Jan 30 2018

Gattaca

The Human Genome Project was started in 1990 and completed in 2003. It took 13 years, multiple labs around the world, and hundreds of millions of dollars to sequence the human genome – this was more than two years ahead of schedule and millions of dollars under budget.

The reason for exceeding expectations is that the technology for sequence the genome was not static – it progressed throughout the project. DNA contains a code of four letters, the nucleotides indicated by the letters G, T, A, and C. This four-letter alphabet creates 64 different three-letter words, which code for different amino acids or operations that control the conversion of the code into proteins. Sequencing the genome essentially consists of discovering the order of these four letters in the string of a DNA molecule.

In 1997 the movie Gattaca, right in the middle of the genome project, portrayed the near future in which a cheek swab would rapidly yield an individual’s genome. It turns out this is not far fetched at all – we are almost living in Gattaca’s near future, at least in terms of sequencing technology. Scientists have just published a report of the nanopore device, which is a hand-held device capable of sequencing an individual’s genome.

This represents one of the greatest technological advancements in our time – the improvement by orders of magnitude the ability to cheaply and quickly read an entire human genome. The company who makes the device, Oxford Nanopore, claims that the small handheld sequencer, the MinION, can sequence 10-20 Gb per 48 hours (a Gb is a gigabasepair, or billion letters in the genome). In the published study the MinION was used to sequence 91.2 Gb of data to complete the sequence:

The final assembled genome was 2,867 million bases in size, covering 85.8% of the reference. Assembly accuracy, after incorporating complementary short-read sequencing data, exceeded 99.8%.

The device costs $1000. So in a couple decades sequencing a genome went from hundreds of millions of dollars to 1000 dollars, that’s at least five orders of magnitude. Sequencing has also gone from 13 years to a few days (shorter if a larger version of the nanopore is used). They also make the SmidgION, which is even smaller and attaches to a smart phone.

The advantages for research are obvious. With rapid and cheap sequencing technology we can sequence the genomes of many plants and animals. This allows us to study evolutionary relationships, to identify new species, and to “barcode” plant species. Medical applications are also obvious – we can identify genetic diseases in individuals, and researchers can more easily locate specific genes that cause or predispose to certain diseases. There are now over 2,000 tests available for human genetic diseases.

There are also some applications which may not be immediately obvious. For example, researchers can track the spread of an infectious disease more easily if they can trace how strains mutate as they spread. This was done to track the latest ebola outbreak, for example.

The Human Genome Project, in addition to being an example of extremely rapidly progressing technology, is also an example of overhype. It was often overpromised in popular coverage of the project that once we sequenced the genome, there would rapidly be numerous medical applications.  Diseases would start falling one by one. Fifteen years later, this hype has not been realized, although it is starting to be. This is partly because being able to sequence the genome is only one piece to the puzzle. We also have to know what all those genes we are sequencing do.

This has led to the proteome project – the effort to map which proteins all those genes code for. We also have to know what the proteins do, how they are regulated, and what goes wrong in specific diseases.

What the genome project has done, however, is made all this later research faster and cheaper. But still, this kind of research takes years and decades. What often happens is that scientific and technological advances are met with unrealistic hype. However, wait 20 years and the hype eventually becomes a reality (sometimes – I’m still waiting for my flying car). We may be getting close to that situation with the human genome, especially now that CRISPR has given us the technology to rapidly and cheaply alter that genome.

What about the abuses of this technology that was the focus of the movie Gattaca? In the film rapid sequencing was used to identify those who were genetically fit (valids) and separate them from the unfit (invalids). This created a social caste system based on genetics. The situation was also tied to the idea of guided vs unguided conception – having children and just throwing the genetic dice, or guiding conception by choosing the best genes for your children.

While I don’t think it will play out as in the movie, these ideas are not far fetched. Superior genes will likely become one more bit of social and biological capital that the wealthy will be able to transfer to their children. The ability to remove genetic diseases, and even reduce genetic predisposition to disease, is overall a good thing. This technology can lead to a healthier population, and perhaps even reduce health care costs by eliminating expensive lifelong illness. It may even be cost effective for society to pay for such genetic treatments for everyone, rather than assume the health care costs of the otherwise avoided illness.

