An extra-uterine system to physiologically support the extreme premature lamb | Hacker News Reader

An extra-uterine system to physiologically support the extreme premature lamb

nature.com

143 pointsartsandsci79 comments

In case you're wondering, the study's authors point out:

> Our goal is not to extend the current limits of viability, but rather to offer the potential for improved outcomes for those infants who are already being routinely resuscitated and cared for in neonatal intensive care units.

One of the biggest current problems with pre-term babies, the study notes, is a respiratory condition called bronchopulmonary dysplasia:

> an arrest in lung development secondary to premature transition from liquid to gas ventilation

So having the lambs (and, eventually, the preterm infants) remain in a liquid environment allows their immature lungs to continue developing, so that when they eventually transition to gas ventilation (breathing air), their lungs are able to function correctly.

>Our goal is not to extend the current limits of viability

In the interest of looking at thing squarely in the face, this can eventually (and therefore will) be used to extend the "current limits of viability".

It's important not to put blinders on because this has a very real impact on medical ethics. Is it ethical, for instance, to develop human embryos outside of the womb for convenience?

>Is it ethical, for instance, to develop human embryos outside of the womb for convenience?

Why not, assuming outcome is identical?

>assuming outcome is identical

Well sure, if we're assuming there's no problem, then there's on problem, but that's a bit ... circular...

Moreover, there's a mountain of evidence showing that prenatal environment shapes a large swath of physical and psychological traits.

That mountain of evidence mostly says that the in vivo prenatal environment is kind of... awful, though. As in, mother and foetus competing for nutrients with better maternal genes resulting in better defenses against the placental "parasite", and thus worse developmental outcomes; and better foetal genes resulting in better parasitic strategies to penetrate the uterine wall, and thus worse perinatal health outcomes for the mother.

I'd honestly stake >$10k, at this point, on the hypothesis that "growing children from embroyos in vitro, hooked up to an unlimited nutrient drip" will result in children much healthier than "regular" children, along every axis we can think of. (Presuming, of course, that we first figure out every micro-nutrient such a drip would be required to provide.)

What would happen though is eventually humans would lose the ability to naturally produce children.

What is "naturally?" At some point in technological progress, we need to build machines to have children. But go a bit further along the line, and maybe we'd find the human body automatically building the machine that builds the human body—in effect, laying eggs.

> At some point in technological progress, we need to build machines to have children

Why?

To outbreed the bad guys.

Er, sorry, I just meant that as "at some [early] point along the timeline of the possible developments in biomedical technology, the world would look like one where—at least early adopters—would need a machine to make children." I didn't mean to imply that there's some sort of imperative to go toward that point.

I've seen this in a bunch of movies but it just occurred to me that this may eventually happen to humanity. Birthing children is dangerous for the mother and child, and if given the choice many women may decide to have one "grown" instead.

There will be enough poor people that can't afford to have their children grown who will still be able to get pregnant.

But the continuation of the human "species" as a single entity would then assume/require class miscegenation to re-constrain the DNA from the in vitro-grown humans every few generations.

Otherwise, you'd now have two diverging human species, who might eventually not even be able to interbreed.

> Otherwise, you'd now have two diverging human species, who might eventually not even be able to interbreed.

It's a possible outcome in a few centuries. We might get one human species that would call themselves robot-overlords, those would be born in artificial wombs have artificially enhanced brains and have very prominent positions on Earth. The plebs would sleep on the stairs and drink their soylent green.

In any reasonably competent universe the costs would head towards zero.

That's a situation we already face. There's a line of humans who can only reproduce with IVF.

That's not a situation "we" as a culture/civilization/species face, it's a situation they face. The rest of us are perfectly capable of doing what our bodies are designed to do without doctors and scientists and other forms of assistance.

IVF babies aren't guaranteed to be infertile, they just have a slightly higher chance of it (because of selection bias in the parents).

My wife and I might well have babies via IVF because she can't get pregnant while on chemotherapy - but that doesn't mean we carry any infertility genes. She just had the bad luck to have some cells mutate into cancer.

What kind of infrastructure will this require? You'll need researchers to learn how such an object can be feasible, engineers to design it, people to construct it, parts must be ordered (some of which you might not even have the capability to make yourself), raw materials to make the parts must be mined, logistics must be done to make sure all of these parts are in the right place at the right time, enterprises must be constructed around building, selling, and marketing these devices.

What kind of power dynamics does that create? It involves the work of hundreds of thousands of people across every sort of country spanning the entire globe, many of whom hold a vast amount of power over you and the rest of whom have no obligation except financial to cooperate with you.

