The Next Wave of Reproductive Technology

 

Embryo,_8_cellsIn following the trajectory of the new CRISPR technology, I found myself digging into data that is relevant to the periodic Ricochet debates on artificial reproductive technologies (ART), specifically in vitro fertilization (IVF). I’ll get to both tech and politics shortly, but I’m going to start with numbers: specifically, using market sizes as a proxy for demand, and an indirect indication of social and political impact. (All of these are public numbers that are “rough order of magnitude,” and I have done some mixing of products and services totals.)

IVF of all kinds is about a $10 billion/year market worldwide. When I compare that to other categories that are somehow connected to fertility, it’s larger than I expected: The total worldwide market for contraceptives is about the same size; Infertility drugs are a bit short of $5 billion world wide; The total global market for erectile disfunction (ED) drugs – Viagra and kin – is $2 to 2.5 billion per year; and Abortion and related services are about the same size (US only). I also looked for figures on surrogacy — the other bete noir here — but they are scarce. The best I could find suggests that surrogacy makes for, at most, a couple of percent of all IVFs in the US, but there are no reliable numbers for elsewhere.

Combining the above categories, about $30 billion a year is spent on the technologies derived from the Sexual Revolution, about $17.5 billion of which goes toward trying to become a parent, and about $12.5 billion spent trying to avoid it. IVF is about a third of the total, so — much to my surprise — it’s something of a whale in the category.

But compared to the overall medical market, reproductive technology is a minnow. One blockbuster drug — Humira, an anti-inflammatory — clocks in at $10 billion a year. The pharmaceutical industry in total is a trillion dollar a year market, before we even get into medical services and devices. If even a few percent of that total medical spending were diverted into ART in general (or IVF in particular), it would cause a revolution in that market and its social impact.

What could cause that to happen? Genomics. Here I’ll steal a chart from George Church:

Technology curves, from George ChurchThis plots technical capability over time on a logarithmic scale. The straight, green line at the top shows Moore’s Law, the trend in semiconductor capability that has changed computers from room-filling monsters, to PCs, to throw-away gadgets within the lifetime of many of the people reading this. Consider all the social change that wave caused, swirl it around in your mind, and savor.

The blue curve, however, is the advance of genomics, as proxied by the cost to sequence a single complete human genome. It’s running much faster than Moore’s Law, at a greater than exponential rate: sequencing the first human genome cost roughly $3 billion dollars; today, there’s limited availability of genome sequencing at $1,000 per person. As technology drivers go, this is a blockbuster, and it’s coming faster than computing did.

How does this drive IVF? Despite the buzz, it’s not in “designer babies.” Most phenotype traits that you might want to select for — appearance, intelligence, etc., — seem to be the results of multiple genes working in combination, as well as complexes of regulators and environmental factors, all of which is poorly understood at this point. Having masses of raw genome data gives us a tool to start picking away at the complexity, but we’re neither there yet, nor likely to be so for a while.

Most IVF today is the result of a couple’s infertility, and comes after a long period of failure and trials with fertility drugs, and those numbers are unlikely to increase much in the foreseeable future, and doesn’t involve genomic technology at all. However, a small fraction — about 3 percent — is subject to pre-implantation genetic diagnosis (PGD). This process is used by parents who know in advance that they are carriers for genetic abnormalities, and who have embryos created, tested, and screened for that abnormality in vitro before implantation.

What happens when our knowledge of genetic risk expands by orders of magnitude, and when we focus on looking for a handful of point mutations, rather than sequencing an entire genome? Massive change. Given the long-term costs of supporting many who are born with abnormalities, the economics of mass screening will be overwhelming. Even at the current $10,000 – $20,000 cost of PGD screening, the economic positives are vastly favorable to long term care costs of those born with defects.

You don’t need designer babies or understanding of development biology to blow up the IVF market: just cheap genetic diagnostics. The less the cost of those tests and the more PGD expands, the further down the list of severity we can screen.

PGD itself is an imprecise method: you fertilize a lot of eggs and try to find a few that pass screening. And this is where I actually entered the story: CRISPR is a fairly new genetic technique that allows site-specific genome editing with precision, eliminating the need for creating so many embryos in the hopes of finding only those who pass. If PGD is a shotgun, CRISPR is a scoped rifle.