There are too many variables to predict how this will play out, but it is not too early to start thinking about possible applications of this technology and how it should be regulated. Like many of our advanced technologies, it can be a great thing, but it can also be abused or lead to unintended consequences. The rate at which such technologies are advancing is also both a boon and a challenge. It doesn’t give us much time to adapt to the advancements.

24 responses so far

24 thoughts on “Gattaca”

  1. carbonUnit says:

    Out of compassion, we have prevented natural selection from removing many defects from the genome. I’m sure those sufferers would like to pass on their genes without the disabling defects which made life hard for them. I’m nervous about designer babies, but all in for getting rid of inherited diseases.

  2. bend says:

    “This technology can lead to a healthier population, and perhaps even reduce health care costs by eliminating expensive lifelong illness. …Like many of our advanced technologies, it can be a great thing, but it can also be abused or lead to unintended consequences.”
    One of those unintended consequences could be the loss of some of the most potentially productive members of society via depletion of neurodiversity. During our last pregnancy, we were asked if we wanted the unborn twins genetically tested for autism markers (we already had a child on the spectrum). Now the genes associated with autism can manifest very differently depending on the person, but sometimes lead to remarkable giftedness that has resulted in a significant fraction of human technological development. As Temple Grandin said, without autism we’d all be a very social bunch of cavemen. But if you, as a prospective parent, had a choice to raise the neurotypical child that you’d always dreamed of or a difficult, developmentally delayed child who struggles or refuses to show affection, then the world might miss out on the next Henry Cavendish. Whether via selective abortion or selective implantation, I don’t know if we’ll be better off by decreasing the wonderful variety of human capacity that spans the gamut from disability to giftedness with the lines, at times, blurry and overlapping. What works well for horses and dogs may not be the best thing for us. As I remember, that was the point of the movie.

  3. Robney says:

    “But if you, as a prospective parent, had a choice to raise the neurotypical child that you’d always dreamed of or a difficult, developmentally delayed child who struggles or refuses to show affection, then the world might miss out on the next Henry Cavendish”

    For some reason I mixed up Henry Cavendish with Henry Caville in my head, and I thought the actor who plays Superman is strange example to use to illustrate your point.

    It’s an interesting point though, because on an individual level a neurotypical child might be preferable for most parents, but what might the net impact on society be if we reduce our genetic diversity in such a way, and what other beneficial neurological traits might we unintentionally removing or selecting for?

    What other psychological traits within the neurotypical range might some parents also want to select against – would we allow, for example, parents to abort a foetus because it shows the markers for poor athletic ability or introversion/shyness?

    If we could select for children who are better at picking up their toys, who can sleep in on a Sunday, and not remove the pillows from my couch every day, then it might be worth the societal risks.

  4. BillyJoe7 says:

    bend,

    “One of those unintended consequences could be the loss of some of the most potentially productive members of society via depletion of neurodiversity”

    Setting aside your next point for the moment, I’m not sure that depletion of the neurodiversity is a problem if you’re depleting from “below the line”. And, on the other hand, we may be able to increase neurodiversity “above the line”, which would be a positive result.

    “..the genes associated with autism can manifest very differently depending on the person, but sometimes lead to remarkable giftedness that has resulted in a significant fraction of human technological development”

    Two questions: Would you be willing to sacrifice your child’s social life for the chance that he might someday contribute to the world’s technological development? Do you have any links to evidence that people with autism have contributed to a significant percentage of human technological development?
    I am not disinterested – I have a 3yo grandson with significant ASD and associated behavioral issues.

