First Human Embryos Edited in U.S
technologyreview.com
technologyreview.com
A more realistic scenario would be to develop a human embryonic stem cell culture that has been edited as desired and then implant this into a developing blastocyst at a point at which it would take over the and develop into the fetus. This is done with mice and there is no reason it wouldn't work for humans. I think that most people would find this much more abhorrent than directly editing the germline. However, it would be much safer for the engineered proband and would not require a "perfect" editing system that we do not have.
Anyway what’s abhorrent about the blastulation method? Furthermore, I don’t think there is a need to only let those with a large number of recessive deleterious alleles use it. It should be more open to let people edit the genome of the embryo to remove even one or two dominant or recessive deleterious alleles. There’s no reason that if the technology exists, is safe, and is regulated that it should be only used for people with a huge number of genetic defects.
And can’t you just sequence or test one of the cells from the morula stage?
As a living, thinking human, I am grateful for everything that was done so that I may live.
If the fertility lab had mixed chemicals differently, or deleted a propensity towards colon cancer, or changed my hair color, there's no way in hell I would have mourned my "unborn" mirror self. I would have been just as grateful to be walking and talking and living!
The slippery slope isn't on the action, it's on the intent behind the action. Designing blond babies isn't evil. Designing babies susceptible to drug addiction is.
So can we please stop with the deification of the default and get on with progress?
Well said! I fear, though, that a problem with this admonition is that some ascribe the default state to a deity.
However, I'm not sure that the characteristics you mentioned are of the same quality.
Hair color, gender, and other traits are neutral in quality - especially if there's risk in the procedure, it would seem wrong to select these superficial changes to fit the parents' preference. And while it would be nice to look into the future and determine what the human being created would prefer, we can't do that.
A propensity towards colon cancer or a propensity towards drug addiction being added or removed would be another class of traits, having a quality based on removing observed defects. I imagine this class is the most likely to be experimented with first.
The third class would be traits which are relative to baseline humans. Increasing intelligence, perhaps, would be the change that could most universally be described as an unalloyed positive change. What hypothetical future human would mourn their unborn mirror self and wish they were less intelligent? Perhaps the acuity of their vision and other senses would also be desirable. You might also consider changing aspects such as their respiratory or cardiovascular capacity - some humans like Chris Froome or Michael Phelps are extraordinary examples of not just training but innate talent, and wouldn't it be nice if we went beyond reducing the risk of heart disease to make everyone innately talented at breathing? And then you get into issues like whether or not to make them stronger (who's healthier, Froome or Phelps?), or taller, or more good looking (who decides what that looks like?).
It would be great if we could help our kids be healthier. And I (and most people) would like it if my parents had made me smarter. But the technology opens the door to dangerous possibilities.
Caution is merited, but inaction carries culpability in the preventable negative outcomes solved in a potential future that we deny through fear.
And not disagreeing with your content, as I agree and think it's well written, but statements like "nice to look into the future and determine what the human being created would prefer, we can't do that" are part of what doesn't parse with me about this debate.
As with the anthropic principle, life has no a priori preferences. It becomes and then it is. Before it is, it doesn't want anything. After it is, it wants to be as it is. Because what is it is its identity.
There's a caveat for physical disabilities, and yes, that's a slippery slope as you've outlined. But how could one want to be another?
If I told you that I could make you smarter, right now, with 100% certainty and safety, but that afterwards... you wouldn't be you as you are now... would you say yes? Possibly, but I feel there's a certain inherent unease with that question. What happens to me if I become other?
My point being that this works in reverse too. If I am now as I was made, how would I feel about the choices made in my making? My assertion is that I wouldn't particularly care, because I am the result. So to wish otherwise would be to wish for the termination of my current identity.
If there's a debate to be had, then let it be one the social or individual merits of the actual change sought, rather than in making changes or not.
This is silly. I don't become some other person when I drink alcohol or wear contact lenses, nor when I break a leg, exercise my muscles, or make any other permanent alteration to my body. A theory of self/identity that "breaks" under new medical advancements because it also breaks under everyday conditions is just a bad theory.
You might identify yourself with a particular functional aspect if your mind, but you're going to have to do a fair amount of scientific work to pick out which functional aspect. Just gesturing to the meat doesn't really pick out anything immutable or specific.
Besides which, the Neolithic Revolution was 10,000 years ago if some damned primitivist really wants to make appeals to the natural order, rather than to the potential benefits and detriments to human health and happiness.
Blond babies might be grateful to be born and not mourn their unborn non-blond selves, but there still exist plenty of less fortunate other babies who do get born non-blond and will suffer as a result.
I don't agree with your wholesale assertion that all of those who are unable to afford cosmetic surgery (larger breasts, hair implants...) are suffering, however.
But if cosmetic surgery made you smarter, then clearly all who couldn't afford it would suffer (relative to those who could). We don't worry about that because cosmetic surgery doesn't have that potential (or does it? I dunno), but with gene editing I think it's a very real potential.
