We would need a very particular set of conditions for embryonic editing to be justifiable under a medical dogma that aims to "do no harm." Both parents would need to carry a large common set of recessive deleterious alleles, as this would make embryonic selection of non-carriers very difficult. Then we would need the editing system to be so reliable as to not introduce off-target mutations. In a preimplantation setting, we can't easily observe if non-desired mutations have been introduced in some cells, as this would require sequencing every cell in the developing embryo. Serious disease introduced through chimeric errors in the editing process would be a real possibility, and there is no feasible way we could guard against this result using sequencing as it would require destruction of the embryo.
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.
The medical dogma never comes down to do no harm, at least today. The Hippocratic oath is largely symbolic today. The main goal of a physician is to ensure the well being of their patient. This means that they will judge the risks/harm to the benefits and make a judgement, and receive informed consent.
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 one of the earlier male in vitro embryos successfully carried to term in the US, I'll claim a unique perspective on the scientific creation of life.
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?
> 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.
Every technology ever has opened 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.
>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?
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.
Technically the mild brain damage of drinking heavily over time is permanent. The nervous system is a biological system made up of organs: it's always changing, often permanently.
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.
As a five-time would-have-been infant mortality case, I emphatically agree with you. Mastering our environment and ourselves to turn them towards our purposes rather than their mere natural flow is what being human is. That's how our species rolls!
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.
Designing blond babies because society slightly prefers blonds, takes an implicit preference and makes it explicit. Not everyone will be able to afford all the "premium" upgrades on designing their babies (and you can bet that cosmetic features will be premium). People who can't afford blond babies or cute-nosed babies or skinny babies or w/e the hell the fad is, will find that their children grow up to be second-class citizens.
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.
All of your arguments could apply to cosmetic surgery just as well.
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.
Cosmetic-only editing is pretty analogous to cosmetic surgery, I grant you that.
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...)
> This means that they will judge the risks/harm to the benefits and make a judgement, and receive informed consent.
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.
> It has been observed (in mice) that editing the germline by directly editing the embryo will result in chimerism in the fetus.
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.
The problem with not editing the germline, is that that could easily be used to implement a DRM scheme. The recipient of this sort of editing might have a very high chance of only producing disabled or dead offspring, as they themselves would have been, without intervention. They, and their descendants, would have to procure this same treatment in order to procreate.
I can’t imagine anybody in their right mind would create a genome that had a DRM. Furthermore, would you sign up for a procedure like that? Also it’s a violation of somebody’s human rights to stop them from reproducing!
What is really happening is that normal copies of the human genome are being incorporated. Which are then passed on to your sperm/ovum.
Starry-eyed young lovers will fall for a DRM scheme, if they can be convinced that it is for the children.
"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.
At first glance, I read: "Starred-crossed lovers will run afoul of DRM scheme - to whit, a remix:
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.
On the other hand, if you make a fish-pig that lives off algae and tastes like bacon, perhaps "terminator genes" is a sensible protection to avoid accidental destruction of the biosphere? (The "terminator genes" could end up going both ways in terms of containing engineered species).
> I can’t imagine anybody in their right mind would create a genome that had a DRM. Furthermore, would you sign up for a procedure like that?
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.
There are enough sociopaths in the world, that nobody needs to sign up for a procedure like that.. its easy enough to buy genetic material, millions of people the world over are desperate enough for a better life that they will sell themselves and each other.
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'm not certain where the premise that our medicine must "Do no harm" comes from. Chemotherapy, for example, is known for being extremely toxic and harmful, yet the justification is that it often yields better outcomes than no treatment. Why can we not use the same justification for editing DNA? Honestly some therapies cause mutations by design, as some cancers are less capable of DNA repair.
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".
Maybe because chemo currently gives you 10% chance, while gene editing at the whole embryo level has 100% chance of resulting in mosaicism.
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.
Mosaicism is not inherently bad. It is definitely case specific. The current technology just doesn't allow much control over how much mosaicism you will get, on top of the off-targets, which is your point basically.
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.
> I'm not certain where the premise that our medicine must "Do no harm" comes from.
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."
It’s a myth that doctors even take this oath. There might be some modern version taken, but it is a symbolic pledge, not a legal requirement. Laws and committees cover issues of ethics these days.
"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.
It's not simply 'net' harm, as we would regard surgeons as breaking this principle, if they were to murder a homeless man and distribute his organs to 5 otherwise terminal patients.
Medical ethics is its own field precisely because overeager and overconfident solutions are fraught with problems.