    “I don’t know if we’ll be better off by decreasing the wonderful variety of human capacity that spans the gamut from disability to giftedness with the lines, at times, blurry and overlapping”

    I don’t agree that disability is wonderful. I would dearly love to have a grandson who responds to me socially and emotionally. I would dearly love for him to be able to interact with everyone on an emotional and social level. I am grateful that he is at least not mentally retarded, and that he has no dysmorphic features. That would be even less wonderful. Of course, we have accepted him as he is and are helping him and his parents out every way we can.
    But, if he ends up contributing to human technological development, I’m not sure if that would be a good trade-off. And, of course, the odds of that happening are pretty low, especially at this stage of our technological development where teamwork has become an essential element.

  5. > bend says:
    > January 30, 2018 at 10:30 am

    > One of those unintended consequences could be the loss of some of
    > the most potentially productive members of society via depletion of neurodiversity.

    That is completely misguided.

    You will have to use cloning, with a small number of clones, to reduce the diversity
    enough to be an issue.

    People, in general, strongly underestimate how diverse “normal people” are under the
    masks that they present to the rest of the world.

  6. Kabbor says:

    Robney,

    “We’ve finally isolated the pillow removal gene so we can eliminate it from the gene pool. Hurray!”
    2 Generations later… The world has become a pillow-dystopia with towers of pillows everywhere and people cannot and will not get rid of unwanted pillows. More pillows a created at a frenzied pace, for surely the righteous pillow will fix our problems and humanity ends not with a bang, but with a pillow.

    Starring: Michael Caine, Anthony Hopkins and Morgan Freeman. Dialogue is almost exclusively in the form of monologues and speeches.

  7. bend says:

    Robney “If we could select for children…who can sleep in on a Sunday…”
    Yes. What do kids have against sleeping in?!

  8. bend says:

    BillyJoe7, “Do you have any links to evidence that people with autism have contributed to a significant percentage of human technological development?”
    I would direct you to the work of Simon Baron-Cohen who is not alone in noticing that autistic traits are over-represented in technological vocations that favor hyper systemizers. These include scientists, engineers, mathematicians, musicians, and artists. Penny Spikins at York and Temple Grandin at Colorado State have also made the point.
    https://theconversation.com/how-our-autistic-ancestors-played-an-important-role-in-human-evolution-73477
    http://www.tandfonline.com/doi/full/10.1080/1751696X.2016.1244949
    Of course it’s always dangerous to make posthumous diagnoses, but there are strong cases to be made that Henry Cavendish and Alan Turing were on the spectrum. But the same genes that have been shown associated with autism are also associated with high achievers in technical fields as well. A popular hypotheses is that these genes contribute to both disability and hyper-ability. Hyperlexia, as a matter of fact, is considered a symptom of ASD. It’s not for nothing that Hans Asperger referred to his autistic patients as “little professors” recognizing innate capacities in some of them for remarkable talents. During the Nazi occupation of Austria, he protected his patients from eugenics by explaining how enhanced pattern recognition that his patients were capable of might be useful for cracking codes to help the German war effort (perhaps a prescient observation considering the success of Alan Turing).

  9. bend says:

    Yehouda,
    I think we may have a misunderstanding here. If you artificially select against genes that manifest in a particular phenotype (or several phenotypes), then you diminish the prevalence of those in the population. This is a loss of diversity. It’s not the complete loss of diversity and I never said that it was. But the population does become less diverse by some degree. Now, in the case of autism you have a genotype that can manifest as either a severe disability or a moderate disability coupled to an extraordinary ability in another area (and everything in between). It may be very difficult or impossible to select against the former without selecting against the latter.

  10. > bend says:
    > January 31, 2018 at 1:48 pm

    > I think we may have a misunderstanding here. If you artificially select against
    > genes that manifest in a particular phenotype (or several phenotypes), then
    > you diminish the prevalence of those in the population. This is a loss of diversity.

    That is wrong. It is true only if you define diversity as variation in the phenotype
    that you select against, and does not count variations of other phenotypes. For example,
    aggressiveness has been selected against in the evolution of dogs, but that did not
    make dogs less diverse than wolves.