That's not to say I'm wholesale against it, nor would I support banning research or anything along those lines. But I think it's clear that it will be a huge shock to society if/when this becomes practical, and I don't think our society is particularly good at dealing with this kind of change that can only exacerbate existing issues of inequality.
Let's hope that as a civilization we have enough sense to sort out making it available to everyone by then, at minimum in the most obvious areas (preventing disease, avoiding birth defects, etc...)
We should remember that it's not just the individual whose genome is edited that may be harmed, but all of their descendants.
> And can’t you just sequence or test one of the cells from the morula stage?
This isn't sufficient. It has been observed (in mice) that editing the germline by directly editing the embryo will result in chimerism in the fetus. This happens because the editing is not 100% efficient in one cell division. So while some cells have the desired modification, others do not, while others still have completely different off-target edits. The resulting fetus may have the right edits in most cells, but the wrong ones in some particular tissue. It could be perfectly healthy except that it carries some alleles that are lethal when they occur in the liver, heart, or brain. It is impossible to avoid this by sequencing a single cell from the blastocyst, and probably it can't be avoided by sequencing any small number of cells.
> There’s no reason that if the technology exists, is safe, and is regulated that it should be only used for people with a huge number of genetic defects.
This technique does not appear to be safe, and it is not easy to control. If it were, I'd think it would be pretty cool. But, I don't see how we could do one-step editing with many edits unless the efficiency of the editing process is ~100%. And, given that the technique involves cutting the genome and hoping that the repair systems of the cell correct the cuts to templates that we've provided, it is very unlikely that it ever will be, because much of the editing process is outside of our control.
I look forward to another editing technique that is more precise. Or, to growing humans from cell culture. Both of these methods would provide the precision and safety that is required.
This is an implementation detail to be overcome, not a problem with the general concept. And this study seems to have overcome it.
> The earlier Chinese publications, although limited in scope, found CRISPR caused editing errors and that the desired DNA changes were taken up not by all the cells of an embryo, only some. That effect, called mosaicism, lent weight to arguments that germline editing would be an unsafe way to create a person.
> But Mitalipov and his colleagues are said to have convincingly shown that it is possible to avoid both mosaicism and “off-target” effects, as the CRISPR errors are known.
What is really happening is that normal copies of the human genome are being incorporated. Which are then passed on to your sperm/ovum.
"Our award winning, holistic, proprietary life-experience program leads to superior outcomes, when compared to competing life experience programs. Doctors know it, children's services favor it. So, what kind of life experience does your future family deserve?" Enter perfect puppies.
Two households, both alike in dignity, In fair Verona, where we lay our scene, From ancient grudge break to new mutiny, Where civil blood makes civil hands unclean. From forth the fatal loins of these two foes A pair of star-cross'd lovers take their life; Whose misadventured piteous overthrows Do with their death bury their parents' strife. The fearful passage of their death-mark'd love, And the continuance of their parents' rage, Which, but their children's end, nought could remove, Is now the two hours' traffic of our stage; The which if you with patented ears attend, What here shall miss, our toil shall strive to mend.
Most problems with the world are because there are a lot of people who don't make decisions based on a right mind. A few are because of insufficient information or insufficient technology to open up other choices, but most problems in economics and politics are caused by people being jerks to each other.
And, for the time being, bags and bags of money! Which currently makes this a vanishingly hypothetical problem of ethics.
One particularly well-known instance: https://en.wikipedia.org/wiki/Haemophilia_in_European_royalt...
As for more modern times, surely the wealthy are especially cognizant of genetics, right?
"Historically, populations of Qatar have engaged in consanguineous relationships of all kinds, leading to high risk of inheriting genetic diseases. As of 2014, around 5% of the Qatari population suffered from hereditary hearing loss; most were descendants of a consanguineous relationship." -- https://en.wikipedia.org/wiki/Inbreeding#Prevalence
I do see one argument, hinging on the difference between an embryo and an adult aged many years. If your argument is that better techniques may exist at the embryonic stage, then I submit to the medical community to ascertain the appropriate course. However, I don't think offsite mutations pose a significant enough risk that one can say that, on aggregate, gene editing won't "do some good".
This more recent work by Mitalipov's group dealt with single cell embryo and still ended up with mosaicism, which I was a bit surprised at first. But when you think about it, this single-cell embryo's genome is actively being replicated, so not 100% of the alleles will be edited.
A way around it, would be to reactivate Cas9 after every cell division event, or maybe applying Cas9 gene-drive to embryo development. Also, I have yet to see a CRISPR paper with ensemble sequencing showing no off-targets. Even all the enhanced specificity Cas9 variants had a small percentage of off-targets.
Many of the worst disorders are lack of function mutations where mosaicism would indeed fix it.
I would be more worried about unwanted edits than missing ones.
The same mosaicism phenomenon which cause tabby cat's coat (especially callico) can be seen in human and would cause that individual to sweat by plaques, instead of the entire body. So you could imagine a scenario where someone would like to select a specific eye, or hair, or skin pigmentation, and end up with inequal pigmentations or a patchwork. That actually sounds cool...
