Today I’m thrilled to dive into the world of polygenic embryo testing (PGTP) and ImputePGTA with my guest, Jonathan Anomaly, Director of Communications at Herasight. Jonathan brings a unique perspective as both a former philosophy professor focused on the ethics of reproductive technologies and a leader at a company developing cutting-edge embryo screening tools. Together, we explore the latest advances in genetic testing and what they mean for families considering IVF.
In our conversation, we unpack the science and ethics behind polygenic testing, discuss how it differs from traditional embryo screening, and address the hopes and concerns that come with these new technologies. We talk about the real-world impact for patients, the importance of informed consent, and how families can make empowered choices about their reproductive journeys. Whether you’re a patient, a provider, or just curious about the future of fertility medicine, this episode is packed with insights.
In this episode, we cover:
- The basics of PGTP and how it compares to PGTA and PGTM
- How polygenic risk scores are developed and validated
- The potential and limitations of predicting disease risk and traits in embryos
- Ethical considerations and common misconceptions about “designer babies”
- The role of family history and ancestry in genetic testing
- How Herasight’s technology can help patients with different backgrounds and needs
- What the future holds for embryo testing, including IVG and gene editing
Resources:
- Herasight: herasight.com
- Jonathan Anomaly’s website: jonathan-anomaly.com
- IVF calculator and white papers on herasight.com
- Subscribe to the Egg Whisperer Show on YouTube and Spotify
Thank you for listening! If you want to learn more or have questions about your own fertility journey, join my next IVF class or reach out through my website.
Full Transcript:
Dr. Aimee: On today’s show, we’re diving into PGTP, the latest polygenic testing for embryos. The title of today’s show is PGTP Explained: The Latest In Polygenic Embryo Testing. My guest is Jonathan Anomaly, director of communications at Herasight, a company that develops embryo screening tools, including polygenic testing for disease risk prediction. Before he joined Herasight, Jonathan was a philosophy professor who focused on the ethics of reproductive technology. I’m excited to include him in my current series about cutting-edge technology and fertility medicine. Welcome, Jonathan.
Jonathan Anomaly: Thanks for having me, Dr. Aimee.
Dr. Aimee: To lay the groundwork for this discussion, can you explain the basics of embryo screening and the differences between monogenic and polygenic tests, how does it differ from PGT-A or carrier screening? Give us the lowdown. What is PGTP?
Jonathan Anomaly: I don’t want to encroach on your territory here, but here’s the overview. Your patients have probably heard of PGT-A, preimplantation genetic testing for aneuploidy, the chromosomal abnormalities like Down Syndrome. That’s been around since the 1990s. We’ve actually hired onto our team now Santiago Munne, who is kind of the pioneer of PGT-A.
There’s also PGT-M, preimplantation genetic testing for monogenic conditions, and that can be things like the BRCA variance that can put you at elevated risk of breast cancer, Tay-Sachs, which is a much worse disease, a protein folding disorder, etcetera. The idea is that a single gene, monogenic, can cause these outcomes. In some cases, just one parent elevates the risk. In other cases, both parents have to have a copy, etcetera. You can do carrier screening through blood tests for the parents to see if they have a copy to begin with. If maybe one or both do, then you test the embryos on top of it.
PGTP is just the latest PGT. P is for polygenic. Instead of one gene causing a particular disorder, the vast majority of diseases and traits, like height or even eye color, are caused by hundreds or thousands of small genetic variants that add up to an overall risk.
Just to take an example of breast cancer, everyone knows if you have one of the BRCA variants, you have an elevated risk of breast or ovarian cancer, 60 to 80 percent in some cases. However, that’s a tiny minority of all breast and ovarian cancers. The rest are caused by environmental conditions and then highly polygenic, hundreds or thousands of variants.
When we really want to test for genetic diseases, polygenic is where it’s at. It’s just that we hadn’t been here before because it took huge data sets, biobanks with half a million to a million people who are genotyped, phenotyped in the sense that we looked at the outward expression of their genes, do they have diabetes, breast cancer, schizophrenia. If you can diagnose them well and then genotype them, you can scan the whole genome and look across the billions of variants that we have which are associated with those diseases. For the first time now, we can test for those and then select an embryo or prioritize one that’s at lower risk of these diseases.
