May 05, 2005
Cells From Ovaries Can Be Turned Into Eggs
Lapascopically extracted cells from human ovaries can be turned into viable eggs.
Research has shown for the first time that human eggs may develop directly from cultured ovarian surface epithelium (OSE) cells derived from adult human ovaries. Oocytes derived from the culture of OSE cells developed in vitro into mature eggs suitable for fertilization and development into an embryo. These findings, published today in the Open Access journal Reproductive Biology and Endocrinology, offer important new strategies for use in in vitro fertilization and stem cell research, and cast doubt on the established dogma on the fetal origin of eggs in adult human ovaries.
It is now well established that fetal mammalian eggs originate from somatic stem cells. More recent research of adult human ovaries has shown that oocytes and granulosa cells (the layer of small cells that form the wall of the ovarian follicle) may originate from OSE cells and assemble together to form new primary follicles – the structures that grow and rupture during ovulation to release mature eggs. However, definitive proof that new oocytes may develop in adult human females will be if they can be found to differentiate in vitro from OSE cells derived from adult human ovaries.
For the first time, Antonin Bukovsky and colleagues from the Department of Obstetrics and Gynecology of the University of Tennessee, United States, have shown that human eggs and granulosa cells) can develop from cultured OSE cells. By scraping cells from the surface of adult ovaries and growing them for 5 to 6 days in the presence of an estrogen-containing medium (phenol red) to stimulate their growth, the team was able to produce new human oocytes in vitro.
The oocytes cultured in this way are viable and went on to successfully complete the first meiotic division to become mature human eggs – capable of being fertilized and developing into an embryo. These in vitro findings support earlier in vivo studies by Bukovsky and colleagues that OSE cells are bipotent; capable of differentiating along two developmental pathways and becoming either egg or granulosa cells. The authors speculate that this bipotent differentiation may represent a sophisticated mechanism created during the evolution of female reproduction, and not seen in ovaries of female prosimians (ancestral primates) or mice carrying germline stem cells.
Women in their early or mid 20s who think they may have many years before they will have children could opt to have some OSE cells extracted from their ovaries to be used 10 or 20 years later to start pregnancies.
The ability to produce mature human eggs from adult ovaries in vitro has several potential applications in human reproduction. The technique of harvesting cells from the ovarian surface is relatively easy, can be accomplished by a laparoscopy technique, and yields more cells for use for in vitro fertilization. The ability to develop human eggs from OSE cells may help women with reduced fertility and premature menopause, who lack follicles in their ovaries, to have a better chance of conceiving through in vitro fertilization. Eventually, frozen OSE cells from younger females may be preserved for later production of fresh eggs. This may prevent the occurrence of fetal genetic alterations, which are often associated with an advanced maternal age. In addition, a colonization of premenopausal ovaries with younger oocyte and granulosa stem cells may establish a new cohort of primary follicles. This may result in a 10- to 12-year delay of the onset of natural menopause. Also, these ovarian stem cells could be used to generate several cell types used in stem cell research, and fertilized eggs produced in this way could produce cells capable of giving rise to embryonic stem cells for use in research and therapeutic applications.
Women whose ovaries are no longer producing eggs might eventually be able to use this technique to have babies. Reproduction will be extended into a woman's late 30s and 40s. Professional women who now pursue career success and delay too long to have children might finally have a biotechnological solution to their predicament. My guess is this technique will be used most heavily by highly educated career women.
Note that this technique will probably be an attractive option for women in their 30s who are still fertile. Old eggs have greater risk of genetic defects. Use of OSE cells extracted and frozen at a younger age would probably lower the risk of genetic risks. Even OSE cells extracted from a women in her 30s when she wants to have a child might produce eggs which are at less risk of genetic defects.
Any woman who has older friends who are going through menopause may be attracted to the idea of delaying menopause. Why be woken up by severe painful hot flashes? Why start feeling like you are crazy or furious or depressed or lethargic? Why lose the ability to concentrate? Why suddenly feel frigid and disgusted at the sight of your husband? ( I'm relaying stories from fifty something women friend talking about themselves and their friends going through menopause) If you can delay all that stuff you might be able to delay it till better treatments for relieving menopausal symptoms become available. On the other hand, by delaying menopause you might also increase your risk for some of the female cancers.