    > It may be very difficult or impossible to select against the former without
    > selecting against the latter.

    Why?
    You are presumably assuming that extraodrinary ability is necessarily a result of the same
    genetic tarits that also cause autism, but this is just “a popular hypothesis”, rather than conclusion
    from actual data.

    The examples that you give in previous message (January 31, 2018 at 1:37 pm) are all folk
    stories rather than serious reaserch.

  11. bend says:

    Yehouda,
    I’m sorry. I didn’t know what your journal access is, so I gave you some Cliff’s notes. Really though, I suggest reading up on Simon Baron-Cohen’s work.
    Here are a couple of his and a couple from other authors highlighting the hereditary association between autism and systemizing occupations (first three) and the propensity for talent in maths in significant fractions of autistic people.

    https://www.ncbi.nlm.nih.gov/m/pubmed/11706868/
    http://journals.sagepub.com/doi/abs/10.1177/1362361398023006
    https://link.springer.com/article/10.1007%2Fs10803-011-1302-1
    http://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(15)00397-1/fulltext

  12. BillyJoe7 says:

    bend,

    I agree with Yahouda’s impression of the literature. At the very least, the hypothesis that genetically eliminating “autism spectrum disorder” from the population would detrimentally affect contributions by people with “autistic traits” to STEM is controversial. The genetics is not known well enough at this stage. It could turn out that a network of genes is responsible for the wide prevalence of “autistic traits” in the population (according to how strictly you define “autistic traits” it ranges from about 20% to nearly everyone), but that there is a subgroup in which one or several mutations in that network of genes or in entirely different gene or set of genes, cause what we label “autism spectrum disorder” in which there is also a combination of intellectual deficits and behavioral symtoms that adversely affect the sufferer. In that case, eliminating the latter would not necessarily negatively affect the former.
    Obviously, nothing is going to be done unless and until the genetics has been worked out.

  13. mumadadd says:

    Bend,

    I have to agree with BJ7’s take on your comment. Don’t know the facts re autism and human progress but if you can produce them I’m all ears (eyes?).

    One thing I will note: so called designer babies and the ethical issues around genetic engineering is obviously a perennial topic. I watched one of those shows where this sort of thing gets thrown to the crowd, which may or may not include relevant experts but generally tries to be representative of all faiths and creeds.

    The impression I got was that the people actually driving the ethical decisions around this pay absolutely no attention to religious objections, but do pay lip service to them and try to make a show of doing so.

    I also noted that the religious crowd (or at least the ones who were invited there specifically to comment on the issue) didn’t mention god or God’s will once.

    They did, however, heavily imply and outright state that the heavily disabled people in the audience were better off for their disabilities. Which is sort of a contradiction in terms. They tried to imply that eliminating genetic diseases was equivalent with wiping the sufferers out of existence. Wishing that this person before you didn’t exist and you didn’t have to look at him.

  14. mumadadd says:

    Goddammit. Apparently there is some new shortcut on my phone I’m not aware if that sends posts to this forum.

    That was not intended for publication in its above form. Again….

  15. bend says:

    Funny. I have another comment that’s been awaiting moderation for some hours before your post. Here are some links from Simon Baron Cohen and others.

    https://www.ncbi.nlm.nih.gov/m/pubmed/11706868/
    http://journals.sagepub.com/doi/abs/10.1177/1362361398023006
    https://link.springer.com/article/10.1007%2Fs10803-011-1302-1
    http://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(15)00397-1/fulltext

    I don’t disagree that we don’t understand the genetics of ASD perfectly (or even reasonably well). And I don’t disagree that the issue is complicated. We’re discussing a highly speculative question here.
    Neither of those facts detracts from (but actually bolster) my argument that we may not be able to always select against one trait that we don’t like without selecting against others that we may.

  16. bend says:

    My comments still aren’t showing up. Is there some filter that forbids comments w/o moderation for those with a high density of comments on a post? Did I get caught in a troll trap? 🙂

  17. BillyJoe7 says:

    bend,

    If you post more than three links your comment automatically goes into moderation.
    Just split it into two or more posts.