In the case of an autoimmune disorder, like type-I diabetes or a blood disorders like beta-thalassemia, you would absolutely need to hit the proper germline which is responsible for creating your diseased cells. So that's a hit or miss, there is no inbetween. If you do have a hit, then while this germline is dividing and differentiating, it would need to reach a threshold at which the disease becomes asymptomatic. I don't what that number is for any of two diseases I just mentioned, but I would think it is higher than 50% of your cells that need to be corrected, so you would need to successfully hit more than one allele in your succesfully hit germline population that will become blood making cells.
It's a lot of moving parts, which needs to align correctly. That being said, I am optimistic that we will eventually get there. I have some doubt about the scientific pertinence of that "breaking news", i.e. I just don't believe they have accomplished anything that wasn't obvious, but being an optimist, I am sure that not all the ink will be a waste.
Nice question.
It comes from the hippocratic oath. "I will apply dietetic measures for the benefit of the sick according to my ability and judgment; I will keep them from harm and injustice."
Not really:
"In a 2000 survey of US medical schools, all of the then extant medical schools administered some type of profession oath. Among schools of modern medicine, sixty-two of 122 used the Hippocratic Oath, or a modified version of it."
Like I said in my previous post, some schools use a modern rendition. The modern versions don't forbid surgery, the use of poison, abortive measures, or compensation for medical training--necessary features of modern healthcare.
I challenge you to find me one med school that uses the original oath.
Medical ethics these days follows a principle-based system. The most common framework employs four basic moral principles: respect for autonomy, beneficence, non-maleficence, and justice. The current system of ethics is far more robust than any of the pledges taken. The pledges are more about personal significance and have no legal or procedural weight.
Obviously it's net harm, not no harm at all.
Medical ethics is its own field precisely because overeager and overconfident solutions are fraught with problems.
But what about if somebody donates a kidney...? Hm
> It is often said that the phrase "First do no harm" (Latin: Primum non nocere) is a part of the Hippocratic oath. The phrase as such does not appear in the oath...
What? I encourage you to read about prescription drug side effects. If a drug were safe, it would be over the counter rather than prescription. Prescription drugs are exactly the kind of harm/benefit bundle GP is describing.
Assessing treatments on thereputic merit - does a treatment create significantly more benefit than it does harm (As chemotherapy is a standard bearing example), is, based on the evidence I've observed, the preferable approach.
What concerns me in the long term is that gene editing will cause human genomes to converge to a single gold standard with proven mental and physical benefits, thereby reducing our species' genetic diversity and leaving us more vulnerable to a mass extinction event. A "zero day exploit" that everyone missed in the popular new cancer-fighting edit.
"Q: What does that mean in human language? A: Any given couple could potentially have several eggs fertilized in the lab with the dad’s sperm and the mom’s eggs. Then you can test multiple embryos and analyze which one’s going to be the smartest. That kid would belong to that couple as if they had it naturally, but it would be the smartest a couple would be able to produce if they had 100 kids. It’s not genetic engineering or adding new genes, it’s the genes that couples already have.
Q: And over the course of several generations you’re able to exponentially multiply the population’s intelligence. A: Right. Even if it only boosts the average kid by five IQ points, that’s a huge difference in terms of economic productivity, the competitiveness of the country, how many patents they get, how their businesses are run, and how innovative their economy is.
Q: How does Western research in genetics compare to China’s? A: We’re pretty far behind. We have the same technical capabilities, the same statistical capabilities to analyze the data, but they’re collecting the data on a much larger scale and seem to be capable of transforming the scientific findings into government policy and consumer genetic testing much more easily than we are. Technically and scientifically we could be doing this, but we’re not.
Q: Why not? A: We have ideological biases that say, “Well, this could be troubling, we shouldn’t be meddling with nature, we shouldn’t be meddling with God.” I just attended a debate in New York a few weeks ago about whether or not we should outlaw genetic engineering in babies and the audience was pretty split. In China, 95 percent of an audience would say, “Obviously you should make babies genetically healthier, happier, and brighter!” There’s a big cultural difference.
https://www.vice.com/en_us/article/5gw8vn/chinas-taking-over...
"This child is still you, just the best of you."
I don't know if the "economic competitiveness" part will be a comforting argument if this ever comes to pass. What I mean is, it won't been seen as "look at how our economy could grow if we do this." That economy would just be viewed as the new standard. This technology will be seen as "do this or you will be left behind." I fear it will be coercive and alienating.
If someone's children will likely have a lower than this minimum intelligence, which you can infer from parent's IQ and other measures, will you encourage or prohibit them to use either embryo selection or genetic engineering? What are the impact on the child's life for each option? Is the 'distaste' more important than giving a better opportunity for the newborns?
Also, what can you do? You cannot put regulations on China or other countries. On this issue, they will not agree on international agreement either. And there will be rich people who fly to other countries to have the procedures done. This will cause even more inequality than allowing it domestically.
Jordan Peterson IQ and Job Market https://www.youtube.com/watch?v=fjs2gPa5sD0
Can it really be inferred? Not including conditions or syndromes of course. The parents' environment may have affected their intelligence and the child may turn out entirely different.
