Big, beautiful, and cancer free

Not long ago the full genome of a humpback whale was decoded. There was a time when decoding a genome of another species was greeted with fanfare, but at the current rate of decoding the DNAs of organisms, this is just another statistic, even if it is for one of our planet’s living giants. After all, there is an ongoing undertaking to decode the DNAs of all the living species on Earth. Capturing the genomic information of every species is significant for many reasons; for understanding the biological functions of the DNA code and the evolutionary patterns, even potentially preserving the information against species extinction. But the decoding of the humpback whale genome was significant for another reason - it provided some clues on why whales have extraordinarily low rates of cancer.

The reason why this is significant and perhaps surprising, is the fact that typically with a larger body size you would expect a higher lifetime risk of cancer due to the greater likelihood of accumulating DNA mutations just from cells dividing over time. With more cells needed to divide to produce an organism, and assuming all cells are prone to a natural random rate of mutation when duplicating the DNA during cell division, then logic dictates, you should observe more mutations in larger animals. The more mutations, the more likely a break in the system of finely tuned cellular regulation so that some cells could become cancerous and start to divide uncontrollably. This pattern does indeed hold true, but not always. The largest animals of our planet such as elephants or whales, do not seem to be more prone to cancer development. In fact quite the opposite! It appears like there was selection for cancer suppression mechanisms in these animals that allows them to grow large yet still be able to successfully reproduce without cancer being a serious impediment.

Overall, it seems that humpback whales as well as the other related species in this family of huge aquatic mammals had various segments of their DNA duplicated or altered in regions related to immunity, aging, cell-to-cell signaling and cell adhesion in order to evolve specific adaptations related to cancer resistance. It appears that understanding these resulting changes could lead to our own improved immunosurveillance against cancer, enhanced response to DNA damage, control of cell death or reduced potential for cancer invasion and metastasis ( important processes which require adhesion molecules).

But the big question that comes to mind is, can we use this understanding to our advantage?

Of course this is not referring to growing gigantic in size - as much fun as the idea is of human giants roaming the Earth may sound - just the anti-cancer stuff.

The authors of the humpback genome paper seemed to think so as they pointed out the potential for learning about these whale defenses against cancer development could help us produce drugs that would mimic such biological outcomes as those seen in whales.

But that is not all we have in mind. What about …

Could we evolve ourselves?

Could we use what we learn from nature to purposefully alter our own genomes to enhance our health? Like redesigning our genomes to reduce the likelihood of cancer development? After all, why are whales and elephants the only lucky ones to be more robust against developing cancer? Why hasn’t our species developed this advantage? Or … Is there an evolutionary advantage to humans having such a different design even if a negative outcome might be more cancer?

Yes, perhaps there is. We have previously pointed out in one of our past posts as to the paradox of more diseases as an outcome of enhanced species adaptability to environmental changes. In essence, by leaving room for mutability, or in other words, ensuring that our DNA can always mutate and change a little bit every time a human being is born, we ensure that there is enough genetic variation among all of us. Genetic variation is important in case something crazy and cataclysmic were to happen to our planet - some of the members of our species would be able to adapt, survive and make sure future generations could keep pumping out articles such as this one. The price to pay for this evolutionary advantage is the scourge of congenital diseases and cancer. If you think about it, that is a very heavy price tag to pay for the benefit of future individuals, potentially ages from now, that we can never meet or maybe even imagine what they might look like by then. That is a lot of love to pay forward, which also makes you ponder why humans have to be so keen on hurting each other right here and now if we are already evolutionarily designed to provide a helping hand to our species in the future by carrying this burden of DNA mutations and resulting diseases.

But do we really need this programming to enhance the survival of our species? Is this really evident? What can whales tell us about that?

First of all, keep in mind that cancer is mostly a disease that is not associated with inheritance, albeit the cancer predisposing mutations that are inherited can be significant. The majority of cancer causing mutations occur in our bodies after we are born. Some of these will be due to exposure to carcinogens, but a large portion is due to the same limitations in our adult cells that produce mutations (somatic mutations) as observed in the sperm and eggs of our parents that gave birth to our own unique mutations that we might have been born with (germline mutations).Thus while our adult somatic cells are expected to experience more mutations than the germline cells used to produce babies, it has been demonstrated that germline mutation rates are related to somatic mutation rates within same species.

This means that by being able to be mutate faster, or evolve faster, we as a species will observe greater rate of cancer, and greater rate of diseases, but also greater rate of producing some super amazing trait that maybe could save our species one day (yeah, seriously, fingers crossed!). The inverse of that is that if whales see fewer cancers, they should observe fewer mutation rates in their adult somatic cells and also in their germline cells. Therefore their genome should indicate a lower mutation rate compared to humans.