> 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...
Chemotherapy is more of an exception than the norm when it comes to what treatments are acceptable. Most other drugs have to be proven safe to use even before showing tangible benefits. And even in oncology there are Phase I studies to ensure that your treatment is not Too toxic either. So yeah, Do Not Harm is very much a thing.
> Most other drugs have to be proven safe to use even before showing tangible benefits.
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.
My apologies, my previous post was not clear on what I was really questioning. I am attempting to hold up chemotherapy as an example of pragmatism which exposes how the premise of "Do not harm" is not a helpful rule. I believe we may be conflating "proven safe" with "does absolutely does no harm", which are much different standards.
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.
It's not exactly an exception; it's just on one end of the spectrum. The more serious the illness, the more serious the treatment side effects we tend to tolerate.
I've seen most of these arguments for and against gene editing before, but the fact of the matter is that it will come down to the economic competitiveness of nations, as always.
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.
From an interview with Geoffrey Miller, an evolutionary psychologist:
"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.
The "fertilizing many eggs and then picking the genetically 'best' ones" is literally a plot point in Gattaca.
"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.
Modern advanced society already requires a high minimum intelligence for people to function in especially to hold a respectable job or be a respectable member of a community. The minimum is increasing when more automation is used for most kinds of automation.
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.
If someone's children will likely have a lower than this minimum intelligence, which you can infer from parent's IQ and other measures...
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.
The quote is accurate, but the plot point is not. In Gattaca, they pick the best of each gene to make an optimized embryo, which is far, far more meddlier than picking the best whole embryo.
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
From a purely functional, non-ethical standpoint, the problem here is that you can't select the smartest embryo from a pile. You can only select the embryo with the most genes identified as correlating with intelligence.
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.
well the answer of course is to let some greater intelligence decide this for you. Something greater than humans. AI? Let data and algorithms that aren't influenced by emotions decide?
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.
"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."
IQ points? Hasn't IQ long ago been discredited as a measure of intelligence?
Short answer: No, IQ has not been discredited as a measure of intelligence, but maybe there is more to the scope of intelligence than what it measures.
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.
"
Q: Could it develop into something more sinister?
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.
Thing is, we are naturally not diverse at all (in part because our nearest ancestors with whom which we, at one time, did have reproduction compatibility with, are no longer here): https://www.ashg.org/education/pdf/geneticvariation.pdf
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. "
This is definitely true, but all of these genes have been vetted by millions of years of evolution, so we know they're rock solid. The edits we're talking about will be happening on a time scale that won't be constrained by natural selection, so by the time a weakness is found in one of these new genes, it's likely that it will already be widely adopted. I guess what I'm saying is that it's hard to anticipate what natural selection will look like when we multiply the "mutation rate" by probably > 10 orders of magnitude.
Certain breeds of dog get hip dysplasia. Dalmations go deaf. Molosser breeds often have respiratory issues, particularly pugs. This has not stopped people from breeding dogs.
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.
>This is definitely true, but all of these genes have been vetted by millions of years of evolution, so we know they're rock solid.
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.
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).
-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.
As for what might explain the near-extinction humanity apparently once experienced, perhaps another kind of catastrophe, such as disease, hit the species. It may also be possible that such a disaster never happened in the first place — genetic research suggests modern humans descend from a single population of a few thousand survivors of a calamity, but another possible explanation is that modern humans descend from a few groups that left Africa at different times.
-It's unlikely that the Toba catastrophe was the root cause of the bottleneck as reasoned in this investigation:
0.1% difference is huge when talking about a ~6 billion character code. The OP is talking about the danger of moving to only a 0.001% difference (600M vs 6M).
This would imply that you had to choose a specialization when the "designed" human could just be best suited for all of those things. Physical and mental perfection.
I think divergence is more likely, simply because of tradeoffs required. For example, physical strength and mental capabilities compete with each other for energy.
Hmm, true. But, can we design for perfection across all traits?
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.
I wouldn't worry too much about that, because I don't see the whole of humanity having access to this technology. Their will remain an underclass who, in general, won't be allowed to have access to this (more due to economics and politics that don't allow access instead of direct prohibition of access, think about how medical care is currently allotted). I think the interesting bit will between what happens between those who have regular access to this technology and those who don't. Could there end up being two human species resulting from this?
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.
I don't think we will converge that much. Most gene differences are insignificant. Is it better to have black, or white skin (or any other skin color)? There is a lot of baggage associated with that question, and some people will make a choice - but not everyone will make the same choice (in a culture I would expect everyone to make the same choice, but other cultures will choose differently), and many people won't care.