Getting parent's DNAs sequenced might be needed but it's affordable now. See gwern's answers and link for more info.
1) life isn't about being smart, far from that (that's national emergent feedback, and I often despise nations as a concept)
2) being smart isn't even needed, a culture of sharing and listening would be enough to uplift life by many points. A culture of recognizing ego and letting him shut down then appreciate everything as a whole. Most brains can do this, if people can pass this down.
I regularly remember how everything was beautiful before, even with flaws and limits.. a race for optimization, especially driven by national interest isn't something I'd like to see.
ps: I'd even say, "intelligence" is an emergency mode for our brains, and cultivating it was a normal response, but it's not supposed to be our main mode
Even assuming that this works, when you do that, you immediately run into the same problem as every other eugenics program: you are reducing the diversity of the population to seek a local maximum. In the analogy for optimization problems of the cows in the field standing on hills and in valleys, you're having all the cows stand on a single hill. You improve the current fitness of the population, according to your metrics, at the cost of the future fitness - you'll never find higher hills to stand upon, and if the fitness function changes, your population will be less equipped to handle it.
I'm not denying science, and how it improves the human condition. But this is the point when it stops improving the human condition, and improves the controlled human condition. not the same thing.
IQ points? Hasn't IQ long ago been discredited as a measure of intelligence?
Long answer:
The g form of IQ is still valid. Based on context in which a test is taken, there may be some type 2 error (people scoring lower than actual IQ), but relatively little type 1 error (people scoring higher than actual IQ).
That said, many researchers have asked if g is the be all and end all of intelligence. Research suggests that g tends to focus on the analytic and verbal parts of our brains. Howard Gardner found through research on aphasia patients that there are areas of our brain that function largely outside of what g measures. Others have found that while IQ floors may exist for certain professions (e.g., 120 for lawyers), IQ is not always the strongest predictor for success -- things like EQ often have stronger predictive value.
Note that some of the derivative works of multiple intelligences, EQ, etc. are twisted interpretations of the original ideas, so be careful when reading the non-seminal works. Some people have co-opted the term "intelligence" in their derivative works in an effort to support a political agenda that may not necessarily be true to the original idea or even constructive.
- Optimizing EQ is probably far more valuable for society.
- I am not sure that EQ can be optimized for in genetics as easily as IQ can.
- On an individual level, putting a child on the right side of their potential IQ curve will probably make their lives easier or better assuming that relatively few of their peers have this same advantage.
- If every child is on the right side of their potential IQ curve, then optimizing IQ will largely just be a different state for society rather than a noticeable improvement. Most (all?) improvements would likely be seen on the high end in terms of theoretical developments.
- Note that if this switch is somehow flipped in a society, I personally believe that there will be a huge EQ intergenerational crisis such that EQ will be valued even more.
A: That same research does open up the door potentially to genetic engineering in the future. But that would take a lot longer to make practical.
===
Q: When do you think the embryo analysis might be implemented on a large scale?
A: Actual use of the technology to do embryo screening might take five to ten years, but it could be just a few years. It depends on how motivated they are.
......"
Specifically, modern humans have, on average, less than 0.1% of differences in their DNA amongst each other: "How diverse are we? Perhaps the most widely cited statistic about human genetic diversity is that any two humans differ, on average, at about 1 in 1,000 DNA base pairs (0.1%). Human genetic diversity is substantially lower than that of many other species, including our nearest evolutionary relative, the chimpanzee. Genetic diversity is a function of a population's "age" (i.e., the amount of time during which mutations accumulate to generate diversity) and its size. Our genetic homogeneity implies that anatomically modern humans arose relatively recently (perhaps 200,000 years ago) and that our population size was quite small at one time (perhaps 10,000 breeding individuals). To put the 0.1% genetic diversity estimate into perspective, it is useful to remember that humans have approximately 3 billion base pairs in a haploid cell. Thus, any pair of humans differs by approximately 3 million base pairs. These differences contain much useful information about the evolutionary history of our species. In addition, the small proportion of differences that occur within genes can lead to critical inferences about the effects of natural selection. "
Natural selection will be out the window. It will be replaced entirely by intentional selection. We will certainly see new diseases rooted in human vanity and hubris, and they will become business opportunities for surgeons and pharmacists, just as our natural and lifestyle ailments have become moneymaking industries.
So the great-grandchildren of people that were gifted by their parents with then-fashionable gene mutations will have all new reasons to pay for health care.
And Sylvester McMonkey McBean simply unveils his star-off machine.
Evolution does not vet for anything except population-level viability. Once upon a time, our population bottlenecked. The return of large-scale genetic diversity is normal for an animal species, especially one that has spread to practically every environment on the planet.
Also, evolution is not a prescriptive standard. Oy.
You haven't talked with my knees recently, have you.
-Another strongly supported hypothesis is that there was an near-extinction event that wiped out all but a pocket of human settlements from which we descended. - The diversity in other species that are about as old as ours is significantly far greater than ours suggesting that it is more likely an event like an unusually strong ice-age period that could've worsened our genetic diversity.