What exactly do we gain from giving so many people such vast power over us?

I'll bet against you. In fact, you inadvertently bring up the very undoing of your hypothetical bet when you say...

>presuming, of course, that we first figure out every micro-nutrient such a drip would be required to provide.

It's important to understand that these micro-nutrients and other chemical signalling-agents vary through time, and in response to such things as social environment, bodily movement of the mother, sensory input (sight, hearing, olfaction, the haptic senses, etc), occasional punctual stress, pleasure etc.

You're ignoring a huge source of complexity which is the systematic variation of these signals in response to the external environment.

Temporal dynamics of signaling pathways matter.

That's simply not the kind of thing we're even remotely close to being able to simulate in a synthetic system. Hell it's not even something we're remotely close to understanding.

Assuming identical outcomes, perhaps there's no issue, but you don't make the leap to identical outcomes without first progressing through outcomes that are probably worse to begin with.

Having just had our first child, I see a lot of room for improvement.

Identical outcomes is a low bar, in the long-term. So then the question becomes, is the short-term pain worth a much safer future.

One of the interesting things about humans is we're all born preterm, because of our large heads and narrow hips. So you can potentially extended gestation by another term.

Because, over the long term, it would reduce the selective pressure on the ability to gestate embryos in vivo, unnecessarily increasing dependence on technology.

We should try to avoid adding extinction to the list of consequences of the collapse of technological civilization.

Providing eyeglasses reduces the selective pressure for good eyesight.

That's actually something I worry about. I'm blind without my glasses, seriously, debilitatingly blind. With them, of course, I have better-than-perfect (for some value of 'perfect') vision. Should I have children? Is it ethical to do so? I honestly don't know.

What is your specific visual condition, if you don't mind my asking. Most people who I'd characterize as "debilitatingly blind" are lucky if they get any benefit from conventional eyeglasses, let alone "better-than-perfect" vision. I have a significant visual impairment myself (myopia, aphakia, and nystagmus) but I wouldn't put myself in that category.

Astigmatism and severe myopia. They're easily correctable, but without glasses I can't see more than about three inches from my nose. At normal viewing distances I simply cannot even see things other people can see, like letters, small animals or children &c.

Without glasses I'd be severely crippled. I've conducted a few experiments trying to move around in public without them, and it's beyond frightening.

Thanks for sharing, and forgive my sounding skeptical. I lucked out because the aphakia and myopia sort of cancel each other out, I still need glasses but they're primarily for near-distance. If I hadn't undergone cataract surgery as an infant, I'd probably have similar challenges.

My view is anything we have technology to cure we shouldn't worry about.

The more problems we can treat with technology the smaller the genetic search space becomes. evolution can focus just on the things we can't easily solve.

Can we keep talking about natural selection when may soon be able to edit our DNA, however?

How could "technological civilization" collapse, at this point? We have extremely well-distributed records—spoken, written, digital, and more—of all of our technology and how to use it. "We forgot how" worlds are just impossible at this point, unless we all get a disease that renders us incapable of tool-usage, reading, and speech. (At which point we're not human anyway.)

Although I agree that this is unlikely, until we are multi planetary, with at least four worlds/stations, this is not the case.

To restate that: what precise type of disaster would destroy "technological civilization"—presumably, all traces of it, because it's pretty easy to bootstrap back up†—but not the human species itself? Because that's the only case where humans not being capable of non-technologically-assisted reproduction would matter.

† See the book The Knowledge, and then consider a world where you have access to not only that, but also hard copies of the US Patent filing database, and 6 billion people to parallelize the bootstrapping process across. (And even that ignores the amount of "skipping ahead" that just the existing knowledge already loaded into people's heads would enable.)

Unless we all got amnesia at once, and all lost the ability to read (and those who can, to read braille), we'd be back to civilization before the generation was over—and back to simple longevity-extending practices like freezing sperm and ova long before that.

Technology onset: Grey-goo type scenario

Human onset: massive cultural shift to demonize knowledge.

It's happened before. It didn't wipe all technology away, but it slowed progress to a stand-still.

Do you think it'd be possible to choose to "demonize knowledge", in a world where we know that the only way to reproduce requires technology? I would expect our biological imperative to reproduce would get the better of that attempted social more quite quickly.

> To restate that: what precise type of disaster would destroy "technological civilization"—presumably, all traces of it, because it's pretty easy to bootstrap back up†—but not the human species itself? Because that's the only case where humans not being capable of non-technologically-assisted reproduction would matter.