To date, CRISPR has not been applied successfully to a human germ cell. There was a recent, bally-hooed Human Gene Editing Summit in DC, that purports to have handed down rules against the practice. Don’t you believe it. It’s already been tried in China, an initial failure. But that is the country that is building an industrial scale cow cloning facility, and has a whole generation of single-child families wanting to make sure each birth preserves their line. It’s coming. And remember, you don’t even need CRISPR to get started down this line: diagnostics and PGD will get you going.

And finally, as to the political debates, both here on Ricochet and elsewhere: to the extent there is a general awareness of the issue, it’s another stick to beat the religious right, as indifferent to those who draw the genetic short straw. That’s unlikely to improve as the technology advances.

As of now, IVF is largely an alternative to barren misery for a small minority of couples. With plummeting prices in gene sequencing/screening and the likely arrival of CRISPR in humans, we’re looking at a shift that will turn it into a way to avoid creating individuals who may endure a miserable lifetime at great social cost, and a way to eliminate specific genetic diseases within within families and, ultimately, populations. The emotional, political, and market appeal of that is difficult to overestimate.

Members have made 26 comments.

  1. Profile photo of Rapporteur Member

    Lots of good information here, Locke. Thanks.

    I guess I’m in the “not a fan” camp when it comes to PGD and CRISPR. The idea of perfecting the human species is just a bit too Marxist for my comfort. Your point about those who “draw the genetic short straw” is genuine – and heartbreaking – but I would not want to see those lives devalued in favor of more perfect specimens.

    I also can’t see the Left embracing this technology. Given the freak-out over genetically-modified organisms (GMOs), can you imagine the hysteria they’d have over the first generation of genetically-modified people? 8^)

    • #1
    • December 7, 2015 at 11:48 pm
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  2. Profile photo of Merina Smith Inactive

    Rap, so agree with you that this is an ethical minefield–devaluing lives and making people think only perfect is acceptable–yup. But it would certainly be good to prevent misery by fixing diseases that run in families. Still, I see Frankenstein on the horizon. I will disagree with you that the left will freak out. They are all about separating reproduction from sex, and they are moving toward the idea, or already there, that everyone has a “right” to a child and of course, that Mom and Dad don’t matter. As usual, they are deeply misguided IMHO.

    Interesting article–thanks Locke. One thing that should be mentioned is that redefined marriage is likely to make surrogacy and various forms of third party reproduction that deliberately separate children from their parents far more common.

    • #2
    • December 8, 2015 at 5:09 am
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  3. Profile photo of Eustace C. Scrubb Member

    So you’re not talking about this?

    • #3
    • December 8, 2015 at 5:51 am
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  4. Profile photo of SoDakBoy Member

    Locke On: We’re looking at a shift that will turn it into a way to avoid creating individuals who may endure a miserable lifetime at great social cost, and a way to clean up germ lines within families and ultimately populations.

    When we decide that some people are less human than others, we end up becoming less human ourselves.

    Your phrasing here is very instructive as to what the world will look and feel like if/when your predictions come true.

    We will see ourselves as “creators” of life rather than recipients of life.

    We will decide which lives are too “miserable” to be worth bearing “social cost”.

    We will view people as a function of their social cost/benefit ratio.

    We will view our families as unclean germ lines rather than as a heritage. We will view our population as an unclean germ line rather than as our ancestors.

    When the end of humanity comes, it will come cloaked in humanitarian language.

    • #4
    • December 8, 2015 at 6:54 am
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  5. Profile photo of Locke On Member
    Locke On Post author

    Eustace C. Scrubb:So you’re not talking about this?

    Relevance?

    • #5
    • December 8, 2015 at 8:40 am
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  6. Profile photo of Locke On Member
    Locke On Post author

    There is a fine line between pity and mercy for those who suffer today, through no fault of their own, and heartlessness towards those who may bear that fate in the future. I suggest you think about where your rhetoric will put you in the public’s view, with respect to that line.

    • #6
    • December 8, 2015 at 8:44 am
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  7. Profile photo of MarciN Member

    Thank you, Locke On, for this information. I have been wondering how big the market is for IVF and gene editing.

    Clearly it is a force to be reckoned with. It affects a lot of people.

    • #7
    • December 8, 2015 at 9:05 am
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  8. Profile photo of Mike H Thatcher

    Why do we celebrate genetic elitism when it is an accident or runs in families, but fear it when it is chosen by individuals?

