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3-D printed ovaries produce healthy offspring in mice (northwestern.edu)
140 points by Kliment on May 19, 2017 | hide | past | web | favorite | 51 comments

The prosthetic ovary consists of a printed scaffold that carries ovarian follicles (egg precursor cells), sourced from natural donor ovaries.

From the Nature article: https://www.nature.com/articles/ncomms15261

> Two mice with sham controls and seven mice with bioprosthetic ovaries were mated with males who had previously sired pups. Three bioprosthetic ovary recipients had litters of one or two pups each, while none of the sham controls had pups. Of the litters produced, at least one pup per litter was confirmed to have resulted from an egg ovulated from the implant.

This is a good demonstration of the point that artificial organs don't have to be the same as the real thing, they just have to be similar enough for the subset of tasks desired.

This is especially true for chemical (liver) or cell (thymus) factory organs. Just because the research community can't yet manufacture blood vessel networks needed for large organs doesn't mean they can't use fully or mostly functional organoids to produce benefits. It is possible in principle to patch a diseased liver with many organoids, or put thymus organoids into lymph nodes, and so forth.

This sort of thing will get underway in earnest if there isn't any real movement on the blood vessel network problem within the next few years.

I've been thinking the same thing for food production.

To me the whole in vitro meat burger thing is the wrong place to start. It's too hard to get taste, texture, and appearance right.

I wonder if it is easier to develop a bio 'machine' that produces chicken eggs. Imagine a world where eggs didn't come from chickens, but they came from a small toaster sized appliance on your counter top. What if this little box could produce eggs daily and you just needed to keep it plugged in and top up the protein/carbohydrate slurry reservoir periodically.

It doesn't matter what this tissue would look like, or taste, or smell. All that would matter is that it produced eggs.

Where does the protein-carbohydrate slurry come from? A farm?

Why not just let the chicken hang out on the farm in the first place, and eat the nutrients itself?

I can't help but feel like the whole in vitro food movement is missing something fundamental. Energy has to come from somewhere. You can make a solar panel that generates food. You can make that food resemble what would come from a farm.

But what's the benefit of having this solar food machine vs an expertly run farm a la http://www.polyfacefarms.com/? The farm makes a bunch of animals and people happy. It is a beautiful place. It is an efficient use of solar resources, probably more efficient than any machine we'll be able to build in the next 50 years.

To me there are two facts that both in vitro meat people and vegans seem to have a hard time accepting:

1) There's a limited amount of solar energy hitting the planet. It's either going to your food, or it's going to a wild ecology. It's a zero sum game, and animals either die, or are ecologically aborted in order for you to live. The only question is the number, and what life is like for the animals in your foodshed, whether you eat them or not.

2) For any given chemical process, there are already animals who are basically doing that process close to optimally.

Replacing an animal with a solar machine isn't actually any kind of kindness. They like existing. They enjoy it. Exterminating a flock of happy chickens and replacing them with machines is mean.

In the long term, it seems obvious to me that some combination of plant-heavy cuisine + expertly run, animal-included farms + ecologically sensitive hunting in wild spaces is the solution that gets you the most animal happiness per square foot of solar activity.

Maybe in vitro meat can help out during this period of excessive meat consumption culture, but I just don't see how the math works out in the long run. And there's still this whole hand-wavy "costs and energy will come down" thing which hasn't technically happened yet, although people like to talk about it like its a foregone conclusion.

Falafel sandwich for lunch, eggs benedict on Sunday, tempeh Reubans on Tuesday. That kind of diet keeps humans and chickens happy and is as close to absolute solar efficiency as I can imagine. I just don't see how a solar egg fits into that picture. Is there some other animal living under the solar panel that you prefer to a chicken? Solar farm snakes or something?

