Top Fertility Doctor: Artificially Created Sperm and Eggs "Will Become Normal" One Day
Kira Peikoff was the editor-in-chief of Leaps.org from 2017 to 2021. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.

A rendering of in vitro fertilization.
Imagine two men making a baby. Or two women. Or an infertile couple. Or an older woman whose eggs are no longer viable. None of these people could have a baby today without the help of an egg or sperm donor.
Cells scraped from the inside of your cheek could one day be manipulated to become either eggs or sperm.
But in the future, it may be possible for them to reproduce using only their own genetic material, thanks to an emerging technology called IVG, or in vitro gametogenesis.
Researchers are learning how to reprogram adult human cells like skin cells to become lab-created egg and sperm cells, which could then be joined to form an embryo. In other words, cells scraped from the inside of your cheek could one day be manipulated to become either eggs or sperm, no matter your gender or your reproductive fitness.
In 2016, Japanese scientists proved that the concept could be successfully carried out in mice. Now some experts, like Dr. John Zhang, the founder and CEO of New Hope Fertility Center in Manhattan, say it's just "a matter of time" before the method is also made to work in humans.
Such a technological tour de force would upend our most basic assumptions about human reproduction and biology. Combined with techniques like gene editing, these tools could eventually enable prospective parents to have an unprecedented level of choice and control over their children's origins. It's a wildly controversial notion, and an especially timely one now that a Chinese scientist has announced the birth of the first allegedly CRISPR-edited babies. (The claims remain unverified.)
Zhang himself is no stranger to controversy. In 2016, he stunned the world when he announced the birth of a baby conceived using the DNA of three people, a landmark procedure intended to prevent the baby from inheriting a devastating neurological disease. (Zhang went to a clinic in Mexico to carry out the procedure because it is prohibited in the U.S.) Zhang's other achievements to date include helping a 49-year-old woman have a baby using her own eggs and restoring a young woman's fertility through an ovarian tissue transplant surgery.
Zhang recently sat down with our Editor-in-Chief in his New York office overlooking Columbus Circle to discuss the fertility world's latest provocative developments. Here are his top ten insights:
Clearly [gene-editing embryos] will be beneficial to mankind, but it's a matter of how and when the work is done.
1) On a Chinese scientist's claim of creating the first CRISPR-edited babies:
I'm glad that we made a first move toward a clinical application of this technology for mankind. Somebody has to do this. Whether this was a good case or not, there is still time to find out.
Clearly it will be beneficial to mankind, but it's a matter of how and when the work is done. Like any scientific advance, it has to be done in a very responsible way.
Today's response is identical to when the world's first IVF baby was announced in 1978. The major news media didn't take it seriously and thought it was evil, wanted to keep a distance from IVF. Many countries even abandoned IVF, but today you see it is a normal practice. And it took almost 40 years [for the researchers] to win a Nobel Prize.
I think we need more time to understand how this work was done medically, ethically, and let the scientist have the opportunity to present how it was done and let a scientific journal publish the paper. Before these become available, I don't think we should start being upset, scared, or giving harsh criticism.
2) On the international outcry in response to the news:
I feel we are in scientific shock, with many thinking it came too fast, too soon. We all embrace modern technology, but when something really comes along, we fear it. In an old Chinese saying, one of the masters always dreamed of seeing the dragon, and when the dragon really came, he got scared.
Dr. John Zhang, the founder and CEO of New Hope Fertility Center in Manhattan, pictured in his office.
3) On the Western world's perception that Chinese scientists sometimes appear to discount ethics in favor of speedy breakthroughs:
I think this perception is not fair. I don't think China is very casual. It's absolutely not what people think. I don't want people to feel that this case [of CRISPR-edited babies] will mean China has less standards over how human reproduction should be performed. Just because this happened, it doesn't mean in China you can do anything you want.
As far as the regulation of IVF clinics, China is probably the most strictly regulated of any country I know in this world.