    Height, intelligence, attractiveness, strength, moral fortitude, and health all have a strong genetic component. Just because we will soon have the ability to actively choose things we already value doesn’t mean those who don’t have those things will be viewed as less human, at least not anymore than people see them now (but everyone’s too PC to admit it.)

    Some qualities are obviously better than others (up to a point), just because we had to rely on luck and self-selection in the mating market up until now doesn’t mean we should deny individuals the ability to give their children obviously better qualities than they are likely to the “natural” way.

    The worst thing we could do is try to regulate it because, as often the case, the true devil will hide in those good intentions.

    • #8
    • December 8, 2015 at 9:23 am
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  9. Profile photo of Doctor Robert Member

    Great analysis, Llockon. I’m a ferility doc and although we limit our PGD services–no elective sex selection–we do prevent heritable blindness, cystic fibrosis, renal disease as a matter of course. The slope from this to cancer susceptibility to eye color is gradual and inevitable. Smart money is on making peace with the technology and steering its use to good, not to frivolity or evil. Misuse and abuse have followed all new reproductive technologies and this will be no exception.

    • #9
    • December 8, 2015 at 9:25 am
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  10. Profile photo of Henry Castaigne Member

    Locke On, will it be forseeable that we will move past IVF within our lifetime? Could we get away from creating (and more problematically) throwing away embryo’s altogether?

    Additionally, on a more personal level, if I could genetically engineer (no abortion just pre-natal gene therapy) my progeny to prevent hemophilia, down syndrome, low-functioning autism and many other horrible maladies I would. Wouldn’t everybody?

    • #10
    • December 8, 2015 at 9:49 am
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  11. Profile photo of Locke On Member
    Locke On Post author

    Henry Castaigne:Locke On, will it be forseeable that we will move past IVF within our lifetime? Could we get away from creating (and more problematically) throwing away embryo’s altogether?

    I’d be interested in a reply from someone who’s more deeply into the biotech, but my impression is this will take quite a while. You’ll have to be able to do a near 100% edit on germ cells and related stem cells in vivo, on either the female or male reproductive system, depending. Meanwhile, either not impacting the somatic cell lines, or fully understanding the consequences of doing so. Much, much messier and harder to control. My guess is it’s PGD for quite a while, since it is reliable, and it goes in vivo only after that process has been well worked out for genetic therapy on post-gestation humans.

    • #11
    • December 8, 2015 at 10:12 am
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  12. Profile photo of Mendel Member

    Locke On:

    Henry Castaigne:Locke On, will it be forseeable that we will move past IVF within our lifetime? Could we get away from creating (and more problematically) throwing away embryo’s altogether?

    I’d be interested in a reply from someone who’s more deeply into the biotech, but my impression is this will take quite a while. You’ll have to be able to do a near 100% edit on germ cells and related stem cells in vivo, on either the female or male reproductive system, depending. Meanwhile, either not impacting the somatic cell lines, or fully understanding the consequences of doing so. Much, much messier and harder to control.

    Well, I do “work in biotech” (but not on these topics), and I mostly agree.

    Technologies are now being developed which allow fetal DNA to be sequenced from a sample of the mother’s blood. This is an amazing leap and appears to be feasible enough to be marketable. Of course, this only deals with the screening side of natural pregnancies, and would lead to an abortion if the baby’s genome was not deemed good enough.

    As to the genetic engineering side, it will likely be quite some time (I would think at least decades if not longer) before any reliable technology could be used in vivo. The CRISPR/Cas9 and related technologies must all be manipulated in vitro, and their efficiency is still low enough that a number of attempts would need to be made to ensure success.

    • #12
    • December 8, 2015 at 10:18 am
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  13. Profile photo of Mendel Member

    One hypothetical possibility is that much genetic engineering will be a one-off affair.

    We know that people generally tend to marry and procreate within their own socioeconomic group. So assuming that, when the technology becomes viable, most rich people undergo genetic editing of their offspring to “correct” deleterious genes, they would then produce an entire generation with “improved” genetics. This generation could then intermarry with a much lower need of again undergoing genetic editing for their own children.