-It's unlikely that the Toba catastrophe was the root cause of the bottleneck as reasoned in this investigation:
https://www.livescience.com/29130-toba-supervolcano-effects....
- I wonder if the hypothesis of leaving Africa in small groups could be effectively tested.
Perhaps the first changes would be to our dietary track to absorb more energy, so we can change more things!
I always imagined it's a bit like the old Mage vs Warrior vs Ninja (or whatever) selections in fantasy games - you can maximize total area under the curve, or you can specialize in certain areas at the cost of others.
Edit/add - A convergence would also indicate there is global agreement on the "gold standard". Sure, maximizing intellect and longevity/health is easy. But, physical appearance?
Canonically it's Thief/Rogue, analogous to the MMO trinity of "healing, tank, damage" aka "wisdom, strength, agility".
Those can also translate into a holistic way: You gotta have the wisdom to know when to retreat/heal, the strength to endure and the agility to hit/get to where it matters. They don't necessarily exclude each other.
Also, as someone else pointed out, it would be more likely we edit different lines of humans. Two people having the best genes for a soldier and having the best genes for a scientist are likely to be better off than a single individual who has the best possible maximum of the two together. Optimizing multiple lines of humans each on a smaller set of traits is likely to produce far better result than optimizing one line on all traits.
There are some genes that I expect to be edited out. I'd give a lot to have the gene causing my high cholesterol edited out, as would my insurance company - the drugs I'm taking are not cheap. There are a number of other conditions that are genetic (and still more that science believes are genetic even though the genes haven't been found). This convergence is good though as these are genes that if you have are known bad - just not bad enough to prevent reproduction.
I think reading plays a more important role than writing.
Couldn't be more excited for what's possible.
Furthermore, right now these weapons just "sit around" - but one day they will be used again. All it will take will be a "brief moment" of insanity by a leader, and by the people he leads, to touch off the tragedy to follow.
Or...more likely...because we know it has happened in the past: It will happen due to a mistake, either by one or more humans misinterpreting what other humans are doing, or by misinterpreting the signals of machines (or machines sending the wrong signals, which are then interpreted correctly by the humans - though the signals are false).
This scenario is far more likely than sheer anger causing madness leading to tragedy - simply because it has historical precedent of happening not once, but multiple times.
Humanity will never be safe as long as these weapons and weapon systems exist.
What if in the future a pandemic rises, and we have "edited away" the only mutation that would give immunity?
There are people resistant to malaria that do not carry the deleterious red blood cell mutation, but a different variant.
I give us decent odds we end up like the bananas.
2) Heterozygous still carry the gene and can pass it on (you're likely to just exclude homozygous people)
3) Sickle-cell disease has a lot of downsides... Yes, it's a disease.
There is little to zero downside in preventing births of homozygous affected people.
There's a difference between editing and replacing. Imagine my father gives me his watch (which he got from his father, etc.). The watch is fine, but the belt has wear damages and the glass could use cleaning. Doing those repairs doesn't mean the watch loses sentimental value for me, and is markedly different from just getting a new watch.
Deep learning texhniques should help us identify the genetic causes of sone diseases but I suspect that our microbiome and epigenetic factors play a much larger role than currently known.
I'm excited to see what we can do with CRISPR, but we should do it fully aware of the ways things could go wrong (so that we can prevent those things from happening).
Many of these have low demonstrated correlation or significance so don't just blindly load everything on that document into your at-home CRISPR kit http://www.the-odin.com/gene-engineering-kits/ but it should be a good starting point for thinking about what can be modified, improved, disimproved, etc.
Specifically for viral interactions I reckon you'd be better off designing a small molecule inhibitor of viral binding via whatever lectin they have to whichever protein (or lipid for that matter) the sugar that FUT2 glycosylates is attached to. This allows for much more precise targeting of the undesired behaviour, rather than just chopping out the whole gene.
"Primer for synthetic biology" http://www.openwetware.org/images/3/3d/SB_Primer_100707.pdf
pretty old presentation but here you go, "Synthetic Biology: A primer" http://cellbase.epfl.ch/twiki/pub/IGEM/PaperCollection/iGEM_...
oh im sure human trials have begun by the time mass articles like this surface.
i've met young gententic research students who told me they went to work for labs based in Latam simply because they were allowed to do perform any experiments deemed illegal in the US - to get a precious few years of a head start.
china in particular does not have the west's historical scruples wrt genetic editing and eugenics. i think this 'debate' will last about as long as it takes for the first generation of modded chinese children with two or three SDs on the mean to be brought into the world.
A lot of people are scared of GMOs, even if it's just a simple alteration to a plant. I doubt that genetic modification of people will begin in the west without significant outcry and pushback.
Sure, you can argue that homosexuality isn't an undesirable defect, but does Trump's victory in the recent US election make you feel like the people regulating this in the future really aren't going to see it that way? What is it you're optimizing for in eliminating mental defects that you're confident couldn't also be objectively be applied to other things this group would find appalling?