    Interestingly, when I log in these days I have to pass a robot test.

  18. > bend says:
    > January 31, 2018 at 6:54 pm

    >

    That is what I meant when I wrote “not serious research”. They show correlations
    which can have many kinds of explanations, and therefore don’t even suggest shared
    genetic traits between autism and any kind of skill. The most obvious explanation is that
    if you look for people which are better in mathematics and logic than in social communication,
    you will obviously find more of these if you look at professionals in fields that require
    mathematics and logic. I don’t see any sign that Simon Baron-Cohen is trying to control for
    that.

    The fact that they are all lead by the same author is quite strong negative. For a theory
    which is at least 20 years old (the earliest of your references is 1998), and was successfully
    published in respectable journals, if it was real you would expect many more scientists to
    start to take it seriously, and to see at least some basic assertions being accepted in general.

  19. In the previous comment there was a reference to the links that Bend gave, and this reference was eliminated somehow. it was simple the string “”, but without the double quotes.

  20. And even with double quotes it eliminates it. It was the smaller-than sign, followed by “some links”, followed by greater-than sign.

  21. mumadadd says:

    bend,

    Please ignore my last post addressed to you. I though I saw a similarity between your position and that of some religious people I’d seen on the show I mentioned, and I know you’re a Christian as you’ve mentioned it before. By the time I finished typing, though, I’d lost confidence in that similarity and I didn’t actually mean to publish that post.

  22. bend says:

    BillyJoe, thanks for the tip. Next time I’ll remember (I probably won’t).
    No worries, mumadadd, and no reason to apologize. I found you comment pertinent and was in no way offended by it.
    Yehouda, You are certainly right that there are deficits in the autism literature (deficits that are not uncommonly exploited by antivaccine cranks and autism biomed practitioners). I’d not dismiss, Simon Baron-Cohen, however, just because he’s written a lot of papers. His prevalence in the literature is reflective of his accomplishment it the field and not that he is a one man crusade for fringe hypotheses. There is no other researcher who better exemplifies the scientific consensus of this area. It should be noted that when skeptics say that evidence demonstrates that it is heredity and not vaccines, gmos, toxins etc. that causes autism, they are referring, in no small part, to the evidence gathered by Simon Baron-Cohen and his teams. The papers I listed are in respectable journals with relatively high impact factors. I tried to pick papers that spanned years to show a history of reproduction and explicit rejection of fleeting and unsustainable (if popular) “theories” of the cause of autism. Of course I wish that our understanding of autism were better, but it’s incorrect to call these “not serious research.”

  23. > bend says:
    > February 1, 2018 at 2:12 pm

    > I’d not dismiss, Simon Baron-Cohen, however, just because he’s written a lot of papers.

    Neither do I . I dismiss him because after more than 20 years, all he got is dubious
    correlations, which he doesn’t seem to even realize how weak they are as evidence.

    >There is no other researcher who better exemplifies the scientific consensus of this area.

    There is no scientfic consensus about autism at the moment, so nobody can
    “examplifies” it.

    In the wikipedia page about “causes of autism” there is a single reference to Simon
    Baron-cohen, and it is about his ” fetal testosterone theory”. Obviously they
    are also not that impressed by his ideas.
    https://en.wikipedia.org/wiki/Causes_of_autism

    The latest review that I can find in PMc is this (free full text):
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5360849/
    They do mention Baron-Cohen and “fetal sex steroids”, but hen go on
    to discuss research that suggest other explanations.

  24. Nidwin says:

    Dr Novella:”The ability to remove genetic diseases, and even reduce genetic predisposition to disease, is overall a good thing. This technology can lead to a healthier population, and perhaps even reduce health care costs by eliminating expensive lifelong illness.”

    Agreed.
    For real/true and well known and defined genetic diseases with a very negative impact on someone’s future life.

    But what I fear will truly happen is folks trying to fix what’s not even broken.

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