In this case, any disaster that prevents the regular maintenance and operation of something like an advanced hospital for at least a few decades. This includes various types of war, energy crises, or the classic SF theme of a society stagnating to point where it can no longer build certain necessary technologies but only operate them.

There's also the related threat to societies/nations that require technology to reproduce. If they get in a war with rivals that can reproduce unassisted, they have extra weak points that can be attacked.

> † See the book The Knowledge, and then consider a world where you have access to not only that, but also hard copies of the US Patent filing database, and 6 billion people to parallelize the bootstrapping process across.

Any scenario where you have to reconstruct knowledge like that will likely be accompanied by strife that will prevent the reconstruction for a time (of decades or more).

Have you ever read A Canticle for Leibowitz?

One good solid exchange of nuclear weapons would do it. Once the manufacturing chains are broken and international commerce is halted, the collapse of civilization would occur pretty quickly. Even among the survivors bent on preserving knowledge, most digital records are on ephemeral media and the components of most electronic devices have a rated operating lifespan of only a decade or less.

Though somewhat dated, James Burke covers this quite well in the first episode of his classic "Connections" documentary. If anything, the situation is far worse now.

I think that's a fascinating concept for a hard-fiction author to go nuts with.

This is such a naive understanding of human history. The defining breaking point between the Homo genus and our ape ancestors is tool use 1-2 million years ago.

Those tools (and our subsequent use of fire) enabled us to dramatically reduce the size of our digestive tract. We get more energy from our food and spend less resources to digest it because of cooking, a technology.

We have thus evolved wherein we are not capable of surviving on an entirely non cooked diet that we would gather ourselves (the energy input to gather the food plus the energy to digest the raw food is too high -- cooking makes it feasible with our technologically adapted digestive tract).

Yet no one worries about us going extinct if we were to lose access to fire or cooking utensils -- because we can recreate them with ease.

Thus, the concern shouldn't be dependence on a technology but on the ease of us losing that technology. Nonetheless, I agree that this technology is much easier to lose than fire or cooking knowledge.

That's ... quite an assumption.

What if it's provably beneficial/better?

What if it isn't?

If it isnt it won't be used. No technology is adopted if it doesnt improve on current state of the art.

More interesting to me is the way it might change the abortion debate. If it were safe and not invasive for the mother to "donate" their not-yet-a-baby, is it moral to simply terminate the pregnancy? If there is a long waiting list of childless couples waiting to adopt, can donating an unwanted zygote be compared to postmortem organ donation?

You can't improve outcomes without altering the limits on viability, unless the technique happens to have a hard cutoff in utility at or after the point currently considered "viable". Viability is, after all, simply a characterization of where the combination of all relevant factors points to a certain level of expected outcome; improving any aspect of outcomes also expands viability, generally.

Just because you're doing X doesn't mean that you've set out to do X. Sometimes it's the goal, and not the action itself, that determines the ethical implications of an action.

No, the goal may determine someone's moral judgement of the actor, but the ethical implications of an action come from the outcomes (at a minimum, those that are reasonably foreseeable), not just the motivation.

To clear some confusion - they did not grow this lamb in the bag starting from conception.

The major limiting factor as to when it can be transferred to the bag is when the umbilical vessels are large enough to safely and efficiently cannulate. Oxygenation, nutrient delivery and waste removal are all done via the umbilical vessels through external devices.

The biggest road block in growing a baby in a bag fully ex utero would be the period before when the umbilical vessels are accessible. Before this time in utero, local mommy angiogenesis in the wall of the placenta serves the role of the umbilical vessels. Replicating this ex utero is a completely different problem.

I imagine they will figure out ex-utero in a couple of decades. Our understanding of genetics will improve too.

I imagine an underground bunker somewhere growing babies in tiny pods in 1000's. Those babies are in pods until full adult hood and an artificial process is injecting memories and skills into the brains of this pod babies.

Bonus brownie points if there is a pod cluster on an alien space. A billion super humans that land on earth who were all manufactured in transport.

Do they treat humans like we treat cows pigs and chicken?

> A billion super humans that land on earth who were all manufactured in transport.

This is a common concept in space-faring science fiction. It's one of the few 'practical' methods of sending a species with a human life span far out into the universe; with an ark filled with genetic material.

Although most stories have the humans being manufactured in the good ole' fashioned way during transport, a few franchises (warhammer 40k, mobile suit gundam, certain entities in mass effect I think, halo to a certain extent, etc) speak of body-assembly-lines.