Really what's being said is that nobody should be allowed to use their resources to improve their offspring beyond the level of random chance. This mentality isn't about ensuring that anyone does well, it's about preventing anyone from doing better, like crabs in a bucket.
I'd like to know what's scientific about it and who reached that consensus. There are a plethora of things to define before we even begin this discussion. What constitutes an enhancement? Isn't removing recessive genes aka "curing genetic deceases" an enhancement? If some people already have these "superior" genes, is it just to keep others from getting them? Who decides what genes are good or bad anyway? What's fundamentally different between trying to improve the germline by these means and the "natural" way of choosing best mates? We are choosing genes in both cases, in case of CRISPR we are trying to do it with better precision and certainty.
Wow, that's a huge deal if it's accurate. (I don't know much about the science involved so I can't judge whether it is.)
Forget racism, what happens when a country can actually make it's people "better" (faster/smarter/live longer/stronger) by significant margins?
Unlike how a lot of science fiction portrayed it, it really does not look like genetic modification is going to be individually costly once it is "production ready". A lot of the fears are of creating an underclass of genetically inferior humans, and then the usual argument is you have to ban improvement based modifications for that reason, but why not just promote not having unmodified births the same way we somewhat incentivize aborting fetuses with significant defects already?
All it is moving the bar higher, so that the "average" natural birth just becomes acknowledged as a defect. This is not new - centuries ago children born with even some of the most debilitating mental retardations could still be useful as manual laborers doing the most simple tasks. The abolition of most of those tasks has made is so extraordinary mental deficiency is almost always absolutely crippling, to the degree parents often do decide to abort over it.
The bar was raised then. People only seem content with it because it is both uncommon and a burden to them to support the deficient. When we have superhumans, are regular humans not then also a burden?
But for genetically modifying stuff, we're doing really well on that track. Most of the tech needed for designer babies is here. The issues with it aren't the tech existing, but our willingness to create massive numbers of defective offspring before we get a viable glow in the dark human. It's not the tech that's lacking, only our appetite for failed runs and a severe distaste for side-effects. But that's proven to work, CRISPR has already proven to be able to make glow in the dark pigs, so it's a matter of refinement. We don't have the slightest clue about terraforming. Just ideas at this point.
"Biologically, the Culture's citizens have been genetically enhanced to live for centuries, and have modified mental control over their physiology, including the ability to introduce a variety of psychoactive drugs into their systems, change biological sex, or switch off pain at will. Culture technology is able to transform individuals into vastly different body forms but, for unclear reasons, the Culture standard form remains fairly close to human."
In short if we want to expand beyond at best 3 planets we need a new solar system. That means we need humans able to make the several thousand year journey in a generation ship to a different star.
I suppose we could also take an earth sized chunk out of Saturn and put it into earth orbit. A generation ship to a different star seems more feasible to me.
I would expect that to happen. It's not a weird approach, it's perfectly reasonable - biology, after all, is technology. A very advanced nanotech that we did not engineer and we don't control yet, but technology nonetheless. Humans are not bound to deal only with metals, plastics and electricity forever.
https://www.edge.org/response-detail/23838
What do you think about this? From what I gather, the Chinese and much of East Asia do not have cultural resistance against using genetic engineering to increase their children's IQs. I will even guess that the governments will encourage their populations to use it.
Will the US, in particular the educated portion of the population, will adopt the practice soon after it is proven safe?
If China starts to do that en masse, Europe and the US will likely criticize them initially. Will they then be forced to adopt the practice soon afterwards? If so, how many years of lag approximately? How much resistance will there be on adopting the practice especially considering the left's belief on everyone's fundamental equality?
The denial about the importance of intelligence is quite obvious now at least by a significant percentage of Americans and Europeans. (They claim "hard work and culture are what matter.", ignoring twins and adopt studies) Will they wait for 1-2 generations until it's so obvious they cannot compete when they start to use genetic engineering themselves?
"Beijing parents splurge £154,000 on street alleyway in catchment area for desirable school
It may be a dusty passageway, ridden with insects and with electric cables dangling precariously from crumbling concrete overhead, but its value outstrips top-end property in Kensington and Chelsea due to rising demand from Chinese parents battling to get their children into elite schools."
http://www.telegraph.co.uk/news/2016/06/23/beijing-parents-s...
but, are there other imaginable economic environments in which intelligence becomes unimportant?
i'm reminded of the saying "China has two words for foreigner: barbarian and master"
China's legendary, long standing emphasis on education and intelligence has served it well for much of its history, but perhaps not all of it.
Hygiene, nutrition and medicine (all good things!) also cause us to remain alive where previously natural selection would not have favoured those bearing too great a mutational load.
I doubt that existing mutations have been fully 'tested'. We know that the majority of mutations are harmful and that the brain is far from fully-developed prior to birth, for instance. Being complex there are many genes which control its development and it seems plausible that the result could be sub-optimal without obvious signs of disease or disability. Other things being equal, we could be slower, less resilient, less fertile, etc, than our 18th century forebears.
