Turning stem cells into human eggs | Hacker News Reader

Turning stem cells into human eggs

conception.bio

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Some more details are in this MIT Technology Review article: https://www.technologyreview.com/2021/10/28/1038172/concepti...

More realistically, because the technology could turn eggs into a manufactured resource, it could supercharge the path to designer children. If doctors can make a thousand eggs for a patient, they’ll also be able to fertilize all of them and test to find the best resulting embryos, scoring their genes for future health or intelligence.

Better still you can do it iteratively. Take cells from one person and turn them into a few hundred eggs. Take cells from a second person and turn them into sperm (or conceivably the same person.) Fertilize the eggs with the sperm, grow them out to blastocysts, biopsy, and sequence. Pick the embryo with the most desirable genotype score, turn the rest of the blastocyst’s cells into sperm and eggs. Rinse and repeat. You’ll end up converging towards the highest genotype score possible given the parental material.

Edit: you probably want to use two embryos in each round to avoid a local maxima. I’m sure someone will work out the math when the time comes.

All that work, when you could just print the optimal (given current knowledge) genome? [1]

[1] https://www.scientificamerican.com/article/whole-genome-synt...

I’d guess synthesizing a fertilized egg from scratch is further away than in vitro gametogenesis. Could be wrong of course.

Yes. That would be the day. I would love to have many children but I hate the notion of pregnancy. Once we can also grow them in labs I think it would be really great day for humanity. You could ship only embroyos to Mars and then let them grow into babies. (You will still need people to take care of them but we can ship only few hundred people with few million embroyos to colonize a distant planet.

Totally agree. The current state of gestation is untenable. The child-bearer is sick for nine months and pretty much incapacitated for a good portion of that towards the end. Their lifestyle choices can cause harm to the fetus. At the end of it all, they face a significant risk of death.

In-vitro gestation is probably not that far off technologically - we’re already very close with sheep (there was a very successful artificial womb experiment there) and the age of viability keeps getting lower. I hope that regulators are willing to take the leap to human trials so we can finally do away with pregnancy for those who want to avoid it but still want children.

The current state of gestation was the same state as of 10,000 years ago. I don't know how you can term it as untenable.

I wouldn't be so optimistic for lab-grown humans. If we are going to be selecting for the best physiological characteristics, we will inevitably end up with a far more homogeneous species. That, apart from all the genetic restrictions the powers that be will create in such an environment.

I’m not suggesting we select for physiological characteristics- I think eugenics is a very bad idea.

I googled the word untenable and I misused it. I just meant bad. Pregnancy is sucks and has always sucked. Most of the world was shitting in its own drinking water supplies until recently - pretty bad. But we invented plumbing and fixed it. I think humanity should do the same thing but for pregnancy.

300 adults to take care of 3,000,000 million kids and maintain the colony. Talk about overworked parents.

300 adults have to take care of may be 600, those 600 can then take care of 1200 and so on. Thought this forum was for folks with basic intelligence.

that solves the genetic bottleneck, but how do you solve the cultural bottleneck? you can send tons of media very compactly but that's a shadow of what you get living in another active culture.

Colonizing mars would be pretty much like Colonization of USA minus the genocide of natives.

The poorest and hated folks would be the first to go to mars, (think of illegal immigrants in USA, both democrats and republicans might agree to give citizenship of their relatives if they volunteer to go to Mars) these people would eventually build their own civilization would be envy of earth.

From the MIT Technology Review article...

>Some researchers sensed that the young entrepreneurs were in over their heads. The science of in vitro gametogenesis is dominated by a small cadre of university research groups who’ve been working on the problem for years. “When I talked to them, they had no clue, absolutely no clue, how to start a project,” says Albertini. “They were asking me what kind of equipment to buy. It was ‘How would you know if you made an egg? What would it look like?’”

To be honest, this was my first thought. I don't work directly in the field, but in a tangentially related field at an R1 research university, and I read through their research team and definitely got the sense that they were... certainly ambitious.

Obviously, I'm always in favor of more research in transformative technologies, in mostly whatever form that takes; but I do wonder about venture capital as the model for this type of research specifically.

