Technology is Redefining the Age of 'Older Mothers'
In October 2021, a woman from Gujarat, India, stunned the world when it was revealed she had her first child through in vitro fertilization (IVF) at age 70. She had actually been preceded by a compatriot of hers who, two years before, gave birth to twins at the age of 73, again with the help of IVF treatment. The oldest known mother to conceive naturally lived in the UK; in 1997, Dawn Brooke conceived a son at age 59.
These women may seem extreme outliers, almost freaks of nature; in the US, for example, the average age of first-time mothers is 26. A few decades from now, though, the sight of 70-year-old first-time mothers may not even raise eyebrows, say futurists.
“We could absolutely have more 70-year-old mothers because we are learning how to regulate the aging process better,” says Andrew Hessel, a microbiologist and geneticist, who cowrote "The Genesis Machine," a book about “rewriting life in the age of synthetic biology,” with Amy Webb, the futurist who recently wondered why 70-year-old women shouldn’t give birth.
Technically, we're already doing this, says Hessel, pointing to a technique known as in vitro gametogenesis (IVG). IVG refers to turning adult cells into sperm or egg cells. “You can think of it as the upgrade to IVF,” Hessel says. These vanguard stem cell research technologies can take even skin cells and turn them into induced pluripotent stem cells (iPSCs), which are basically master cells capable of maturing into any human cell, be it kidney cells, liver cells, brain cells or gametes, aka eggs and sperm, says Henry T. “Hank” Greely, a Stanford law professor who specializes in ethical, legal, and social issues in biosciences.
Mothers over 70 will be a minor blip, statistically speaking, Greely predicts.
In 2016, Greely wrote "The End of Sex," a book in which he described the science of making gametes out of iPSCs in detail. Greely says science will indeed enable us to see 70-year-old new mums fraternize with mothers several decades younger at kindergartens in the (not far) future. And it won’t be that big of a deal.
“An awful lot of children all around the world have been raised by grandmothers for millennia. To have 70-year-olds and 30-year-olds mingling in maternal roles is not new,” he says. That said, he doubts that many women will want to have a baby in the eighth decade of their life, even if science allows it. “Having a baby and raising a child is hard work. Even if 1% of all mothers are over 65, they aren’t going to change the world,” Greely says. Mothers over 70 will be a minor blip, statistically speaking, he predicts. But one thing is certain: the technology is here.
And more technologies for the same purpose could be on the way. In March 2021, researchers from Monash University in Melbourne, Australia, published research in Nature, where they successfully reprogrammed skin cells into a three-dimensional cellular structure that was morphologically and molecularly similar to a human embryo–the iBlastoid. In compliance with Australian law and international guidelines referencing the “primitive streak rule," which bans the use of embryos older than 14 days in scientific research, Monash scientists stopped growing their iBlastoids in vitro on day 11.
“The research was both cutting-edge and controversial, because it essentially created a new human life, not for the purpose of a patient who's wanting to conceive, but for basic research,” says Lindsay Wu, a senior lecturer in the School of Medical Sciences at the University of New South Wales (UNSW), in Kensington, Australia. If you really want to make sure what you are breeding is an embryo, you need to let it develop into a viable baby. “This is the real proof in the pudding,'' says Wu, who runs UNSW’s Laboratory for Ageing Research. Then you get to a stage where you decide for ethical purposes you have to abort it. “Fiddling here a bit too much?” he asks. Wu believes there are other approaches to tackling declining fertility due to older age that are less morally troubling.
He is actually working on them. Why would it be that women, who are at peak physical health in almost every other regard, in their mid- to late- thirties, have problems conceiving, asked Wu and his team in a research paper published in 2020 in Cell Reports. The simple answer is the egg cell. An average girl in puberty has between 300,000 and 400,000 eggs, while at around age 37, the same woman has only 25,000 eggs left. Things only go downhill from there. So, what torments the egg cells?
The UNSW team found that the levels of key molecules called NAD+ precursors, which are essential to the metabolism and genome stability of egg cells, decline with age. The team proceeded to add these vitamin-like substances back into the drinking water of reproductively aged, infertile lab mice, which then had babies.
“It's an important proof of concept,” says Wu. He is investigating how safe it is to replicate the experiment with humans in two ongoing studies. The ultimate goal is to restore the quality of egg cells that are left in patients in their late 30s and early- to mid-40s, says Wu. He sees the goal of getting pregnant for this age group as less ethically troubling, compared to 70-year-olds.
But what is ethical, anyway? “It is a tricky word,” says Hessel. He differentiates between ethics, which represent a personal position and may, thus, be more transient, and morality, longer lasting principles embraced across society such as, “Thou shalt not kill.” Unprecedented advances often bring out fear and antagonism until time passes and they just become…ordinary. When IVF pioneer Landrum Shettles tried to perform IVF in 1973, the chairman of Columbia’s College of Physicians and Surgeons interdicted the procedure at the last moment. Almost all countries in the world have IVF clinics today, and the global IVF services market is clearly a growth industry.
Besides, you don’t have a baby at 70 by accident: you really want it, Greely and Hessel agree. And by that age, mothers may be wiser and more financially secure, Hessel says (though he is quick to add that even the pregnancy of his own wife, who had her child at 40, was a high-risk one).
As a research question, figuring out whether older mothers are better than younger ones and vice-versa entails too many confounding variables, says Greely. And why should we focus on who’s the better mother anyway? “We've had 70-year-old and 80-year-old fathers forever–why should people have that much trouble getting used to mothers doing the same?” Greely wonders. For some women having a child at an old(er) age would be comforting; maybe that’s what matters.
