Fertility 'breakthrough' as human eggs grown in lab for first time
independent.co.uk
independent.co.uk
1. Women will soon not need to go through the painful (and expensive) process of freezing eggs. (soon being when this is shown to be safe and equivalent to existing eggs). This will enable older women to have kids and solve some reproductive issues.
2. This will lead to a massive rise in availability of human eggs for scientific research, accelerating many fields. Lack of availability of eggs (as they get prioritized for other uses) restricts things like embryo research and other genetic analysis of human germline
3. Potentially this could lead to gay couples being able to have genetically descended children (obviously male couples here, but similar work on sperm is being done that could potentially enable lesbian couples to have kids too). This can be done as skin cells can be turned into pluripotent stem cells, and then maybe into the eggs (still some missing pieces in this process)
AFAIK, there's far more problems to solve than just this before older women in general can just have kids like they're 20 again.
Don't forget embryo selection: if you can create on demand several dozen or hundred eggs, the estimates of gains from embryo selection go from ~0.5 IQ points to 5-10 IQ points (and similarly for any other trait you might want to select for). 0.5 points is pretty trivial and no one will be beating down doors for that; 10 points, however, is a different proposition.
Perhaps more importantly, it's a step towards iterated embryo selection - fertilizing, selecting, then regressing to stem cells, and progressing to sperm/eggs - and doing so for multiple generations, getting +10 points each time, for largely unbounded gains.
(To save you the trouble, it's +1.16SD vs +2.51SD; the difference is actually much bigger than it looks because you lose so many embryos in the IVF process, so it's really more like X_1 vs X_196 or +0.56 vs +2.48SD, but to be more precise, you need to go into the weeds of PGSes and per-stage losses in IVF etc. But the order statistics are a good starting point.)
Of course, there's no way to definitively prove there's any potential to reach above that short of the existence proof of actually creating such people, but there's a lot of considerations which point to much more being possible: many complex traits have been pushed by selective breeding by many SDs, no one has ever been remotely close to genetically optimal and humans are minimally selected for intelligence, there's a large mutation load in terms of gene breakage, absolute measures of cognitive functioning like vocab size or digit span or reaction time generally show humans are nowhere near limits, brain scaling laws do not put humans at near any 0 marginal returns point, etc.
Even if there really is a bound at +100 and being able to increase IQ that much doesn't impress you for some reason, then you can simply spend your selection power on selecting for everything else... I shouldn't need to point out that many other traits are very important aside from intelligence.
Pulling numbers out of a hat here: if we could have even, say, 0.015% of the global population, approximately 1 million people, with an IQ of ~200, the effects on the evolution of knowledge could be staggering.
EX: Garry Kasparov is often said to have a sky high IQ but he tested at 135. He did however have an unusually good memory.
For that, consider the case of distinguished mathematicians who did not score high on IQ like tests.
We already have the tech to do selection as above but it is cost prohibitive to produce the number of embryos required to do it at scale.
Where you misunderstood was that this is selection, not modification.
We do not know which genes to modify specifically.
We can however, using commonality and statistics, select embryos for increased likelihood of increased intelligence based on a number of different phenotypes.
That's where my understanding ends but the link below has more.
The interesting idea was that we can repeat the selection process using the already selected for embryos - effectively skipping potentially many generations. As in, your kids could more correctly be your great great great great great grandkids.
What I want to know is how far you could theoretically take it before the statistical analysis starts to break down.
As in, can we get to twice as intelligent? Does our statistics / scoring even know what that might look like?
Could we be looking at human induced evolution?
[1] https://www.gwern.net/Embryo-selection#polygenic-scores-for-...
No to your second question; that being the case, your first question has no meaning.
We don't score intelligence with cardinal numbers, which would be required for "twice as intelligent" to make sense as a concept.
We actually do score intelligence with cardinal numbers if one wants to. As I mentioned in my other comment, a number of subtests have absolute scales with true zeros: digit span, vocab, and reaction time come to mind. Quite helpful for cross-species comparisons like humans and chimpanzees...
Or in other words, the fact that one person can be twice as fast as another person in the 100m dash does not make it meaningful to say that one person is twice as athletic as another. In particular, we don't expect the person who is twice as fast to also be twice as flexible or throw the shot-put twice as far, even if those can be made true statements for small (e.g. 5%) difference with appropriate multiplicative factors (e.g., a 5% increase in top-speed predicts a 10% = 2*5% increase in shot-put distance).