Because if you've see the kind of "farm" most eggs come from you'll know it's a horrific kind of place.

true, but consumer can choose with their wallet if they're so inclined, you just need the right incentives and at least full knowledge (because market ain't free without knowledge)

i.e. here in Italy you get a code to distinguish between happy chicken in a farm, free range chicken, closed range non intensive and intensive.

besides most of the 'horrible living condition' propaganda is aimed at the uneducated. of course in a large operation as huge as chicken farming there are gonna be mutated ones that get direct to waste - there's an estimate 7.2 billion chicken going around, even only considering normal genetic mutations there ought to be hundred millions yearly to go around to be used in those 'look these horrible sad chicken' videos, that are just a production of numbers and proportions more than actual cruelty (as compared to, say, foie gras)

consumers cant choose with their wallets.

you cant choose with your wallet to buy a model S because your wallet is not fat enough.

most consumers cant choose with their wallet to buy "fair trade happy animal farm" things because their wallets are not fat enough.

then there's even a better value in low price intensive farming, which is availability of food for the poor

I think your second point of the harder one. The optimization of a cow is not toward making meat. Rather, it is toward making more cows. In vitro meat does not need to have a digestive system. It does not need to have skin, or teeth. It does not need to avoid necrosis. All it needs to do is taste good and provide nutrition.

If the end goal is meat, I think there are a lot of places where gains in efficiency are possible.

I don't share your same values. The end goal for me is not just meat. I don't see the sun as just a think that's there to produce meat for me.

That's my point. I think you can get much more off of a square of solar exposure than just meat. And I think a cow is more than a meat factory. The cow's life is intrinsically valuable, and especially if we can have a relationship with the cow, it can make our lives more valuable.

Let's say you succeed in making a beef factory that's more efficient than an optimal cow pasture. Great, what are you going to do with the extra space? Make a movie theater? A theme park? A nature preserve? A cow pasture is a nature preserve!

I think a cow pasture is actually pretty nice. I don't think we need nearly as many of them as we have, and we could stand to eat a lot more plants, but I don't think replacing the cow pasture with a meat machine is really a step forward.

I'd hope it does avoid necrosis, though.

I agree with your ecological point but photosynthesis is a 1% efficient process and solar panels are easily available at 17%. So if you can gather the energy to perform the reactions to make the substrates to. Hold protein and carbohydrate in an industrial process, given the losses at each stage (some of which, as you identify, may be highly desirable - cow poo is a great fertiliser and there is a whole ecosystem supported in a hundred acres of land which could easily support 100 head cattle) your efficiency of generation would end up being orders of magnitude higher - quick fermi equation of 17x at solar conversion and guess at somewhere in the order of 50x for direct conversion to protein/cabs and you really do have a highly energy efficient process

That 50x number... you just made that up? Are you thinking about all of the different chemicals in food, or are you just imagining like, a dextrose factory?

I'm deeply skeptical of that number, but let's assume you can make your machine. Why? What good does it do? Why would you want to have a solar food factory when you can just live in an ecology? What's your vision for the Earth? Mine is that it's covered in healthy ecologies that sustain the plants and animals that live in them. It's not just about food, it's about how to enjoy being alive. It's about being connected with the plants and animals that sustain you, not for their sake, but for yours: so you might learn about yourself. Because we're just them, added together.

I don't think an egg protein solar factory that's attached to a VR pod facility is an improvement on a rainforest. I'm happy for the VR pod/egg factory to exist, but I don't think a world covered in them is anything but a dystopian future for us.


At no point did I say it was a good idea, you're projecting your fears of a technical dystopia upon my pseudo-scientific hypothesising. In fact, if you re read my thread you'll see that I say I AGREE with your ecological point - i.e. I want garden earth. Don't be careless at comprehension. I just said it appears practically possible to improve significantly on the energy conversion of sunlight into not just dextrose but the full biological stack - fats, amino acids and subsequently proteins.

Re the numbers, as I said that was my fermi equation method of getting to it. I know ballpark figures for most of the numbers so in true fermi fashion it's within an order of magnitude of the true figure. I don't care if you're skeptical of the figure, that's not the point of a fermi equation (unless you're the great man himself and get within 5kt of the yield of the trinity nuclear test by dropping a piece of paper)

> Where does the protein-carbohydrate slurry come from?