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 am so insanely excited for the potential of this technology. There are many ethical questions here, but the potential benefits far outweigh the downsides. In the near future, we can detect and eliminate genetic disorders, ensuring no child has to suffer from these defects any longer. Long term, this gives us a tool to take control of our own evolution in a way never before possible.
While I appreciate the optimism in this sentiment, the similarity to the early atomic age gives me pause.
Human beings have shown time and time again that they cannot be absolutely trusted.
There's an anthropic problem there. Unless you assume humans are alone in a single universe with no branching, or that there are a large number of worlds where an atomic age (as well as any other equivalently stage of dangerous technological advancement) is infeasible, surviving the atomic age tells us that the probability of us surviving events in that reference class is non-zero, but it doesn't tell us much more.
We are still in the "atomic age" - and will be for as long as nuclear weapons continue to exist.
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.
Maybe. I think it's difficult painting these things as having a net value. There's good and bad, and they co-exist, one doesn't come without the other.
Sort of I guess, every activity puts us in a new place. We know we can't stand still. Doesn't mean we can't be careful, but handwringing won't help much.
Why vest absolute trust in anything at all? Just figure out how much trust is justified and act accordingly. And remember: the conservative, do-nothing choice is also a choice, because the world still does its thing even if you do nothing.
I agree for deadly genetic disorders, but we can't be sure if a harmful mutation will be important in the future. For example sickle-cell disease make people immune to malaria.
What if in the future a pandemic rises, and we have "edited away" the only mutation that would give immunity?
Why is that unlikely? As cost approaches zero and benefits increase we can assume we get pretty close to 100%. In fact holding a portion of the population back, even if well meaning, will be discriminatory.
this does not edit embryos, this only select the ones without defect and trash the defective ones. Very different from editing, especially for couple that only get bad embryos, they'd love to "fix" it.
Or they could use a different source for sperm or eggs, especially that they are supposedly not attached to their own genetic code (being willing to "edit" it anyway).
> especially that they are supposedly not attached to their own genetic code (being willing to "edit" it anyway)
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.
Just barely... only for single nucleotide disorders and we are finding that a lot of the coding in the genome is not continuous and can be broken up by hundreds if not thousands of base pairs.
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.
Have you read some dystopian fiction? For example, Margaret Atwood's Oryx and Crake?
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.
I can't speak for all the genes on that list, but I wouldn't go around knocking out FUT2 just yet. We don't know the full extent of biological roles for it, and the functionality is probably redundantly encoded in multiple genes too.
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.
Agreed. I'm a non-secretor and I've benefited from not getting a norovirus when I really ought to have. But if such a valuable trait hasn't reached fixation in the population there's bound to be a reason. It also has a variety of effects on susceptibility to other diseases, some positive, some negative.
Is there any differences in the amount of work (or tech) necessary for editing these "enhancement" genes as compared to what the guys in the article did? In other words, is it any harder to edit some genes as compared to others?
Many things in biology could be construed to be pointers if you squint hard enough--- promoters, transcription factors, all sorts of far-reaching regulation-effecting small molecules and proteins and variations of DNA/RNA molecules. Is "guide RNA" a pointer? what about the other gene targeting techniques-- like TALENs? see http://diyhpl.us/wiki/gene-editing/
"Although none of the embryos were allowed to develop for more than a few days—and there was never any intention of implanting them into a womb—"
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.
Ethics questions need to be raised now, and guidelines have to be decided. The future of humanity is in gene editing. It should not depends on the lazyness of law makers and outrage of godfearing creatures to decide the fate of humanity. It is time we take our evolution into our own hands.
Most agree that it is unethical to purposely have a disabled/diseased child if it possible to not have a nondisabled one. In that case, I think it is quite ethical for this technology to be used on those with debilitating genetic defects. We’re in no rush to allow any genome editing other than that.
> We’re in no rush to allow any genome editing other than that.
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.
I don't think you can make a very strong argument for the "west's historical scruples wrt genetic editing and eugenics" when you look at the prevalence of convenience abortions and the history of eugenics in America.
The west has been very anti-eugenics for over half a century at this point, but I agree it isn't very historical. That being said, there's a big difference between genetic editing and abortions of fetuses with genetic disorders (which is what I assume you mean by "convenience abortions").
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.