And that is exactly what was observed! When the authors compared multiple different whale genomes to that of human but also some other mammals such as elephant, mouse, dog, cow, plus of course, opossum (the list could never be complete without opossum!), whales showed the lowest number of DNA mutations per million years of evolution.

Take that whales! So in theory we can gloat we are evolutionarily more robust.

Except… whales have been around for millions of years!

Their reduced cancer rate along with the reduced genome mutation rate surely did not seem to endanger the species for millions of years! With those odds, that resistance to cancer seems like a serious advantage to individual survival! With cancer being one of the largest causes of death for humans, imagine if that problem did not exist and if we were able to evolve some of the adaptations that are found in whales. Imagine if that entire burden of fear was completely removed because cancer did not exist.

So could cancer cease to exist if we willfully altered our genomes to enhance our species to gain the benefits seen in whales? First let us assume that the adaptation seen in whales is not something that can only be specific to whales and that similar adaptions could be observed in humans. And let us assume that these mechanisms could be completely worked out.

Do you think humans would do it? Evolve themselves through specific DNA manipulation to eliminate cancer? Do you think they should do it?

We think they will! Not necessarily adopting the exact adaptations as seen in whales, but yes, we think that humans will commence altering their genomes in an attempt (misguided or not) to enhance themselves. From both medical perspective and even otherwise (such as enhanced performance).

Expected Human genome modification

Medical reasons will act as the primary justification for any attempts humans will undertake in evolving their genome further. Cancer eradication will very likely be an excellent argument for such move forward, considering the level of suffering realized as a consequence of this disease.

But that will require very sophisticated knowledge of genome function and manipulation that is currently not possible at such a complicated level. Prior to the cancer card being used as an argument for artificially evolving our species, eradication of other diseases that are governed by simple DNA alterations will be done first (including some deleterious heritable cancer predisposition mutation). For many of the diseases, this might not even require genetic alteration of the genome, simply careful reproductive planning.

Those conditions that are referred to as recessive, and require mutated input from both parents for the condition to materialize in the offspring, they can easily be prevented by simply making sure that parents do not combine such mutations in their children. This is referred to as carrier screening and is already taking place and in fact, advocated for families with history of serious impact recessive conditions. This is a non-invasive form of manipulating our genetic evolution and one could argue to a degree we already have been employing this technique forever based on the visible traits of how we select our partners. Now you can push it to a genetic level as well.

But not all diseases are recessive, and some conditions only require a mutation from one parent to materialize. Here too one could employ screening opportunities. If a parent is known to be genetically affected, the fertilized eggs can be screened genetically to ensure that the condition has not been passed on prior to implantation.

These are innocuous methods as they do not actually require DNA alteration of our species, only its analysis prior to implantation to determine if condition is present or not. While screening fertilized eggs might not yet be too common, screening our DNA for potential health impact of mutations is slowly becoming increasingly so. This step already starts determining what to watch out for.

The complex cases that would require actual intervention into our genetic make up to be eradicated, such as cancer, are in a different league. Here we would be talking about altering our species to bring forth these advantages as many changes in the DNA would likely be required, and ones that are not necessarily immediately obvious to be linked to disease. It will require a very thorough understanding of the underlying system being modified, not unlike what is currently often essential for successful drug deployment. It is quite possible that bizarre clinical trials will take place where volunteers will be genetically modified for such complex disease eradication and compared to equivalent control groups over their lifetimes.

Perhaps this might even become a necessity! One theory proposed suggests that with current advances that already greatly promote individual survival, such as medical advances, might mask the negative effect of mutations in our species to a point that accumulation of these deleterious mutations within our species is unrestricted. Now, instead of providing an enhanced genetic variability that could enhance the survival of the species, this unchecked build up of mutations in our species could lead to genetic deterioration instead, potentially putting our species at risk. If that would be the case, then genetic improvements that decrease the rate of mutations leading to cancer would also decrease the rate of germline mutations, or those in our gametes. That is feeding two birds with one seed (and throwing away the stone) - reduce the rate of cancer development that threatens individual survival, and reduce the rate of build up of mutations threatening the survival of the species.

The big potential problem, once we start tinkering, is it will most likely not stop with just medical advances in combating diseases. The second most obvious desired enhancement would be genetically modified increased longevity, a topic we have already explored. But we believe this will go even further into the enhancement of our powers: cognitive, physical, and the like. Humanity seems to know no boundaries and justification will always be found to execute the wildest plans people will conjure up. And it might have already started.

