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.
On today’s podcast episode, I had a chance to speak with Shai Efrati, a physician and professor in the schools of medicine and neuroscience at Tel Aviv University. Efrati also directs the Sagol Center for Hyperbaric Medicine and Research, and our conversation in this episode focuses on the potential health benefits of hyperbaric oxygen therapy.
Efrati's studies point to a connection between the use of hyperbaric chambers and improvements for a range of health problems such as Long Covid, strokes and traumatic brain injuries. Plus, Efrati has an early line of research suggesting that hyperbaric oxygen therapy could help protect against cognitive decline in healthy people and perhaps even slow down the overall aging process.
We talk about what’s going in on the body during hyperbaric oxygen therapy that could possibly lead to transformative benefits for patients, some of whom had searched for treatments previously and come up empty. We also discuss exactly where Efrati is with this line of inquiry, both what his studies have shown and the great deal of additional research that’s needed before the healthcare system can and should fully embrace hyperbaric oxygen therapy.
Efrati and I talk about why you can’t just go on Amazon and buy something that says hyperbaric – the only way it can have a positive effect is if you access the real version of the chamber and use it correctly under the supervision of a knowledgeable physician.
I also ask Efrati what we know about the short- and long-term risks for those who follow the research-based protocol on a regular basis. And what about accessibility to people without a lot of extra cash to spend on their health? Efrati is already rolling out this therapy at a small number of specialized clinics in places like the Villages retirement community in Florida.
Shai Efrati
A vaccine for Lyme disease could be coming. But will patients accept it?
For more than two decades, Marci Flory, a 40-year-old emergency room nurse from Lawrence, Kan., has battled the recurring symptoms of chronic Lyme disease, an illness which she believes began after being bitten by a tick during her teenage years.
Over the years, Flory has been plagued by an array of mysterious ailments, ranging from fatigue to crippling pain in her eyes, joints and neck, and even postural tachycardia syndrome or PoTS, an abnormal increase in heart rate after sitting up or standing. Ten years ago, she began to experience the onset of neurological symptoms which ranged from brain fog to sudden headaches, and strange episodes of leg weakness which would leave her unable to walk.
“Initially doctors thought I had ALS, or less likely, multiple sclerosis,” she says. “But after repeated MRI scans for a year, they concluded I had a rare neurological condition called acute transverse myelitis.”
But Flory was not convinced. After ordering a variety of private blood tests, she discovered she was infected with a range of bacteria in the genus Borrelia that live in the guts of ticks, the infectious agents responsible for Lyme disease.
“It made sense,” she says. “Looking back, I was bitten in high school and misdiagnosed with mononucleosis. This was probably the start, and my immune system kept it under wraps for a while. The Lyme bacteria can burrow into every tissue in the body, go into cyst form and become dormant before reactivating.”
The reason why cases of Lyme disease are increasing is down to changing weather patterns, triggered by climate change, meaning that ticks are now found across a much wider geographic range than ever before.
When these species of bacteria are transmitted to humans, they can attack the nervous system, joints and even internal organs which can lead to serious health complications such as arthritis, meningitis and even heart failure. While Lyme disease can sometimes be successfully treated with antibiotics if spotted early on, not everyone responds to these drugs, and for patients who have developed chronic symptoms, there is no known cure. Flory says she knows of fellow Lyme disease patients who have spent hundreds of thousands of dollars seeking treatments.
Concerningly, statistics show that Lyme and other tick-borne diseases are on the rise. Recently released estimates based on health insurance records suggest that at least 476,000 Americans are diagnosed with Lyme disease every year, and many experts believe the true figure is far higher.
The reason why the numbers are growing is down to changing weather patterns, triggered by climate change, meaning that ticks are now found across a much wider geographic range than ever before. Health insurance data shows that cases of Lyme disease have increased fourfold in rural parts of the U.S. over the last 15 years, and 65 percent in urban regions.
As a result, many scientists who have studied Lyme disease feel that it is paramount to bring some form of protective vaccine to market which can be offered to people living in the most at-risk areas.
“Even the increased awareness for Lyme disease has not stopped the cases,” says Eva Sapi, professor of cellular and molecular biology at the University of New Haven. “Some of these patients are looking for answers for years, running from one doctor to another, so that is obviously a very big cost for our society at so many levels.”
Emerging vaccines – and backlash
But with the rising case numbers, interest has grown among the pharmaceutical industry and research communities. Vienna-based biotech Valneva have partnered with Pfizer to take their vaccine – a seasonal jab which offers protection against the six most common strains of Lyme disease in the northern hemisphere – into a Phase III clinical trial which began in August. Involving 6,000 participants in a number of U.S. states and northern Europe where Lyme disease is endemic, it could lead to a licensed vaccine by 2025, if it proves successful.
“For many years Lyme was considered a small market vaccine,” explains Monica E. Embers, assistant professor of parasitology at Tulane University in New Orleans. “Now we know that this is a much bigger problem, Pfizer has stepped up to invest in preventing this disease and other pharmaceutical companies may as well.”