Why would it be easier to make a biological mechanism that produces whole and usable chicken eggs rather than a commercial-scale process for ground beef? It's not like they're trying to create a whole cow, and the ground aspect is easier than the texture requirements of something like a steak.

A chicken egg is a single "cell" grown over a number of weeks, whereas beef is composed of many tissues with varying cell types grown over several months.

I'm not a biologist, butcher or genetic engineer...so take my answer with a dash of seasoned salt.

EDIT - Corrected

Egg yolks are one of my favorite examples of things that look simple but really, really, really are not.

    Its structure is intricate, much like a Chinese set 
    of nested spheres carved from a single block of jade. 
    We see the first layer of structure whenever we cut 
    into a hard-cooked egg. Where heat gels the white 
    into a smooth, continuous mass, the yolk sets into a 
    crumbly mass of separate particles. The intact yolk 
    turns out to consist of spherical compartments about 
    a tenth of a millimeter across, each contained within 
    a flexible membrane, and so tightly packed that 
    they’re distorted into flat-sided shapes (much like 
    the oil droplets that egg yolk stabilizes in 
    mayonnaise; see p. 626). When a yolk is cooked 
    intact, these spheres harden into individual 
    particles and give the yolk its characteristic 
    crumbly texture. But break the yolk out before you 
    cook it so that the spheres can move freely, and it 
    becomes less granular.
    What’s inside these large yolk spheres? Though we 
    think of the yolk as rich and fatty, in fact its 
    chambers are filled mostly with water. Floating in 
    that water are sub-spheres about one hundredth the 
    size of the spheres. The subspheres are too small to 
    see with the naked eye or to be broken up by a 
    kitchen beating. But they can be seen indirectly, and 
    disrupted chemically. Yolk is cloudy because these 
    subspheres are large enough to deflect light and 
    prevent it from passing through the yolk directly. 
    Add a pinch of salt to a yolk (as you do when making 
    mayonnaise) and you’ll see the yolk become 
    simultaneously clearer and thicker. Salt breaks apart 
    the light-deflecting sub-spheres into components that 
    are too small to deflect light—and so the yolk clears 
    And what do the subspheres contain? A mixture similar 
    to the liquid that surrounds them in the spheres. 
    First, water. Dissolved in the water, proteins: hen 
    blood proteins outside the subspheres; inside, 
    phosphorus-rich proteins that bind up most of the 
    egg’s iron supply. And suspended in the water, 
    subsubspheres about 40 times smaller than the 
    subspheres, some of which turn out to be familiar 
    from the human body. The subsubspheres are aggregates 
    of four different kinds of molecules: a core of fat 
    surrounded by a protective shell of protein, 
    cholesterol, and phospholipid, a hybrid fat-water 
    mediator which in the egg is mainly lecithin. Most of 
    these subsub-spheres are "low-density lipoproteins,"
    or LDLs—essentially the same particles that we keep 
    track of in our own blood to monitor our cholesterol 

    Stand back from all these spheres within spheres and 
    the picture becomes less dizzying. The yolk is a bag 
    of water that contains free-floating proteins and 
    protein-fatcholesterol-lecithin aggregates—and these 
    lipoprotein aggregates are what give the yolk its 
    remarkable capacities for emulsifying and enriching.
    McGee, Harold. On Food and Cooking 
    (Kindle Location 2093). 
    Simon & Schuster, Inc.. Kindle Edition.

Please don't use code blocks (indentation) to quote text as it makes it difficult to read due to side-scrolling, particularly on mobile devices. A common method of quoting on HN is to prefix paragraphs with ">". You can also use asterisks to italicize text, which further highlights the text.