Oocytes are one of the most difficult cells to engineer as well... The mitochondria in Oocytes are turned off from birth because otherwise reactive oxygen species will damage the mtDNA. One would have to use CRISPR to re-build the mtDNA, use telomerase / crispr to get the telomeres to exactly the right length, fix any mutations within the genome, etc. There are many many technical challenges to overcome, requiring further development of multiple immature technology stacks, and the bar is much higher than it is for mice since you would want a baby with the cellular metabolism profile of a 30y/old.

My cousin is an Ob/Gyn who was chased to the Midwest by the high cost of malpractice insurance for those who deliver babies. I can't imagine what the liability would be for something like this but I'd imagine you'd need both insurance and an ironclad waiver.

This raises an interesting point in general in any area where consciousness is taking more control over things that have always been subject to unconscious nature.

In this case, when natural conception results in deformity, genetic illness, or just generally unfit offspring, there's no one to blame. I suppose you can get mad at God, but we have yet to figure out how to sue them.

But when human actors start making choices that nature previously made, suddenly, we have someone concrete to blame when things go wrong, even if things go wrong much less often and less severely.

> I suppose you can get mad at God

Do you think God has sovereign immunity?

No. It's just super hard to subpoena someone who doesn't exist.

> I suppose you can get mad at God, but we have yet to figure out how to sue them.

That is actually a plot of a Bollywood film "OMG: Oh my God" where after an earthquake demolished the protagonist's shop and denied insurance payment due an "Act of God" clause, he sues God in court.

Haha. Seems like a "Bruce Almighty" kind of film.

Millions of same-sex couples may benefit from this research in the future if it helps make it possible for them to conceive (directly biologically related) children.

EDIT: Oh gosh, it's right there in TFA, that's what I get for skimming instead of reading deeply. All I saw were comments on the ethical implications of the biology work when I commented.

That's explicitly mentioned at least two times in the article as a primary motive of the founder.

It's in the mission statement at the top of the link:

> and potentially allow male-male couples to have biological children.

Of course they'd still need a surrogate to gestate the baby. Which ain't cheap.

https://jpia.princeton.edu/news/lessons-ukraine-shifting-int...

And it’s getting more expensive, because the number of women who want to be surrogates and who are also not suffering from abject poverty is low.

Until we perfect artificial wombs.

I wonder if it would make sense to use a surrogate to gestate the very early stages, and then transfer the fetus to an artificial womb for the later stages. There would probably be many more women willing to do this since it's the later stages of pregnancy and birth that creates the most wear and tear on the body, not to mention emotional trauma with immediately losing the baby you carried.

Hell, even women having their own babies might choose this route if it becomes feasible, like many preemptively choose c-sections now.

NICUs are basically artificial wombs that can keep a baby alive starting at a minimum of 22 weeks, out of 40 weeks for standard gestation.

The minimum age, cost, and risk of NICUs is just going to keep dropping as the tech and experience improves.

The problem creating demand for later-in-life fertility services for women is that the current structure of our society heavily penalizes women who don’t career-optimize during the years in which child-rearing would be (physically and mentally) least taxing and difficult. Long-term, I suspect the best answer will involve changing this structure rather than relying on complex medical interventions.

One scheme I think might make sense for the modern life trajectory is to have child-rearing skip a generation. This has a lot of medical, social, professional, and economic upside, and I suspect it more closely mirrors the way humans evolved to manage family groups.

You think pre-historic humans skipped generations?

More like the older people would probably be less likely to be out hunting elk or whatever physical activities and more likely to be watching the children. I doubt it would have been codified or anything.

I still don't understand the distinction you are making. At first I thought that you meant that literally a generation would not procreate. But now I think you are trying to say that young adults would not be doing child rearing. Are you suggesting that mothers would return to physical labor right after birth to defer child rearing to elders, or after breast-feeding? That mothers would somehow not be present as much as elders?

Correct - child bearing obviously continues as normal, but child rearing is delegated to the grandparents. This seems like an advantageous setup in both a pre-modern and post-modern context, where there’s significant value placed on women performing labor during the age of lowest-difficulty child-bearing.

In certain cultures rearing by grandparents already happens. I’d be interested in any longitudinal studies, though it’s hard to disentangle confounders.

That said, I don’t know that economic factors are important as social ones. If they were you’d expect to see something different in couples where the husband earns much more than the wife, but in my observation those women wait about as long as their friends in marriages where the salaries are more similar. The social context seems far more determinative.

To be fair, I would rather have me at 40 instead of 20 raising my own kids, instead of relying on my parents.