It does make it meaningful to say they are twice as fast, though. Which provides a basis for discussing improvements to the general factor. Since there are meaningful zeroes for speed or flexibility or throw distance, it must also be meaningful to discuss doubling the effect of fitness on them. Whether it works out in practice is the question, but it is meaningful and not nonsense.
I feel like something's gotten switched around here. We can measure reaction time with cardinal numbers. Check.
This makes it meaningful to talk about doubling or halving reaction time. Check.
We could attribute part of reaction time performance to the general factor of intelligence. OK... but this will be variable.
It's not obvious to me that if we allot responsibility for someone's reaction time scores among several factors, perform an intervention, get improved reaction times, perform the same allocation, and calculate that the contribution from g has doubled, that we can then conclude that the subject's g has itself doubled.
We want to measure that g has doubled, and we have no numbers for that.
If the effect of fitness on speed is small (as a fraction of absolute speed), then doubling the effect has little to do with doubling speed. If it's large (order unity), then we don't generically expect to be able to double the effect while staying in the regime where intelligence is well defined. These two notions of double are just completely different -- one is a derivative, one is a magnitude -- and it's a mistake to link them.
It will also mean a massive rise in the availability of human eggs for turning into embryos, which in turn will mean the ability to be much more selective about which embryos to to implant during IVF.
Currently egg harvesting is such an arduous process that embryos can only realistically be selected for viability and a handful of generally fatal diseases. When you are choosing 1 out of 7-10 embryos, you can't be all that picky. But between having access to hundreds of eggs, sperm obviously not being an issue, the ever decreasing cost of genomic sequencing, and the ever increasing knowledge of how specific genes relate to traits, parents undergoing IFV could start to apply many selection criteria. That wouldn't be genetic engineering in the classic sense, nothing would be available that wasn't in one of the parent's DNA, but it would get a lot of the way there.
Edit: If I was going to be beaten to the punch by anyone on this subject, I'm happy it was gwern.
We may be there soon, but we're definitely not there yet.
Cite? The research I found on this indicated that IVF children were exactly average, and IVF with use of sperm donors actually had considerably lower risk of birth defects.
https://www.ncbi.nlm.nih.gov/pubmed/29164811
If you're curious you can probably just stop by your local teaching hospital and ask for a copy of the 50+ page contract with all the informed consent details.
> If you're curious you can probably just stop by your local teaching hospital and ask for a copy of the 50+ page contract with all the informed consent details.
What a contract says is of little scientific value, unless one is studying tort law and the finer details of butt-covering.
> What a contract says is of little scientific value, unless one is studying tort law and the finer details of butt-covering.
They have actual statistics though if not references to the primary sources, so that was more the reasoning.
My point is that a congenital heart defect is something that should strike early, especially in childhood (and that's one of the usual ways to find out about it, kids dropping dead for no good reason, like after being lightly hit in a football game). If a doubling of defects can be detected, so too should a doubling of heart-related mortality. There's on the order of a million IVF kids annually in the USA alone; it's not possible for that to have gone unnoticed. So either their risk is the same as their non-IVF peers and such defects are just common among older mothers, or the defects are not actually serious (pace studies showing that things like cancers or spinal anomalies are common among healthy people, or, more IVF related, that many embryos discarded for chromosomal abnormalities turn out, when implanted, to work perfectly fine because the abnormal cells die or the embryo otherwise recovers during development).
Keep in mind that 93% of heart defects are detectable via an echocardiogram around week 24 of pregnancy. So I would imagine that in most cases where the heart defect is fixable then it's repaired, or else if it's not fixable but also not serious then the kid is just prevented from doing sports. Or else if it's serious and not fixable then pregnancy is terminated.
So I would expect the actual mortality to be substantially less than 2x. And given that heart-related mortality in children is extremely rare, I suspect it would be quite tricky to detect. Especially when you need to account for confounding issues like maternal age during pregnancy, ICSI use, etc.
Given that there are around 5,000 CHD-related deaths in children per year, and around 1.5% of babies are IVF births, we're talking at most 150 deaths per year instead of 75, probably less due to the reasons mentioned above. And once you start trying to take into account imperfect data confounding variables, it's hard to say whether having definitive proof one way or the other is even within the realm of science at that point.