(and in the case of Halo or Warhammer40k, yes -- the clones are quite often treated as expendable cattle.)

The placenta, however, would be a sweet target for 3D tissue scaffolding: grow the embyro on one plate and maternal on the other.

Yes, a different problem. But at the other end, it is already possible and even routine to raise fertilized ova into implantable embryos in vitro.

This new method however does fill a medical need, or at least shows the road to filling that need, meaning the problems of raising prematurely born infants.

Yes, but that does not require complicated structures like blood vessels. Embryos and ova are small enough to grow on cell culture in which diffusion is enough to provide oxygen and nutrients, with only the need to replace culture fluid every few days.

I have been reading the ["The Vorkosigan Saga"](https://en.wikipedia.org/wiki/Vorkosigan_Saga) and one of the consistent themes is the "Uterine Replicator". Sounds very much like what this could become in the future.

Not only is this book series great and very entertaining, I think it tackles some technology and social ideas that others in the genre do not.

In part this is the result of being written by a female, strongly feminist author who has the gender implications of sci-fi technology in mind.

On a separate note, I quite enjoy the way that she also explores the relationship of a "backwards" polity with a more advanced international community.

This is one of the most important and powerful work/research I have seen in over a decade, I'm literally at tears realizing the potential of this technology. Thank you so much for working on this, history will remember it and be thankful.

What makes you say that? What are some of the potential benefits?

Extreme premature births are the leading cause of infant mortality in the US. Even if the infant survives, they often have incredibly complex consequences that cause lifelong issues because, e.g. the lungs have not fully developed but are required to be used after birth.

It's possible that keeping extremely premature infants in an 'artificial uterus' could decrease some of these complications, especially those related to respiration.

What an amazing idea, pushing the boundaries of medicine...

In the table with experiment outcomes I see one lamb that survived for a while without mechanical ventilation... Was this the best outcome of the set? I couldn't make out if some of them were actually viable, and survived?

Couldn't understand, too, if their lives were terminated on purpose or all couldn't survive outside the environment. I'd appreciate any insight of it.

Sounds like the lambs were terminated immediately after coming out of the biobag, so the researchers could get a clear picture of how lung development progressed in the biobag without confounding factors coming from spending too much time in the open air.

It seems there was one individual that was kept alive post-"delivery," and it got tests and imaging six months later that confirmed that it was developing normally, but that the others were terminated so they could be autopsied. The assessments of, e.g., brain morphology, require sectioning the brain and examining it under a microscope.

While this is amazing and I'm certain it's going to save a number of lives.. Does anyone else get the sense that we're going to start seeing "farms" full of these bags in an effort to save time / money / stress on cows and sheep?

Or not to need cows and sheep any more for the reproductive part at all.

Milk comes from cows that would otherwise nurse their calfs, so you need to get them pregnant anyways. At least that is my understanding...

Remember that this technology does not cover the full gestation period. It only works starting at the edge of viability.

In order for an extremely premature lamb to end up in one of these bags, either preterm birth must be induced, or surgery must take place. Neither of those options is low-cost or without the potential for significant complications. You would likely end up with high rates of mortality and morbidity, and even if the BioBags were able to successfully sustain the animals, they would probably never be considered suitable for anything other than research.

There may come a day when a BioBag is able to cover the full gestation period, but even then, I highly doubt that it would be cheap enough for use with livestock.

This kind of research has been going on for quite a while:

http://www.nytimes.com/1996/09/29/magazine/the-artificial-wo...

http://www.hcs.harvard.edu/~hsr/wp-content/themes/hsr/pdf/fa...

Not discounting what you are saying; just wanted to add some more context...

Maybe my imagination it too dystopian today but I'm imagining artificial insemination to get a dozen lambs gestating and then you could C-section (or slaughter) the ewe after a few months.. That would take you from 1-2 lambs every 2 years to a dozen lambs in year 1.

That's basically how you get mice embryos at the moment. There are several companies that provide this service.

Super interesting research! I wonder: is there a limit on how long the lamb could be kept in this extra-uterine system? In other words, could the lamb be grown in this system until it's an adult?

CHOP regularly does top-notch work. This looks super cool.

In case anybody else is confused:

https://en.wikipedia.org/wiki/Children%27s_Hospital_of_Phila...

It is an amazing place - it has been consistently ranked as the best children's hospital in the US, though at that level it ends up depending more on specialty and who's doing the rating.

Brings Axlotl tanks to mind.

Wake me up when we can make women obsolete

this tech will render invalid the whole pro-life/pro-choice argument.

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