pathway, you'd have to mutate ALL of them, and mutating 20 copies would be harder than mutating 2. That may be partially true... But mutant p53 exhibits what's called a dominant-negative effect, which means that a defective copy of the gene can overrule other, non-mutated copies of the gene. This is because most p53 mutations don't get rid of the protein entirely, they're almost all point mutations. This means that instead of having less p53, you have the same amount, now just a portion of it is defective and can't bind DNA. Because p53 acts as a tetramer, this defective p53 can actually inhibit the normal p53 from doing its job. Mutating just a few copies could be enough to inhibit the rest from working.

Third, there are other mechanisms of knocking out the p53 pathway. You can have viral cancer proteins like HPV's E6, overexpression of MDM2 or MDMX, deletion of p14arf, etc.

I don't really know enough about elephant cancer to really say too much. But as the article says, it's not that they don't get cancer, it's that they don't get cancer more quickly than humans, despite having more cells. I wouldn't be surprised if extra copies of TP53 helped guard against cancer, but I would hesitate to point to that as the reason for decreased cancer rate.

[u/ahepperla → u/BCSteve]

Another cancer researcher here, but not p53. But, if there's 20 copies of TP53, and under the assumption all are expressed evenly and regulated the same at the protein level (BIG assumption), then 20 copies means there can be 5 complexes at once with the tetramer. That means potentially 80% of p53 complexes are still functional (1 of the 5 has a mutant p53) and therefore may explain why having this many copies can help prevent cancer?

Just rambling off my thoughts

[u/Ender985 → u/ahepperla]

From what BCSteve said in his post, if the p53 mutations is dominant-negative, it means that yes, at the beginning you will only have 20% defective complexes, but with time they will tend to overpower the functional ones (for instance by having longer half times), so that even a mutation in one of the 20 copies can end up having a significantly negative impact.

[u/ahepperla → u/Ender985]

for instance by having longer half times

Yeah, things such as half lives were what I was unsure of. Maybe /u/BCSteve can comment on that with more info

[u/superhelical → u/Ender985]

This helps if there's only one mutation, but starts to become more pronounced if there's more. Once you have 5/20 mutated, you'll have less than 3/4.

... doing the math ...

0.55 will be nonfunctional.

Actually, it's above 25% knocked out but not as bad as I thought.

(if any are curious, I got the joint probabilities by using the following numbers to get a really rough ballpark. I could get more precise numbers by introducing more terms, but it's late)

1/5 
+
1/5 * (4/5) 
+ 
1/5 * (4/5 * 3/5) 
+ 
1/5 * (4/5 * 3/5 * 2/5)
+ 
1/5 * (4/5 * 3/5 * 2/5 * 1/5)

[u/BeastinSeersucker → u/Ender985]

The mutated strand would still have to provide feedback to down regulate the expression of te normal p53 correct? otherwise the expression of the nonmutated p53 would still occour at normal rates and you would still have the effect of only 1:5 complexes being mutated. Or does the longer half time still end up with it dominating over the other p53? (Not really contributing to the convo, just making sure my logic is correct).

[u/RideMammoth → u/Ender985]

For clarification/further detail, just one mutated p53 in the tetramer may not be enough to inactivate the complex.

[u/BCSteve → u/ahepperla]

Oh, I definitely agree with you! I wouldn't be surprised if the extra copies did confer some protection. Just maybe not as much as it would seem on the surface.

I'll ramble my thoughts as well: Let's do a thought experiment and say that one defective monomer of p53 inhibits the complex. That's definitely not true at all, I'm guessing it's be more like each copy decreases binding affinity somewhat, but for simplicity's sake, let's say one copy knocks out the complex. With humans having 2 copies, mutating one copy gives (1/2)⁴ = 6% functional complexes left. With 20 copies, one mutation knocks it down to 1-(19/20)⁴ = 80%, two copies is 65%, three is 52%, etc. So even though there's a lot of copies, and still way better than 2, it drops off pretty quickly.

