The Point Is Not to Produce “Designer Babies” but To “Fix” Embryos With Severe Single-Gene Diseases
A post from The Reproductive Times Editorial Staff
A July posting, for the first time, noted that commercial market forces, in addition to preimplantation genetic testing for aneuploidy (PGT-A), had started to aggressively market, in association with in vitro fertilization (IVF), yet another genetic test of preimplantation-stage embryos, so-called polygenic risk scoring (PRS). In reference to PGT-A and preimplantation genetic testing of embryos for single gene (monogenic) diseases (PGT-M), this new test is, therefore, also called PGT-P. More blatantly than PGT-A, which in over 20 years of use has been unable to prove any clinical utility and, indeed, for many infertile patients actually reduces pregnancy and live birth chances, PGT-P, however, creates even more obvious additional ethical, clinical, as well societal concerns. We, therefore, here return to the subject for some additional commentary and take the opportunity to inform our readers—without press release—how the CHR decided to get more directly involved in addressing this issue.
The above-noted July posting was inspired by a previously published article in The Washington Post that featured a California company called Orchid and its founder, Noor Siddiqui, a former Thiel fellow (for those who do not know the meaning of being a Thiel fellow, you will be informed below).
Lo and behold—and so typical for The Free Press—it published on August 11, 2025, a very informative article by Johanna Berkman, which, almost miraculously following The Washington Post article of a few days earlier, appeared to demonstrate the likely unpreventable consequences of PRS/PGT-P. Under the title, “The race to make Designer Babies,” Berkman offered an at times almost comical, but in its relevance very serious story of two prominent individuals strongly determined to take the next step in human embryo manipulation, the genetic editing of an embryo’s genome to correct genetic abnormalities detected in embryos by preimplantation genetic diagnosis for so-called mono-genic diseases (PGT-M), the oldest and most accurate form of testing embryos for a genetic abnormality, in this case caused only by a single gene mutation.
PGT-M is, in the CHR’s opinion, indeed, the only form of preimplantation-stage genetic embryo testing (PGT) that, at the current state of medical art, makes sense. The reason is simple: It tests for often quickly terminal diseases and it does so, in contrast to PGT-A and PGT-P, with very high accuracy. In other words, it really accurately predicts whether an embryo should or should not be transferred, a quality standard that PGT-A and PGT-P do not even come close to.
The testing of embryos before embryo transfer arose for the first time as a concept in the late 1990s with the recognition that genetic material from an in vitro produced embryo could be obtained right after fertilization and before embryo transfer, thereby allowing PGT of preimplantation-stage embryos and the deselection of embryos from embryo transfers that were judged to be genetically unworthy of such transfers.
In principle, two indications were pursued: (i) testing for single-gene diseases, PGT-M; and (ii) testing for chromosomal abnormalities (now called PGT-A). While PGT-M has been a solid success from the earliest days of utilization, PGT-A has become increasingly controversial, with the American Society for Reproductive Medicine (ASRM) and Society of Assisted Reproductive Technology (SART) in late 2024, finally (and in the CHR’s opinion years overdue) issuing a guidance that for the first time clearly noted that PGT-A in over 20 years of clinical use has been unable to demonstrate any beneficial cycle outcome utility.1
But here is where this story really becomes interesting because, if one does not want to chase after the fantasy of PGT-P for such crazy purposes as choosing eye color or trying to improve the intelligence of one’s offspring, curing an embryo from a monogenic disease would seem like a very reasonable and desirable goal. Indeed, in a very aged infertile patient population like the CHR’s, where women only rarely produce large egg and embryo numbers, every “cured”—and therefore transferable—embryo is, of course, symbolically speaking, worth gold.