You can read the abstract for the research paper or the full research paper (the latter is PDF format).
Given the choice, I'd still rather conceive a child naturally than opt for IVF. I'm a young professional woman with a PhD who has opted to go through the natural progression of life without trying to manipulate everything to the nth degree.
As for menopause, not all women experience severe symptoms. There are naturopathic remedies that can smooth the transition.
Life isn't all about staying young and fertile
Life isn't all about staying young and fertile
Perhaps - but it would be nice to have the option...
Mr. Econotarian, Some scientists are predicting a disturbance to social order if we are able to live far longer than the current average of 77 years. I posted on this topic just last week in my Genetics and Public Health Blog.
Responding to your post point by point:
1. Lefties and luddites always like to bring out the "growing gap between rich and poor" assumption without any empirical support or plausible argument, and then always seem to ignore the fact that the poor keep getting richer and richer.
2. Having lots of old people around does not affect the life transitions of people in the first 100 years of life. Why would it?
3. Leon Kass is handwaving. Lots of really old youthful people might lead to hedonism and sexual license, or it might not. Frankly, nobody knows and anybody who pretends to is either a liar or a fool.
4. Warren Buffet's continued Chairmanship of BerkshireHathaway hasn't seemed to keep folks from advancing and prospering under him. And it certainly did not prevent boatloads of dotcom millionaires from sprouting up. Or is someone suggesting anyone will cling desperately to their middle-management drudgery even after they have put aside enough money to live comfortably goofing off for the next 10 to 50 years?
5. Why would anyone care whether people divorce after 50 years of marriage? The grandkids would be having kids by then. It's not like humanity evolved a crucial role for great-grand-parents. Randall's great grandfather was 5 years old already when Santa Anna's men attacked the Alamo, and three of my great-grandparents were dead before I was toilet trained. Did you have a close and enduring bond with any of your great-grandparents?
6. Why would anyone assume a society with the means to rejuvenate the elderly lacking the means to rejuvenate them to fecundity? I suppose that might happen, but I find it unlikely. #3 above assumes a lot of seemingly procreative activities, and #5 above suggests a lot of new relationships starting up. Why doesn't #6 here assume some folks will miss the pitter patter of little feet? Especially when their first/earlier set(s) of kids have the grandparenting market cornered already?
7. Old country/young country? Who cares? Just sounds like another dimension affecting marginal advantage. At least the older countries will have a clue about the advantages of free trade.
8. Why assume dictators will live longer and cause more suffering? I suspect the fact folks just wait for Fidel to die helps keep Castro around. Why go to all the bother of ousting someone who will probably die next year anyway? I worked with a cuban 10 years ago: In Cuba, the called Castro "The Old Man" back then. If Cubans expected him to live another 10 years, I suspect some of them might have done something about him.
9. If we can rejuvenate people to live very long lives, why not assume we can rejuvenate them to maintain quick reactions? Personally, I suspect the opposite problem. Youthful hormones and bodies may make the extremely old lose their tendency to think first.
I think it is very important for people to think about these issues and to discuss these issues. I suspect that's one reason why Randall has this blog. However, I don't think "scientists" have any particular advantage when it comes to handwaving speculation. In fact, I suspect mastery of a very narrow topic may constitute a disadvantage. The polymaths I have run into all seem to favour eternal youth.
Bob, Thanks for participating in the discussion. I presented the issues posed by The Atlantic article because I've never seen anyone addressing the possible outcomes of an aging population aside from the death of social security. While I wouldn't mind having eternal youth for myself, I do think the possibility of achieving it within my lifetime is slim.
Aubry de grey addresses all of the naysayer criticisms of immortality on his website at www.gen.cam.ac.uk/sens.
I read Mann's article in the Atlantic and found it excreable. All of his arguments against anti-aging are based on the notion that economics being a zero-sum game, which is completely irrational.
The development of immortality will not be socially disruptive (at least not in the West or East Asia) because we have already gone through the social disruption phase since around 1980. In terms of life style choices and options, we are already a post mortal society. We're just waiting for the biomedical technology to catch up with our life style choices.