For example:

> Its structure is intricate, much like a Chinese set of nested spheres carved from a single block of jade. We see the first layer of structure whenever we cut into a hard-cooked egg. Where heat gels the white into a smooth, continuous mass, the yolk sets into a crumbly mass of separate particles. The intact yolk turns out to consist of spherical compartments about a tenth of a millimeter across, each contained within a flexible membrane, and so tightly packed that they’re distorted into flat-sided shapes (much like the oil droplets that egg yolk stabilizes in mayonnaise; see p. 626). When a yolk is cooked intact, these spheres harden into individual particles and give the yolk its characteristic crumbly texture. But break the yolk out before you cook it so that the spheres can move freely, and it becomes less granular.

It really is quite an annoying problem. Does anyone know why the owners of the site don't fix it? I feel like I could submit fixed CSS in a few hours.

There is also the part of "Please, insert insects, grain, live worms and lots of dirt in your machine". The problem is that powder processed protein could be more expensive than eggs.

In most basic form, isn't this what a pace maker is? Its not a heart and doesn't replace an organ but serves a functional purpose.

Finally, a possible solution to mouse infertility! I dream of a day when we can apply similar technology to humans and restore our dwindling population.

This is pretty insensitive. There's a lot of women that would love to have this technology available instead IVF or other options.

Or transgender men and women who would love a natural source of hormones instead of being resigned to pills or regular injections for the rest of their lives.

I'm not sure if that's a realistic hope. IANAB, but FtM individuals don't have a Y chromosome to work with, so I don't see how they could get the genetic coding to make testes work. You could use a biological male's DNA, but then you're trading hormones for anti-rejection pills.

I believe there's only one gene on the Y chromosome that really kicks off "maleness", the SRY gene, and it doesn't code for "testicles". The SRY gene just kicks off another process, the genes for which are present in everybody. I think there would still be a few steps left to create the seed cells, but that would be the case in trans women as well, as it seems the mouse pseudo-ovaries were seeded with the mice's harvested eggs.

I think there are genes on the Y chromosome which code for sperm cells, so trans men wouldn't be fertile with one of these testicle-chips, but even getting an endogenous source of hormones would be awesome.

Also, I'm not sure what "IANAB" means. I am not a "?"

IANAB = I am not a biologist.

I know there's SRY, and that does kick things off, but I also know there's a disorder where SRY translocates to the X chromosome. It causes otherwise XX individuals to develop as a male, but they don't produce testosterone and they require augmentation. That makes me believe that the testosterone producing genes are probably on the Y chromosome as well.

They may not produce sufficient testosterone, but testosterone production definitely occurs in XX individuals.

I will take you word for it. As I said, IANAB, but I thought testosterone production in XX individuals was near 0.

Testosterone levels vary wildly from person to person based on different conditions, but if you look around you can find reference ranges for men and women. The reference ranges for "Average" male and female adults from one source are:

  Avg. Adult Male   270 - 1,070 ng/dL
  Avg. Adult Female  15 -    70 ng/dL
So the top end for women is much smaller than for men, but it's not actually that far from the lower end of the male range. These are "normal" ranges, and some (otherwise) perfectly healthy men are below the bottom end, and some women are above the top end.

One might expect that ovaries don't produce testosterone, but in a typical healthy XX woman the testosterone in her bloodstream is produced by multiple parts of the body. So while an XX individual has low levels, there are multiple sources of it in their physical makeup, and it's at least theoretically possible you could increase production.

As far as estrogen goes there are some easy ways to produce it for an XY individual but the side effects are pretty severe :) Some otherwise healthy XY men have various genetic or other maladies that cause their body to produce unusually high levels of estrogen by itself, so assuming you could control for the undesirable side effects, it's clearly possible to do that too.

Personally, I don't think we're going to get a good handle on producing the hormones necessary for MtF and FtM trans people in the body naturally anytime soon, but it seems feasible to me. And it would certainly be helpful to cis people with unpleasant hormonal disorders.

Interesting, I truly had no idea women produced any amount of testosterone. Maybe it would be possible to ramp that up, and that would be a big development!

Re: Males producing estrogen, that's why I focused on the FtM in my previous reply. I knew it was possible for men to produce estrogen pretty easily, and I figured that's a much quicker path than the other way around.