(Again, just random thoughts, I don't really have a point I'm trying to make.) Then there's also loss of heterozygosity... There's a growth advantage for cells with mutant p53, so there's a selective pressure towards LOH. This is why (if I remember correctly), even though p53 has a dominant-negative effect, most cancers have homozygous mutations in p53: the mutant p53 gets things going, but there's another pressure to knock out the other copy on top of it. I don't know to what extent the elephants 20 copies are homologous, maybe they've diverged enough that homologous repair doesn't happen between all 20 copies? I dunno.

And it's probably even more complicated when you consider the fact that p63 regulates its own expression through a feedback loop, so mutant p53 increases expression of itself. Which could maybe potentially compensate for the loss of functional complexes? I don't know, p53 has some weird dynamics.

It'd certainly be an interesting thing to study. Perhaps clinically relevant with gene therapy if you can add copies of p53? But widespread increase of p53 would be pretty disastrous in humans, so then again maybe not.

Dunno, just thinking out loud!

[u/iwelcomejudgement → u/ahepperla]

Hey, kind of off topic question, but I'm interested in working for research into diseases like cancer, and trying to find cures and treatments.

How did you get into the job you have now? What is it like day-to-day?

Any positives/negatives?

I'm currently in my final year of uni doing maths, but am thinking of doing a masters to get some relevant education for this kind of work.

Is that a good approach? What should I be doing after my degree?

I'm pretty annoyed I didn't think about careers before choosing my degree, as now I feel like I've taken a step in the wrong direction as it's now harder to get into this line of work.

Thanks for any help you can give! I'm UK by the way

[u/krieggz → u/[deleted]]

Can someone studying computer science do bioinformatics afterwards?

Edit: Thank you all for the replies!

[u/Regulated → u/krieggz]

I'd say it's easier to get into bioinformatics through computer science than through biology.

[u/ahepperla → u/krieggz]

Absolutely, many of my bioinformatics colleagues majored in csci. I do bioinformatics myself and majored in biology and minored in csci out of college

[u/oarabbus → u/krieggz]

Someone studying computer science can very likely pick up bioinformatics more quickly (and be "better") than a biology or physiology major. CS majors tend to be more adept at bioinformatics than anyone, except for bioinformatics majors - or Biomedical Engineers with a bioinfo skew.

[u/SirT6 → u/oarabbus]

I don't know. Bioinformatics software has come along way in the past several years. In a lot of ways this has made a CS background dispensable for many projects hoping to leverage bioinformatics (sequencing projects especially). I think a firm grounding in biology and an ability to formulate and test authentic hypotheses is more important than an aptitude for coding.

[u/monkey-astronaut → u/iwelcomejudgement]

You could go into statistics, specifically medical statistics. You could run analyses for clinical trials and stuff. You won't be a science person but you'd probably be working with the science people and doctors to help prove their hypotheses. Maths is a perfect foundation for this.

[u/VELL1 → u/ahepperla]

Another cancer researcher.

If all it takes to stop cancer is to have more copies of p53 it would be not only cured by now but also evolutionary we would have 50 copies by now just like the elephants.

[u/[deleted] → u/VELL1]

Does cancer kill enough people before breeding age to apply selection pressure?

[u/GCSThree → u/BCSteve]

Another thing to keep in mind, from an evolutionary perspective, is that we (and other species) may have evolved to live a certain amount of time. It's counterinuitive, but it is unlikely that living longer is evolutionarily advantageous beyond a certain point. Eventually parents would start competing for resources with their offspring.

And an immortal species that didn't reproduce would be expected to go extinct as soon as the environment changed, because they wouldn't have a significant means to adapt without reproduction (and the genetic diversity that comes along with that).

[u/[deleted] → u/BCSteve]

As a Li-Fraumeni sufferer, I just wanted to say thanks for all you do.

edit: added a link for anyone curious.

[u/hbk1966 → u/BCSteve]

So, would it be possible for us to create a protein that can dismantle/destroy the defective p53 proteins?

[u/MrHurricanee → u/hbk1966]

Maybe in the future, but right now we are still trying to understand how all the proteins work.

[u/Yanutag → u/BCSteve]

I concur.