    This, of course, assumes that there is no slippery slope. We tend to think there is always a slippery slope, but bear in mind that other “artificial health improvement technologies” such as plastic surgery, surrogate motherhood, etc., all seem to have an upper limit of desirability. Even among the rich, there seems to be a need to keep at least some part of the natural reproductive process intact.

    • #13
    • December 8, 2015 at 10:23 am
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  14. Profile photo of Mendel Member

    [Some slight nitpicking: the image shown actually does not represent the CRISPR genetic editing process, which is an artificial manipulation of the naturally-occurring CRISPR/Cas enzymes. The image instead shows the naturally-occurring function of CRISPR, namely as an immune system for bacteria to defend against invading viruses.]

    • #14
    • December 8, 2015 at 10:26 am
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  15. Profile photo of Locke On Member
    Locke On Post author

    Mendel:[Some slight nitpicking: the image shown actually does not represent the CRISPR genetic editing process, which is an artificial manipulation of the naturally-occurring CRISPR/Cas enzymes. The image instead shows the naturally-occurring function of CRISPR, namely as an immune system for bacteria to defend against invading viruses.]

    Blame that one on the editors. 😀 They definitely helped my prose, however.

    I suspect you are right that for some socio-economic strata, this will be a one-and-done phenomenon once the basics are worked out, but it’s liable to spread as costs come down, both by class and geography.

    As far as eventual percentage of adoption / the slippery slope, let’s face it, the ‘competition’ is free, fun and effective for most couples. That’s why I see the driver as genetic testing, not ART for its own sake. You don’t have to look too far out to see a genetic screen as a socially accepted, if not de facto required step before child bearing. One of the current problems of widespread screening of post-gestation humans is there’s not much you can do with the results as yet – except raise troubling issues about the future of health ‘insurance’. Not so in the fertility planning case, you can do plenty.

    • #15
    • December 8, 2015 at 1:40 pm
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  16. Profile photo of SoDakBoy Member

    Mike H:Why do we celebrate genetic elitism when it is an accident or runs in families, but fear it when it is chosen by individuals?

    I don’t think I fear “genetic elitism”, but I do fear living in a society that freely discards living human beings because they are not genetically elite. If there were a way to do this without killing human embryos, I would be all for it.

    • #16
    • December 8, 2015 at 1:48 pm
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  17. Profile photo of SoDakBoy Member

    That is to say, I would be all for preventing disease and suffering. I am not sure if I would be in favor of using this technology to improve the genome by selecting desirable traits over less desirable, but still normal, traits.

    Prevent the transmission of cystic fibrosis? Yes.

    Prevent the transmission of short stature or an IQ of 100? Not sure, but probably not in favor of this.

    • #17
    • December 8, 2015 at 1:52 pm
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  18. Profile photo of Merina Smith Inactive

    SoDakBoy:That is to say, I would be all for preventing disease and suffering. I am not sure if I would be in favor of using this technology to improve the genome by selecting desirable traits over less desirable, but still normal, traits.

    Prevent the transmission of cystic fibrosis? Yes.

    Prevent the transmission of short stature or an IQ of 100? Not sure, but probably not in favor of this.

    Number two reeks of Brave New World. There are profound implications in terms of valuing humans for for their designer traits–for what they are instead of just because they are.

    • #18
    • December 8, 2015 at 2:03 pm
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  19. Profile photo of Mike H Thatcher

    SoDakBoy:That is to say, I would be all for preventing disease and suffering. I am not sure if I would be in favor of using this technology to improve the genome by selecting desirable traits over less desirable, but still normal, traits.

    Prevent the transmission of cystic fibrosis? Yes.

    Prevent the transmission of short stature or an IQ of 100? Not sure, but probably not in favor of this.

    I agree. I also don’t want to live in a society who would look down upon people who chose not to give their kids higher IQ, but that doesn’t mean I want to prevent those who wish to give their kids higher IQ from doing so, either.

    One thing that really seems to influence IQ is prenatal and early childhood nutrition. This is my guess for the Flynn effect. I can see people looking down on others because they didn’t get a cheap and easy gene switch that boosts average IQ 20 points just as people look down on those who smoke, drink, or eat especially poorly while pregnant. And I can’t see a real moral difference between the two.