Most people I know (especially in California and the "sun belt", but also Seattle and Portland) already no longer live the "conventional life cycle" many of them are divoriced or on second or third marrage. Many have chosen to not have kids. Noone that I know, and I mean noone, works for the same employer for their entire life anymore. I, personally, have had three "jobs" already: engineer, sales, and import/export.
The recent social-economic changes in life already place a premium on self-reliance, flexibility, and the ability to always acquire new skills and abilities and to adapt to new situations. Are these not the traits that would be favored in a post-mortal society?
With the declining birthrates and what not, I think it will be far more socially disruptive and far worse, economically speaking, if we fail to develop a cure for aging in the next 30 years, than if we success. A post-mortal society means a society of "young" people. Such a society will be far more economically and technologically dynamic than anything we see now. It will be far more entreprenurial as well. "Young" people are risk takers and, once the certainty of old age is eliminated, more people will feel the freedom to try new things, take more risks (economically speaking), and be generally more innovative in life, both economically and in life style choices. The resultant economic dynamism will create lots and lots of opportunity for anyone who wants it, regardless of how "old" they are.
The only "bad" thing that post-mortality will do will be to bankrupt the social security system. Since, by definition, everyone will be "young", ponzi schemes such as social security will no longer be necessary and, therefor, can be eliminated with minimal disruption.
The fears of "social disruption" caused by a cure of aging are completely unfounded. I look forward to being a full participant in an ever expanding post-mortal society.
Disturbances of the social order are not all inherenetly bad. We've changed our social order in countless ways in the last few hundred years. Some changes have been good and some bad.
Rejuvenation as a method of extending life would bring many changes to the social order that would be beneficial. For example:
- Long lived people would care more about environmental damage that accumuluates over longer periods of time because they'd live to suffer the consequences. So they'd be more opposed to pollution and habitat destruction today.
- Long lived people would be more opposed to war because they'd see the threat of death as costing them many more lost years than short lived people do.
- Long lived people experiencing centuries of youthfulness would feel less urgency to reproduce since their biological clocks would not be ticking toward infertility and they could count on having youthful energy to raise children hundreds of years into the future.
- Long lived people would be less inclined to make enemies because they'd have to deal with the consequences of having enemies for longer periods of time.
- Youthful long lived people would have more energy to expend to escape from a tyrannical government.
- Youthful bodies would be far more productive at work.
- The absence of old people as a result of rejuvenation therapies will remove a huge burden on younger people for their care.
I'm not saying there would not be downsides to eternal youthfulness. But to weigh the effects of rejuvenation therapies one needs to consider the potential pluses as well as the potential minuses.
Thank you all for your thoughtful responses. One of the key premises of The Atlantic article was that anti-aging/youth preserving technology would not be able available to everyone and might be limited to the very top of the income and power scale. The positive scenarios you all presented would require that the technology be affordable and widely available. When that happens, maybe everything will be all fine and dandy. And maybe they won't.
I am not a technophobe, but I do think it's valuable to consider all the pluses and minuses as we have done here. None of us can predict the future and will have to wait to be proven right or wrong.
Long lived people experiencing centuries of youthfulness would feel less urgency to reproduce since their biological clocks would not be ticking toward infertility and they could count on having youthful energy to raise children hundreds of years into the future.
I'd think that youthfulness would almost certainly include all the characteristic horniness, and people would get upset if it didn't.
Perhaps we'd find a way to modulate this urge, and reduce it in adolescents to help them moderate their risky behavior while turning it up when they finally find a mate.
Horniness and the desire to procreate are two different things. Long lived youths will certainly be horny but will probably lack the procreation compulsion that is present in women in their 30s and early 40s whose reproductive clocks are nearly run down.
In our society women are urged to skip early marriage and child bearing in order to fulfill themselves in a successful career. Thus by the time the career tops out in their forties and fifties they have missed the reproductive window. Multiple public pronouncements of woe to this effect reach us daily from the electronic media.
The solution is for high school girls to take a year off and have a child. Their parents (both sets of grandparents) will then raise the child while the girl continues on her career path. Then when she is successful in her early middle age, her own son or daughter will be in their birth year, which will give her the child to raise that she craves. Sharing the duties of child-raising with the parents of her own child's partner will ease the transition.