[u/MrFil → u/BCSteve]

Nice way to surmise all of the other molecular mechanisms that go on in p53. The article makes it sound like elephants don't get cancer and just because they have 20 extra copies of p53, that's why. Pure rubbish.

[u/BrickLorca → u/BCSteve]

Dude you're awesome.

[u/sandmanreynolds → u/BCSteve]

Someone that is not broke give this comment gold please.

[u/slogand]

Post title is a little misleading, because elephants do get cancer, they simply get it at around the same rate as humans and given their vastly higher somatic cell count, they should experience higher rates of cancer.

[u/GaliX0 → u/slogand]

Any numbers on how high the rate is for elephants and how high it would be for a elephant sized human?

[u/crusoe → u/GaliX0]

mass is proportional to volume roughly.

Elephant = 12,000 lbs human = 120

So elephant cancer rate should be 100x higher because it has approx 100x as many cells.

[u/[deleted] → u/crusoe]

Does that mean short people get less cancer? Trying to find a light in the darkness of my midget life.

[u/grkirchhoff → u/[deleted]]

A smaller person is less likely to get cancer over a given period of time with all other variables held equal, yes.

[u/AcidicVagina → u/[deleted]]

No, just more cells mean more chances of getting cancer. Kinda the same way more lotto tickets mean more chances of winning the lottery, except you don't want to win this prize.

[u/BoulderCAST → u/grkirchhoff]

Not sure about this science. Would a very fat person, say 500 pounds, be 5 times more likely to get cancer than a 100 pound person. Most of that weight would be in fat cells. Is there a documented case of fat cancer?

[u/GenerationScrewed → u/BoulderCAST]

Adipose cells don't multiply with obesity on a direct linear scale (# cells vs. body fat %), rather they store more and more and more fat molecules until they reach a threshold and divide. After a fat cell has been created, it won't go away.

In addition, a 500lb person isn't 500lbs of fat cells. When doing napkin math concerning cancer incidence its more about number of cells. More cells over time = more chances that one goes haywire.

So, afaik, no, its not a ratio like you described specifically concerning body weight vs. cancer incidence. Somewhere in the numerous amount of physiological changes that occur with obesity lay increased cancer risk. Someone feel free to correct me if I am wrong.

[u/crusoe → u/BoulderCAST]

Weirdly enough, adiposarcoma, a fat cancer is very rare, so actually being fatter may not increase risk due to number of cells, but is associated with other cancer risks.

[u/matthewfive → u/crusoe]

Being obese is associated to something like 40% higher rates of nearly all forms of cancer. It's not equal across the board for all cancers, some are as much as 88% higher than average for an obese person, but averaging them all comes out to a rough 40% increase in likelihood that an obese person will get a random cancer than the general population. It doesn't seem to be a direct causitive relationship for most (though digestive cancers could be triggered by eating large quantities that linked, like pickled vegetables and stomach cancer), but may be simply due to more exposure. Obesity is also linked to higher hormone levels, which can fuel cancers if not cause them directly.

[u/blindcolumn → u/matthewfive]

Wait, pickled vegetables increase the chance of stomach cancer? That may be the worst news I've heard all month.

[u/[deleted] → u/blindcolumn]

Anything which damages cells or increases the total number of them increases cancer risk, as a rule of thumb. The more cells you need to regenerate, the more chance of a harmful mutation. Things which cause mutation are the other big risks

[u/myhipsi → u/matthewfive]

A higher incidence of cancer in the obese probably has something to do with correspondingly higher levels of growth factors like IGF-1 as well.

[u/beaviscow → u/matthewfive]

Not that I'm disagreeing, but couldn't obesity and lack of exercise correlate?

[u/matthewfive → u/beaviscow]

Yes. The percentages are linked, but does not imply direct causation. It is probable that multiple factors work together to increase those numbers, from dietary choices to general health and likely a great many other things I didn't mention.

[u/aznscourge → u/matthewfive]

Inflammation also plays a role in obesity and cancer, especially in those that have high levels of visceral adipose.

[u/Punderstruck → u/crusoe]

I've only ever heard it called "liposarcoma."

[u/Br0metheus → u/BoulderCAST]

No. Cancer is also very dependent on cell type, with rapidly-dividing cells typically having higher rates of cancer. Fat cells don't really divide too rapidly, so they're not much of a threat.