    • #19
    • December 8, 2015 at 2:04 pm
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  20. Profile photo of Tom Meyer, Common Citizen Contributor

    Mendel:[Some slight nitpicking: the image shown actually does not represent the CRISPR genetic editing process, which is an artificial manipulation of the naturally-occurring CRISPR/Cas enzymes. The image instead shows the naturally-occurring function of CRISPR, namely as an immune system for bacteria to defend against invading viruses.]

    Apologies for that. My bad, since corrected.

    • #20
    • December 8, 2015 at 2:52 pm
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  21. Profile photo of Eustace C. Scrubb Member

    Locke On

    Eustace C. Scrubb:So you’re not talking about this?

    Relevance?

    Sorry, “Inter Varsity Fellowship” is another IVF.

    • #21
    • December 9, 2015 at 9:17 pm
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  22. Profile photo of Henry Castaigne Member

    Merina Smith: There are profound implications in terms of valuing humans for for their designer traits–for what they are instead of just because they are.

    Um, sorry for posting so late in such an interesting podcast, but as it is now do people value other people, ‘just because’ or do they value them for what they do.

    My (vague) sense, is that everybody says they value people for who they are and then do the exact opposite. But I have horrible empathy so I am unsure.

    • #22
    • December 17, 2015 at 1:03 am
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  23. Profile photo of Tom Meyer, Common Citizen Contributor

    Mike H: I can see people looking down on others because they didn’t get a cheap and easy gene switch that boosts average IQ 20 points just as people look down on those who smoke, drink, or eat especially poorly while pregnant. And I can’t see a real moral difference between the two.

    Seconded (on the assumption that the process needn’t involve abortion).

    • #23
    • December 17, 2015 at 4:32 am
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  24. Profile photo of Midget Faded Rattlesnake Moderator

    Henry Castaigne:

    Merina Smith: There are profound implications in terms of valuing humans for for their designer traits–for what they are instead of just because they are.

    Um, sorry for posting so late in such an interesting podcast, but as it is now do people value other people, ‘just because’ or do they value them for what they do.

    My (vague) sense, is that everybody says they value people for who they are and then do the exact opposite. But I have horrible empathy so I am unsure.

    Not necessarily the exact opposite. But not even parents who conceived you naturally value you simply because you are – even the most natural of children are also valued according to what they do. And would parents be doing their children any favors if they did not do this?

    Disobedience, criminality, and underachievement are, after all, traits that good parents will try to discourage.

    • #24
    • December 17, 2015 at 7:59 am
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  25. Profile photo of Merina Smith Inactive

    Henry Castaigne:

    Merina Smith: There are profound implications in terms of valuing humans for for their designer traits–for what they are instead of just because they are.

    Um, sorry for posting so late in such an interesting podcast, but as it is now do people value other people, ‘just because’ or do they value them for what they do.

    My (vague) sense, is that everybody says they value people for who they are and then do the exact opposite. But I have horrible empathy so I am unsure.

    That’s not my sense of things. I have a Sunday School class of 15 teenagers. Some are more talented than others. I don’t value the more talented any more than the less talented. I love them all the same. Same with my own kids. They are all equally precious to me. Do I want them to develop skills and talents? Am I disappointed if they don’t live up to their potential? Sure–in a way–but I don’t value them less if they don’t. Now, if I’m hiring a plumber, I do value the more talented more for his plumbing skills, but as a person I value the less and more talented plumbers the same.

    • #25
    • December 17, 2015 at 9:23 am
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  26. Profile photo of Tom Meyer, Common Citizen Contributor

    Skeptics Guide to the Universe had a good segment on CRSPR in its last episode. Stephen Novella summed up the (long term) possibilities of genetic engineering as follows, in order of increasing difficulty:

    • Editing-out specific genetic diseases (Tay-sachs was his example).
    • Editing-out genetic dispositions toward disease (e.g., propensity for certain forms of cancer).
    • Editing genomes so that children preform toward the top of the current human spectrum (i.e., ensuring that children are smarter, better-looking, more athletic, etc., than is currently the average, but not super-humanly so. Basically, so that Natalie Portmans, Hedy Lemar, and James Garfield are closer to average than not).
    • Editing genomes so that children have capabilities beyond those of current humans.

    The first two are — to his mind, as well as mine — ethical no-brainers, putting aside the issue of abortion, which may be possible at some point. The others are more powerful (and potentially both more beneficial and troubling), though aren’t likely in the near term.

    • #26
    • December 17, 2015 at 10:53 am
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