Which brings us back to the original story in The Free Press, involving two very interesting individuals, a Chinese scientist, He Jiankui, PhD, who already in 2018 made headlines all around the world for applying in vivo gene-editing to two female embryos in an attempt to eliminate any future HIV risk for these embryos by manipulating a single gene in their genome. This, at the time, obviously prematurely executed experiment (it did not follow standard ethical and medical-legal practice for experimental medical treatments) did not earn him the scientific applause he had expected and, instead, rewarded him with a prison sentence in China. In the international press, it also awarded him with the nickname, “Chinese Frankenstein” (a name also given by some prominent media outlets to early IVF researchers out of fear that IVF would produce Frankensteinian monsters). The second player in this evolving tragicomedy was an at the time, still only a 28-year-old additional Thiel fellow by the name of Cathy Tie, who, at that young age, already was a serial entrepreneur who had founded several companies and, on the side, was trained as a concert pianist.
So, who are all of these Thiel fellows? Peter Thiel is a many-times-over billionaire, co-investor, and friend of Elon Musk. He, in addition, is also a founding partner in many highly successful companies in Silicon Valley unrelated to Musk. In 2011, he established the so-called Thiel Fellowship. This announcement made headlines around the world (originally named “20 under 20”) because, already 15 years ago, Thiel recognized what nowadays represents the much more prevalent opinion that, for carefully selected individuals, college represents a waste of time. They, as well as society in general, might be better off if so-talented candidates started “something new” instead of attending college. Creation of the Thiel Fellowship was then the next logical step. And to quote the website: “The Thiel Fellowship gives $200,000 to young people who want to build new things instead of sitting in a classroom.” 2 And— interestingly—two female Thiel fellows, Noor Siddiqui and Cathy Tie, are now central players in the story we are telling here.
The following are other worthwhile quotes from the website of the Thiel Fellowship to understand who the candidates are who, like Noor Siddiqui and Cathy Tie, became Thiel Fellows, with many among them by now already prominent actors in the business world of Silicon Valley and beyond.
“Knowledge that is acquired under compulsion obtains no hold on the mind.”
-Plato
“My grandmother wanted me to have an education, so she kept me out of school.”
-Margaret Mead
“That major that she majored in don’t make no money / But she won’t drop out,
Her parents’ll look at her funny”
-Kanye West
A little bit more relevant history
Tie traveled to Beijing to meet He, who, by then, had resurfaced in public in China after having spent three years in jail for practicing medicine without a license (when performing the HIV-prevention experiments in 2018). And the two were now openly planning such in vivo human embryo editing experiments to cure by PGT-M diagnosed embryos suffering from monogenic diseases through a new start-up company in Austin, Texas.
It appears that the Chinese government was not very happy about He’s resurfacing in the public eye because he was travel restricted and not permitted to leave China, while Tie was access restricted to China. As a consequence, Tie split from He and decided to do all of this with a new scientific partner-founder, Eriona Hysolli, PhD, a former postdoc in the George Church, PhD, laboratory at Harvard University, who, before partnering with Tie, was the Scientific Lead of the famous/infamous Woolly Mammoth De-extinction Project at the Colossal® company.3 The duo’s new project, interestingly, was called the Manhattan Project (if the name sounds familiar, it probably is not coincidental!). Tie earlier in the years already had launched a Los Angeles Project with famous/infamous biohacker Josie Zayner, PhD.
Human genetic embryo editing, of course, represents the logical next step following a genetic diagnosis of a single (i.e., monogenic) pathological human trait in an embryo. But this apparently is not what Noor Siddiqui’s Orchid (and other new start-up companies in the field) appear to consider their future main business to be. Practically all of these companies are instead pursuing the concept of genetic germline editing with the goal of “improving” PRS/PGT-P results (i.e., changing the alleged risk for one or more polygenic diseases). They, indeed, are planning to go even a step further by moving from using germline editing from “correction” to “enhancement” of human embryos, for example, claiming to be able to improve the intelligence of offspring through whole genome screening. Siddiqui’s Orchid, indeed, claimed to be able to perform the required whole genome screening for PSR/PGT-P from the DNA of as few as five to six trophectoderm cells of a blastocyst-stage embryo, a by several experts we spoke to not considered a very credible claim.