And if she finds that she likes the new experience, then IVF using one of the new techniques of egg formation will be practical and available. Artificial wombs cannot be far behind. You know that the uterus is mostly muscle? It is the placenta that is the marvel of life support, and the placenta comes programmed in the zygote. The womb itself is fairly simple.
I find the idea that only the extremely rich will afford life extension as ridiculous as the idea that only the extremely rich can afford televisions, telephones, breast implants, phen fen or viagra.
While I am sure initially some will see rejuvenation as a prestige item, I don't think that will last long at all--certainly not much longer than the personal computer was a prestige item. As Kurt mentions above, the whole thing seems premised on marxist/malthusian fantasies of how economic systems work. In real markets, one makes the big money selling the masses what they want to buy.
And who doesn't want eternal health?
When it comes to handwaving speculation, here's some to consider:
During the brief period when rejuventation is an expensive prestige item, I predict employers will offer rejuvenation to valued employees nearing retirement in exchange for employees agreeing to continue on the job. And as incentives to motivate sales people. And as hiring bonuses.
That will introduce selective pressure that will change the average genetic makeup of the population as those who make themselves valuable to companies live and those who do the minimum to get paid retire and die. When that starts happening, the unions will get in on the deal and start demanding employer paid rejuvenation as part of the collective bargaining negotiations.
If employers don't offer such incentives, some bright people will figure out they can retire early, take their pension as a lump sum payment, turn around and use the lump sum to pay for rejuvenation, and then go right back to work again.
And some other bright people will create a long-term debt market to pay for rejuvenation. Others will create an insurance market for it. I can hear the salesmen overcoming objections already: "Yes, I know you will still be paying off the loan 60 years from now, but in 20 years when you need this treatment again, it will be so cheap you won't need to finance it. If you don't get it done now, though, you won't even be here in 20 years. You'll be dead." "Okay, where do I sign?"
The sheer size of the market will drive down the price.
As a 26 year old female with premature ovarian failure since age 15, I find these results extremely encouraging. Not all of us are able to conceive naturally, Lei, so this type of research is not necessarily just for those "trying to manipulate everything to the nth degree."
I have read de Grey's site. He is widely optimistic about the transition from the current social order to the new. He does a LOT of hand waving. I agree that it is coming but I do not foresee it going over easily. I would expect the high-tech west to start the transition first, maybe even be complete, prior to the poor areas (most of Africa, etc) going for it. Even low costs (say $10K/person - $70 TRILLION for the world) lead to very expensive total costs. If you make the cost even a little higher (say $100K) and it becomes prohibitive for most countries to do this for anyone other than their elite.
And I don't foresee some great humanitarian urge in the wealthy countries to help the poor masses - I point to current conditions throughout Africa, large chunks of Asia, and the inability of the west to remove vile dictators (Saddam being the exception that proves the rule). This also assumes no religious objections.
And all this assumes that this procedure would work for all. What happens if it doesn't? What happens if having a Y chromosome makes the procedure not work? Or if it needs to be done prior to puberty- and is expensive?
My favorite is the scenario where the procedure works in 10%, has no effect on 80%, and is fatal for 10%. (And you get only one chance). Would you take the gamble? More importantly would the no-effect people (through the government) let you?
I think SENS is coming; the technology is on the way. But the belief that it won't be a bloody and violent change I think is naive and not backed by a look at human history.
Why do you expect violence? Seriously.
First of all, we already have life expectancy differences between the worst in Africa and the best in the industrialized countries of about a factor of 2. Is the huge die-off in Africa due to AIDS causing a rebellion of Africans against the rest of the world? NO. NO. NO. Are premature deaths from malaria, dysentery, and other diseases causing World War III? Er, NO.
Also, look, if SENS tech was developed tomorrow and cost $1 million a pop tomorrow would there be rioting in the streets? Again, a big fat NO. Why? Because most people are younger and not facing immediate threat of death from old age. A person who is 20 years old will think "Hey, they just have to get the cost down by the time I'm near death 50 or 60 or 70 years from now - no rush". Old folks who may be desperate for the treatment will be too weak to rise up and overthrow the capitalistic world order. That great South Park episode of the oldsters taking over the town notwithstanding, in the real world old folks don't fight in violent revolutions.