First human genome modification

In November 2018 the world learned about the first human babies born with artificially modified DNA performed prior to their birth. The tinkering into the human genome was justified as an apparent attempt to reduce the children’s chance of being affected with HIV virus, and yet was met with extreme worldwide condemnation.

But apparently the gene being modified, CCR5, whose function is not even fully understood, appears to be involved in the development of intelligence. This has previously been observed in mice already in 2016, where deletion of the CCR5 gene improved memory of mice. But since then, deletion of this gene has also been demonstrated to help in cognitive recovery of stroke patients, so it has direct benefits to humans.

This begs the question: could China have been covertly involved in experiments on human intelligence modification? Sounds far fetched but… there is a rich history of covert experimentation on human subjects, so have we learned any moral lessons from the past mistakes? Whether true or not, China now apparently has multiple genetically modified human beings that can be studied for the remainder of their lives for the impact of selected modification which also will include intelligence development. No one else can make that claim in the world.

And if it has already been done, how likely is it that it will not be done again?

But is all this ethical? It is easy to argue for medical advances and point to eradication of diseases caused by viruses such as polio or small pox as great achievements to help the well-being of humanity as a whole. The same achievements can be provided for genetically inherited diseases. But unlike the eradication of virally produced diseases, there is a difference here in that we are talking about tinkering with the DNA of our species, not fighting some virus. Once tinkered with, it can be propagated to subsequent generations, so the modification stays with us. We can easily think of at least two reasons against it.

First is the unknown consequences of altering our genome, a topic we breached before. And the Chinese babies with the CCR5 gene mutations might be a perfect example. Since the infamous announcement of the birth of the designer babies, this gene has received lots of attention. Studies since have also shown that individuals with deletion in the CCR5 gene are 21% more likely to die of any cause before age of 76, presumably due to increased susceptibility to other infectious diseases.* Infections that sadly might be more common than the HIV virus (with multiple such examples being scientific demonstrated). Will those Chinese designer babies ever be asked, hey, how comfortable are you with the trade of being smarter for dying younger? Would you take that? Super sad what was done to those kids.

The second reason is that not all the resulting conditions are detrimental to the well being of the afflicted individuals. For example people afflicted with Down syndrome or genetically based hearing loss . And at least in the case of Down syndrome, there is certainly a concerted effort to eliminate this condition through provision of screening opportunities to pregnant women early in pregnancy so that termination of pregnancy is an available option upon discovery of the condition. The Canadian Down Syndrome Society actually sees this fact as enough of a serious threat, this gradual cultural eradication, to have launched a campaign for Down syndrome individuals to be recognised as an endangered species by the International Union for the Conservation of Nature - a move that certainly stirred controversy. Willful destruction of a category of human populace through deliberate elimination of DNA responsible for their development. A form of eugenomics if you will.

What the Canadian Down Syndrome Society seems to be getting at is that we need to protect our natural diversity; otherwise we run the risk of losing the value delivered to us from that diversity. For example the positive attributes described by families with Down syndrome children – being very social, enthusiastic, and affectionate – which, if harnessed properly, and perhaps even emulated by wider society, could be very beneficial to enhancing the collective well-being. The point is that the value might not always be obvious, so we should not be so quick to come to conclusions of what should be eliminated.

But now that Pandora’s box has been opened, human genome modification seems inevitable. This could be to meet societal demands, or military demands. In a dystopian future the tweaking of our genetic code to create designer babies that are more intelligent, with increased strength and endurance, enhanced power of our senses, less prone to diseases, longer lifespans, shooting lasers out of our eyes could be the norm. Just kidding about that last one, well, at least that probably will not be a genetic accomplishment.

Luckily, we are nowhere near the technology for designer babies at the moment, and hopefully we will have ample of time to think about the potential consequences of genetically evolving ourselves into the new and “improved” species - Homo “oh-crap-I-thought-this-was-gonna-be-better” insanus. Even for such high profile advantages as eradicating cancer development (and a nice whale blowhole to go with it).

For now, happy genome sequencing and wise learning.

*This scientific article has been retracted in October 2019. Please see "Invited posts" side bar for more information.

This article has been produced by Merogenomics Inc. and edited by Jason Chouinard, B.Sc. Reproduction and reuse of any portion of this content requires Merogenomics Inc. permission and source acknowledgment. It is your responsibility to obtain additional permissions from the third party owners that might be cited by Merogenomics Inc. Merogenomics Inc. disclaims any responsibility for any use you make of content owned by third parties without their permission.

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