Actually medical ethics struggles with this question. The right of deaf parents to have deaf children so that they can understand deaf culture is a major case study. Here's one article, the ethics community hasn't answered this one as far as I understand (there are many more recent articles). http://www.independent.co.uk/news/science/deaf-parents-could...
Hmm. Including myself, anyone with an IQ less than 2.5 sigmas above average, or with strong enough emotions to make bad decisions that contradict correct analyses, or with not enough ambition to want to attempt anything useful with their high IQ in the first place ... is thusly "debilitated" and should have been allowed genetic engineering.
So you're saying the world would hands-down be a better place if we could eliminate kids with Down syndrome? Where do you draw the line between that and not wanting your kid to have to deal with gender dysphoria or same-gender attraction in our current political climate? Should parents have the option of eliminating that too?
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?
That some people are too vain to adopt is not a good enough justification. It is a foundational point of ethics that medical experimentation must be voluntary.
I realize that scientific consensus is that gene editing should not be permitted to enhance human performance - be it mental or physical.
But if one nation ignores this consensus, and starts producing "super humans" wouldn't other nations be compelled to follow?
Otherwise, over time, wouldn't their citizens, and their nation, slowly fall behind as a country of power and status?
Just a thought.
Assuming it becomes possible - why shouldn't people edit their genes to produce superior children? We're already talking about just that, when we discuss editing out congenital diseases and the like. The only difference between the two cases is that one is eliminating unexpected weaknesses and the other is eliminating generally-expected weaknesses.
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.
This isn't just a theoretical concern. Several genes known to improve cognitive skills harm social skills. (social skills and empathy are not the same, but they are related)
>I realize that scientific consensus is that gene editing should not be permitted to enhance human performance
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.
>Given the Mendelian genetic lottery, the kids produced by any one couple typically differ by 5 to 15 IQ points. So this method of "preimplantation embryo selection" might allow IQ within every Chinese family to increase by 5 to 15 IQ points per generation.
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.)
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?
The fact that more people aren't terrified of this worries me. Hitler may have been wrong with his "aryan superman" view but what happens when there is science backing it up? Not really looking forward to a genetically-enforced caste system.
Gene editing is probably the only way humans can colonize space. By adapting people to different gravities, air chemistry and pressure, radiation, etc., the need for life support equipment can be significantly reduced, and the quality of life of the colonists can be improved.
Let me start by saying I'm not a biologist. However, it would seem prudent to think we are much much farther from doing most of what you said than doing terraforming at small levels when we just started editing embryos. Ostensibly the science doesn't even yet exist to do what you are describing whereas funding is the majority of the problem for terraforming at small levels.
Even small adjustments can make things better. One example is how melatonin levels in people vary based on what latitude they came from. Native Eskimos can digest different foods. The ability to synthesize vitamin C. Some people are more adapted to lower pressures (high altitude). Smaller body size can reduce life support requirements. It's endless.
I'm confused. Terraforming is 1000+ years away, if we are ever even able to do it at all. I'm unclear of what you mean by 'small levels' because either you are terraforming, or you aren't. You have to create an atmosphere, you need to create a planets worth or water, you need to inject a crap ton of CO2 into the atmosphere to create the material plants will use as building blocks, to create the O2. All of this is millennia away. We've been non stop injecting CO2 into the atmosphere since the beginning of the industrial era, and that (while a bit of an issue today), isn't nearly enough carbon to begin to terraform a planet.
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.
Iain Banks' Culture series (sci-fi novels) explores this subject in a way I enjoyed greatly.
"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."
That is true, but not really useful. There are only a few planets that we can inhabit. Not enough energy (sunlight) reaches Saturn to make it a useful planet even if you can stand the gravity.
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.
There is a lot of stuff floating around the solar system (asteroids, small moons) that can be mined. We need to automate that process and that of habitat construction, then the Asteroid Belt could hold 7,500 trillion people, if thoroughly reshaped.
Asteroids can also serve as giant "yachts" to move around the solar system. Find one in the right orbit, land on it, and hitch a ride. You've got all the radiation shielding needed, plus plenty of raw materials to build out the "spaceship".
On the flip side, if we have a problem with racism now just on the basis of skin color/ethnicity/(culture), just imagine what sort of conflicts would arise once there are actual different human races. Even more so if they cannot reproduce with one another.
I agree with the others that this is a long way off. But just imagine, if 200 years from now, you could grow a space-worthy carapace overnight, with attachments for gear. And organs that transform a dense solid into maneuvering gas and oxygenated blood. In fact, we could just do away with the whole breathing thing, that is so unreliable and unhygienic.