Why’s that? NB You’d also have your spouse’s parents.

Seems completely unethical to me. This would be more of an advancement for eugenics than anything else. Would people be scared of giving blood at blood drives? Could celebrities who don’t want to have children have cells taken from them and put through this process?

Eugenics has obvious issues when applied to mature individuals or groups, but I'll need convincing that the same moral position is warranted if we're talking about cells.

> We want to help parents have kids when it otherwise wouldn’t be possible.

Sounds to me like those eggs are bound to become mature individuals.

I could have been more clear, the distinction is semantic. I was referring to culling/sterilization to prevent reproduction in the sexually mature. Unborn persons are not adults, even if they will be.

Could you please stop creating accounts for every few comments you post? We ban accounts that do that. This is in the site guidelines: https://news.ycombinator.com/newsguidelines.html.

You needn't use your real name, of course, but for HN to be a community, users need some identity for other users to relate to. Otherwise we may as well have no usernames and no community, and that would be a different kind of forum. https://hn.algolia.com/?sort=byDate&dateRange=all&type=comme...

science fiction reference for cells eugenics: gattaca https://en.wikipedia.org/wiki/Gattaca

I always felt like Gattaca was unrealistically pessimistic. I'm unconvinced that the "best possible person" (if you grant such a thing even exists) is that much different from an average person.

It seems more likely that we would just eliminate some genetic diseases and cancers, and vain/rich parents would select for taller children. Most other differences seem to be too weakly correlated with genes we've identified to result in such a stark change to society. It's less like taking a bunch of dials tuned to 5 and turning then all up to 11, and more like increasing some dials from 5 to 6, and arbitrarily spinning some others because they weren't labeled to begin with.

> I always felt like Gattaca was unrealistically pessimistic. I'm unconvinced that the "best possible person" (if you grant such a thing even exists) is that much different from an average person.

To simplify the scenario to a single dimension, imagine how much different the NBA would look like if there were 10,000 Lebron James's and Shaq's being born every year. I'd expect it will take a few generations for sufficient predictive confidence to develop though.

That does get at my point though. While there obviously isn't a single "Shaq gene" or "Lebron gene", I also don't think we could reliably identify even a very large suite of genes that could be tweaked to result in increased "Shaq-ness" or "Lebron-ness". And beyond that, we certainly aren't anywhere close to identifying a "likes basketball" gene.

While I agree with the difficulty to impossibility of finding those specific genes, a whole genotype 'nearest neighbor' or other classification criteria is very interesting:

Considering that both the 'Shaq' phenotype and genotype are known, it wouldn't be too difficult[0] to rank 10,000 embryos per couple in terms of closeness to the 'Shaq' genotype. Then cross reference and weight the 'Shaq-likeness' ranking with the 'Jordan-likeness' ranking and the 'Gretsky-likeness' ranking. To me anyway, that seems like a recipe[1] for, statistically, dramatically improving one's offspring's odds at being a professional basketball player.

[0]Mathematically, anyway

[1]As a counter point, I'd expect to see this sort of thing take off in horse racing if it was productive. Big money and looser ethics.

There is a genetic mutation that allows a person to function normally on just 4 hours of sleep. A person who needs 8 hours of sleep in this world would probably always be behind the rest.

> I'm unconvinced that the "best possible person" (if you grant such a thing even exists) is that much different from an average person.

This seems like an absurd thing to believe for anyone who has a solid grasp of how evolution by natural selection works.

Or rather, it's absurd to believe that even a small improvement from the average isn't a HUGE advantage for a person's success in life and genetic legacy.

We bypass natural selection all the time. Some people are more vulnerable to certain pathogens. We give them medicine or vaccines to mitigate mortality. Natural selection would have us let nature take its course. Some people have religious beliefs that in fact route people towards nature or God determining mortality rather than medicine.

True, and there's nothing wrong with that. I think it's right and good to alleviate suffering where we can.

But we still stand to suffer as a civilization if the average quality of individuals doesn't improve, or even declines. Especially as the challenges we are capable of facing become more complex and challenging. Idiocracy comes to mind.

Then again, maybe our future is one where we develop sentient AIs that can independently keep civilization running, while humans can be left to degrade into a kind of pet that doesn't do any work and exists only for the benefit and good will of the AI.