4) On China's first public opinion poll gauging attitudes toward gene-edited babies, indicating that more than 60 percent of survey respondents supported using the technology to prevent inherited diseases, but not to enhance traits:
There is a sharp contrast between the general public and the professional world. Being a working health professional and an advocate of scientists working in this field, it is very important to be ethically responsible for what we are doing, but my own feeling is that from time to time we may not take into consideration what the patient needs.
5) On how the three-parent baby is doing today, several years after his birth:
No news is good news.
6) On the potentially game-changing research to develop artificial sperm and eggs:
First of all I think that anything that's technically possible, as long as you are not harmful to other people, to other societies, as long as you do it responsibly, and this is a legitimate desire, I think eventually it will become reality.
My research for now is really to try to overcome the very next obstacle in our field, which is how to let a lady age 44 or older have a baby with her own genetic material.
Practically 99 percent of women over age 43 will never make a baby on their own. And after age 47, we usually don't offer donor egg IVF anymore.
But with improved longevity, and quality of life, the lifespan of females continues to increase. In Japan, the average for females is about 89 years old. So for more than half of your life, you will not be able to produce a baby, which is quite significant in the animal kingdom. In most of the animal kingdom, their reproductive life is very much the same as their life, but then you can argue in the animal kingdom unlike a human being, it doesn't take such a long time for them to contribute to the society because once you know how to hunt and look for food, you're done.
"I think this will become a major ethical debate: whether we should let an older lady have a baby at a very late state of her life."
But humans are different. You need to go to college, get certain skills. It takes 20 years to really bring a human being up to become useful to society. That's why the mom and dad are not supposed to have the same reproductive life equal to their real life.
I think this will become a major ethical debate: whether we should let an older lady have a baby at a very late state of her life and leave the future generation in a very vulnerable situation in which they may lack warm caring, proper guidance, and proper education.
7) On using artificial gametes to grant more reproductive choices to gays and lesbians:
I think it is totally possible to have two sperm make a baby, and two eggs make babies.
If we have two guys, one guy to produce eggs, or two girls, one would have to become sperm. Basically you are creating artificial gametes or converting with gametes from sperm to become egg or egg to become a sperm. Which may not necessarily be very difficult. The key is to be able to do nuclear reprogramming.
So why can two sperm not make offspring now? You get exactly half of your genes from each parent. The genes have their own imprinting that say "made in mom," "made in dad." The two sperm would say "made in dad," "made in dad." If I can erase the "made in dad," and say "made in mom," then these sperm can make offspring.
8) On how close science is to creating artificial gametes for clinical use in pregnancies:
It's very hard to say until we accomplish it. It could be very quick. It could be it takes a long time. I don't want to speculate.
"I think these technologies are the solid foundation just like when we designed the computer -- we never thought a computer would become the iPhone."
9) On whether there should be ethical red lines drawn by authorities or whether the decisions should be left to patients and scientists:
I think we cannot believe a hundred percent in the scientist and the patient but it should not be 100 percent authority. It should be coming from the whole of society.
10) On his expectations for the future:
We are living in a very exciting world. I think that all these technologies can really change the way of mankind and also are not just for baby-making. The research, the experience, the mechanism we learn from these technologies, they will shine some great lights into our long-held dream of being a healthy population that is cancer-free and lives a long life, let's say 120 years.
I think these technologies are the solid foundation just like when we designed the computer -- we never thought a computer would become the iPhone. Imagine making a computer 30 years ago, that this little chip will change your life.
Kira Peikoff was the editor-in-chief of Leaps.org from 2017 to 2021. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.
Pioneering XPRIZEs, Longevity and Mindset with Dr. Peter Diamandis
XPRIZE founder and chairman Peter Diamandis launches XPRIZE Healthspan at an event on November 29.
A new competition by the XPRIZE Foundation is offering $101 million to researchers who discover therapies that give a boost to people aged 65-80 so their bodies perform more like when they were middle-aged.
