“Genetics Advice for Generation Starships” by Dan Koboldt

Disclaimer: This article is for entertainment purposes, and should not be considered medical advice. Also, it discusses primarily the science, and does not attempt to address relevant ethical, social, cultural or political issues in depth.

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Recent years have seen a rapid acceleration of the discovery of exoplanets—planets that reside outside of our solar system. Though most of the planetary bodies discovered so far are not suitable for human life, it's only a matter of time until we find some that are. The challenge, of course, is that space is pretty huge. Beyond our solar system, the closest star (Proxima Centauri) lies 4.243 light years away. The fastest man-made spacecraft yet recorded (Helios 2, an unmanned probe that reached a speed of just over 157,000 miles per hour) would realistically require 19,000 years to make the journey.

Let's say, for the sake of argument, that we can send a nuclear rocket at one percent of the speed of light, and make the trip in about 424 years. That's around seventeen generations. Once the ship arrives, the descendants of those brave travelers will be expected to colonize the new world. Yet there would only be room for so many individuals on board the ship, which raises the question: who should we send?

I should disclose at this point that I'm not a physicist or an aerospace engineer. I can't help you design the ship. However, as a human geneticist, I can offer some advice on choosing the founders of your future colony.

There are a few stages of a generation ship's journey when human genetics considerations come into play. The first, of course is before the ship leaves, when we're deciding who should take part in the crew. Assuming that there are many more volunteers than berths on the ship, there would necessarily be a selection process. As the ship's crew is selected, we're witnessing the first step in what's called a population bottleneck: a small number of individuals chosen from the larger population, who will go somewhere else and become the founders of a new population.

Population Bottlenecks in Human History

There have been several population bottleneck events in human history that should be informative. One of my favorite examples took place in Finland. In the sixteenth century, most of Finland's population lived in the southern and coastal regions. The king of Sweden—who ruled both countries at the time—sent families to settle in Finland's northern regions. One group of about twenty families undertook the longest journey north to the Lapland region. Over time, the founding families married and had children.

Since then, the population of Finland has grown rapidly, rising from a few hundred thousand people in the eighteenth century to 4.5 million Finns today. Yet there is also a strange phenomenon in modern-day Finland: a number of extremely rare genetic disorders are far more common there than in the rest of the world. The reason for this has to do with the population bottlenecks of the middle ages. During those early migrations, some extremely rare genetic variants that cause recessive disease (meaning you need two copies of the variant to get the disease) were selected for the journey north. Many others were not, and generally won't be found in the Finnish populations today.

But the handful of rare variants that tagged along remained in the population as it grew. And because of the limited number of founders, a lot of people who had children were distantly related to one another. This dramatically increased the odds that a child born in Finland will inherit two copies of a recessive disease gene.

The Finns call this their "rare disease burden" and although it is devastating for the patients and their families, it has also provided a remarkable opportunity to study recessive genetic disorders that are rare elsewhere in the world. Many of the diseases that we know and can diagnose today were first studied in Finnish populations. Yet, coming back to the generation starship, this rare disease burden is something we'd like future generations to avoid.

How do we go about doing that? Step one is simple: maximize the input diversity. That means (1) sending as many colonists as possible, and (2) selecting colonists from a wide range of genetic ancestries.

The human genome comprises 3.2 billion base pairs. Most of these are the same from one individual to the next (we’re all 99.99% identical at the DNA level). Even so, Each of us has about four to five million genetic variants. Most of the variants in a given person are common in the population, having arisen a long time ago. In terms of sequence diversity, people with African ancestry have the highest, followed by European ancestry and then by Asian ancestry. There are also ancestry-specific variants that arose after ancient migration events, i.e. expansion out of Africa into Europe, Asia, and elsewhere. We want to capture all of it.

Next, we come to another important consideration for generation starships: genetic testing. Thanks to recent advances in DNA sequencing technologies, we can sequence a person’s entire genome in about a week, at a cost of around $1,200. It stands to reason that by the time we can build a fast enough spaceship, genetic technologies will have progressed even further. Any candidates for the ship would undergo genome sequencing. We’d use the data in a couple of ways: first, to catalogue the genetic variation, and second, to screen for possible disease-causing alleles that we might not want to allow on the ship.

On the Generation Ship

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Now we get to the fun part: the journey on a generation ship. The passengers and crew will get together and have children. That's kind of the point, isn't it? Unfortunately, as geneticists sometimes lament, it's not ethical to carry out carefully-designed breeding programs in humans the way we do in mice. Free will and all of that.

However, I think that those aboard the generation ship would employ a couple of strategies to look out for future generations. Some of these touch on ethical issues on which there may not be a consensus. I think that the organizers of the mission, in consultation with geneticists and medical professionals, would need to plan this ahead of time and write it into the mission charter. Some of these measures may seem severe, but they're all part of a common goal: ensuring the health of future generations and the colonists on the distant world.

1. Continued Genetic Screening.

Given the relatively small and completely isolated population size aboard a starship, couples should receive genetic counseling prior to starting a family. Part of that discussion would include testing to determine whether or not they're distantly related.

