Axolotl Genome Slowly Yields Secrets of Limb Regrowth | Hacker News Reader

Axolotl Genome Slowly Yields Secrets of Limb Regrowth

quantamagazine.org

166 pointsdevy45 comments

In terms of gaining knowledge about the most relevant mechanisms in proficient regeneration, ARF seems important, and human ARF can shut down zebrafish regeneration [1]. That implicates the evolution of cancer suppression mechanisms as the reason why most higher species are not all that great at regeneration. Further, the dance between macrophages and senescent cells during regeneration seems highly influential in the quality of regeneration, whether the path to scarring versus the path to regrowth is chosen. This is found in the few examples of proficient mammalian regeneration such as the spiny mouse [2], as well as in salamanders and zebrafish. Salamanders exhibit much more efficient creation and clearance of senescent cells in regenerating tissue, for example. [3]

[1]: https://www.ucsf.edu/news/2015/11/251746/human-gene-prevents...

[2]: https://uknow.uky.edu/research/uk-researchers-identify-macro...

[3]: http://dx.doi.org/10.7554/eLife.05505

Based on your post and profile, mind if I ask a question?

How much further does this move us along on human regeneration as it relates to aging?

One would have to speculate; it is very unclear. Proficient regeneration seems like it would be a good thing to pair with restoration of stem cell function, but without the restoration of stem cell function it might not be too helpful.

As a general rule building a new human biology is hard. Even making tiny tweaks to our existing biochemistry, such as calorie restriction mimetics, is proving to be very challenging to do effectively and safely. Reverting to the known good youthful state on the other hand, is less complex. So I'd expect delivery of replacement stem cell populations to be a going concern long before adjustments that produce MRL-like or spiny-mouse-like regeneration in humans.

The feature of aging that proficient regeneration seems most likely to help with is the business of fibrosis (liver, kidney, heart, lungs), where regeneration runs awry into excessive scarring, and damage to organs like the heart that do not repair themselves. Equally, it might have to be controlled very carefully in organs where structure is important, which would limit any early application. Recent experiments with cell therapy in the heart in monkeys produced disruption of heartbeat because of the formation of biological pacemarkers outside the normal parameters, for example.

Thank you for taking the time to reply.

"replacement stem cell populations" You expect us to be able to revert the ageing process through stem cells? Any stem cells or specifically those of the host? How far off do you estimate (order of magnitude - 10/100/500 years?)

Red/Green/Blue Mars implies that it's within the lifespan of the current generation between 30 and 50.

I can’t help but feel a little bad about the mass amputation happening in these labs. Of course these are lower animals, but don’t we lose a little of our humanity doing this?

I am roughly equal parts excited and sad.

If they regrow it and it is painless... it is like removing the wool from a sheep.

Why would it be painless?

If the chances of dying after loosing a limb aren't very high it just doesn't make sense to develop (extreme) pain from an evolutionary perspective.

The chance of me dying from placing my finger on the stove is 0%, but I assure you the pain is severe.

You can't regrow your finger, and having working fingers would've been useful for survival for nearly 100% of your ancestors (the ones that had digits, that is).

There are lizards who lose their tails painlessly as a way to escape predators. If they felt pain in that situation, they might die, so it would've been selected out over time.

Yeah but regrowing limbs arrived after, it's built on top of their tetrapod ancestry. So it's entirely possible that pain is still here as a leftover from when it was a very critical condition.

They have a nervous system and DO feel pain, afaik the extent of pain they feel is not really known. A vet had to amputate a limb of an Axolotl I keep as a pet because he got into a fight with another one and he did not even finch.

But we kill millions of animals every day for eating and not because we need to, because we enjoy it.

This x 1000. The chicken, beef and pork you eat is probably treated worse than the mice in the labs.

If you at all care about Animal welfare then spend sometime researching into Animal farming. It gets dark pretty fast.

Most people don’t know how their chicken gets to the shelves.

I think this is more of a problem in certain parts of the world than it is in others—particularly those parts that receive large subsidies to increase production capacity so as to fuel discounts that would draw otherwise hesitant commercial activity.

This is an important question, but it's also been debated to death in the scientific community.

I have a friend who raises mice and then has to break their necks to euthanize them before experimenting on them. Another of my friends has to give mice cancer.

The former friend's lab has come up with life-changing treatments for muscular diseases, and the latter friend is helping to develop immunotherapy methods.

While it's awful to think about the price, it's important to think about why the price is paid and how much suffering can be prevented.

Another note: there are strict codes of ethics for how animals are treated in labs, so in most reputable organizations, the suffering is as minimal as possible (sometimes no suffering at all).

I really wish there was more oversight into Animals being used for testing.

Dogs are probably the most humane treated animals on the planet. I wish other animals got the similar treatment as well.

Would love to read some of those debates. Don’t get me wrong. I am in support for using mice for medical reasons.

In most countries, there is an ungodly large amount of oversight that goes into animals used in scientific research. The problem is that when the media reports animal testing, they skew the facts in order to make them sound dramatic, when in reality animal well-being is taken very seriously. Lab mice in general live much better lives than your pet mouse.

I didn’t know about this. I think my impressions have mostly come from movies like “planet of apes” so yes, they have been skewed by media.

If you care about animal cruelty, the real problems are habitat loss leading the starvation and habitat loss, followed by overhunting/fishing, followed by industrial scale agribusiness where animals are kept in horrible conditions for life, followed by shitty slaughter practices of some small scale farmers, then shitty pet owners, and waaaay down at the bottom is researchers who sometimes treat the animals poorly.