For today’s podcast episode, I talked with Dr. Peter Diamandis, XPRIZE’s founder and executive chairman. Under Peter’s leadership, XPRIZE has launched 27 previous competitions with over $300 million in prize purses. The latest contest aims to enhance healthspan, or the period of life when older people can play with their grandkids without any restriction, disability or disease. Such breakthroughs could help prevent chronic diseases that are closely linked to aging. These illnesses are costly to manage and threaten to overwhelm the healthcare system, as the number of Americans over age 65 is rising fast.
In this competition, called XPRIZE Healthspan, multiple awards are available, depending on what’s achieved, with support from the nonprofit Hevolution Foundation and Chip Wilson, the founder of Lululemon and nonprofit SOLVE FSHD. The biggest prize, $81 million, is for improvements in cognition, muscle and immunity by 20 years. An improvement of 15 years will net $71 million, and 10 years will net $61 million.
In our conversation for this episode, Peter talks about his plans for XPRIZE Healthspan and why exponential technologies make the current era - even with all of its challenges - the most exciting time in human history. We discuss the best mental outlook that supports a person in becoming truly innovative, as well as the downsides of too much risk aversion. We talk about how to overcome the negativity bias in ourselves and in mainstream media, how Peter has shifted his own mindset to become more positive over the years, how to inspire a culture of innovation, Peter’s personal recommendations for lifestyle strategies to live longer and healthier, the innovations we can expect in various fields by 2030, the future of education and the importance of democratizing tech and innovation.
In addition to Peter’s pioneering leadership of XPRIZE, he is also the Executive Founder of Singularity University. In 2014, he was named by Fortune as one of the “World’s 50 Greatest Leaders.” As an entrepreneur, he’s started over 25 companies in the areas of health-tech, space, venture capital and education. He’s Co-founder and Vice-Chairman of two public companies, Celularity and Vaxxinity, plus being Co-founder & Chairman of Fountain Life, a fully-integrated platform delivering predictive, preventative, personalized and data-driven health. He also serves as Co-founder of BOLD Capital Partners, a venture fund with a half-billion dollars under management being invested in exponential technologies and longevity companies. Peter is a New York Times Bestselling author of four books, noted during our conversation and in the show notes of this episode. He has degrees in molecular genetics and aerospace engineering from MIT and holds an M.D. from Harvard Medical School.
Show links
- Peter Diamandis bio
- New XPRIZE Healthspan
- Peter Diamandis books
- 27 XPRIZE competitions and counting
- Life Force by Peter Diamandis and Tony Robbins
- Peter Diamandis Twitter
- Longevity Insider newsletter – AI identifies the news
- Peter Diamandis Longevity Handbook
- Hevolution funding for longevity
XPRIZE Founder Peter Diamandis speaks with Mehmoud Khan, CEO of Hevolution Foundation, at the launch of XPRIZE Healthspan.
Hevolution Foundation
Matt Fuchs is the editor-in-chief of Leaps.org and Making Sense of Science. He is also a contributing reporter to the Washington Post and has written for the New York Times, Time Magazine, WIRED and the Washington Post Magazine, among other outlets. Follow him @fuchswriter.
Important findings are starting to emerge from research on how genes shape the human response to the Covid virus.
From infections with no symptoms to why men are more likely to be hospitalized in the ICU and die of COVID-19, new research shows that your genes play a significant role
Early in the pandemic, genetic research focused on the virus because it was readily available. Plus, the virus contains only 30,000 bases in a dozen functional genes, so it's relatively easy and affordable to sequence. Additionally, the rapid mutation of the virus and its ability to escape antibody control fueled waves of different variants and provided a reason to follow viral genetics.
In comparison, there are many more genes of the human immune system and cellular functions that affect viral replication, with about 3.2 billion base pairs. Human studies require samples from large numbers of people, the analysis of each sample is vastly more complex, and sophisticated computer analysis often is required to make sense of the raw data. All of this takes time and large amounts of money, but important findings are beginning to emerge.
