An ultra-sensitive on-off switch helps axolotls regrow limbs
scopeblog.stanford.edu
scopeblog.stanford.edu
Genetic information is code - code that has been written over millions of years. Nature is full of such wonderful programs and hacks. We don't yet know how to write even the simplest one, or even know about most of them. Yet, we're turning a blind eye to the current destruction of biodiversity and not thinking twice about it.
I don't understand why the Hacker News community isn't more interested in biodiversity loss, or why articles about climate change and biodiversity loss are not welcome here.
We're in the sixth mass extinction event, defined as a 75% loss of species, primarily caused so far by animal agriculture or, more precisely, by our food preferences. This situation is soon to be worsened by climate change.
But when someone mentions veganism around here, all those hackers flag his post to oblivion.
What makes all those javascript frameworks so important, and the code created by nature unimportant?
https://www.scientificamerican.com/article/biologys-beloved-...
Biology's Beloved Amphibian - the Axolotl - Is Racing toward Extinction
https://daily.jstor.org/the-race-to-save-the-axolotl/
The Race to Save the Axolotl - when an axolotl loses a limb, it regrows, and nary a scar remains. But this incredible creature is on the brink of extinction.
The first robust count of axolotls in 1998 estimated that around 6,000 animals lived in each square kilometer ... in 2015, he only found 35 per square kilometer.
The axolotl is the world’s the oldest self-sustaining laboratory animal population.
But it is unknown how long researchers will still be able to work with the axolotl: Like many lab animals, they are highly inbred, which could threaten their survival. To measure how small a gene pool is, scientists use an “inbreeding coefficient:” identical twins have an inbreeding coefficient of 100, completely unrelated individuals a coefficient of zero. For healthy growth, a captive population should have a coefficient of 12.5 at maximum. The notoriously inbred Spanish Habsburgs had a coefficient of 20; the coefficient for axolotls is 35.
https://i.cbc.ca/1.4204289.1499983814!/fileImage/httpImage/e...
Countries should work towards stabilising their populations first otherwise it's all for naught.
The population growth is already starting to decline; for example, Europe is already experiencing a decline, the population growth in the US has recently flatlined.
https://www.census.gov/library/stories/2021/12/us-population...
U.S. Population Grew 0.1% in 2021, Slowest Rate Since Founding of the Nation
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393076/
Major Trends in Population Growth Around the World
https://www.pewresearch.org/short-reads/2019/06/17/worlds-po...
World’s population is projected to nearly stop growing by the end of the century
> overpopulation is the root cause of all this yet an incredibly taboo issue to discuss
The root cause is overshoot. Climate change, resource depletion, deforestation, loss of biodiversity, pollution, overpopulation, soil erosion, and overfishing are all but symptoms of ecological overshoot.
https://www.eurekalert.org/news-releases/917471
Feeding 10 billion people by 2050 within planetary limits may be achievable on plant-based diets.
https://www.mdpi.com/2071-1050/14/21/14449
How Compatible Are Western European Dietary Patterns to Climate Targets? Accounting for Uncertainty of Life Cycle Assessments by Applying a Probabilistic Approach
“Without concerted action, we found that the environmental impacts of the food system could increase by 50-90% by 2050 as a result of population growth and the rise of diets high in fats, sugars and meat,” he continued. “In that case, all planetary boundaries related to food production would be surpassed, some of them by more than twofold.”
https://pubmed.ncbi.nlm.nih.gov/26231772/
The consumption of animal-sourced food products by humans is one of the most powerful negative forces affecting the conservation of terrestrial ecosystems and biological diversity.
A little math might help.
environmental_impact = number_of_individuals * mean_individual_consumption
We can either choose how to lower mean_individual_consumption, or wait for nature to reduce number_of_individuals forcibly. One way is better than the other.
Urbanization is often touted as the solution to habitat loss; concentrate people in high density urban areas to preserve the environment in the rest of the world. But in the case of Axolotl, they don't care for the rest of the world. They care about that specific piece of land that is under one of the largest metro areas in the world.
Not an expert by any means, but, as I understand it, Lake Texcoco National Park[1] is a fairly radical project (given the tendencies of urban politics) to move towards answering those questions.
> The main objective of this project is to reclaim the site to a green infrastructure in the valley of Mexico City. Rather than returning the area of an intact ecosystem from before the Spanish colonization, the key is to create a complete balance between infrastructure and nature.
[1] https://en.wikipedia.org/wiki/Lake_Texcoco_Ecological_Park
Veganism would help solve climate change (15-25% co2, also methane and n20), deforestation, pollution, soil erosion and overfishing (5 things out of 7 causing overshoot of the carrying capacity of our environment).