We're still subject to natural selection and that's all still technically natural selection. The selection pressures have just changed.

natural selection is a cultural myth (like everything talking about an undefined "nature"), may be you'r thinking about evolution theory which is driven by reproduction success, but we already bypass it, living far beyond our fertility time :)

Agreed, though I intentionally conflate the two concepts as one. That is just my own personal view of evolution and natural selection. I for one would like to do an experiment where we pass a law allowing the removal of all warning signs, warning labels and guard rails both literal and visual.

Can you explain what you mean by "natural selection is a cultural myth"?

It is possible that we can "naturally" evolve to live far beyond our individual fertility, and humans did live long before civilization. Complex species like humans require a ton of knowledge and skill training. Old and experienced people can be incredibly valuable to a tribe if they can teach and care for the young, even if they can no longer reproduce themselves. It's not enough to just squirt out offspring. You need to invest in them so they can become successful enough to squirt out their own.

There are other examples like this. Like why various types of animals having warning calls for predators. These things don't make sense for an individual to develop, because the warning call actually draws the predator's attention to the individual making it. The best thing for the individual to do is stay quiet and hide. But the call increases the fitness of the individual's kin, so the trait survives.

Homosexuality might be another instance of this, the "gay uncle" theory. Similar to the reason we live long after fertility, a tribe with a minority of young non reproducing members can be helpful for taking care of and training the children.

It's called kin selection, https://en.wikipedia.org/wiki/Kin_selection

> It is possible that we can "naturally" evolve

there is no doubt on that, we're evolving, we're even able to trace some minor genetic evolutions over the 7k last years. but the cultural myth of "natural selection" or "naturally" evolving is in the question : what is "natural" and by extension, what is'nt ? kin evolution or social behaviors always end up as reproduction success, and the failure to do so, "naturally" or "artificially" end up in extinction, that's all. there is nothing specifically "natural" or "artificial" here. when talking about genetics the involved time scales badly fit cultural consideration like thoses. it is not less "natural" to gain reproductive success by genetic intervention than without, unless you are able to explain what is this "nature". or in other words : there is nothing to bypass unless you'r able to say/describe/explain what :)

Oh. Are you just saying that everything we do is natural? That the idea that we are somehow separate from nature is bullshit?

as long as "nature", being highly polysemic, is'nt defined, yes.

We aren't comparing the global average to the global "best person". We're comparing the typical outcome of a pair of parents with the best possible child those parents could have. Any effects on the outcomes of that child's life based on their genetics will be completely outstripped by how they're raised.

We also aren't discussing selective breeding, the same distribution of people would be pairing and having children.

After several hundred years I could plausibly see a stratification happening among those with the earliest and most advanced access to a technology like this. But given all of the above limitations, I think it would still be fairly limited.

> We're comparing the typical outcome of a pair of parents with the best possible child those parents could have.

I'm still not sure I agree with this. There's huge variability between the reproductive fitness of siblings, even excluding genetic illnesses and deformities. Might be intelligence, body type, attractiveness, etc.

The real problem I see is that qualifying the "best" traits might be impossible, because what's best is highly subjective to the environment and the environment that we all live in is constantly shifting and seems to be doing so at an accelerating rate.

The film Gattaca actually gives an interesting take on how this drive for "best" might play out. Those born into the privilege of having the "best traits" a) don't feel as strong of a need to struggle and overcome adversity, b) dismiss people who are "lesser" than they are, and end up surprised and unable to compete when they fall behind, and c) people who are "lesser" are filled with motivation and drive to prove themselves. I could even see some parents intentionally giving their child a minor disability to give them an edge over their "perfect" peers who all flit their lives away thinking everything will be handed to them on silver platter. Similar to how some parents are starting to realize how damaging massive trust funds and inheritances can be to people that receive them.

> Most other differences seem to be too weakly correlated with genes we've identified to result in such a stark change to society.

These findings were always driven more by politics than science.

Considering that the gap between currently existing "best people" and the average is already really really immense I have the opposite opinion as you.

it’s kind of disturbing, what about pair bonding? imprinting stuff like that at a young age, also will people grow cold towards these people or treat them as subhuman one day? i know this sounds negative but i worry that this will lead to some type of genetic war eventually.

it sounds sci-fi’ish/black mirror but honestly this seems like it will eventually happen, given how terrible some people treat others purely based on their eye color, height, skin tone etc. or what’s more, will this create people so perfect or beautiful that natural humans decide to worship them?

it already happens with celebrities. what if one of these people end up being extremely handsome and but extremely deceptive, like hilter meets [insert attractive person here], or add to that highly intelligent as well. people already have followed cult leaders for their charisma and honesty it doesn’t seem like society has changed enough to not do any of these things. for example this year/last year and the year prior was a already a good sample size of the madness that people are okay with being. anyways something for all of us to think about.