Consanguineous unions between blood relatives (even distant ones) should be avoided if at all possible. The devastating effects of such unions are apparent in groups that are geographically and/or culturally isolated, such as Amish communities and Ashkenazi Jews. These groups arose from relatively small founder populations, and only married within their communities. This dramatically increased the odds that two people each carried one defective copy of a gene (i.e. heterozygous carriers).

If you learned about genetics and inheritance with Punnett Squares—probably during your Biology 101 class—then you might remember that about one fourth of the offspring from two heterozygous carriers of a recessive gene will get the recessive disease. This is why there's a much higher burden of rare metabolic disorders in Amish, Ashkenazi, and other isolated communities.

Any recessive genes that make it onto the generation ship—or arise during the voyage—would have similar consequences over time. It's a game of chance that no one on a generation starship would want to play.

2. Genetics meets in vitro fertilization.

Children born on the ship would undergo genome sequencing, both to record which genetic variants were inherited from the parents and to catalogue any new mutations that appear. Each of us is born with fifty to sixty mutations that arose after conception, meaning that they're not present in our parents. These de novo mutations occur somewhat randomly throughout the genome. Most of them will have little to no effect, but if they land in the wrong place they can have severe consequences. I happen to study rare genetic disorders in children, a significant proportion of which are due to unlucky de novo mutations.

If disease-causing mutations do arise (or slip past the screening), it might be possible to prevent them from being passed on to future generations. Doing so would require in vitro fertilization, during which fertilized embryos would be screened for the mutation. Only non-mutation-carrying embryos would be implanted.

Recent technological advances have greatly improved our ability to make precise, directed changes to the DNA of living cells. In principle, this opens the door to gene therapy for patients suffering severe genetic disorders. On a generation ship, human genome engineering would be a huge asset to remove deleterious mutations from the population before they can rise to prevalence.

Of course, these powerful technologies would allow for genetic manipulations well beyond preventing disease. Everything from physical appearance to athleticism to baseline intelligence might be on the table. This raises the difficult question of whether people aboard the ship would be permitted to design their babies any way they want.

That's a tough decision. I can't offer many arguments why this should not be permitted, as long as it doesn't get in the way of more medically important decisions. However, I will say that many of the traits we might want to propagate in our offspring are also exceedingly complex, and result from subtle variations in many genes. Thus, it would be much more challenging, borderline impossible, to design a baby exactly the way one would like. Besides, any time you make a change to DNA, even a well-intentioned one, there are risks involved. Current technologies have "off-target" effects that can alter sequences other than the desired ones. This is an argument for only permitting genetic alterations that have a medical necessity.

3. Population Control

So here's a tricky issue about generation ships. For the reasons we've discussed, genetic diversity should be maximized by bringing as many unique chromosomes as possible. At the same time, procreation during the journey will increase the size of the ship's population in a finite space. As fun as it might be to allow the passengers to reproduce freely, population controls would be necessary. I don't want to go into the math, but not everyone who wants to have a child will have that luxury.

Birth control would be mandatory for everyone aboard the ship. Genetic counseling, too, and it might even come into consideration when passengers choose mates. A lottery system might be employed to select which couples were allowed to have a child. I can't imagine that any couples would be allowed more than one. This seems harsh, but it's a necessity of living within the finite resources of a ship that has a long way to go.

One could imagine that it also opens some interesting social opportunities, because there would be far fewer children than everyone might want. I'm not a sociologist, but I think the role of biological parents might change to involve more members of the community in raising children.

Populating the Distant Planet

On the new world, we can reasonably assume that the population would grow rapidly. Some genetic variants will disappear, while others will become more prevalent. This is called genetic drift, and there’s no way to predict how it will go.

However, the colonists will need these processes when adapting to a new environment. The population bottleneck of the ship, and the ensuing voyage, will have reduced the overall genetic diversity. That's going to hurt the colony initially, especially when it comes to things like immune resistance. Even so, the success of bottlenecked populations in human history—like those who migrated out of Africa into Europe and Asia—suggests that the colonists have a good chance.

Ironically, the colonists may consider relaxing their efforts to (artificially) remove newly arisen variants from the population. A mutation that appears deleterious in one context may be favorable in another. Sickle cell disease offers a classic example of this. SCD is a recessive disorder, so you need two altered copies of the gene to get the disease. One would think that natural selection over time would keep SCD at very low levels in the population. However, it remains somewhat prevalent because, while two copies of the gene gives you SCD, having one copy of the gene is protective against malaria. In central Africa and other areas where malaria is endemic, this offers a strong survival advantage.

One can imagine how such scenarios might arise on a new world. Although the colonists should continue genetic testing, counseling, and surveillance, it may be best to let nature take over.

Copyright © 2019 Dan Koboldt

Dan Koboldt is a genetics researcher at a major children's hospital. In the last fifteen years, he has published more than seventy papers in Nature, Science, The New England Journal of Medicine, and other scientific journals. He is the author of the Gateways to Alissia series with Harper Voyager, and the editor of Putting the Science in Fiction, a collection of expert-written advice published by Writer's Digest. Koboldt's previous articles for Baen.com include “Chimeras: Science and /Science Fiction,” and “Dark Matter of the Human Genome.”