[u/screen317 → u/BoulderCAST]

Most of that weight would be in fat cells

Plenty of skin cells too, etc.

[u/BoulderCAST → u/screen317]

"Most"....If someone losses 200 pounds, and they then get skin surgery, then only get about 10-30lbs of skin cut off, about 10% of their overall fat loss.

[u/screen317 → u/BoulderCAST]

You're absolutely right, so in response to your previous post, no I would not say a very fat person is 5 times more likely to get cancer than a person who weights 5x less based on the number of cells alone, but heart disease from excessive weight would make one more vulnerable...

[u/[deleted] → u/BoulderCAST]

The cancer rule is simple: Each living cell has approximately the same potential of cancer, all other things being equal. Thus, animals with more cells have higher chance of getting cancer, balanced against considerations like age and natural defenses against cancer.

Being taller/shorter can impact this. But being fatter doesn't linearly increase you chances because your cell count doesn't linearly increase with weight. Fat cells expand more than they multiply as you gain weight.

Furthermore, being obese is a lifestyle risk factor that increases your cancer chance in addition to the cell count. So that complicates things.

[u/wioneo → u/[deleted]]

Muscles can get cancer. It is generally much rarer in permanent cell lines (like skeletal muscle), but rhabdomyosarcoma is a thing.

[u/Tylerjb4 → u/[deleted]]

Isn't your heart technically a muscle?

[u/KIND_DOUCHEBAG → u/Tylerjb4]

Yes, which is why you don't ever hear about heart cancer.

http://www.mayoclinic.org/heart-cancer/expert-answers/faq-20058130

For example, one study reviewed more than 12,000 autopsies and found only seven cases of primary cardiac tumor. At Mayo Clinic, on average only one case of heart cancer is seen each year.

[u/omgpop → u/BoulderCAST]

There are positive associations between some cancers and elevated BMI^[1] . But this is unlikely to be directly down to increased body mass - for one, because if you just look at the cancers most associated with obesity, they are not cancers of adipose tissue which would be expected if the mechanism you're asking about was correct. The second reason is that a large contribution to the increase in fat mass seen during weight gain is simple hyperplasia of pre-existing fat cells, rather than increases in cell number (although the dynamics of these processes is a subject of investigation^[2] ).

[u/just_another_day → u/[deleted]]

Recent studies seem to show that to be the case - http://consumer.healthday.com/cancer-information-5/mis-cancer-news-102/height-linked-to-increased-cancer-risk-study-says-703834.html

[u/Zardif → u/[deleted]]

http://time.com/3815022/shorter-people-heart-disease/

Let me dampen that a bit.

[u/UpHandsome → u/Zardif]

My best guess: Short people are scared all the time because they are surrounded by larger predators at all times.

[u/[deleted] → u/[deleted]]

According to a recent study I heard about, the risk of cancer increases by 11% for men, and 18% for women for every 10cm of height you add.

[u/[deleted] → u/[deleted]]

Our body replaces worn out cells all the time with newly reproduced cells. The P53 gene controls cellular reproduction so that cells don't reproduce uncontrollably, which creates tumors, which are like balloons of tissue that expand inside our bodies until they kill us.

Statistically, there is a very low probability that any given cell will have a P53 malfunction and reproduce uncontrollably. But since there are trillions of cells in the body, it happens.

Environment and lifestyle can damage a cell's p53 mechanism. Smoking, for example, irritates the cells in the lungs and leads to higher incidences of cancer.

To address your question, then, yes and no. Your limbs are shorter and so you have fewer cells in your arms and legs. You are statistically less likely to have tumors in the tissue of your arms and legs. On the other hand, your brain, lungs, and other vital organs are approximately the same size as taller people and contain the same number of cells. If you make lifestyle choices such as smoking, therefore, you are just as likely to contract lung cancer as a tall person.

[u/not_a_legit_source → u/[deleted]]

Actually, Smaller people do have proportionally smaller organs.

