Choice Over Chance: Polygenically Screened Babies
“All of humanity's problems stem from man's inability to sit quietly in a room alone.”
- Blaise Pascal
Sorry I was MIA last week. I had another loaded week so I decided to skip the newsletter. Nevertheless, we are going to be looking at some pretty cool but possibly controversial stuff today.
Polygenically Screened Babies
Nearly 43 years ago, the first IVF baby was born in England. Last year, the first polygenically screened baby was born. This is her:
It is a big deal for humanity because with this technology, we can go baby-shopping. Yep, we can walk into a genome screening center, check out a bunch of different embryos, see which one has blonde hair and purple eyes, and bring that embryo to life. Commoditizing babies now, are we?
But there are far more important use-cases than just being able to shop for different physical traits. It can help us prevent genetic diseases like schizophrenia, diabetes, heart disease, and breast cancer. Before we get happy (or outraged) about this development, let us first understand what goes on behind the scenes.
We will be covering the following today:
1️⃣ How does IVF work?
2️⃣ Types of genetic problems
3️⃣ How Polygenic screening works & why it is a big deal
4️⃣ Producing designer babies
5️⃣ Are humans playing god?
In Vitro Fertilization (IVF)
To understand how polygenic screening works, we first need to understand how IVF works. From Mayo Clinic:
During IVF, mature eggs are collected (retrieved) from ovaries and fertilized by sperm in a lab. Then the fertilized egg (embryo) or eggs (embryos) are transferred to a uterus.
People opt for IVF for a variety of reasons such as infertility issues or to ensure their baby isn’t born with genetic disorders.
The latter reason is of particular relevance to this post. How exactly does IVF prevent genetic disorders from getting passed down? By screening the fertilized eggs (i.e embryos) for genetic problems. Not all genetic problems can be found using this method though and this is the gap Polygenic screening (PGT-P) is trying to address.
Before we talk about PGT-P, let us first look at the types of genetic problems that get passed on.
Types of Genetic Problems
A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be:
1️⃣ Monogenic: caused by a mutation in a single gene. Examples: sickle-cell anemia and cystic fibrosis
2️⃣ Polygenic: caused by a mutation in multiple genes. Examples: diabetes, breast cancer, and schizophrenia
3️⃣ Chromosomal: when there is a missing, extra, or structurally damaged chromosome. Example: Down syndrome
Today, we are only able to screen for monogenic and chromosomal abnormalities in embryos produced via IVF. That is still fucking great. I have a friend who has a family member with down syndrome and the stories I hear are unimaginably painful.
Polygenic disorders, on the other hand, have been elusive. They are more difficult to detect since they involve interactions between thousands of different genes and we have been able to screen for them so far. But this is where we have achieved a breakthrough with PGT-P.
How Polygenic Screening (PGT-P) Works
You get the eggs from the female, you fertilize it in a lab by injecting the sperm and you create multiple embryos. So far, we could only scan these embryos for chromosomal and monogenic disorders and choose the healthiest among them.
With PGT-P, we can screen embryos for polygenic disorders too. Thanks to this screening, you can evaluate which embryos are at risk of which polygenic disorders. Like this:
You can see how the risk percentage (column 1) for each disease is calculated for this embryo and you can compare it against the average risk percentage (column 2) to see whether your embryo is on the safe side or not for a particular disorder. There is also an overall score called the Embryo Health Score (EHS) that tells you the health of each embryo.
(For a better understanding of EHS, check this video by LifeView, the company that did the polygenic screening for Aurea)
All of this makes it easy to detect and choose a healthy offspring.
Producing Designer babies
So far we have looked at polygenic screening for disease prevention. But there is another interesting application: designer babies.
Diseases are not the only polygenic outcomes. Traits like height, skin color, and hair color are also the result of interactions between thousands of genes (i.e polygenic). Now that we have the technology to screen and read genes for polygenic traits, we can shop for babies with specific physical attributes. This means you can choose a baby with blue eyes or white skin. You can even possibly choose between embryos of low IQ and embryos of high IQ.
This is where things get interesting and gray. From this ACX blogpost:
In theory, you're not supposed to use polygenic screening to produce designer babies. What about in practice? Screening companies will give you the raw data if you ask for it, so if you want to screen for an embryo with green eyes, all you need to do is find some third party algorithm that can screen genomes to figure out the baby's eye color and plug in your data. Does anything like this exist? I don't think so, but I think it would be trivial for a genetics PhD student to make.
[edit: existing polygenic screening companies might not read enough genes to do this. Although it would be easy to offer a more complete service that reads most genes, banning the more complete version might be one way regulators could prevent this otherwise hard-to-prevent thing.]
Imagine a future where we can buy “mods” to augment our capabilities and traits from skin color to skin texture. We could have bulletproof skin or be able to jump 30 ft into the air thanks to the ‘ultra-kangaroo-jump’ mod. It sounds like Sci-Fi to us today but it will be the reality for our grandkids. In such a future, shopping for ‘designer’ babies won’t sound so unethical.
In today’s world, however, it is pretty clear that this is unethical and we need strong regulations to prevent the misuse of this technology. So let us get to the most interesting part of this discussion: ethical considerations.
Playing God
With PGT-P and with IVF, we are choosing which lives should be born and which shouldn’t. In some sense, we are playing god. This is where some ethical questions are raised. Who are we to choose which lives should be born and which shouldn’t? But I submit to you that this objection is stupidly absurd.
We are a species of problem solvers who innovate and engineer solutions to reduce suffering. PGT-P should be welcomed and encouraged because it is a solution to remediate a problem we are facing today: inheriting horrible genetic disorders.
If you had to choose between less suffering and more suffering, which one would you choose? It is actually great that we get to play god because, for the first time in our life, we can choose less suffering instead of leaving it up to choice.
Wait, what if someone wants to choose more suffering? While it sounds ridiculous and is antithetical to the human struggle, I can certainly imagine some people doing it. For example, someone might feel extreme pity for the embryo with Schizophrenia and wants to desperately care for it and nurture it. Maybe he feels guilty about how he could never take good care of his schizophrenic mom and he wants to compensate for that by caring for the embryo which has a high risk of schizophrenia. Another scenario could be if the to-be-parent had masochistic or perhaps even sadistic tendencies.
The patients or to-be-parents should have no say in choosing the embryo for two reasons:
1️⃣ They are biased
2️⃣ They might just not know enough about the disease and its implications so their judgment would be based on insufficient information
Policymakers and regulatory bodies have a crucial role to play here in ensuring embryos are chosen in an objectively sound fashion. It should be made illegal to select an embryo that does not have the highest EHS and IVF centers should, by law, be asked to choose the embryo with the highest EHS without consulting with the parents.
In the near future, polygenic screening technology will become universally available and will be bundled together with IVF by default.
In the far future, we will have gene editing capabilities far more advanced than what we have today (like CRISPR) that will allow us to not just detect gene abnormalities but also modify those genes and fix those abnormalities.
The future is surely exciting.
Thanks to Pranati & Pragya for reading drafts of this.
All views expressed by the author are personal.
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