> because the tiny extent of their natural habitat is underneath what is now Mexico City
I'm aware.
I was responding to the question why I'm interested in these topics, and I never suggested that axolots' problem could be solved by veganism.
You're right that veganism would not (probably) help in this specific case, but that was not the point of the comment you were reacting to.
I do believe HN is full of intelligent and compassionate people. Perhaps it's compassion fatigue? (Too many horrible things happening, can I even make a difference through my individual actions?) Maybe we just needed you to make a good analogy, to illustrate the problem?
Thanks for making "code written by nature" comment. Knuth also agrees that bioinformatics has many more fantastic problems than computer science because its much much older.
I was in awe of planeria when I first saw it regenerating from its parts first time.
Veganism will never save us there.
It's because meat tastes good. That's literally all there is to why we aren't all vegan. Humans will not voluntarily give up one of the nice things they currently have access to and enjoy. Nobody cares about delayed indirect consequences on a planetary scale. Our brains aren't wired to think that way, since it provides no instant gratification.
If someone came up with a novel way to create a meat-like material that actually tastes as good, without involving inefficient animal farming, it will be a much more successful approach at solving this problem.
Plenty of people have, somewhat nullifying your comment.
On a finite planet with 8 billion people, to feed everyone the "western diet," we would need 2-5 such planets. It's simply not longer possible.
Veganism grows very fast, though. It's already starting to influence meat and dairy sales, enough to make some producers very nervous (wood milk ads, for example).
---
https://www.youtube.com/watch?v=ao2GL3NAWQU
The Secret Reason We Eat Meat - Dr. Melanie Joy
https://www.plantproteins.co/vegan-plant-based-diet-statisti...
As many as 6% of U.S. consumers say they are vegan — a 6x (500%) increase compared to just 1% in 2014.
U.S. retail sales of plant-based foods have increased 11 percent from 2018 to 2019, hitting a plant-based market value to $4.5 billion.
This is one reason why the rise of meat-like alternatives that nevertheless taste like meat are one of the most subersively impactful ways of turning someone vegan. I suspect once we as a species transition fully to lab grown meat, we will all basically be vegan. But the reason why so few people are vegan these days (out of the overall human population) because it is simply less convenient than eating meat, given that we like the taste of meat. There really is no alternative currently that still satiates people's demands for the taste of meat.
I wish... there are many obstacles to implementing that on the scale and timeline needed. I worry we don't have time to wait for that, while we already have plants that could sustain us completely and easily (82% of calories, 63% of proteins).
https://ourworldindata.org/land-use-diets
> it is simply less convenient than eating meat
Tradition, culture, convenience, taste. The only reasons.
> There really is no alternative currently that still satiates people's demands for the taste of meat
It's starting to change. Plant-based alternatives for meat (junk food) are getting better everyday (at least where I live).
In the last years came new bacon and sausages, which my SO refuses to eat because they're "too meat-like".
Have an upvote for that line. Me like. It's how I think of it.
Most people are just employees in FAAG or some VC-funded firms.
And to be honest I don't even think most people here are informed enough to discuss biodiversity. I definitely am not.
Land clearing happens for ranching purposes, but is also happens for peanuts, coconut oil and all sorts of other products. Rice[1] is a cash crop associated with land clearing.
For example a practical sustainable diet for the world would be much more efficient if it included goat milk and meat, because goats can subsist off of marginal lands and foods which humans can't.
Ranching takes 80% of the agriculture land, 50+% pastures were forested in the past.
https://ourworldindata.org/drivers-of-deforestation#beef-soy...
Combined, beef and oilseeds account for nearly 60% of deforestation (majority of oilseeds are mostly used for animal feed).
> goats ... can subsist off of marginal lands and foods which humans can't
That's the typical argument of animal ag farmers. That land should be rewilded and afforested, to enable return of the wildlife.
Goats and grazing are a recipe for desertification:
https://journals.sagepub.com/doi/full/10.1177/09596836166704...
Blame it on the goats? Desertification in the Near East during the Holocene
https://grist.org/climate-energy/cattle-grazing-is-a-climate...
Cattle grazing is a climate disaster, and you’re paying for it
https://www.oxfordmartin.ox.ac.uk/publications/grazed-and-co...
Grazed and Confused?
> Veganism has nothing to do with biodiversity loss though
https://pubmed.ncbi.nlm.nih.gov/26231772/
Biodiversity conservation: The key is reducing meat consumption
https://www.unep.org/news-and-stories/press-release/our-glob...