Dr. Aimee: I imagine that if I went into a waiting room at a fertility clinic, and I walked around the waiting room – I’m not going to do that, but I think about doing these things – and I went up to people that are doing genetic testing of their embryos, I think most people already think that these things are being done, that their embryos are genetically screened and that means they’re looking for things like increased risk for schizophrenia and other things, especially autism. But they’re not. All they’re doing is looking at chromosomes, which is so basic.
Now, what you guys are doing is so impactful because you’re finally able to see the things that I’ve always wanted to be able to see in embryos. They’re going to have healthier babies, potentially.
Jonathan Anomaly: Yes. Exactly. How much healthier depends on your family history. Some people have just a low overall set of risks in their family history. You could still have a kid with a polygenic disease, but where it’s really impactful is if you have a grandparent or a parent with schizophrenia or some other disorder, you can dramatically reduce the risk in those kinds of cases.
Dr. Aimee: What about for patients who, like you said, are low risk, how can this help someone who is just doing IVF, growing their family, wanting to bank embryos?
Jonathan Anomaly: One thing that we do that’s related is, you might call it a kind of carrier screening, a kind of polygenic carrier screening, where we actually sequence the parents and then we do a simulation 500 times over of what realistically they can expect from a round of IVF.
Dr. Aimee: Just 500 times, that’s it?
Jonathan Anomaly: Exactly. Just to see how their genes might combine and recombine, so we get an average sense of this is what you can expect in terms of your risks. What’s neat about that is then when you do a round of IVF or if you’ve already done one, you can see did we get genetically lucky or unlucky. Maybe our embryos are a little bit higher risk than average, so what we should do is another round of IVF. Or maybe we got lucky and there’s no point in doing another round of IVF. That’s kind of neat, that’s a preemptive move that you might do.
Dr. Aimee: The carrier screening that we’re offering patients now is pretty basic as well, and you guys are taking it up a notch.
Jonathan Anomaly: Exactly. You could do monogenic carrier screening, and now you can do a polygenic version of that.
Dr. Aimee: For people who need to do PGT-M, this technology replaces the need to create a probe?
Jonathan Anomaly: Okay. There are different kinds of sequencing, so in some cases, it can replace it. In other cases, it’s still better to do the traditional version of it. We have a lab where we’re going to offer A, M, and P, just because it’s easier sometimes to put those all together. But sometimes, it’s still worth getting a specialized test.
Dr. Aimee: If you’re doing P, that includes A.
Jonathan Anomaly: Yes.
Dr. Aimee: If you’re doing the polygenic testing, you’re also going to find out about the chromosomes. Is there something about Herasight’s technology that makes looking at the chromosomes more accurate than the traditional PGT-A companies out there?
Jonathan Anomaly: Two answers to that. On one hand, our version of PGT-A, that’s just PGT-A in our lab, it is a little bit more powerful than the average on the market. We’re sequencing at a greater depth so that we can see the chromosomes better. On the other hand, we have a truly revolutionary technology, which I guess I’m going to say it here for the first time. We’re going to be announcing this in November. Thanks to the genius that is Alex Young, our statistical geneticist at UCLA who worked for quite a while on this, we can take parental DNA, whole genome sequence the parents, then take the genetic data from the PGT-A test, which is just meant to count chromosomes, and we can put that together to algorithmically recreate the whole genome of each discrete embryo.
The reason that is of enormous importance, not just for us but any customer, is that it means we can serve people anywhere there’s an IVF clinic. Why? Because these are two commodities. Anyone can go to an IVF clinic and request a PGT-A test. Not everyone does. Maybe they’re young and they don’t need to, but they can. Furthermore, anyone can get a whole genome sequence. That’s a commodity that costs around $500, people are doing it all the time. We can put those together to recreate the whole embryo and then subject it to polygenic testing.
Why is that interesting? It’s way easier and cheaper than directly whole genome sequencing the embryo. That’s actually extremely difficult to get enough DNA from the embryo, from a few cells. So, there’s actually two things that we can do with PGT-A. One is just a higher resolution version of it, so we have fewer false positives and false negatives. The other is this entirely new thing, which is to sequence the parents, take the PGT-A data, and then understand the entire embryo genome.