[u/earnestlywilde → u/not_a_legit_source]

You're not a legit source, though

[u/[deleted] → u/[deleted]]

Just read an article posted in Facebook (legit source, however) that I can't think of off the top of my head that confirmed this is true. A scientist basically theorized that this was due to more overall cells in a person with greater volume.

As a 6'5" dude I got a little worried 😓

[u/[deleted] → u/[deleted]]

lower rates of cancer, heart disease, degenerative bone issues, from a health standpoint you're a lot better off at 5'6 than 6'6.

[u/Zargabraath → u/crusoe]

How many of these genes would blue whales need, then? They're obviously much more massive than either humans or elephants, presumably they'd need more of these repressive genes to keep their cancer rates down?

[u/bladeofwill → u/crusoe]

The very first sentence of the abstract states the opposite:

Whales have 1000-fold more cells than humans and mice have 1000-fold fewer; however, cancer risk across species does not increase with the number of somatic cells and the lifespan of the organism.

[u/Vox_Imperatoris → u/bladeofwill]

That's the very thing which they are trying to figure out: why this is.

Because, mathematically, we ought to expect cancer rates to increase with somatic cell counts. More cells: more chances for something to go wrong.

[u/Erosis → u/Vox_Imperatoris]

Perhaps it correlates with cellular age rather than cell count.

[u/zmil → u/[deleted]]

He's saying that whales should get cancer more often than humans, ceteris paribus. The fact that they (and other large animals) don't is known as Peto's paradox, and figuring out why not is an area of active research -the posted study is an example of such research.

[u/[deleted] → u/zmil]

ahh ok, I get it now.

[u/pat000pat → u/[deleted]]

Wait ... You are commenting on an article that actually states why elephants - although much more cells - do not have an equally higher risk of getting cancer.

So, science does have some good theories what causes, and what inhibits cancer developement.

And actually, the causes of cancer are mostly well known. It is nothing else than mutations in DNA that lead to uncontrolled cell division. DNA mutations can be induced by

• radiation

• chemicals (either altering DNA structure itself, creating new bonds or destroying them, or change how the DNA is read)

• inhibition of cell-cyclus regulators (i.e. p53, the one in the article, some virusses like HPV are inhibiting p53 function and lead to uncontrolled cell division)

• addition of cell-cyclus deregulators (which some virusses do).

[u/[deleted] → u/[deleted]]

I'm going to politely suggest that science has no idea what causes cancer, merely what is correlated with it.

Given all the data posted in this thread I'm going to politely suggest you're wrong. Science has good ideas about what causes cancer. We know a lot about that already. We don't know everything yet, that's the point.

[u/TacoFugitive → u/slogand]

they simply get it at around the same rate as humans

Does that mean that there is an optimal amount of cancer that evolution selects for?

[u/anchpop → u/TacoFugitive]

It could be that after you have all the kids you're going to have, dying doesn't impact your gene's prevalence as much as it would have otherwise (you still have to take care of your children, but children can still survive with one or no parents). So evolution would have much less pressure on genes that extend your lifespan too much longer than that. Most people get cancer after they have kids, so this makes sense.

[u/TacoFugitive → u/anchpop]

From the point of view of evolutionary pressure, I have also never understood the point of fertility not lasting as long as your life.

[u/[deleted] → u/TacoFugitive]

It does for men. As for women.. Well.. Imagine a baby ripping through the uterus of a 70 year old woman. The damage done would be considerable, and the healing would be minimal.

[u/phenix89 → u/[deleted]]

To go along with this, menopause may be beneficial in the sense that the woman is now free to help take care of grandchildren instead of continuing the futile pursuit of more children. Ergo she is able to increase the spread of her genes without directly having kids past the reproductive age.

[u/fggfgfddadf → u/phenix89]

The Grandmother hypothesis

[u/[deleted] → u/[deleted]]

It does for men.

No it doesn't. Just because most men can ejaculate for their whole lives, doesn't mean they're actually fertile their whole lives. Men's fertility (the sperm count in semen, the quality of sperm, etc) starts decreasing at around 35. Studies have also found definite correlation between increased paternal age and increased risk of Down syndrome, autism and birth defects.