Our global food system is the primary driver of biodiversity loss
https://phys.org/news/2023-04-climate-crisis-biodiversity-ap...
The climate crisis and biodiversity crisis can't be approached separately, says study
https://www.vox.com/future-perfect/22287498/meat-wildlife-bi...
The way we eat could lead to habitat loss for 17,000 species by 2050
https://www.nature.com/articles/s41893-020-00603-4
In terms of carbon sequestration and dealing w/ climate, it is clear that agricultural land use(especially land used for animal feed) is the largest barrier to ecosystem restoration. Potential for carbon sequestration is enormous (literally enough for the entire 1.5C carbon budget)
https://www.theguardian.com/environment/2018/may/31/avoiding...
Avoiding meat and dairy is ‘single biggest way’ to reduce your impact on Earth
Then just a quick dismissal of goats because it's devastating to your overall point if "vegan" isn't actually the solution and no answer at all to the existence of cash-cropping other then to say 'oh yeah it's probably animal feed'.
Really? Rice is animal feed? Give me a break. There's a reason no one takes vegans activists seriously - you're as loose with the truth and reality as any politician.
What's wrong with that? Show me a similar list of papers proving that animal agriculture is the solution for our problems, and I'll happily change my viewpoint. The problem is that no such independent and peer reviewed studies (can even) exist.
> Then just a quick dismissal of goats
Yeah, I think that grazing is extremely destructive for the ecosystems. Not when you've got a single goat or two, but at the scale yes. It's not a secret that previous civilizations had environmental pressures that contributed to their collapse, and overgrazing could be one of those reasons. A lot of those previous civilizations places are now deserts. Coincidence? I'd bet not :)
> existence of cash-cropping other then to say 'oh yeah it's probably animal feed'
We would need just a fraction of resources if it were not for pastures and the need for animal feed. It's not probably, it's for sure. Again, science.
> Really? Rice is animal feed?
I never said that. I'll give you this link/graph again:
https://ourworldindata.org/drivers-of-deforestation#beef-soy...
Rice is 5.6%, animal ag (incl. feed) 60%.
Or are you vegan because of a moral objection to eating nervous-system bearing animals for food?
No words and social media comments can describe the sheer amount of destruction animal ag. is causing.
I learned to appreciate the moral aspect of it later. Carnism is a helluva drug.
Let's fund this instead of shitcoins, layers of indirection around POSIX.
It seems very likely to me that our views are too reductionist, and the much of the key information isn't even encoded at the level of DNA as previously assumed.
The cells multicellular organisms are constructed from are all shockingly similar... "cells" are basically a solved problem for this type of life, and somewhat frozen in their functionality because major changes would disrupt the larger systems that they make up.
They are not. They vary greatly in structure and function.
Sure, of course the different multicellular eukaryotes vary, but the diversity is very low compared to what we see across all life, look at Figure 1 here for example [1].
I am looking at it from the perspective of the structure of the metabolic network, as this is my area of research. There is a huge amount of diversity in the fundamental structures of metabolic networks, types of metabolites and enzymes produced, etc. across all life, but from that perspective the differences between one multicellular eukaryote and another are slight in comparison. Multicellular eukaryotes have evolved very different behaviors, shapes, sizes, etc. from a relatively conserved biochemistry. When taken out of the context of an organism in cell culture, the cells are similar enough that their behavior under diverse experimental conditions can be predicted by nearly identical metabolic models, whereas you would see nothing of the sort with distantly related bacteria- the metabolism can be massively rearranged.
Levin's research begs to differ. He did successfully regrow an amputated leg in a frog.
This is the paper: https://www.science.org/doi/10.1126/sciadv.abj2164 and it clearly states they treated a frog (xenopus, a common model organism), which does not normally regenerate when it's an adult. The paper clearly states that they treated with a set of factors that they believe induced a developmental plan- implemented by the transcription of DNA, translation of RNA, and expression of proteins. The initial treatment was removed, and the effect continued.
Also there's nothing about ion channels in this- the factors they used must have been actively transported- they bind to protein receptors.
So from a high level they say they have figured out how to “speak” to cells in a sense and instruct them to start building certain structures. And they emphasize that they aren’t making any changes to the genome or manage any of the low level processes themselves.
The celular machinery and its goals are separate from genes and can be controlled without "touching genes".
All the cellular machinery ultimately derives from genetic regulation and protein expression. You can't make more of it wihtout making more mRNA, translating that to protein.