Dr. Aimee: You’re saying patients of mine who have already gone through IVF and they’ve done the more standard PGT-A panel, they can still benefit and do PGTP without double biopsying their embryos and putting them through something risky?
Jonathan Anomaly: Exactly. Where they might lose some of them or damage them. The amazing thing here is there are millions of embryos in freezers right now, and many of them have been PGT-A tested. What people thought they were getting was a Down test, but what they were actually getting was a height test, a schizophrenia test. You can unlock that with just simple parental sequencing.
Dr. Aimee: You just said you’re launching this, you just said it for the first time here today.
Jonathan Anomaly: That’s true.
Dr. Aimee: How do we know that it works?
Jonathan Anomaly: Specifically for polygenic testing, how we know it works, and I can talk about the reconstruction of embryos, that’s a separate test. When we do polygenic testing, I guess it’s worth saying very quickly and simply, it relies on a technology called polygenic scores. I’ve already hinted at how that works. You have a huge biobank, hopefully racially diverse people, ancestry diversity matters here because there are some genetic differences between people.
You want to get an adequate set of people, a big set, half a million or more, and then people who have diabetes and people who don’t have diabetes, people who have whatever it is, tall height and short height, that sort of thing. Whatever it is that you’re interested in understanding the genetics of, you have to have a representative sample.
From that training data – and that term training data from AI now is common parlance, but we use it in genetics, too – what you can do is create a score where you look at all the variants across the genome, you have this polygenic score, and you say we think this polygenic score, which gauges the likelihood that you’ll develop schizophrenia or you’ll be six feet tall, we think it works. How do we know it works? It’s actually fairly straightforward. The statistics are hard, but it’s easy to understand.
Think about embryos in a petri dish as unrealized siblings. They have the same relationship genetically to each other and to their parents as a set of siblings who are 30 years old, 50 years old, 100 years old. If we can use our polygenic scores and take the DNA, with consent of course, from a bunch of adult siblings, run them through our scorers, we can guess their height within an inch, or we can guess whether or not they have schizophrenic symptoms, whether or not they have Type I or Type II diabetes.
You’re going to need large samples, because once in a while, you’ll get it wrong. You might get height off by a couple of inches, even if most of the time you are within half an inch. If you have a big enough sample, you can see does this predict the traits of adult siblings. If it does, since your DNA doesn’t change from the time it’s an embryo to the time you’re 100 years old, then it’s going to predict at least the genetic component of embryos.
I should say, just really quickly, obviously things like height or intelligence or something like schizophrenia risk, there’s a lot that depends on the environment, there’s a lot that depends on things we don’t know. We’re just addressing the genetic part of that.
Dr. Aimee: Thank you for that. As you were talking about predicting things, I imagine if I had more kids, I would want to make sure they had hands as large as mine or a nose as large as mine. I’m just kidding. But can you do that?
Jonathan Anomaly: Well, in the future, I assume so. I think facial features will be pretty easy to do and there will be large demand for it, but you would need to phenotype people. You would need to measure that stuff for millions of people. For obvious reasons, if you take a biobank like the UK Biobank, what do they want to do, what do they exist for? To promote health. That’s their mission. Of course, their main thing is they want researchers to develop polygenic scorers that help existing adults predict their own life trajectory. Am I at high risk of prostate cancer or schizophrenia? If I am, maybe I’ll intervene early. Similarly, and for the first time in the last few years, for embryos. So, I take it that the UK Biobank is not going to want to predict nose shape or whatever.
Dr. Aimee: An earlier intervention would be an earlier nose job. I’ve never had one. I think that’s what ethicists are worried about is that people are going to use this irresponsibly, they’re going to create embryos that are going to be unused, for the purpose of finding a perfect child who has large hands like me.
Jonathan Anomaly: As a surgeon, it is a good trait.
Dr. Aimee: It is a really good thing to have as a fertility doctor. I’m sure you get a lot of that kind of pushback.