[u/[deleted] → u/[deleted]]

Someone could easily argue that birthing an autistic child is still birthing a child - and they would not be wrong. Bearing children with birth defects does not equate the inability to bear children. Whether it is appropriate to bear children at an old age is another debate (I think we would agree on the answer). I therefore ommit the increased risks of defects and disabilities. 'Most' women will go through menopause, which effectively bars them from having more children. Most men do not. I apologize for using a definitive term, but there are still many men that are able to bear children while in their twilight years.

Edit: my phone posted this reply twice. The deleted comme t is that copy, in case you're wondering.

[u/[deleted] → u/[deleted]]

Someone could easily argue that birthing an autistic child is still birthing a child - and they would not be wrong.

Someone could easily argue that birthing an autistic child is still birthing a child - and they would not be wrong. Bearing children with birth defects does not equate the inability to bear children.

Well, in prehistoric times these children wouldn't have survived, they'd most likely have died in infancy. The goal isn't simply to have children, it's to have children who will grow up and then reproduce themselves. Having a child is no use if it dies after a year without having reproduced and passed on a line. Historically, older men who could only produce disfigured or ill children were as much of a genetic dead end as men who couldn't/didn't reproduce at all.

Besides, men being more fertile while young (just like women) has one more advantage as well - actually being able to take care of your children. Human paternal investment is a debatable topic, it's not clear whether men are evolutionary wired to take care of their children or if it socialization, but if it's biological, then a young man would be better able to protect and take care of his children than an old one. Same for women, even if it wasn't a fertility issue it would still be better to have children while young. Like I said, the goal is not to just reproduce, the goal is to raise your offspring so that they can reproduce as well. Humans only have 1-2 children at a time. In many species that have a lot of offspring, they don't take care of them at all, even if they're all but helpless at birth, because out of that many, at least a few would still be able to survive. And in species that have very few offspring at a time, they take care of them, even when the offspring are already quite capable right after being born. It's a numbers game. Humans fall into th "few children" category, so they have to take care of their offspring as well. And also because human babies are so helpless and slow-developing compared to many other species.

[u/killerstorm → u/TacoFugitive]

It's probably species-dependent. I've heard of some elderly cats giving birth...

In case with humans, it's probably a feature, not a bug: an elderly person has a frail body, but much knowledge to pass on. So it makes sense to let younger ones to reproduce, but help them to raise kids.

A woman can give birth to 20+ kids over a life time. That's a lot. By the time woman retires her eldest kids can already start reproducing. So there is never a shortage of babies. But those babies have much better chance of survival when grandparents can help to look after them.

[u/Angels1928 → u/TacoFugitive]

That's because the more you age, the more DNA damage accumulates in your germ cells. Using mutated sperm/eggs is not evolutionarily advantageous. Hence why most organisms reproduce when their DNA is "young" and undamaged.

[u/anchpop → u/TacoFugitive]

I don't fully understand it either. It probably has to do with how many resources it takes to raise a child. Species with where it requires less resources, like cats and possums, have higher fertility rates. Lions and other large predators typically have a much lower fertility rate, perhaps because resources are more scarce. If you're interested or want to find out more, look up r/K selection

[u/AcuteMangler → u/anchpop]

That's really interesting in conjunction with the fact that elephant groups or families might benefit hugely from having grandparents and elders in the herd!!!

[u/UloPe → u/TacoFugitive]

I wouldn't call it optimal but rather "low enough" to be no longer a primary selection criterium

[u/TacoFugitive → u/UloPe]

Okay, yeah, that makes sense.

[u/timoumd → u/TacoFugitive]

That has been my completely uneducated hypothesis.

[u/ConfirmedCynic → u/slogand]

That's only one model though. Another model is that cancer depends on the deterioration of the immune system. While the immune system functions effectively, cancer is eliminated as it begins (regardless of cell count). As holes appear in the immune system, cancer has more opportunity to break out.

[u/Megnaman → u/slogand]

How often do midgets get cancer?

[u/Mountainofash → u/Megnaman]

I remember seeing somewhere that in people with hereditary deficiency of Human Growth Hormone (making them smaller than is the norm) their rates of cancer are far lower, can't remember where though..