The claim, indeed, reminds us of Elizabeth Holmes and, if this name doesn’t sound familiar, it, indeed, should: because this young society lady with excellent family connections founded Theranos. This health technology company claimed to have developed a revolutionary blood testing technology that needed only a drop of blood to do multiple tests at once. In what has been estimated as a ca. 700-million-dollar fraud, she fooled even sophisticated investors and—unless pardoned—will likely still be spending a good number of years in prison.
In contrast to Holmes’ never-realized new technology, the CRISPR technology used in potentially editing the germline of human embryos is not only already well-established but has been rewarded with a Nobel Prize. It has also been the foundation for the establishment of private and public companies by now worth in excess of $20 billion. Proof of principle for the technology has been, moreover, already repeatedly established, and it concomitantly has been relatively “derisked” many times over, including in above above-noted experiments of the Colossal company and in the recent treatment of a neonate.
In somewhat of an analogy, above above-noted Washington Post article pointed out that several leading genomic experts they had queried about Siddiqui’s testing claims of being able to assess the complete genome from only, on average, the DNA of ca. five to six trophectoderm cells, had expressed significant doubts about the accuracy of extensive genomic amplifications from only so few embryonic cells.
And if we, indeed, want to explore this claim a little further, one also must consider where Siddiqui and co-workers published their formal report about Orchid’s allegedly quite revolutionary amplification method: The paper appeared in one of the only recently established extension journals of Fertility and Sterility, named F&S Reports, not really where one would expect a first report to appear about such an important new technology. Hard to believe that a credible new technology of such importance, if technically indeed solid, would not have been published in a Nature or Science journal with a much higher impact factor. One wonders which journals had rejected the paper before F&S Reports accepted it, and why?
An additional claim made by Orchid—according to The Washington Post article—was that these microtrophectoderm biopsies of DNA through the above-noted whole genome amplification can accurately predict polygenic risks of preimplantation-stage embryos for basically every polygenic disease, from diabetes to hypertension, cardio-vascular disease, cancer, etc. And this claim is, of course, even more incredulous because even adult medicine is still struggling with the concept of risk prediction through polygenic risk scoring, and, in adult medicine, validation studies have already been going on for years. We, in contrast, are unaware of any published validation studies of significance in human embryos.
And then there is, of course, one additional major problem when it comes to PSR/PGT-P: In polygenic inheritance, it is correct that multiple genes on multiple chromosomes establish risk for the occurrence of polygenic diseases. This genomic risk represents, however, only a very small fraction of the total risk of developing a polygenic disease. A large majority of this risk has nothing to do with an individual’s genome, but derives from environmental factors affecting an individual’s genomic risk. One, therefore, really must wonder how Siddiqui’s corporate laboratory plans to account for future environmental risks of embryos, starting during 40 weeks of pregnancy (the time period most important for the establishment of epigenetic effects on the genome) and then after birth over an undetermined lifespan.
Consider for example (rightly or wrongly) that a patient’s embryo has a 2.7% chance of developing type 2 diabetes, a 3.1% chance of becoming hypertensive, and a 4.5% chance of having a heart attack The patient’s second embryo may have a 1.6% chance of having a heart attack later in life, but a 3.2% chance of diabetes, and a 5.8% chance of developing hypertension. Which of the two embryos should, or would, a patient then choose?
All of this, of course, assumes these embryos even implant, are not miscarried, and end up delivered, which, of course, is an incorrect assumption because only a small minority of embryos ever implant and, depending on age, between at least a third to over half of all pregnancies end up as miscarriages. Moreover, assuming the multifactorial often barely different risk percentages for various diseases based on the germline alone, does a choice between two embryos, so-defined, in most cases really make sense? We don’t think so!