Jonathan Anomaly: Of course. First of all, we’re not really offering much in the way of aesthetic traits. We do some. For example, height. We’ve watched a lot of people make their decisions. I usually don’t, it’s a genetic counselor or that sort of thing, but I have had experience with the customers. Usually, they’re not obsessed with one particular trait, especially not height. The first thing they’re going to do, typically, is look at their family history, look at the risks that really detract from quality of life. Then they are going to look a little bit at superficial stuff, we all do. Why wouldn’t we?
It’s not like everyone is maximizing height or that sort of thing. In fact, our CEO is extremely tall, and he wants to select for shorter children if he can because there are real health risks if you’re above, I think the line is 6’4” or 6’6”, something like that. Once you get up to seven feet and above, you live substantially shorter, you have heart defects, you have all kinds of problems, so it is a real worry.
Dr. Aimee: Every single one of the families that I’ve worked with that are working with Herasight, not one of them are doing it for aesthetic reasons. It’s all about having healthy children.
Jonathan Anomaly: Yes.
Dr. Aimee: For me, the thing is these numbers are already being created, the data is there, everyone has the right to learn whatever they want to learn from their embryos and make the best decisions for themselves.
Jonathan Anomaly: That’s kind of what we do. We actually have a couple of genetic counselors, and that team will grow, I’m sure, as our customers grow. We want to make sure that everyone understands their results and that they have zero pressure to select in one way or another. In fact, we even have mechanisms where if you don’t want to see certain traits, we can basically blank them out so that you can’t see them. Some people just want to focus on health traits. It’s very rare to get just an obsession with that.
Let me say one other thing, though. You mentioned fears about the perfect child. One way in which we visualize the choice between embryos is we have this embryo comparison tool. It just plots for any given embryo, is it high risk of diabetes, low risk of breast cancer, high risk of this or that. Every embryo is really a trade-off. The idea that there is this perfect embryo is just wrong because that’s not how things work.
Everyone has their own values. I like to say I prefer having a healthy life early in life, but other people want to live as long as possible, even if it means they have a higher risk of Alzheimer’s or whatever. People make their own choices and their own trade-offs.
Dr. Aimee: What about birth defects? For me, when I transfer an embryo that is described as chromosomally normal, it’s just heartbreaking for that baby to have a severe heart malformation. Is there anything about Herasight’s technology that could predict that?
Jonathan Anomaly: Various versions of it. We have a really good scorer for coronary artery disease, which is the main cause of heart attacks later in life. I like to use this as an example, our lab always uses this as an example. People who are skeptical of polygenic testing say stuff like, “It doesn’t work very well. It reduces risk a little bit, but it’s not worth it.” What we like to say is even with just a few embryos, if you have a background with coronary artery disease, your parents had it, your father in particular, our technology is actually as good or better than a statin. It’s remarkable. Statins are considered a modern miracle, all these men are living past the age of 60 or 70 when they often would have died of heart attacks in their early-60s back in the 1970s. When you think about that, you can basically prevent a lifetime of taking statins. It’s not a big deal to take a statin, but that’s a pretty effective intervention.
How much risk reduction you get sometimes depends on the number of embryos, but even with just three or four.
Dr. Aimee: What is a statin? For those who don’t know what that means.
Jonathan Anomaly: A statin is just one of these drugs that reduces the risk that you’ll have a heart attack.
Dr. Aimee: What about the birth defects of cleft lip, cleft palate, anencephaly, things like that?
Jonathan Anomaly: Some of those things we can predict. Anencephaly, I actually don’t know much about the origin of that.
Dr. Aimee: It’s a neural tube defect. None of them are genes, that’s the thing.
Jonathan Anomaly: Developmental disorders, okay, got it.
Dr. Aimee: The point that I want to make is that anytime you say, “I want to get pregnant and have a baby,” you also still say anything could happen. This screening will not predict whether the baby will have a birth defect like that. You could still go to the 20-week anatomy scan and find out that the baby has a birth defect, because those things can just happen.
Jonathan Anomaly: Yes. Some of those developmental disorders just happen. Even the genetics that we can predict, there are things you can do. If you don’t give your kids iodized salt, they’ll lose 20 IQ points or whatever it is, right there. Lead paint. There are all kinds of things we can’t control, but we can shift the probabilities. Maybe that doesn’t matter if you have a really trivial problem or the wrong shape nose. But if you have a serious risk of schizophrenia, it’s devastating. People who know actual diagnosed schizophrenics, nobody would choose to have that disease. That’s really what we’re doing.