In this view, it is scarcely surprising that parents would want to give their kids viable genetic information just like they want to give their kids a good home, healthy food and challenging education.
This desire to ensure the good of the kids is a strong force pushing humanity forward and I see no reason to object.
Unequal access to shelter, food, education or genetic techniques is a different matter. But our failure to ensure universal access to the spoils of a new invention does not imply that there is something wrong with the invention. The real problem is more like the lack of compassion for other folks...
So let's not throw the baby out with the bathwater.
I would actually argue that the latter (lesbian couple->kids) will become feasible first - https://www.theguardian.com/science/2016/feb/25/lab-created-...
What steps are missing? I'm extremely interested in this but I've had a hard time finding more information.
Depending on where you are, that's not really a problem. We did IVF, and we still have an embryo left over. When we asked about donating it to science, they told us not to bother because it would just be thrown away, since they already have too many in California (the embryos can't cross state lines apparently).
Under 35, the success rate for IVF is ~40%. Between 35 and 42, it's about 10%. After 42 it's about 4%. Each time you try it costs around 20k, albeit sometimes the first one or two tries are subsidized by insurance or state grants. And there are also all sorts of health risks to both the mother and baby.
So even if you can safely create unlimited eggs at a nominal cost, I don't see this having any practical effect on family planning. (Other than as a treatment for certain infertility issues.)
Given that it takes around two years to have a baby, pragmatically you're still going to ideally want to start having kids no later than 35 - 2 * (desired kids), at least for the foreseeable future.
This has many implications, not the least of which that the simplest way to reduce carbon emissions is fewer people.
Using strips of ovarian tissue removed in a biopsy, it
represents an advance on IVF (in vitro fertilisation),
where a mature egg is fused with a sperm in the lab and
the fertilised embryo is implanted.
For these reasons, there's lots of pressure to delay starting a family, and it's no surprise that IVF has seen increased demand. Some companies (i.e. Facebook) even provide their female employees a benefit that covers freezing their eggs. This is somewhat controversial, as some would argue that Facebook (and other companies, and perhaps our culture in general) should instead focus on reducing the professional cost of starting a family.
Therefore, these findings about growing human eggs could have great significance. I have friends grappling with this issue right now, so I understand how this discovery could be a great help to them. I hope that provides some useful context...
That's a pretty critical view of things. I think a more objective view is that motherhood is costly for the mother in time and attention, and generally reduces the time and effort she puts into her career.
Whether people operating in the business world should be encouraged or forced to give preferential treatment to mothers so that motherhood doesn't become a career disadvantage is an open question. One could argue it would be unfair to those women who choose to forego or forestall motherhood to dedicate more time to their careers.
Few professions are important enough to spare a passing thought over compared to the importance of raising children IMO.
I mean Facebook? Do people working there, for example, really think social data mining for advertising is important in some way? Sure, income is important, but people don't say they want to protect their income, they always talk about career progression (which is conceptually unrelated).
We've got plenty of people, making ways for people to sacrifice everything to a job without failing to reproduce seems pretty counter to any need.
Only a generation ago the median age of birth was like 23 and now it's 27 or so, but that doesn't account for the edge cases. A lot of women have careers now that they didn't have a generation ago and delay childbirth because of it.
Also, there are a lot of studies coming out recently that male fertility is 1/2 of what it was just a generation ago (we make 1/2 as much sperm as we used to). No one know why yet, they assume it's environmental or diet related.
Male testosterone production has been decreasing as well, at a population level. https://www.ncbi.nlm.nih.gov/pubmed/17062768
Also interesting to note that medical academia has been gradually lowering the requirements for what is considered a healthy testosterone concentration. Minimal acceptable bioavailable testosterone for a healthy young man used to be considered on the order of 500ng/dL, now it’s generally considered around 300ng/dL.
Now, the tech has gotten good enough, and the price -- while still out of reach for many -- is affordable for an increasingly large segment of the population.
TLDR: It's not being driven by an increase in demand, but rather an increase in supply.
With nearly 8 billion people on the planet, the answer to that is a resounding NO. Go and look at the charts...