How Silicon Valley has gotten interested
According to media reports, the evolving commercial concept surrounding the popularity of PRS/PGT-P in Silicon Valley appears no longer to be only the mass production of “designer babies.” The new goals are “super babies,” uniformly conceived through IVF (goodbye to sexual intercourse for conception!). Under this business model, allembryoso will undergo genetic testing before transfer into a uterus (i.e., except for unwanted “accidents”, reproduction will, therefore, primarily occur through IV). And, based on the test results obtained, the embryo will then, through genomic manipulations, be made “more super,” whatever that may mean for the future parents.
Some very prominent names in Silicon Valley have been mentioned in media reports, who, allegedly, have already had children who, as embryos, have undergone all of this absolutely nonsensical testing and enhancement. We’d better get ready not only for PRS/PGT-P, but also for the genetic editing of embryos through various techniques and with different technologies. The editing of embryos at very early stages of development (where an embryo at the cleavage stage has only 6-8 cells and a blastocyst stage has roughly 250-300 cells) can also not be equated with using CRISPR therapy in already born babies. A first case of a temporary clinical cure of a single-gene disease was recently reported in a newborn.4
That there are distinct ethical as well as clinical distinctions between modifying the germline in a preimplantation stage embryo and in a newborn is, of course obvious: With all the special considerations given by society (including the research community) to human embryos, preimplantation-stage embryos, whether in nature or in an IVF cycle, much more likely will never implant in a uterus than achieve successful implantation. But at the same time, while there is almost no chance for either ethical or clinical abuse in trying to cure an embryo or a newborn from a deadly disease, the opportunity for abuses is wide open in modifying the genome of a preimplantation-stage embryo in an IVF laboratory for a distinctively defined genetic modification of embryo enhancement rather than embryo cure from a terminal disease.
And then something interesting happened at the CHR
As fate at times plays an unpredictable role in life, at exactly the time when the CHR started addressing above above-noted articles in The Washington Post and The Free Press in the CHRVOICE and The Reproductive Times, the CHR’s Medical Director and Chief Scientist, Norbert Gleicher, MD, suddenly found one morning an e-mail in his inbox from none other than Cathy Tie and Eriona Hysolli, PhD, expressing interest in having a chat. As it turned out, a very prominent reproductive biologist at a university on the West Coast had referred them to Dr. Gleicher because they were interested in establishing a relationship with a knowledgeable clinician-scientist in the IVF field.
Tie and Hysolli had, in the meantime, decided to establish their new company in New York City, naming it the Manhattan Laboratory and the project they wanted to pursue in their company, to “fix” genetically abnormal embryos prior to implantation, the Manhattan Project. Tie as well as Hysolli moved to NYC and, as of October, the company also has offices and a brand-new research laboratory in the city. After several meetings, Gleicher accepted an invitation from Tie and Hysolli to join the company’s scientific advisory board.
For Gleicher, this development closed a very personal research circle because he, already in 2003, published a study that proposed already then the concept of “curing” embryos from single gene diseases prior to embryo transfer at preimplantation stages.5 He and the CHR are now looking forward to helping in making this over 20-year-old dream come true, utilizing all the amazing new technologies now available to scientists to edit the germline by following the highest ethical study principles and, of course, obtaining first all appropriate regulatory approvals for the development of such treatments.
References
Practice Committees of the American Society for Reproductive Medicine and the Society for Assisted Reproductive Technology. The use of preimplantation genetic testing for aneuploidy: a committee opinion. Fertil Steril 2024;122(3):421-434
Thiel Fellowship.™ https://thielfellowship.org/
Colossal. https://colossal.com/mammoth/
Children’s Hospital of Philadelphia. May 15, 2025. https://www.chop.edu/news/worlds-first-patient-treated-personalized-crispr-gene-editing-therapy-childrens-hospital
Gleicher N, Tang YX. Fertil Steril 2004;81(4):977-981