Dr. Aimee: You just mentioned something that made me think of another question. How many embryos does a person need to benefit from this technology? Should people do it if they just have one, should it be three, what’s the magic number?
Jonathan Anomaly: I guess it partly depends on what your plans are for IVF. If you just have one embryo and you’re deep into your forties, you might not get another viable embryo, so you might want to just implant that. A little bit depends on whether you can and feel like you can afford another round of IVF, etcetera, so that you can have some comparison. It’s, of course, conceivable that you wouldn’t even use a single embryo if it had something really terrible. Most polygenic traits are not going to be like that. It’s usually going to be monogenic. If you had Tay-Sachs, most people just choose not to implant, for obvious reasons, it’s devastating as bad as the disease gets.
Otherwise, even with just a few, there’s a little bit of genetic luck. Sometimes you’re going to get some that cluster closer to each other genetically, so there’s not as much difference. Other times, there is. It just depends on that round. Even with as few as four or five embryos, you can get pretty significant differences in the traits that you care about.
Dr. Aimee: I have a lot of patients who see me over the age of 45. As we all know, age damages eggs, so they’ll often use egg donors. In those cases, patients have many embryos. Do you see people in the future using Herasight’s technology when they’re using an egg donor?
Jonathan Anomaly: Yes. We do have a fair number of egg donors. We also have some who are doing IVF electively. Quite a few are doing it electively, some even without a family history of disease, but simply because they can afford to do some extra genetic testing and they want to take every measure they can to reduce risk. If you give people even a 20% risk of a better life genetically at the beginning, it’s a one-off cost and everything is a little bit easier after that. It makes sense even when you have just a few embryos.
Dr. Aimee: When I do genetic testing for my patients, they actually assume that I’m screening their embryos for autism. I’m really not. Can you tell us a little bit about how Herasight helps with screening embryos for autism?
Jonathan Anomaly: Sure. The idea is we don’t have a comprehensive test for all forms of autism, but we do have a neuro risk score which is associated with some forms of low-functioning autism. There’s a portion of the population that has these rare genetic variants that interfere with normal neurological development. Some of that is conditions like dyslexia. Others are associated with low-functioning autism, which is a much bigger deal. We’re starting to capture the full genetics of it, but we’re not quite there yet. Some portion of it is environmental in the sense that male age is also a proxy for low-functioning autism, and we can’t do anything about male age. If you have an older client, we’re going to serve them and there is going to be a slightly higher risk of autism.
Dr. Aimee: That’s a really important point. When I have an intended father or a patient who is over the age of 50, I make sure that they know that from the outset. Then I say to them, “It’s really important that you know this before you start trying to grow your family, because I would hate for you to find out later that maybe you should have used a sperm donor.” Women at 50 are all using egg donors, so there’s no reason why men shouldn’t be counseled in the same way.
Jonathan Anomaly: That’s right. I could say one more thing. It’s not really a plug for us, but it’s this idea of freezing your sperm when you’re young. I actually really like the idea. People talk about freezing eggs. It’s very easy and very cheap to freeze your sperm. Now, it’s not that they’re in short supply, as you know. With eggs, the quality and quantity decline with time. With sperm, the quality does decline, but the quantity doesn’t. For that reason alone, why not just freeze sperm when you’re 20 and bank it, keep it in a freezer for a couple thousand dollars, and use it later.
Dr. Aimee: Exactly. I started egg freezing parties back in 2014. I actually did start sperm freezing parties, but I thought that was weird because you could actually freeze sperm at those parties. I’m like I’m done, that got a little awkward.
Jonathan Anomaly: Sounds like a fraternity party.
Dr. Aimee: It does. But I definitely promote that concept. A lot of the information you’re sharing with us today is complex. For some people, it might be too much, but yet they’re still interested in learning more. How can someone learn more about whether this is for them or not?
Jonathan Anomaly: There’s the usual, ask your doctor and do some research. The problem is a lot of doctors, even fertility doctors who are specialists, they don’t and can’t keep up with all of the latest statistical genetics research. How could they? These are PhDs in completely different areas that are totally specialized.