Asymptomatics
About half the people exposed to SARS-CoV-2, the virus that causes the COVID-19 disease, never develop symptoms of this disease, or their symptoms are so mild they often go unnoticed. One piece of understanding the phenomena came when researchers showed that exposure to OC43, a common coronavirus that results in symptoms of a cold, generates immune system T cells that also help protect against SARS-CoV-2.
Jill Hollenbach, an immunologist at the University of California at San Francisco, sought to identify the gene behind that immune protection. Most COVID-19 genetic studies are done with the most seriously ill patients because they are hospitalized and thus available. “But 99 percent of people who get it will never see the inside of a hospital for COVID-19,” she says. “They are home, they are not interacting with the health care system.”
Early in the pandemic, when most labs were shut down, she tapped into the National Bone Marrow Donor Program database. It contains detailed information on donor human leukocyte antigens (HLAs), key genes in the immune system that must match up between donor and recipient for successful transplants of marrow or organs. Each HLA can contain alleles, slight molecular differences in the DNA of the HLA, which can affect its function. Potential HLA combinations can number in the tens of thousands across the world, says Hollenbach, but each person has a smaller number of those possible variants.
She teamed up with the COVID-19 Citizen Science Study a smartphone-based study to track COVID-19 symptoms and outcomes, to ask persons in the bone marrow donor registry about COVID-19. The study enlisted more than 30,000 volunteers. Those volunteers already had their HLAs annotated by the registry, and 1,428 tested positive for the virus.
Analyzing five key HLAs, she found an allele in the gene HLA-B*15:01 that was significantly overrepresented in people who didn’t have any symptoms. The effect was even stronger if a person had inherited the allele from both parents; these persons were “more than eight times more likely to remain asymptomatic than persons who did not carry the genetic variant,” she says. Altogether this HLA was present in about 10 percent of the general European population but double that percentage in the asymptomatic group. Hollenbach and her colleagues were able confirm this in other different groups of patients.
What made the allele so potent against SARS-CoV-2? Part of the answer came from x-ray crystallography. A key element was the molecular shape of parts of the cold virus OC43 and SARS-CoV-2. They were virtually identical, and the allele could bind very tightly to them, present their molecular antigens to T cells, and generate an extremely potent T cell response to the viruses. And “for whatever reasons that generated a lot of memory T cells that are going to stick around for a long time,” says Hollenbach. “This T cell response is very early in infection and ramps up very quickly, even before the antibody response.”
Understanding the genetics of the immune response to SARS-CoV-2 is important because it provides clues into the conditions of T cells and antigens that support a response without any symptoms, she says. “It gives us an opportunity to think about whether this might be a vaccine design strategy.”
Dead men
A researcher at the Leibniz Institute of Virology in Hamburg Germany, Guelsah Gabriel, was drawn to a question at the other end of the COVID-19 spectrum: why men more likely to be hospitalized and die from the infection. It wasn't that men were any more likely to be exposed to the virus but more likely, how their immune system reacted to it
Several studies had noted that testosterone levels were significantly lower in men hospitalized with COVID-19. And, in general, the lower the testosterone, the worse the prognosis. A year after recovery, about 30 percent of men still had lower than normal levels of testosterone, a condition known as hypogonadism. Most of the men also had elevated levels of estradiol, a female hormone (https://pubmed.ncbi.nlm.nih.gov/34402750/).
Every cell has a sex, expressing receptors for male and female hormones on their surface. Hormones docking with these receptors affect the cells' internal function and the signals they send to other cells. The number and role of these receptors varies from tissue to tissue.