Thanks for the information! It was truly informative.

Biologist I think.

I wonder how immunologically different the proteins on an artificial testicle that had the host's DNA aside from a single close-relative donor Y chromosome would be.

Along those lines it seems like an artificial pancreas could be made in a similar fashion and end Type 1 diabetes.

Although this also would be a huge boon for Type 2 diabetics like me, I thought that the pancreas generated insulin from the Islets of Langerhans (or something like that - IANAB), which sounds a lot more complex to replicate than a scaffolding to support egg precursors - but this may just be my ignorance. Is there any progress in this regard that you could point me to?

Pancreatic islet transplantation is already a thing. Islets are isolated and are introduced into the portal circulation. They embed themselves into the liver.

This is normally only done in patients with brittle diabetes because of the need for immunosuppression. This is a less complex procedure than a full pancreas transplant.

Thanks, that's informative. It doesn't seem like a 3D printing application, though, am I right?

An artificial pancreas can solve a lot more problems than just type 1 diabetes :)

I understand that perspective, but the #1 threat to our habitat is more inhabitants. It's hard to celebrate investing in a longshot technology that will ultimately exacerbate our problems. An individual's desires have to take a backseat sometimes.

A wider choice in family planning has never shown to result in overpopulation.

Overpopulation is almost always a result of the opposite.

I think only Eastern Asia really has this problem at the moment while some areas have the opposite.

Did you mean South Asia? China has gotten to the point where they are able to lift the one child per family policy, after seeing that it made very little difference when they previously relaxed the policy in cases where both parents were only children. Meanwhile, Japan has to resort to advertising and public service announcements to encourage young people to date due to their low birth rates and declining population.

No they don't.

Although it may sound cold to some, the truth is that people don't consider the global population count in regards to their concerns about growth. Population growth is usually something one considers in regards to their own country, and within that country it's not uncommon to consider one's own demographic groups primarily.

As an example, I highly doubt a Japanese person concerned about birth rates is concerned about the boom in Africa and other distant nations. Japan's population is going to decline drastically in the coming years, and they don't want lots of immigration to make up for it. It won't surprise me if they do something weird eventually, like the state paying women to have children the state itself would raise. Technology like this could open up even more strange doors.

Did you actually read the article? They are already thinking about applying it to humans. This kind of thing is almost always first tried in mice or other animals.

Also, the dwindling of our population is mostly due to societal changes like people wanting fewer children on average, or not finding a partner. Infertility is not the major problem, if you even want to call it a problem at society level (personally, it can very well be, of course).

I'm sorry, I was being sarcastic. (Rather irresponsible here, where it's justifiably uncommon.) Part of my sarcasm stems from the fact that non-human models very often do not translate well to human models, yet people are happy to celebrate health victories in those species. So I always think it's funny to celebrate any victory in the non-human model as though it were the goal. "E.g., cancer cured in rats! Finally! Those poor rats suffer so much." (Which brings up another issue about the actual suffering that animals endure for our immortality...)

Regarding dwindling population, that was sarcastic too; while human population growth has subsided in some areas, there's still a net explosion of humans on this planet. So that makes advances in fertility seem absurd when looking at the big picture.

Finally, for those of us who believe that humans are responsible for many of the ills we're seeing in our habitat, a logical conclusion is that more humans equals more problems.

I could tell that you were being sarcastic, but to me it looked like a typical response from someone who had only read the headline and didn't bother to click through and read at least some paragraphs from the article. (That's also why I was a bit more condescending than usual.)

> Regarding dwindling population, that was sarcastic too; while human population growth has subsided in some areas, there's still a net explosion of humans on this planet.

A declining growth rate (as we've had since the peak in the 1960s) is not a "net explosion".


>who still subscribes to Gould's discredited religion of blank-slatism and thus views Europeans and Africans as interchangeable.

Can you explain what you mean by this, please? I'm rather unfamiliar with Gould, or what you're trying to say here.

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