It’s easy to figure out PGT-A and PGT-M, they’ve been around for 30 years. PGTP is really new, and there is quite a bit of difference between the companies that are offering it. You can read about it in general at our website.
We have, for example, an IVF calculator. You can see your age, your station of life, what’s the likelihood you’ll get a certain number of eggs and how many embryos you’re likely to get from those, how many euploid embryos, etcetera. We have a tool where you can plug in the number of embryos you have or expect to have, three, five, ten, and your ancestry, which matters quite a bit, East Asian, Hispanic, and kind of mix and match that, and then you can see what real risk reduction you can get. If you want an explanation of that, and a justification because everyone should demand evidence from any company that offers this, we publish our research in journals, but it’s on our website first. We have our whitepapers, our shortened Substack post version of it, the easier version, and then Tweet threads and stuff.
On Herasight.com, we have these tools and we have these papers. Of course, for our customers, we have genetic counseling. We try to make absolutely certain that people understand all of this is probabilistic. But life is probabilistic, right? Every time you get in a car, there’s a probability you’re going to crash or you’re not going to get to work on time. I think people are going to have to get used to the fact that medicine is probabilistic, polygenetic selection is probabilistic. As mentioned, even the BRCA genes for breast cancer, if you have one, they don’t guarantee you get breast cancer. It’s about a 60-70% risk. People are already thinking like this. I think they’re capable of going another step and treating all of the other diseases as probabilistic just like that.
Dr. Aimee: A patient goes to her doctor and says, “I want to work with Herasight’s platform. Please run those tests for me,” and the doctor says, “I don’t believe in it. It’s unethical.” What is a patient to do?
Jonathan Anomaly: Go to Dr. Aimee, obviously.
Dr. Aimee: But let’s say there’s no Dr. Aimee. What else?
Jonathan Anomaly: There are clinics across the country and across the world where doctors are quite receptive to this. There are quite a few in California, for example. Unfortunately, you might have to move clinics. You might have to have your doctor with the company, that sort of thing. Some are open-minded, some aren’t. I think that’s always going to be true for cutting-edge technology.
I just wrote a paper on this with Santiago Munne, on the history of PGTP and even IVF. We looked at the headlines in the 1970s of doctors expressing shock that anyone would dare to do in vitro fertilization. Just a few years later, when it was clear that it was helping people grow healthy families, universal support. Now, I don’t know that there’s going to be universal support for what we’re doing. There are some objections that are religious and so on. We have a professional debater in a way. I’ve written a book on this, I was a philosophy professor, but I have no interest in persuading everyone you have to do this. People make their own decisions.
Dr. Aimee: Do you have a “find a clinic” search?
Jonathan Anomaly: We do, yes. It’s not on our website yet. It will be in a month or two. We have a person who specializes in matching patients with clinics. Our go-to is always Dr. Aimee, but obviously, if you’re in another part of the world, and this is going to be an increasing audience because we have this way of reconstructing entire embryo genomes. We have some people who are in Europe, and it’s illegal in lots of Europe, but maybe their spouse is in a country where it is legal, so they would go there.
Dr. Aimee: I can’t imagine there’s going to be more to come in five to ten years. Do you see anything revolutionary happening five to ten years from now?
Jonathan Anomaly: Yes. I saw something revolutionary happen this week, which you probably read about. I don’t think it’s ready to go yet. We’ve had in vitro fertilization for decades now. Then we had these preimplantation genetic testing, these new versions of it with A, M, and now P. The next big thing that’s coming, I think, is IVG, in vitro gametogenesis. That idea will freak some people out. Other people will love the idea. It wouldn’t put you out of business, but it would change your business quite a bit. Right?
Dr. Aimee: Yes. I want it to, actually.
Jonathan Anomaly: This is the idea that, thanks to a Japanese researcher, I believe in 2010, in rats, he figured out how to take an adult cell, like a skin cell or a blood cell, it could be marrow or whatever, turn it into a pluripotent stem cell, the kind of cell that basically embryos have. The reason for this is, remember, back in the early 2000s there were the stem cell wars of should we be doing research on this or not. A lot of that research went overseas to Japan. They figured out that we don’t need embryos to create these pluripotent cells. We can take your own cells, basically reverse age them, and put them in a prior state.