I do see the argument you are espousing but I would only suggest that you consider the broader context of what happens when new species arise. I suspect you care more about the elimination of alleles (which is surprisingly hard to do), but this is a good example for why I disagree:
One possibility for speciation is the creation of a new niche (lets say a new type of tree grows on an island, its seeds having been carried there by an unusual current). Here, organisms might have increased reproductive opportunities over their neighbors by exploiting this new tree. In time, one could imagine organisms that live in the new tree, like microbes, could acquire enough new features to constitute a new species.
Consider the case where organisms from the original population become unable to grow on the new tree. If the new species is also unable to grow in the original environment, how can we say either is more or less resilient?
(1) humans have universal intelligence which gives us the ability to adapt to any environment, (2) human evolution is now swamped by the evolution of memes, not genes. We now decide what to do (including whether to speciate or not)
A more realistic analogy from the animal kingdom would be something like the case of farmed salmon which within a very few generations are less healthy than wild salmon. Also the famous 'mouse utopia' experiment. Both situations where the environment has been artificially manipulated by (human) ideas, just as our present environment is. Mutational loading is one explanation for the results.
So have you considered the issue of mutational load: what's the greatest load we can sustain and what's its present level? Is it responsible, for example, for the declining birth rates in the West or is the explanation for that purely sociological?
I would like to know the answers. However I presume that we'll start by using CRISPR or similar tech to eliminate known genetic diseases like Huntington's and Tay-Sachs. From that precedent should follow the identification and elimination of new and more silent genetic abnormalities. Which is reassuring.
But to your example, one issue with the farmed fish is that they now constitute a closed gene pool - we can easily explain their decreased fitness with the likely rise of harmful alleles.
With the explosion of population, I don't see much relationship between the salmon and humans.
This seems like a reasonably accessible (college-biology level) discussion of what evolution would look like in the human gene pool:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2933187/
----
EDIT:
I suspect you'll need a university library to access this, but Dr. Pardis Sabeti is well known in this area and also an amazing person - she played a big role in the molecular biology work that underlay the US response to the Ebola crisis. She wrote a review that explains the tools we currently have to ascertain human evolution:
I go for dumber people helping each other to live happy, fulfilled lives over intelligent super people destroying one another so they can control the most resources.
The problem though is that happy dumb people will have an even harder time competing for scarce resources against genetically engineered unemphatic super geniuses than they do against the current crop of sociopaths that run the global economy.
Also, to support your claim, one would need evidence that the child mortality of the past reflected genetic unfitness (as opposed to poverty or the unavailability of antibiotics).
In any case, we have to go back to the question that the GP asked, that dogs are malleable doesn't help us. Does reduced child mortality really cause more mutations to accumulate?
However, dog breeds are not species and, given their non-random mating, don't really tell us much about whether 200 years is long in vertebrate evolutionary time.
As far as humans go, I will grant that allele frequencies may have changed if you pick an isolated subpopulation of humans (say, everyone in Greenland) but even that seems extremely unlikely.
As an aside, there are researchers who are using the caste system in India as a way to explore genetic architectures within a civilization. As these castes have existed for considerably longer than the period we're discussing, meaningful allele frequency changes may arise.
http://wasdarwinwrong.com/korthof97.htm
I would guess it is wrong; we are on a track where genetic manipulation to treat blatant defects will (relatively shortly) be cheaper than the traditional medical treatments.
Parents could choose to have children created from their healthiest genes, rather than leaving children to be shotgunned with a random and increasing fraction of damaged genes. Genetic repair would replace the ancient cruelty of natural selection, which only fights entropy by tormenting organisms because of their genes.
The concern espoused above is that we won't be able to fix the problem.
Now that's a limited view of the process that created life. Natural evolution also pays back by upgrading the gene pool.
The broader problem is that the educated and wealthy will probably either sterilize themselves or use birth control to avoid having "normal" children, whereas the poor either won't know, won't care, or won't be able to consistently afford it.
The society in Gattaca has used their advanced technology to imprison themselves and eliminate social mobility rather than expand it.
I was never a big fiction reader but I can't get enough of these books... Jehoshaphat!
Because science and technology alone cannot save us from destroying ourselves. Einstein, MLK, Carl Sagan and many others warned of how our scientific progress has been outpacing our human social progress.
Case and point - our scientific progress has led us to create tools of global genocide. Technology has always been a double edged sword.
People never needed technology to commit genocide - there are plenty of examples throughout our whole history.[1][2][3]
If anything, now that a significant portion of the world has nukes, we haven't had two developed countries at war for perhaps the longest period in recorded history.
1 - https://en.wikipedia.org/wiki/Siege_of_Baghdad_(1258)
2 - https://en.wikipedia.org/wiki/Albigensian_Crusade
3 - https://en.wikipedia.org/wiki/Thirty_Years%27_War
---
Case and point -> You meant to write "case in point".
Technology was used in all of those examples.
Technology by itself didn't create mass murder, but it does makes it much easier to do.