Gabriel began her search by examining whole exome sequences, the protein-coding part of the genome, for key enzymes involved in the metabolism of sex hormones. The research team quickly zeroed in on CYP19A1, an enzyme that converts testosterone to estradiol. The gene that produces this enzyme has a number of different alleles, the molecular variants that affect the enzyme's rate of metabolizing the sex hormones. One genetic variant, CYP19A1 (Thr201Met), is typically found in 6.2 percent of all people, both men and women, but remarkably, they found it in 68.7 percent of men who were hospitalized with COVID-19.
Lung surprise
Lungs are the tissue most affected in COVID-19 disease. Gabriel wondered if the virus might be affecting expression of their target gene in the lung so that it produces more of the enzyme that converts testosterone to estradiol. Studying cells in a petri dish, they saw no change in gene expression when they infected cells of lung tissue with influenza and the original SARS-CoV viruses that caused the SARS outbreak in 2002. But exposure to SARS-CoV-2, the virus responsible for COVID-19, increased gene expression up to 40-fold, Gabriel says.
Did the same thing happen in humans? Autopsy examination of patients in three different cites found that “CYP19A1 was abundantly expressed in the lungs of COVID-19 males but not those who died of other respiratory infections,” says Gabriel. This increased enzyme production led likely to higher levels of estradiol in the lungs of men, which “is highly inflammatory, damages the tissue, and can result in fibrosis or scarring that inhibits lung function and repair long after the virus itself has disappeared.” Somehow the virus had acquired the capacity to upregulate expression of CYP19A1.
Only two COVID-19 positive females showed increased expression of this gene. The menopause status of these women, or whether they were on hormone replacement therapy was not known. That could be important because female hormones have a protective effect for cardiovascular disease, which women often lose after going through menopause, especially if they don’t start hormone replacement therapy. That sex-specific protection might also extend to COVID-19 and merits further study.
The team was able to confirm their findings in golden hamsters, the animal model of choice for studying COVID-19. Testosterone levels in male animals dropped 5-fold three days after infection and began to recover as viral levels declined. CYP19A1 transcription increased up to 15-fold in the lungs of the male but not the females. The study authors wrote, “Virus replication in the male lungs was negatively associated with testosterone levels.”
The medical community studying COVID-19 has slowly come to recognize the importance of adipose tissue, or fat cells. They are known to express abundant levels of CYP19A1 and play a significant role as metabolic tissue in COVID-19. Gabriel adds, “One of the key findings of our study is that upon SARS-CoV-2 infection, the lung suddenly turns into a metabolic organ by highly expressing” CYP19A1.
She also found evidence that SARS-CoV-2 can infect the gonads of hamsters, thereby likely depressing circulating levels of sex hormones. The researchers did not have autopsy samples to confirm this in humans, but others have shown that the virus can replicate in those tissues.
A possible treatment
Back in the lab, substituting low and high doses of testosterone in SARS-COV-2 infected male hamsters had opposite effects depending on testosterone dosage used. Gabriel says that hormone levels can vary so much, depending on health status and age and even may change throughout the day, that “it probably is much better to inhibit the enzyme” produced by CYP19A1 than try to balance the hormones.
Results were better with letrozole, a drug approved to treat hypogonadism in males, which reduces estradiol levels. The drug also showed benefit in male hamsters in terms of less severe disease and faster recovery. She says more details need to be worked out in using letrozole to treat COVID-19, but they are talking with hospitals about clinical trials of the drug.
Gabriel has proposed a four hit explanation of how COVID-19 can be so deadly for men: the metabolic quartet. First is the genetic risk factor of CYP19A1 (Thr201Met), then comes SARS-CoV-2 infection that induces even greater expression of this gene and the deleterious increase of estradiol in the lung. Age-related hypogonadism and the heightened inflammation of obesity, known to affect CYP19A1 activity, are contributing factors in this deadly perfect storm of events.
Studying host genetics, says Gabriel, can reveal new mechanisms that yield promising avenues for further study. It’s also uniting different fields of science into a new, collaborative approach they’re calling “infection endocrinology,” she says.