Also, no, you won't have to have SENS therapies when you are young or they won't fail to work on males. Be serious. Think about what SENS therapies will amount to in practice. One form of such therapies will be organ replacements. Well, old folks get organ replacements and joint replacements now. There'll just be a lot more organs available. Cell therapy will be another form of rejuvenation therapy. Well, we already know from limited experiments so far that older animals and older humans can handle cell therapies.
I am not arguing against SENS or even slowly its development. I just have a very negative expectation that the transition will go over smoothly. It may in the US. (I have never seen the Southpark episode and rarely watch TV). But I do have no problem seeing the dictatorial elites in some countries using it and keeping the masses on the normal path. Is their any doubt that this would occur in North Korea? Saudi Arabia? Cuba? As Bob put it so well there are many advantages for a country with SENS. All translate into military advantages. Which places others at a distinct disadvantage.
And I would expect rioting in the streets if SENS were available today at $1M a pop. That's $300 Trillion to do the US population. Now even if we ration it for only the elderly, reduce cost to say $30 trillion do you not think there will be tons of complaints? Even rioting? Note the success of Viagra, and all the cosmetic surgery. And who wouldn't want to feel 25 again? And once the first success happens the demand will go nuts. The 20 year olds can wait. It’s the masses in the 35-65 range that will be less tolerant of waiting. Yes, over time demand will drop the price. I am worried about just the first few years as society changes. I know of very few major societal shifts that were not violent - I feel we will be lucky if we get off with a level of violence equivalent to the civil rights movement. People are not patient.
A lot will change if you can push the average life span out. Even doubling to 150 would be shattering (due to the rate of change (think US Civil War to today)). I do think it will be worth it. And, yes, Social Security would go. And I would have three more kids! (for 6 total).
I assume you plan to get the organs by growing them and not Niven's gruesome Organ Banks. As for the idea that the procedures will work universally - I tend to agree. I do expect a non-zero fatality rate though. Even getting your appendix out can be fatal at times. If the rate is relatively low I expect no problems, but if its not? Could the lawyers kill the technology in its infancy?
The question I was posing was how to deal with SENS if it’s not universal - for whatever reason. This non-universal problem is far more likely in the IQ enhancement question - but that's another thread. And personally I feel the tough questions will be in the implementation of these new genetic/medical miracles than the actual technology. If we get lucky and have a slow implementation this may not be a problem – just I may not live long enough to survive.
Again, why do you expect rioting? Or, to put it another way, which age group do you expect to riot? Twenty somethings have the energy to riot. But they also have no need for SENS. Thirty somethings are still at little risk of death from degenerative diseases. So, again, where the motive to riot?
Seventy somethings rioting? I have a hard time picturing it.
If dictatorial regimes withhold SENS from their masses those masses will be no worse off than today. But the regimes will be worse off in competition with the rest of the world. Their masses will be unwilling to fight for them once the masses realize that their countries do not have SENS due to their leaders. Their leaders, and not the populations of other countries, will look like the enemy.
No, the lawyers will not stop organ transplants. Organs grown to be immunologically compatible will be far less problematic than today's donor organs and lawsuits over donor organs are rare.
Lack of universality: This will not cause riots. This will not cause revolution. It will not even cause war. The biggest possible problem would be incredibly high taxes to pay for SENS treatment of the very old.
Why should a 50 year old riot? We'll have tests that predict disease development years and even decades in advance. A 50 year old who can be assured of 20 more years of healthful living can wait patiently while the costs of SENS treatments drop.
I think we agree on more than we differ. If you are just stopping aging I doubt the 50 year old will wait 20 years. Why not stop aging now? Same with the 25 year old. As for reversing aging, the demand will be even greater. I doubt your 45 year old or 55 year old will wait patiently while others de-age back to 25 while he/she continues to age for 20 years and keeps the same maladies that he's had. I work with a lot of old guys and they are, as a rule, in bad shape, have lots of health problems (mostly minor), and would kill to get back to 25. I doubt many would wait while the rich and famous and connected get the treatments. And they all vote. Look at the current political situation in the US over universal health care, taxes, social security etc. Then think of the same situation multiplied overseas with entire countries waiting just to start on their elderly (who are dieing while they wait). Yes it can get very ugly, very fast. And how do you plan to handle the masses in China? Envy can be a very powerful emotion.