Well, not immediately fatal, anyway. What if a gene modification is developed that halves the rate of aging? Is it a birth defect to have a maximum life expectancy of only 120 years instead of 200 years?
The issue I have with this type of engineering is there is no means of egress (if you will), no thought about how a recall would be implemented.
Humans are flawed. The history of engineering displays those flaws. But instead we purposely stand in our own blindspot and insist "no. THIS time I'll be different" completely forgetting the countless times that was said previously.
Long to short, our certainty is likely overstated. It wouldn't be the first time either.
Pity evolution didn't give us the intelligence, restraint and good judgement to make sure that we will not screw this up. And we will.
A myriad of reasons will be given. Medical reasons - how could one refuse? Then parents: "Harvard is expensive and I want to give my child the best chance I can afford". Then nation states will feel pressure to 'level the genetic playing field'.
On the other hand, with AI soon replacing us, apparently, we can fight back and enhance ourselves!
Because this is how we grow up. We screw up, again and again, but as long as we come out stronger each time, I'd say it's worth it.
That's why I believe a top priority today should be ensuring that our technological civilization does not collapse - through neither technological mistakes, nor through social upheaval. And if we were not given enough intelligence, restraint and good judgement to avoid making stupid errors, then maybe at some point, we'll fix that too.
Either way - hopefully, when this tech is completed, we will be able to accept and enjoy that our descendants will literally be superior beings to us, and not look upon them with too much envy.
>The earlier Chinese publications, although limited in scope, found CRISPR caused editing errors and that the desired DNA changes were taken up not by all the cells of an embryo, only some.
Instability is an inherent property of genes.
Seems a little early for such a claim based on embryos that only developed for a few days.
We've been at a point, where it's viable for human application, for quite a while. But the ethical and religious stigma is preventing us from going the full distance.
As of right now, it is very likely that the first genetically engineered/enhanced human will be a Chinese person because they are way more pragmatic about those issues.
It is often said that companies would intentionally prefer not to cure major diseases. Then Gilead (Pharmasset), goes ahead and does so, while charging less for the cure than the cost of healthcare for living with HepC (much less all that is lost from HepC, including quality of life and economic contribution) - and for doing so, they were treated as a villain due to what they charged. For such reasons, I doubt we'll ever see drug prices high enough to deliver trillion dollar outcomes. Throw on top of this, that the last bastion of crazy drug prices - the US - is nearing an end on its tolerance for such.
[1] http://www.randalolson.com/2015/03/01/design-critique-puttin...
The very specific problem is the rest of the world will never pay it, and the US is aiming to stop paying it (exorbitant prices). Nothing is going to change that, it's a fact of life when resources such as income and wealth are inherently limited and expand fairly slowly overall. If you come up with something spectacular that is very valuable, they're still not going to pay it - it was demonstrated overwhelmingly by the HepC cure (and has been demonstrated by vaccines as another for decades; what's more life saving than vaccinations? and yet the developing world simply will not - and frequently can't - pay high prices for such).
Vaccines have saved hundreds of millions of lives. Give me an example of something that is going to beat that. Now take a look at the extraordinarily unspectacular financial outcome for the vaccination market (particularly compared to the trillion dollar premise being discussed). Why would anyone by default believe something amazing that comes out of CRISPR, would produce a dramatically superior financial outcome versus what vaccines have produced?
I'm not sure current demographics allows for more than one such company in any given sector, and it would need to have a virtual monopoly on whatever it were selling.
10K is already well within the range people spend on births (currently about $8k including prenatal and postnatal care).
Not to mention the cost involved in raising the child to adulthood. :-)
You might even be able to charge $50k or $100k, if it actually got to the point of design-to-order (which, granted, would be orders of magnitude more difficult than simply removing one bad gene).
How much would a parent pay to have a kid with the mind of Richard Feynman and the body/appearance of David Beckham, or the mind of Marie Curie and the body/appearance of Kiira Korpi?
Quite a lot, I'd imagine.
All of the above costs are mostly covered by insurance, but if you work them out, a $100k treatment can pay off in as little as 10 years.
Of course there is a difference between ensuring someone's kids don't have a condition and fixing it in someone who is already alive. Will parents make this choice even if insurance pays for it?
And of course someone is paying for the insurance. Even if it's given as part of your employment, that's money that your employer could otherwise be using for other things (maybe even giving it to you as your salary...that's how we got into the employer-provided health insurance mess in the first place -- salary was taxable, insurance wasn't).
https://www.technologyreview.com/s/608073/gene-editing-compa...
I thought the original authors had a rebuttal, but I can't seem to find it.
Perhaps that's too much of a selection bias for you, so I'll offer this critique: if you wanted to measure the off target effects of Cas9 in an organism, you would probably sequence the organism before you edited it, and then sequence it again after you edited it. But that's not what they did.
(Then again, this is a lay-press article, so I don't entirely expect a lot of detail)
What would you call them in this case? Science press?
Still - not enough room in an article like this for too many details.
I subscribed for a while, I stopped after the number of eye rolls had gotten too high.