> Could celebrities who don’t want to have children have cells taken from them and put through this process?

Later, they will be sued for child support, of course.

> We want to help parents have kids when it otherwise wouldn’t be possible.

I'm going to preemptively address a point that I often come across when discussing that kind of topic: some are going to say that it's going against "natural selection", and it might undermine our future ability to reproduce naturally.

This is true. However, that also considerably expands the gene pool. Lots of children who would have died in the past are alive and well, have (grand)children of their own. This is great for genetic diversity.

And should our technology level suddenly regress to the stone age, the selection will be swift and hard, especially on the first generations. However, a more diverse gene pool makes for better survival odds.

If you want to contribute to genetic diversity, stop killing species. Right now what humans do is impoverishing the global biodiversity by burning and cutting down forests, building houses, streets and plants, polluting the seas, and being the one major driver for the climate getting warmer instead of cooler which would be the natural course of events. It's not like the human diversity is really challenged with ~8 billions humans being alive.

No Ethics personnel on the team?

Let me help you out with my automated bioethics bot.

val bioethics = function(proposal) { return "That's unethical"; }

My current level of cynicisms says that if you make someone a gatekeeper, they will use that power.

At minimum, to justify their salary.

> Our Mission

> We want to help parents have kids when it otherwise wouldn’t be possible.

What is so unethical about that?

Sure, that end is noble, but the ends don't always justify the means.

I don’t understand. Are you saying there’s some negative impact to allowing people to have children who otherwise couldn’t? What problems do you foresee?

I commented above a few of the issues I see. For example, would Lebron James (or any celebrity or person that has genetics that are profitable) be afraid of giving blood for fear of someone making Lebron 2.0 without his permission?

Or, literally some kind of false paternity fraud - such a child would come with certain legal rights and privileges.

That's not a new problem, in the USA even a man who is raped can be forced to pay child support to his rapist.

Obviously these child support laws are in need of reform.

Once humans (and other animals) can be created without parents being involved, there will be many ethical issues.

At what point do they attain human rights? At conception? At "birth" from an artificial womb? What defines "human" in "human rights"? (Can they knock out a few genes and make a sentient creature that is capable of suffering but not human? We have sentient non-humans suffering in factory farms already.) How will we prevent people/corporations/governments/religions from just deciding to create a bunch of people? What does regulation look like in this inevitable future?

>At what point do they attain human rights? At conception? At "birth" from an artificial womb?

This is hardly a new issue

The issue is currently limited to pregnant women.

> Are you saying there’s some negative impact to allowing people to have children who otherwise couldn’t?

In and of itself, no. I'm saying there's issues with some particular ways of doing so.

Personally, I foresee breeding programs for armies to create perfect soldiers. I foresee breeding programs for a permanent slave underclass. How can you not see the problems?

Governments buying soldiers from birth.

Obviously, but this is not so different from "regular" IVF for example. I'd have liked a little bit more explanation from GP about why these particular means go too far for them whereas current fertility treatments don't, instead of just throwing a blanket suggestion of unethicalness out there.

Because the road to hell is paved with good intentions. I can see many ways this spirals into something different.

Having Ethicists making these decisions is paving another road with good intentions.

“We do not take the development of this technology lightly. Our hope is that it will one day be used to bring healthy kids into the world, so we must hold ourselves to very high safety and ethical standards. Our plan will be to work closely with scientific, regulatory and ethical experts to ensure this technology develops safely and responsibly.”

From their homepage

How much does ethics even matter in this specific case? If they develop this technology and use it in a "maximally ethical" way, whatever that is, what is stopping the next person to get their hands on it from using it unethically? It seems to me that the ethics question was "Should we have this technology at all?" and not "What do we do with it?" and it's already been answered.

I agree with you completely - I was just trying to make the point that they claim to care about ethics and yet have no ethicists from what it appears.

if they ever succeed what would happen with the failure tests over the process ?

ethics aside, this is very, very cool, and very, very important research!

Reply on news.ycombinator.com