And the technology to enable older women to have children is already here or coming very soon. That, perhaps, matters even more. Researchers have already created mice–and their offspring–entirely from scratch in the lab. “Doing this to produce human eggs is similar," says Hessel. "It is harder to collect tissues, and the inducing cocktails are different, but steady advances are being made." He predicts that the demand for fertility treatments will keep financing research and development in the area. He says that big leaps will be made if ethical concerns don’t block them: it is not far-fetched to believe that the first baby produced from lab-grown eggs will be born within the next decade.
In an op-ed in 2020 with Stat, Greely argued that we’ve already overcome the technical barrier for human cloning, but no one's really talking about it. Likewise, scientists are also working on enabling 70-year-old women to have babies, says Hessel, but most commentators are keeping really quiet about it. At least so far.
Few things are more painful than a urinary tract infection (UTI). Common in men and women, these infections account for more than 8 million trips to the doctor each year and can cause an array of uncomfortable symptoms, from a burning feeling during urination to fever, vomiting, and chills. For an unlucky few, UTIs can be chronic—meaning that, despite treatment, they just keep coming back.
But new research, presented at the European Association of Urology (EAU) Congress in Paris this week, brings some hope to people who suffer from UTIs.
Clinicians from the Royal Berkshire Hospital presented the results of a long-term, nine-year clinical trial where 89 men and women who suffered from recurrent UTIs were given an oral vaccine called MV140, designed to prevent the infections. Every day for three months, the participants were given two sprays of the vaccine (flavored to taste like pineapple) and then followed over the course of nine years. Clinicians analyzed medical records and asked the study participants about symptoms to check whether any experienced UTIs or had any adverse reactions from taking the vaccine.
The results showed that across nine years, 48 of the participants (about 54%) remained completely infection-free. On average, the study participants remained infection free for 54.7 months—four and a half years.
“While we need to be pragmatic, this vaccine is a potential breakthrough in preventing UTIs and could offer a safe and effective alternative to conventional treatments,” said Gernot Bonita, Professor of Urology at the Alta Bro Medical Centre for Urology in Switzerland, who is also the EAU Chairman of Guidelines on Urological Infections.
The news comes as a relief not only for people who suffer chronic UTIs, but also to doctors who have seen an uptick in antibiotic-resistant UTIs in the past several years. Because UTIs usually require antibiotics, patients run the risk of developing a resistance to the antibiotics, making infections more difficult to treat. A preventative vaccine could mean less infections, less antibiotics, and less drug resistance overall.
“Many of our participants told us that having the vaccine restored their quality of life,” said Dr. Bob Yang, Consultant Urologist at the Royal Berkshire NHS Foundation Trust, who helped lead the research. “While we’re yet to look at the effect of this vaccine in different patient groups, this follow-up data suggests it could be a game-changer for UTI prevention if it’s offered widely, reducing the need for antibiotic treatments.”
MILESTONE: Doctors have transplanted a pig organ into a human for the first time in history
Surgeons at Massachusetts General Hospital made history last week when they successfully transplanted a pig kidney into a human patient for the first time ever.
The recipient was a 62-year-old man named Richard Slayman who had been living with end-stage kidney disease caused by diabetes. While Slayman had received a kidney transplant in 2018 from a human donor, his diabetes ultimately caused the kidney to fail less than five years after the transplant. Slayman had undergone dialysis ever since—a procedure that uses an artificial kidney to remove waste products from a person’s blood when the kidneys are unable to—but the dialysis frequently caused blood clots and other complications that landed him in the hospital multiple times.
As a last resort, Slayman’s kidney specialist suggested a transplant using a pig kidney provided by eGenesis, a pharmaceutical company based in Cambridge, Mass. The highly experimental surgery was made possible with the Food and Drug Administration’s “compassionate use” initiative, which allows patients with life-threatening medical conditions access to experimental treatments.
The new frontier of organ donation
Like Slayman, more than 100,000 people are currently on the national organ transplant waiting list, and roughly 17 people die every day waiting for an available organ. To make up for the shortage of human organs, scientists have been experimenting for the past several decades with using organs from animals such as pigs—a new field of medicine known as xenotransplantation. But putting an animal organ into a human body is much more complicated than it might appear, experts say.
“The human immune system reacts incredibly violently to a pig organ, much more so than a human organ,” said Dr. Joren Madsen, director of the Mass General Transplant Center. Even with immunosuppressant drugs that suppress the body’s ability to reject the transplant organ, Madsen said, a human body would reject an animal organ “within minutes.”
So scientists have had to use gene-editing technology to change the animal organs so that they would work inside a human body. The pig kidney in Slayman’s surgery, for instance, had been genetically altered using CRISPR-Cas9 technology to remove harmful pig genes and add human ones. The kidney was also edited to remove pig viruses that could potentially infect a human after transplant.
With CRISPR technology, scientists have been able to prove that interspecies organ transplants are not only possible, but may be able to successfully work long term, too. In the past several years, scientists were able to transplant a pig kidney into a monkey and have the monkey survive for more than two years. More recently, doctors have transplanted pig hearts into human beings—though each recipient of a pig heart only managed to live a couple of months after the transplant. In one of the patients, researchers noted evidence of a pig virus in the man’s heart that had not been identified before the surgery and could be a possible explanation for his heart failure.
So far, so good
Slayman and his medical team ultimately decided to pursue the surgery—and the risk paid off. When the pig organ started producing urine at the end of the four-hour surgery, the entire operating room erupted in applause.
Slayman is currently receiving an infusion of immunosuppressant drugs to prevent the kidney from being rejected, while his doctors monitor the kidney’s function with frequent ultrasounds. Slayman is reported to be “recovering well” at Massachusetts General Hospital and is expected to be discharged within the next several days.