This is bio 101, basic stuff, unless I'm completely misreading what you're saying.
Does Michael credit Becker for any of his work?
Imagine if we can get to a world where the difference between not having health insurance and having insurance means either you wait for your body to naturally regrow a limb or your insurance covers a more quickly lab grown one.
Imagine a world where organ transplant wait lists aren't a thing.
Imagine a world where Ukrainian landmine victims are walking on new limbs.
We can have this, but instead our best minds are fucking around with optimizing web ads, or they're figuring out how to tweak assembly lines that shit out McDonald's Happy meal toys.
Limb regeneration is useful for more than just landmines.
Does the kind of comment you made really contribute to the conversation?
america moment
I'm not sure what's wrong with that.
> Yes I'm trying to frame it in terms the audience of HN can understand.
> I'm not sure what's wrong with that.
What's wrong is that it's orthogonal to the problem, so it risks creating a pointless discussion about health insurance instead of focusing on the technology. The key problem is the ability to regrow limbs is not yet within our technological reach.
Having (or not) health insurance won't get you another pair of legs if you walk on a mine. Maybe you'll get very fancy prosthetics, but it will not be flesh and bone.
In a world where this is known technology, even if the costs may initially put it out of reach of people without insurance, should it just be a gene edit AND we have the ability to gene edit like we now have the ability to 3d print, the cat will be out of the bag, and it will be like people buying 3d printers to 3d print guns in countries where gun ownership is forbidden, or people ordering drugs on the dark web: it may be illegal, but people with addictions (or here, without legs) may not really care about the legality.
Or they will just do a road trip to Mexico, like how it is for dental work.
Health insurance is rarely the #1 issue: I think even Europeans do similar trips when they want something immediately instead of accepting long waitlines or some procedures not being officially available in their country. The only difference is they don't go to Mexico but to Turkey, the Balkans or Eastern Europe.
What we need is more technology, and fewer legal limitations, like how it was pointed out last week about how the FDA risk aversion costs human lives in a way that's impossible (or extremely hard) to measure.
We're very lucky the Trump administration (and a few others around the world) decided to bypass the regular vaccine safety process during operation warp speed: regardless of what you think about Covid vaccines, we now have mRNA vaccine technology, which is already being tested for many other things.
Is that an accurate interpretation of your comment? What am I missing?
EDIT: done, also I see we may have similar opinions given how you submitted https://news.ycombinator.com/item?id=34327992 about 3d guns in Canada
We currently live in a wonderful technological future where we can transplant organs AND we still do not have universal health coverage.
The future will be very much the same, and material inequality will very likely increase in the near future.
From a humanist perspective the best we can do is empower individuals with endogenous technology that minimizes their dependency on rent seekers and the innate ability to regenerate limbs and organs fits the bill nicely.
Can we? I think a necessary step towards this direction is a complete genetic model of the human body, which we haven’t even the ability to compute until very recently (if at all).
I feel like we need to solve the bioinformatics thing before we’re able to gcc new body parts. Which I think is incredibly solvable, though ofc it’ll take decades.
PS: those adtech folks are destroying the planet by boosting consumption
An interesting question would be how long does it take a baby to gain the mass of a limb?
Another interesting question would be how fast can an adult gain weight?
Another interesting question would be if it takes a person 18 years to reach 6' and 160lbs and then they stop growing, how long would it take them to grow another foot or two if they didn't stop growing?
I don't mean to ascribe intention to nature, but rather state that social systems which get far enough for its members to discuss it freely on the internet likely converge on this feature.
One could argue that eternal life unlocks the next phase of a civilization, but I am unconvinced that humanity is even properly equipped for the level of technology we have today, much less tomorrow.
> I am unconvinced that humanity is even properly equipped for the level of technology we have today, much less tomorrow.
If you had 1,000 years to figure everything out, you would be more than properly equipped. Instead we all have to operate with this arbitrary 80ish years to just barely figure anything out and then most of us die before we can do anything with the knowledge. It is a horrible and unfair system. Imagine if Einstein were still around today and was able to keep building on top of the knowledge he had before. Surely in that time he would have gotten things done that the vast majority of people could not begin to imagine.
This sounds nice and idealistic on paper, but like a hellscape in reality. A ratio of 1% good people does not a society make.
Why would you want that? Sounds like a terrible society to live in. Imagine if Einstein still existed, sure, but also imagine if a hundred serial killers or Hitlers still existed.
I've heard it said that corporations solve this problem. Death doesn't serve this purpose any more.