As for higher taxes - wouldn't it be much cheaper to save just the best and brightest and let the rest die off?
The real question is how long from now? How old are you? I'm 43, and would have to live to at least 70 and more likely 90 to make it. My 4 year old has a pretty good chance though.
I think lack of universality will only be a problem if a majority (or mabye even a large minority) cannot take the treatment. A small minority will just be ignored and allowed to die while the rest of us live to a 1000. I doubt a majority would tolerate a small minority that can live that long - I'm just a pessimist in that way.
I expect the period during which SENS treatments are expense to be fairly short for each treatment.
I expect all the treatments will not come at the same time.
I expect that some treatments will get cheap to extend the lives of many people so that they can wait till other treatments become cheap.
Higher taxes: But in a democracy the majority can vote for confiscation of the assets of the wealthier minority. That is the most likely scenario that I see to pay for SENS.
Suppose only a small minority can afford life extension. I predict they will rejuvenate their internals more than their externals so that they can pass for older people.
Envy between nations is only a problem in the case where the envying nation is powerful. Whether, for example, the Cameroonians or the Burmans feel envy doesn't matter much. With China envy could be a problem. But they will have their own upper class and most of the envy felt by the populace will be directed toward their own upper class rather than toward other countries.
How long from now: Keep in mind that a lot of life extending treatments are going to come down the pike in the next 20 year. By the time you are 63 I expect Alzheimers to be curable. Ditto for diabetes and obesity. I also expect most cancers will be curable in 20 years. I also expect some great cell therapies and replacement organs in the next 20 years.
What the majority will tolerate: The majority of the world right now lives on less than $5 a day, doesn't it?
Good points! I just hope I get to see the Brave New World!
Thanks for the blogging.
Note that I said "marginal advantage" and not simply advantage. Marginal advantage is a two-way street.
Marginal advantage is why Dole owns an entire Hawaiian island but imports pineapples from Thailand instead of growing them in the US. Does that make Thailand advantaged over the US?
Good point. I expect Dole to import from Thailand for that very reason (its generates a higher profit margin).
I really hope Randall's positive changes happen (and soon!). My basic worry? fear? concern? is that a rapid change in life expectancy will have huge societal impact both in the US and world-wide. If it phases in more slowly, say taking 100-150 years for lifespan to reach an average of 150, I foresee no problems. (I won't see it period!). If it happens rapidly, say pushing past 150 in a breakthrough surge (Say happening over a 10 year period), then I believe you will have lot's of instabilities. There are many parts of the US economy and society based on the reality of retirement at 65 and death around 80. The senate/house have members who only leave when rolled out (does anyone believe Sen. Kennedy or Byrd would EVER leave), the supreme court, pensions, li fe-in sur ance, social security, tenure, etc all assume people die.
The entire justice system is very much based on life-spans and loss of vigor with age. How do you afford keeping people in for 'life' when it could be hundreds of years? Do criminals get SENS treatments? This would make a great case for the return of capital punishment for many crimes. To take a simple example. I work my way up in a big company on the financial side. I steal $20-30M and put it offshore. Get caught, do 10 years (who cares I'm living to 300!), and go sail the Caribbean in my 40 footer. Will anyone care that I stole money 100 years ago?
Lastly, expense. Even small costs, when multiplied by large numbers become a real problem. Note the current medicare/caid costs. Add life-extension treatments, which all will demand, that come quickly and you can have a real problems. I would not want to live in a society that confiscates peoples assets - societies that do that tend to be totalitarian (USSR) and evil. Soaking the rich is not the solution. (that envy thing coming to play again).
You guys have a much greater belief in patience of people when their lives and well-being are on the line than I do. We live in interesting times.
what about the women who are going through the menopause thing and had everything removed but their ovaries can we use this method to have children by another person that's what i need to know. Can someone please answer this questtion for me
Can this be used in the treatment of osteoporosis, since the lack of estrogen is the culprit.Can it help you feel youthful and vibrant?
Is there any further info on this treatment? Is it available yet anywhere?