Despite innovations, patient communities and their representatives remain ambivalent about the idea of a vaccine. Some of this skepticism dates back to the failed LYMErix vaccine which was developed in the late 1990s before being withdrawn from the market.
At the same time, scientists at Yale University are developing a messenger RNA vaccine which aims to train the immune system to respond to tick bites by exposing it to 19 proteins found in tick saliva. Whereas the Valneva vaccine targets the bacteria within ticks, the Yale vaccine attempts to provoke an instant and aggressive immune response at the site of the bite. This causes the tick to fall off and limits the potential for transmitting dangerous infections.
But despite these innovations, patient communities and their representatives remain ambivalent about the idea of a vaccine. Some of this skepticism dates back to the failed LYMErix vaccine which was developed in the late 1990s before being withdrawn from the market in 2002 after concerns were raised that it might induce autoimmune reactions in humans.
While this theory was ultimately disproved, the lingering stigma attached to LYMErix meant that most vaccine manufacturers chose to stay away from the disease for many years, something which Gregory Poland, head of the Mayo Clinic’s Vaccine Research Group in Minnesota, describes as a tragedy.
“Since 2002, we have not had a human Lyme vaccine in the U.S. despite the increasing number of cases,” says Poland. “Pretty much everyone in the field thinks they’re ten times higher than the official numbers, so you’re probably talking at least 400,000 each year. It’s an incredible burden but because of concerns about anti-vax protestors, until very recently, no manufacturer has wanted to touch this.”
Such was the backlash surrounding the failed LYMErix program that scientists have even explored the most creative of workarounds for protecting people in tick-populated regions, without needing to actually vaccinate them. One research program at the University of Tennessee came up with the idea of leaving food pellets containing a vaccine in woodland areas with the idea that rodents would eat the pellets, and the vaccine would then kill Borrelia bacteria within any ticks which subsequently fed on the animals.
Even the Pfizer-Valneva vaccine has been cautiously designed to try and allay any lingering concerns, two decades after LYMErix. “The concept is the same as the original LYMErix vaccine, but it has been made safer by removing regions that had the potential to induce autoimmunity,” says Embers. “There will always be individuals who oppose vaccines, Lyme or otherwise, but it will be a tremendous boost to public health to have the option.”
Vaccine alternatives
Researchers are also considering alternative immunization approaches in case sufficiently large numbers of people choose to reject any Lyme vaccine which gets approved. Researchers at UMass Chan Medical School have developed an artificially generated antibody, administered via an annual injection, which is capable of killing Borrelia bacteria in the guts of ticks before they can get into the human host.
So far animal studies have shown it to be 100 percent effective, while the scientists have completed a Phase I trial in which they tested it for safety on 48 volunteers in Nebraska. Because this approach provides the antibody directly, rather than triggering the human immune system to produce the antibody like a vaccine would, Embers predicts that it could be a viable alternative for the vaccine hesitant as well as providing an option for immunocompromised individuals who cannot produce enough of their own antibodies.
At the same time, many patient groups still raise concerns over the fact that numerous diagnostic tests for Lyme disease have been reported to have a poor accuracy. Without this, they argue that it is difficult to prove whether vaccines or any other form of immunization actually work. “If the disease is not understood enough to create a more accurate test and a universally accepted treatment protocol, particularly for those who weren’t treated promptly, how can we be sure about the efficacy of a vaccine?” says Natasha Metcalf, co-founder of the organization Lyme Disease UK.
Flory points out that there are so many different types of Borrelia bacteria which cause Lyme disease, that the immunizations being developed may only stop a proportion of cases. In addition, she says that chronic Lyme patients often report a whole myriad of co-infections which remain poorly understood and are likely to also be involved in the disease process.
Marci Flory undergoes an infusion in an attempt to treat her Lyme disease symptoms.
Marci Flory
“I would love to see an effective Lyme vaccine but I have my reservations,” she says. “I am infected with four types of Borrelia bacteria, plus many co-infections – Babesia, Bartonella, Erlichiosis, Rickettsia, and Mycoplasma – all from a single Douglas County Kansas tick bite. Lyme never travels alone and the vaccine won’t protect against all the many strains of Borrelia and co-infections.”
Valneva CEO Thomas Lingelbach admits that the Pfizer-Valneva vaccine is not perfect, but predicts that it will still have significant impact if approved.
“We expect the vaccine to have 75 percent plus efficacy,” he says. “There is this legacy around the old Lyme vaccines, but the world is very, very different today. The number of clinical manifestations known to be caused by infection with Lyme Borreliosis has significantly increased, and the understanding around severity has certainly increased.”
Embers agrees that while it will still be important for doctors to monitor for other tick-borne infections which are not necessarily covered by the vaccine, having any clinically approved jab would still represent a major step forward in the fight against the disease.
“I think that any vaccine must be properly vetted, and these companies are performing extensive clinical trials to do just that,” she says. “Lyme is the most common tick-borne disease in the U.S. so the public health impact could be significant. However, clinicians and the general public must remain aware of all of the other tick-borne diseases such as Babesia and Anaplasma, and continue to screen for those when a tick bite is suspected.”