My friend has to take a rat and surgically implant an EEG electrodes to their brains, then put the processing unit in their belly, sew them back up. They typically die within 3 weeks or so, usually in a lot of pain.. but the researchers gather valuable data regarding their lifecycle.

With this method, they've been able to develop medication for a few diseases that save thousands to tens of thousands of humans a year (related to epilepsy).

Is it wrong?

Morally, more people are saved from this experiment, than the rats that gave their lives and far more "suffering" has been removed. On the other hand, that depends on your moral code. For me, it's about "what helps / makes me suffer less (short and long-term", so I think it's fine! For others, it's society, it's about the net positive for society - for them it's also fine. So, really, it's just those who empathize with the animals; which I think we all do, we just balance the perspective.

Personally, I couldn't do it, but I support the net gain to society.

> Morally, more people are saved from this experiment

That's not the biggest difference though. The elephant in the room is that animals are not humans, and they are worth less than humans. Else, why not use humans?

The article mentions planaria, a type of flatworm that can regenerate from a small piece of tissue. Many experiments with these animals involve cutting them up various ways.[0]

I agree that animal testing is integral to modern medicine, but I also agree with the parent that unnecessarily inflicting pain on even lower animals reflects badly on humanity. How many of these experiments are actually necessary? Do research institutions make the researcher convince them that the suffering is really necessary for medicine, rather than merely to satisfy some curiosity?

[0]: https://en.wikipedia.org/wiki/Planarian#Regeneration As a side note, the next section of the Wikipedia article, describes even more grotesque experiments.

I'd never thought they would actually assemble this genome. But put together the father of string-graph assembly (Eugene Myers) and a shitload of money (PacBio reads), and you get an assembly of a 32gb genome.

I just looked up how large the human genome is in bits (when the 4 bases are packed into 2 bits per base) the size of our genome is about 770MB.

Is the Axolotl's genome really 42.5 times larger than ours?

3 billion bp in a haploid human genome, 6 billion in a full diploid one. If you store the masked/unknown/variable ranges as annotations on the side, you can get away with close to 2 bits per base, as you suggested.

The axolotl haploid genome is 32 Gbp, which, in 2-bit encoding and ignoring masked bases, takes 8GB to store.

Axolotl, like humans, is diploid, meaning it has 2 copies of each chromosome.

That’s only about 10 times the size of the human genome. That being said, the complexity of a genome doesn’t scale with size. Many plant genomes are gargantuan but highly repetitive. The Kolmogorov complexity of a genome would better predict the complexity of the organism than a genome’s length would.

I wonder how that competes with the latest generation of Flash memory in terms of (physical) storage size and mass.

Though storage capacity is growing, it seems DNA still wins by some margin though

Flash memory has considerably better read/write speeds. It can also be read electronically instead of chemically. I don't think it makes sense to compare them.

It’s also error-prone. That being said, research in the area has been ongoing for years. For example, see [0].

[0] https://arstechnica.com/science/2013/01/mp3-files-written-as...

Wait until you hear the genome size of an onion (~16 billion base pairs, compared to human ~3 billion base pairs)

Fascinating animals, I keep several of them as pets. Sadly they are basically extinct.

The wild ones, yes. But the ones used in research and kept as pets are essentially domesticated and breed readily.

""" In 1952, a scientist named Charles Breedis injected coal tar and other known carcinogens into the arms of more than 500 newts — amphibians related to salamanders that can also regenerate. Only two animals grew tumors. Much more often, the newts responded by sprouting an extra arm. If scientists can crack how a carcinogen triggers that kind of regenerative growth, it would be “some kind of holy grail” for this area of research, Whited said. """

the article has an editorial tone around the distinction of lab vs. natural populations. it starts with an acknowledgement of the consequences of the lab on the animals (losing limbs).

hard to argue with the holy grail, tho.

Is there a catch to regenerated limbs? Maybe weaker, more cancer prone, or faster aging?

What I read once: when you're a wild animal in the wilderness, just scarring over the wound sometimes gets you back in action faster than regrowing the limb, and that's a survival advantage.

If that's the main reason evolution usually went this direction, then maybe there's not much downside for modern folks.

No? Fun fact: young children who have finger tips cut off sometimes can regrow them

https://www.npr.org/sections/health-shots/2013/06/10/1903854...

If the cut is clean, i.e. amputated by a scientist or vet there are no drawbacks to the regenerated limbs, but if they get into fights with other axolotls and the limbs are "half-off" they sometimes regrow deformed.

> they hardly get cancer

this is based on what, a few thousands individuals from that specie? on that kind of sample size humans also hardly get cancer, unless humans get really old. Not sure that statement can be substantiated.

The singular of species is species. The only person allowed to say "specie" is Vincent Price at the beginning of Alice Cooper's song "Black Widow", because he's a badass like that.

"specie" is money in the form of coins. Nothing badass about it!

According to American Cancer Society[1], 40% of humans get cancer. Of those, more than half are killed by it.

Further, half of all cancer cases are seen in people under 50[2].

Axolotls are amazing and unusual in many ways, and their cancer rates are one of those ways.

1. https://www.cancer.org/cancer/cancer-basics/lifetime-probabi...

2. https://www.cancerresearchuk.org/health-professional/cancer-...

An N of a few thousand should be high enough to have a fairly high confidence for the more common cancers.

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