- artificial uterus - check
- human factory - pending
And its not that lab meat is cheaper in a vacuum right now, more that huge meat subsidies (either direct, guarantees and insurances from the state, and allowing meat producers to externalize a huge portion of their water / pollution costs) hamper investment into lab meat that would exist in a purely free market. Traditional meat is just artificially cheap.
In contrast parent ju-st talks about artificially fertilising livestock, perhaps with accelerated growth.
In terms of ethics, the second procedures seems at least not worse than factory farming. The animals in the second one would need to live less long in order to produce the same amount of meat, and also you'd stop having some unwanted animals like male chicks.
However I really hope that lab-grown tissue becomes the standard for meat production.
- Alpha, Beta, Gamma, Delta, or Epsilon - negotiable
It's wonderful we can make a human egg and all, but we still can't figure out why babies die, so forgive me if we're still not that impressed by medicine, and think we're misallocating resources.
I get you're venting some pain here, but that's kind of looking a gift horse in the mouth. Modern medicine hasn't figured out every single mystery, but it's certainly impressive what we have figured out.
Studies on sudden infant death and pregnancy loss are actually few and far between compared to studies on helping older women with poor egg quality conceive. Both the friend I talked about and my wife and I are in our early 20s. The last 'breakthrough' with regard to stillbirth and late miscarriage was made in the 80s with the discovery of anti-phospholipid syndrome, but there has been no new conditions or treatments in the past 40 years. Most of this is due to a lack of research and funding, in comparison to infertility, which for some reason is incredibly well-funded.
I'm just saying we should question if we're actually spending our resources equitably.
There is. They’re medical geneticists. They’ve got relatively large departments at NYU, Brigham and Women’s, and NYP-Cornell.
It’s not under-funded, it just usually goes under the radar as “genetics,” rather than a clinical specialty.
Moreover, almost every study into the matter shows that the more pregnancy losses a couple has had, the less likely it is that any of them were due to aneuploidy, so again, genetics (while important for single miscarriages or stillbirchs) is an unlikely explanation for recurrent losses, unless a parent carries a balanced reciprocal or robertstonian translocation (which none of us do).
The MFMs that we have spoken with have all suggested various blood issues and some auto-immune issues which we are now being tested for. I don't see how geneticists (who are usually not doctors themselves) could possibly have the level of expertise to handle these cases.
I’m sorry I wasn’t clear - I meant Medical Geneticists (MDs) not geneticists (phds). That said, their work on these issues tends to be oriented to the basic science side, so that it can be applied as screenings and other genetic tests for couples in the future. Most Medical Geneticists are part-clinical and part-bench scientists; I don’t know of any that are purely clinicians. Their clinical side tends to be pre-conception screenings and genetic counseling.
It seems like what you’re saying you want is a medical specialty that deals in particular with individual couples that keep losing children, as though it’s a clinical problem.
Admittedly, there are some exceptions (eg, anti-phospholipid syndrome), but that already has a relevant specialist: OBs are supposed to identify that a patient may have it, and the relevant specialist (rheumatologist, usually, for the autoimmune stuff) confirms and treats.
Nevertheless, I think your focus on medical genetics is quite misguided. For example, we know several causes of recurrent stillbirth and infant death that are not genetic in nature. For example, NAIT certainly has a genetic predisposition, but the primary treatment is immune and hematologic in nature. There's no reason this would fall under a geneticists area of expertise, and given the rarity, it's not clear most OBs would know about it either. Several couples I've met in online support groups have had a lot of trouble finding a doctor knowledgeable enough in NAIT to properly treat their pregnancies (which are actually remarkably successful, when treatde). Given the importance that we ought to be giving to lives of young children, it seems that simply lumping known non-genetic causes with genetics is the wrong approach. A better approach -- in my admittedly biased opinion -- would be to have one specialty with a wide breadth of knowledge who could specialize in teasing out what may be causing any particular issue.
For example, it seems somewhat ludicrous to believe that a woman who loses several babies consecutively in the third trimester due to premature labor while the baby is still alive is being affected by the same pathology that causes another woman's babies' hearts to just keep stopping. Unfortunately, these distinctions are rarely made in studies.
And while OBs are the ones on the front-line of treatment, they're also mainly a surgical / low-risk specialty. There does need to be some specialized care for the higher-risk couples. Multiple studies in other countries (we're in America) have shown that simple supportive care (including heavy monitoring, constant reassurance, and dedicated clinics) increases the live birth rate in couples with recurrent stillbirth or other forms of pregnancy loss.