If you have a pluripotent stem cell, it can become any kind of cell, and that means it can become an egg. That means you could imagine a vial of blood or a bunch of skin cells, you wouldn’t need to do IVF, you could create a thousand eggs just from your own skin. We were talking beforehand about what are the worries people would have. It’s a real legal risk. What if you steal someone’s hair?
Dr. Aimee: That’s exactly what I’m thinking. Someone is going to come up and pinch me and I’ll be like, “You just stole my eggs.”
Jonathan Anomaly: Exactly. You stole my eggs. Then you’re just going to have a slew of children that are related to you.
Yes, I think that’s going to require a legal framework change. I think before this scales, it’s going to be easily a decade. But it also means imagine the selection that you can do. Two schizophrenic parents could almost guarantee a non-schizophrenic child. That’s pretty remarkable. Whereas, with just two to four embryos, you’re going to be able to reduce the risks even substantially, but not get them down to near zero.
Again, this is going to freak some people out. I think it’s great. I think it’s interesting.
Dr. Aimee: Since I started as an IVF doctor, I’ve always said there will be a day when women can get pregnant through IVF without injections, without a needle into the ovary, and I just knew the day would come. I used to say I will not be alive to see it, but I think I might just be alive to see it.
Jonathan Anomaly: I’ll tell you one other thing that’s maybe even more interesting. I try to talk with people who are interested in gene editing, the Church Lab at Harvard, MIT, and people at the forefront of this. I’m not capable of fully understanding what they do, so I just take their summaries of what they’re up to. They tell me that, contrary to what a lot of people think, gene editing is a long way away.
CRISPR-Cas9, the system that many people have heard of, actually up the street at Berkeley, Jennifer Doudna is one of the co-discoverers of that and won the Nobel Prize for it, that’s the main editing system that is used with lab rats and so on. There are too many off-target mutations. If you want to target one particular genetic variant so that you don’t have a disease or whatever, there is some probability that it will accidentally target other genes. Secondly, the kinds of things that would benefit a lot of people would be highly polygenic and it would require hundreds of edits, or even thousands. Not only are we not ready because of those off-target mutations – I’m not involved in this at all, I mean we as humanity – we also don’t know the genetic architecture of a lot of complex traits.
The cool thing about selecting between embryos is you don’t have to know what every single gene does. You’re choosing among whole natural embryos the parents produce. As long as we know a lot of the correlations and some of the causes, what we can do is dramatically reduce risk of disease or increase whatever trait you’re talking about. But if you want to edit all of those genes, you better know exactly what every single one of those genes are doing and that you didn’t misedit it.
I actually thing, IVG, which we just talked about, is going to be much more transformative and it’s much closer than something like gene editing.
Dr. Aimee: I hope to be alive to see that. Maybe I need to have an offshore clinic, because I’m not sure it’s going to be legal in the United States.
Jonathan Anomaly: Fair enough.
Dr. Aimee: We’ll see. People criticize me for offering PGTP. I don’t really care, because all I care about is doing the very best for my patients. For me, informed consent when it comes to genetic screening is making sure that patients know all the different options that they can choose from, so then they can make their own decisions.
Jonathan Anomaly: Exactly.
Dr. Aimee: There are trolls out there – yes, I did call those guys trolls – who are saying that I’m unethical, that I’m creating designer babies. For you guys as a company, what is your stance on that?
Jonathan Anomaly: First of all, we accept the bioethics consensus, which is informed consent. That’s the bedrock of modern medical ethics, and there’s a reason for that.
Back before World War II, in the United States, for example, sometimes doctors would perform procedures during surgery – there’s a famous case of a hysterectomy – without telling you they were going to do it. They’d just go in there, look around to see what the problem is, and just do something. After that, the Supreme Court and others have ruled doctors can inform their patients, they can even urge them in some circumstances, like I would or wouldn’t do this or I would recommend this, but what they can’t do is control what they do with their bodies, or with extensions of their bodies, their embryos, their eggs, their sperm, etcetera.
We accept that entirely. Each of us in the company all have our own views on different things, what we would and wouldn’t select for, what policies we want, but we all accept that, and I think it’s fairly clear.