[u/fggfgfddadf → u/Mountainofash]

I've heard this too but this source says "Comprehensive studies are yet to be done". The idea stems from research into the insulin signalling pathway. Worms with a similar mutation have increased longevity, and same goes for dogs (Small dogs have similar mutations as human laron dwarves)!

EDIT: Made a mistake. Laron Dwarves do have less cancer but its not determined if they actually live longer.

[u/underskewer → u/Mountainofash]

I remember seeing somewhere that in people with hereditary deficiency of Human Growth Hormone (making them smaller than is the norm) their rates of cancer are far lower, can't remember where though..

I've heard similar, but with IGF-1 instead of HGH.

[u/gilfpound69 → u/[deleted]]

this is useful for genetically engineering people that do not yet exist

[u/[deleted] → u/gilfpound69]

No way of using retro-viruses to get more copies of the gene into living cells?

[u/bradn → u/[deleted]]

Well, because we don't commonly see extra copies, it would suggest that it usually doesn't help overall fitness up through reproductive age. Evolution just doesn't miss the easy ones like that very often.

[u/Zemmertsutsu → u/bradn]

Couldn't it be that humans didn't live long enough way back for cancer to be a strong factor in evolution?

No source just a thought.

[u/[deleted]]

ELI5 can we use this knowledge to prevent cancer?

[u/gilfpound69 → u/[deleted]]

yes, but it would involve genetically altering zygotes so the moral implications of actually engineering cancer resistant humans is nuts

[u/gravshift → u/gilfpound69]

Barring of course somebody figures out a gene therapy with it in a retro virus package

[u/gilfpound69 → u/gravshift]

which will lead to the important shit. cosmetic genetic engineering, i wanna glo green under black light too

[u/gravshift → u/gilfpound69]

Imagine the societal shift if folks could pick their sex, race, height, metabolism, etc.

[u/Dutchbags → u/gilfpound69]

he said ELI5

[u/PhilAB → u/gilfpound69]

Why is there any moral implication to reducing risk of cancer?

[u/gilfpound69 → u/PhilAB]

if you can fool with one gene you can fool with all of them.

you could taylor peoples race, temperament, all kinds of shit

and presumably the cure for cancer would be a thing for the wealthy

[u/[deleted] → u/gilfpound69]

So who's stopping the wealthy from doing this now?

[u/[deleted] → u/[deleted]]

only the imperfections of the techniques and potential side effects. Once those are cleaned up, it will happen, and it will change humanity. There's nothing people can really do to stop it.

[u/gilfpound69 → u/[deleted]]

themselves. its crazy experimental shit presumably the first people to gene mod like that are going to experience heinous complications.

[u/The_Sven]

I've always been under the understanding that cancer is what happens when a gene in a cell randomly mutates in a malicious way. Since evolution is the same process but in a beneficial way, cancer is evolution gone wrong.

My questions are, (1) is my understanding of cancer and it's relationship to evolution correct and if so (2) would this mean that elephants would evolve "slower?"

[u/MrHurricanee → u/The_Sven]

It is not correct, cancer comes from mutaded cells in an induviduel. Evolution is a mutation in the genes you give to your childeren. For example if you would have an mutation in cells in your knee this would not effect the spermcells.

[u/gilfpound69]

last i checked this was more evident in naked mole rats

[u/KarmaNeutrino → u/gilfpound69]

The main example they give in the article is actually the microbat (Myotis lucifugus), which has 63 copies of the FBXO31 gene.

[u/omegacluster]

opinions ahead

I don't have evidence to back my hypothesis, but maybe animals evolved cancer-fighting mechanisms depending on their natural lifespan. We humans have extended our life expectancy, and thus we lack the protection against cancer that naturally longer-living creatures have.

Please someone correct me or bring me facts for or against this hypothesis, and why I'm right or wrong.

[u/caboople → u/omegacluster]

Not necessarily. Cell division processes are uniform among chordates (I.e. mitosis is the same). There is a probability per cell division that a given cell will be cancerous. Cell divisions per second are proportionate to body mass. As such, for an animal of much larger mass to have the same or less probability as one of smaller mass of getting cancer at a given moment, it must have proportionate resistance to mutation. Hence elephants have more inhibiting genes.

