For Our Kids, We Will Always Want To Know

Re: The Last Children of Down Syndrome

Sara Eshelman
Nov 23, 2020 · 6 min read
Photo by JESHOOTS.COM on Unsplash

An article published in the Atlantic this week, provocatively titled “The Last Children of Down Syndrome,” describes the widespread use of prenatal screening and genetic testing under a universal access program in Denmark. The piece focuses specifically on the ethical and cultural ramifications of the program on Down syndrome. Fewer than a dozen babies are born with Down syndrome per year in Denmark, compared to 5–6x that in the US (population-adjusted).

It’s a long read filled with the wrenching stories of families who have and have not had babies with the condition. Upon first skim, I assumed that the program involved the widespread use of non-invasive prenatal screening (NIPS). NIPS tests for life-limiting chromosomal disorders and other genetic abnormalities as early as 10 weeks into a pregnancy, using a simple blood draw from the mother. NIPS was introduced in 2011 and began to see global adoption by 2012. By one estimate, 4–6M pregnant women elected to do NIPS from 2012–2017. Because labs don’t report individual test volumes, it’s difficult to estimate the exact number of NIPS tests conducted each year, but based on the above, we can assume a “run rate” far in excess of 1M per year. The US represents a sizable portion of this figure: with 4M births per year, it’s safe to say it’s fast becoming mainstream here as well.

Upon closer examination, it appears that NIPS is actually less common in the country, which instead relies on a combination of cumulative risk scoring and ultrasound findings followed by more invasive testing for high-risk women.

Genetic testing, especially of fetuses and embryos, has long been a fraught ethical debate. Indeed, the article devotes the vast majority of its word count to this dimension. There’s a mother of a child with Downs syndrome who gives advice to pregnant women to help them make their decisions, but worries that she’s helping create a society where her son has less of a place and fewer resources; then, there’s a second mother who was wrongly told her baby would be healthy who wishes she’d had the chance to have a different family.

But here’s my takeaway: Families want peace of mind and sometimes, as a result, they’re faced with heavy decisions that they’d most certainly rather not have to make. But they want to know. The invasive procedures used in Denmark carry a small, but non-zero miscarriage risk — a risk that many people I know have agonized over. But still, they want to know. And they want to know about as many risks as they possibly can.

This is fundamentally different from the way adults view genetic testing. A year ago, I wrote about how even if it’s free, many adults would choose not to undergo genetic testing. They would rather not know about risks that most of them will not be able to manage any differently or better than they’re already doing through traditional means. A recent study by Mayo Clinic reinforces this: family members of cancer patients found to have a genetic mutation were offered free genetic testing. Only 1 in 5 accepted it.

But for our kids, we seemingly always want to know.

The same article talks of “knowing” even further upstream. What families once found out halfway through a pregnancy can now be gleaned at 10 weeks, and increasingly, during IVF, through preimplantation genetic screening (PGS).

I expect to see more and more of this. And as the price comes down, more still. So the next question is: if genetic testing becomes a cornerstone of our reproductive journey in the future, what else happens?

Here’s my preliminary list. All comments, critiques, and additions welcome.

  • NIPS becomes an entirely mainstream method of evaluating risk, non-invasively. There is a mounting body of evidence (and recommendation by ACOG this summer) that NIPS should be an insurance-reimbursed test for all women, both high-risk and low-risk, because of its superior performance. It’s only a matter of time before every pregnant woman does NIPS.
  • Carrier screening becomes a couple’s first encounter with their own genetics. Carrier screening has already expanded from a few dozen genes to hundreds. If this continues, it may soon represent the first significant encounter with genetic screening by men and women alike. There’s no technical reason why carrier screening wouldn’t eventually include autosomal dominant traits such as BRCA mutations, along with recessive ones for which the parents could be carriers. Again, it’s only a matter of time before this increasingly common screening step reveals important information about the health of the parents, in addition to that of their potential offspring.
  • We continue to improve our knowledge of genetic variants. There are vast swathes of the genome that we are utterly in the dark about. We need to continue to improve our knowledge of the impact of certain variants on health and disease. This means more sequencing of diverse, healthy and sick adult populations, more GWAS studies, more data sharing.
  • The imperative to counsel patients with empathy and efficiency grows. I should probably write a whole piece about genetic counselling, an area of particular passion. But the short form is: it can be an enormously important consultation that helps patients and families understand their results, make sense of complex probabilities, and make hard decisions based on life stage and risk tolerance. We have too few counsellors to meet patient demand. We need better, more automated systems that enable genetic counsellors to focus on patients and families facing the most complex questions.
  • Systems develop to empower kids and families to monitor and enhance their genetic findings over the course of their lives. If they were sequenced, this means continuing to monitor the literature around VUS and alert them of reclassifications. If they were genotyped, this could mean enhancing their genetic coverage as lower-cost sequencing becomes available and relevant given their health and life stage.
  • Create community around the journey. Becoming pregnant goes from something that’s unplanned or semi-secretive to a journey in itself. Families, and specifically women, rely on one another for support during other phases of their pregnancy and parenthood journeys, and this will be no different. I’ve long hypothesized that genetics could be an ultimate source of network effects. Our genes connect us inextricably to one another, and they also directly affect our experience of life. The connection and engagement that takes place among rare disease patients and their families — a connection based on shared genetics — foreshadows how a broader set of patients will interact. Adding genetic understanding to the journey of becoming parents pulls forward a complex set of questions and decisions. As “knowing” becomes increasingly mainstream, the families who have traveled a similar path will play an essential role in supporting those that come after them.

Many people have advanced thoughtful critiques of the future outlined in this article, and I want to acknowledge the value — and necessity — of those critiques. There is an undeniable “dark side,” in which this technology creates a society many of us would not want to live in. I believe the only way to mitigate this is by backing mission-driven founding teams whose vision of success for the company contributes to a future that’s equitable and inclusive for everyone. That’s what I aim to do as an investor, and I’m heartened by the number of founders I’ve already met who are taking this responsibility in stride.

I want to thank Jeremy Grushcow, who was instrumental in helping me understand what’s possible and cultivate (and fact check!) this point of view. He and his incredible team at Embryome are making key parts of this future a reality.

Spero Ventures

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