I will say in defense of people who worry about this, there is one problem which is extremely, what we like to call asymmetric information, where one party knows a lot more than another, they can manipulate it. I think it’s really important for doctors and companies like ours to be as absolutely clear as possible, this is what we’re doing and what we’re not doing. If there are downsides to what we’re doing, here they are. It’s up to you to navigate that, we’re not going to decide for you.
I think it’s pretty straightforward. We should inform people as much as possible and then defer to their values and their choices.
Dr. Aimee: What about the critics who say this is just for wealthy people?
Jonathan Anomaly: Like all technologies, of course, wealthy people are going to afford it first. Markets naturally drop prices and increase quality. The other thing is there are places like California, for example, that have just decided to subsidize IVF. I think Israel has decided, China, and other countries, too. There is some worry that over the next 10 to 20 years some of these technologies will be more affordable to the rich, some of that is inevitable. But there are solutions, insurance companies, government mandates, etcetera.
I get a little worried about governments going too far in this realm. In the Middle East, Qatar and some of these countries are making genetic testing mandatory. I don’t know if that’s too far or not, but I do worry a little bit as the government gains more power over reproductive choices. I think there are solutions to this problem of access, but every solution has a trade-off. How much do you want to empower governments to engage in these kinds of mandates?
Dr. Aimee: Jonathan, thank you so much for coming on today. Is there anything else that you’d like to add or feel fertility patients need to know about testing?
Jonathan Anomaly: Definitely doing your research. Caveat emptor, as the Latins say. Buyer beware is always the best advice. There are a lot of companies out there, and probably physicians as well, that offer polygenic scorers now. There are a few of them, and some are better than others. I’m not going to try to self-promote too much. But ask them, “How did you validate your test results? How do you know they work? Have you published papers and put them on your website, showing the extent to which they work? Have you validated across diverse ancestry groups?”
If a company is offering polygenic scorers and they don’t take account of your family history of disease or your ancestry, they are either deceiving you or they don’t know what they’re doing because this is a real issue. Until we have perfectly diverse ancestry groups represented in all biobanks, we actually have to adjust for ancestry. It’s really important to ask those companies, “How do you know this works? Prove it to us.” We’re happy to do that. Then ask, “How do we know it works for our specific ancestry?”
Dr. Aimee: Where can people find you and Herasight?
Jonathan Anomaly: We’re at Herasight.com. That’s Hera like the goddess, Hera, and sight like insight. I have my own website, but who cares about me. That’s just Jonathan-Anomaly.com.
Dr. Aimee: You have to tell us about your name, Jonathan Anomaly. What an anomaly. Tell me about that name.
Jonathan Anomaly: Okay. Last time we spoke, I learned that we were at Berkeley at the same time. That’s when I changed my name. It was actually because on both sides of my family… On one side, it’s an Ellis Island name because it’s Jewish and they changed their name to sound less Jewish. On the other side, it’s Dutch and Irish, and we had a corrupted version of the original name. I thought about having this arbitrary name, I was at Berkeley, there were a lot of free spirits at Berkeley, and I just thought I kind of want to change my name.
What gave me the initial idea to do it was reading ‘1984’, and I know Eric Blair was his real name and George Orwell was his pen name. A lot of these authors had pen names, and I thought that was kind of cool. I thought I would do it, and I did. I was only 20 years old, and maybe it was a mistake, but becoming Dr. Anomaly or Professor Anomaly sounds like an evil superhero, so I kind of like it. I don’t know.
Dr. Aimee: What did your parents say?
Jonathan Anomaly: They didn’t mind, but I didn’t tell them at first. But they really didn’t mind. I was raised in a nontraditional way, let’s say.
Dr. Aimee: Jonathan, thank you so much for joining us and sharing your expertise.
To our listeners, you can learn more about Jonathan and Herasight by visiting Herasight.com. If you want to dive deeper into fertility, IVF, embryo testing, check out DrAimee.org or join my next IVF class where you can ask me your questions directly and get guidance tailored to your journey. Don’t forget to subscribe on YouTube or Spotify and share this episode with a friend who might find it helpful. I’m Dr. Aimee, The Egg Whisperer. Thanks for listening.