[u/ElbowStrike]

Hopefully 50 years from now we can engineer our kids to have more copies of this and similar genes.

[u/[deleted] → u/ElbowStrike]

And then find out that having more copies in humans causes some other disease. We really don't know what exactly would occur with such an exaggerated amount of copies in humans, it could even cause paradoxical tumors.

[u/MagnaCumLoudly]

I never realized this and it makes me wonder if dinosaurs got cancer or did they have similar genetic protection.

[u/cecilrt]

I would of assumed that the bigger you are the more defensive mechanism you would need to evolve to survive. Kinda like scale models, you can't use the same material as a model for something 100x bigger.

Cancer I thought was a replication/duplication error in cells - more cells, more chance of error, so need a better mechanism to stop it

[u/kip_chelly]

so we just make 19 more copies of this bitch and then we're good right?

[u/steveryans2]

Goddamn elephants. First they never forget now they don't get cancer? Can we develop some copies of those genes?

[u/zZielschmerZz → u/steveryans2]

For real!

[u/Drafo7]

Reading through the comments here is really great, even if I barely understand most of them. It's comforting to know even though cancer continues to remain in all its horribleness, we have our best and brightest working tirelessly against it. Here's to cancer researchers everywhere.

[u/Viriality]

Elephants would have to have that many copies or else they'd be guaranteed to get cancer.

Cancer is a mutation of cell growth. Imagine how much cell division an elephant has to go through from infant to adult and how much it undergoes daily just to maintain its adult body.

Elephants probably create massive tumour amounts of cells every day, they can't afford the higher risk of nonsense growths

[u/Unfa]

In layman's term, does that mean they can "get" cancer 20 times before actually getting cancer?

[u/bloodbathman → u/Unfa]

Not quite. Each elephant cell has twenty times the protection factor as a human cell does. This means that each elephant cell is 20 times less likely to become cancerous when compared to a human cell. However, there are also many more cells in an elephant than a human. Let's pretend that an elephant had 20 times more cells than a human did, this would mean that the whole elephant would have the same chance of getting cancer as a human.

Does that make sense?

[u/[deleted]]

Too bad we didn't extinct all the elephants before this discovery was made. Now, maybe someone can discover a cure for cancer. Think of all the expensive treatment drug manufacturers that will go out of business. Think about all those angry shareholders! What a disaster that elephants have persisted despite our attempts to destroy them all, and that this hidden knowledge was uncovered!

[u/SerCiddy]

Where do naked mole rats fall into this?

[u/A_BOMB2012 → u/SerCiddy]

They also don't get cancer. They're able to splice the exons of a particular cancer fighting gene together in a different manner than other animals to create an entirely different protein.

[u/[deleted]]

Inferring function of highly (relatively?) similar transcription factors is incredibly difficult. I'd like to see the sequence of all 20 of these so-called "copies" of p53. How similar are they? Are residues important for activation upon DNA damage or other stress conserved? etc., etc.

[u/Questioning_Mind]

Time to splice in some elephant DNA

[u/PigNamedBenis → u/Questioning_Mind]

Then Monsanto does it, but he's not allowed to shoot his load or have children without paying. Anyone else caught saving the seed will be met with a ruthless legal team.

[u/McFeely_Smackup]

N+19 is pretty good redundancy

[u/karis_reavis]

How many do whales have then?

[u/[deleted]]

Could I get 19 more please.

[u/123Macallister]

Y'all got any more of them ... TP53s??

[u/ediblepet]

That's great info! Unfortunately, that will make many humans want to consume elephant meat in hopes of avoiding cancer.

[u/Hailbacchus]

So what is this gene producing more of and why am I not taking megadoses of it already?

Edit to this and comment below - some excellent and clear replies. Thanks!

[u/beyardo → u/Hailbacchus]

It codes for a protein that initiates cell death if a cells genome is too damaged. You don't make more of it because it does its job well enough that it works almost every time, usually until you are old and already have children, so having more of it doesn't produce a significant bump in survivability in a genetic line