We live in the bay area, we have managed to make appointments with several specialized doctors, including the department chair of obstetrics and gynecology at one of the large academic hospitals here (after much consternation with the nurses on the phone). They have told us that they do not know. She also told us that she's never really seen too many cases of sudden cardiac arrest in mid-pregnancy fetuses. She did not send us to anyone else -- believe me, my wife and I would hop on the opportunity to find another doctor with relevant experience.
I’m gonna leave it at this: if you’re willing to take a trip, NYU has a dedicated repeat pregnancy loss center (Phone: 212-263-6359).
(And for what ever a strangers internet words are worth: I do earnestly hope that they or someone else succeeds in helping you.)
(I want to echo the good vibes here, too.)
Perhaps I haven't made my complaint clear. The doctors exist, but they aren't helpful.
We don't expect miracle answers, and realize medicine may not know, but it would be nice to have a dedicated clinic to work with you through it, or at least a doctor willing to establish a long-term relationship. I expect it would also help researchers formulate new hypotheses if they kept in contact with couples who are 'unexplained'.
We have been to three recurrent loss clinics at UCSF, Stanford, and the Mayo Clinic. There are doctors there who do research in this area, but if you don't have any of the limited number of conditions that they know about, they aren't helpful, nor are they willing to help you find clinical trials that may apply or willing to explore research with you or stick with you. I've read many brochures and websites that claim that the doctors will work with you to determine the cause of miscarriage, stillbirth, etc, but in our experience they work with you until they give up, then they don't want to see you anymore.
This is a bit different than other specialties. I don't have much experience with doctors, but I do have some older family members with chronic illnesses, a few with rare, unexplainable ones. In that situation, it's common for doctors to establish long-term relationships with patients and suggest clinical trials or research opportunities they can participate in. The approach seems different than what we've seen.
Once we're done with our next round of appointments, perhaps I'll call NYU. We have a few more appointments coming up with some more research doctors; hopefully, they will be more willing to keep track of our case.
I think part of the problem is that there's likely a large amount of problems that lead to stillbirths and SIDS, so it's hard for researching to get funding to study a very general problem. Most the time they need to have a clear purpose and idea of what it is they are trying to figure out. And in the case of IVF/embryos there has been a much clearer path for them to take.
Not saying that's right, but it's often how it goes in science in general. If you're got something specific where a study will likely lead to meaningful and actionable results you're both more likely to get funded and more likely to have collaborators, etc.
Yeah, I totally agree that the magnitude of the problem is certainly part of the issue, and that IVF offers an easy path forward for those who can't conceive. Still it's depressing when you conceive easily, lose the baby, and the doctors have no clue (a few of my friend's stillbirths have been birth control failures, so they weren't even trying).
If the money was in "preventing infant deaths" then physicians would specialize in it. But when you have a huge supply of people willing to spend hundreds of thousands on fertility, lots of docs will respond to the market.
I get your point, it would be nice. It would also be nice if everyone working at facebook and snapchat would work on making our healthcare system more efficient. But money talks...
But this is exactly what an MFM (maternal fetal medicine specialist) does. I'm not sure that the one MFM you tried to consult with is indicative of the whole of the field.
2016 numbers because recent ones make me cry.
Infertility: 86m Birth /infant health: 240m SIDS: 16m
Not sure I see the misallocation.
An amazing result is that the proteins humans produce for priming their follicles to release an egg. Can be transplanted into fruit flies. With an analogous priming of fruit fly follicles for ovulation. Suggesting that genes regulating fertility and reproduction are conserved across the full spectrum of Animal Kingdom phyla.
Zinc-finger transcription factor Hindsight regulates ovulation competency of Drosophila follicles
Both my kids came from IVF, and we harvested eggs twice. Besides all the shots, which are painful enough, my wife had to have a very invasive procedure to collect the eggs that left her bruised for days.
If the collection is easier, I can see doctors opting for this as a way of keeping the mother less stressed before implanting an embryo, increasing the chance for success!
Note: This is a serious scientific question.
Babies die or have extreme developmental issues without physical contact https://www.google.hr/amp/s/www.psychologytoday.com/blog/bor...