It also prevents good people from remaining alive forever :(
(read the whole thing carefully)
> Axolotls, they discovered, have an ultra-sensitive version of mTOR, a molecule that acts as an on-off switch for protein production. And, like survivalists who fill their basements with non-perishable food for hard times, axolotl cells stockpile messenger RNA molecules, which contain genetic instructions for producing proteins. The combination of an easily activated mTOR molecule and a repository of ready-to-use mRNAs means that after an injury, axolotl cells can quickly produce the proteins needed for tissue regeneration.
From "Reactivating Dormant Cells in the Retina Brings New Hope for Vision Regeneration" (2023) https://news.ycombinator.com/item?id=35871887 :
> "Direct neuronal reprogramming by temporal identity factors" (2023) https://www.pnas.org/doi/10.1073/pnas.2122168120#abstract :
> Abstract: Temporal identity factors are sufficient to reprogram developmental competence of neural progenitors and shift cell fate output, but whether they can also reprogram the identity of terminally differentiated cells is unknown. To address this question, we designed a conditional gene expression system that allows rapid screening of potential reprogramming factors in mouse retinal glial cells combined with genetic lineage tracing. Using this assay, we found that coexpression of the early temporal identity transcription factors Ikzf1 and Ikzf4 is sufficient to directly convert Müller glial (MG) cells into cells that translocate to the outer nuclear layer (ONL), where photoreceptor cells normally reside. We name these “induced ONL (iONL)” cells. Using genetic lineage tracing, histological, immunohistochemical, and single-cell transcriptome and multiome analyses, we show that expression of Ikzf1/4 in MG in vivo, without retinal injury, mostly generates iONL cells that share molecular characteristics with bipolar cells, although a fraction of them stain for Rxrg, a cone photoreceptor marker. Furthermore, we show that coexpression of Ikzf1 and Ikzf4 can reprogram mouse embryonic fibroblasts to induced neurons in culture by rapidly remodeling chromatin and activating a neuronal gene expression program. This work uncovers general neuronal reprogramming properties for temporal identity factors in terminally differentiated cells.
>> Is it possible to produce or convert Müller glial cells with Nanotransfection (stroma reprogramming), too?
Muller glial cells and mTOR: https://scholar.google.com/scholar?hl=en&as_sdt=0%2C43&as_vi... :
- "Genetic and epigenetic regulators of retinal Müller glial cell reprogramming" (2023) https://www.sciencedirect.com/science/article/pii/S266737622... :
> A number of factors have been identified as the important regulators in Müller glial cell reprogramming. The early response of Müller glial cells upon acute retinal injury, such as the regulation in the exit from quiescent state, the initiation of reactive gliosis, and the re-entry of cell cycle of Müller glial cells, displays significant difference between mouse and zebrafish, which may be mediated by the diverse regulation of Notch and TGFβ (transforming growth factor-β) isoforms and different chromatin accessibility.
From "Fiber-infused ink enables 3D-printed heart muscle to beat" (2023) https://news.ycombinator.com/item?id=36894749 https://seas.harvard.edu/news/2023/07/fiber-infused-ink-enab... :
> In a paper published in Nature Materials, researchers from the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) report the development of a new hydrogel ink infused with gelatin fibers that enables 3D printing of a functional heart ventricle that mimics beating like a human heart. They discovered the fiber-infused gel (FIG) ink allows heart muscle cells printed in the shape of a ventricle to align and beat in coordination like a human heart chamber.
> “People have been trying to replicate organ structures and functions to test drug safety and efficacy as a way of predicting what might happen in the clinical setting,” says Suji Choi, research associate at SEAS and first author on the paper. But until now, 3D printing techniques alone have not been able to achieve physiologically-relevant alignment of cardiomyocytes, the cells responsible for transmitting electrical signals in a coordinated fashion to contract heart muscle.
Hydrogel and gelatin.
Regenerative medicine: https://en.wikipedia.org/wiki/Regenerative_medicine
Regeneration in humans > Induced regeneration: https://en.wikipedia.org/wiki/Regeneration_in_humans#Induced...
quote:
"It was a 180-degree flip when we realized that when an axolotl loses a limb, it actually increases protein synthesis despite the energy cost," Barna said.
questions:
what is the conventional wisdom on how limb regeneration occurs w/o increasing protein synthesis?
inferring from other passages, it seems like conventional research focuses on mRNAs, not actual protein synthesis. why?
As for focusing on mRNA- biologists study where the light is, not where it isn't, and mRNA is incredibly easy to study compared to protein synthesis. It's much easier to just convert that mRNA back to DNA and sequence it and get loads of identity and abundance information.