> But just imagine, if 200 years from now, you could grow a space-worthy carapace overnight, with attachments for gear. And organs that transform a dense solid into maneuvering gas and oxygenated blood.
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.
"The BGI Cognitive Genomics Project is currently doing whole-genome sequencing of 1,000 very-high-IQ people around the world, hunting for sets of sets of IQ-predicting alleles. I know because I recently contributed my DNA to the project, not fully understanding the implications. These IQ gene-sets will be found eventually—but will probably be used mostly in China, for China. Potentially, the results would allow all Chinese couples to maximize the intelligence of their offspring by selecting among their own fertilized eggs for the one or two that include the highest likelihood of the highest intelligence. Given the Mendelian genetic lottery, the kids produced by any one couple typically differ by 5 to 15 IQ points. So this method of "preimplantation embryo selection" might allow IQ within every Chinese family to increase by 5 to 15 IQ points per generation. After a couple of generations, it would be game over for Western global competitiveness."
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?
The average Chinese also values education and intellgence much more than the average American.
"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."
The talk is of 'genetic enhancement' but the potential benefit seems more boring and necessary to me: removal of many new and as-yet-unidentified mutations. It is thought that these have been accumulating generation by generation since about 1800 when child mortality started to fall.
Why would you throw away the biodiversity of our species? You're forgetting about the huge bulk of mutations that have been tested (and were embryonic lethal). Our rapidly growing species has only accumulated mutations that don't cause us to die, and that's an immensely valuable resource to have. The evolution rate of a species is proportional to its genetic diversity.
>Our rapidly growing species has only accumulated mutations that don't cause us to die
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 don't think you can remove a discussion about changes in allele frequencies from environments. Thus, making 'other things being equal' is not a reasonable premise from which to discuss evolution.
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?
That's a pretty subtle case but I don't think it's relevant to the issue of human evolution for at least two reasons:
(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.
I guess I would need to see an analysis of whether there's been any change in human allele frequencies. I suspect there hasn't.
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.
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:
Species also evolve in response to environmental stimuli. Nowadays anyone of any relatively normal genetic disposition can reproduce almost as much as they want. There is no selection bias in our children on a structural level - the beautiful smart people aren't having dramatically more babies. If anything, we are culturally selecting for poverty since the poorer you are the more children you have on average. Poverty itself is not a genetic trait, but the negative traits that can lead one into poverty are obviously going to be much more abundant.
The "negative" traits that lead to poverty in our Western Democracies might arguably include such things as empathy, charity, and a preference for cooperation instead of conflict. Selecting for people who "win" at Western capitalism seems likely to usher in a much worse distopia.
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.
Absolutely true. I was concerned more with traits that can drive people from fiscal stability to poverty, like an addictive personality, how gullible they are, etc.
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.
I would be very interested to read an academic paper that made this point. 200 years is a blink of an eye in almost any vertebrate's evolutionary time.
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).
This isn't an academic paper but at least one academic, John Tooby, has gone on the record as strongly believing that mutations are accumulating in the human population due precisely to this: https://www.edge.org/response-detail/26714.
200 years is a decent chunk of time from an evolutionary standpoint. We feel it's short because of how long our history has been. But within 200 years you can manufacture N new breeds of dogs, for example. We just underestimate how much change takes place in the world.
Dogs are fertile at 1 or 2 years of age. You can do an awful lot more in 100-150 generations than you can in 10-15 generations (probably more like 6-8. Checking my family tree, many of my great-great grandparents were born ~1850, so for me personally, 5 or 6 generations).
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?
I think you're misunderstanding my point, but maybe I shouldn't have taken vertebrates as an example; we can of course imagine some island where massive selection pressures lead to speciation. I would be interested if you have such an example.
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.
I'm not making a formal claim just sharing my thoughts. Though I do believe at least one evolutionary biologist has written about this: Hamilton W.D. (1999). The hospitals are coming. Narrow roads of gene land (Oxford University Press). Btw the phenomenon of 'mutational meltdown' is a closely related topic and may re-pay googling.
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.
Your link proposes that we will be able to manage mutations using genetic engineering.
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.
As if there wasn't enough inequality in the world, now the rich will be able to afford to make their offspring genetically superior to everyone else's. Have fun with a 1% that are literally overlords.
The tech isn't that expensive, it is the R&D into knowing what you are doing. Once we have "perfect" embryos cloning and implanting them will be an expense almost anyone in the world could afford, especially if global incomes in the poorest regions keep rising as they have been the last 20 years.
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.
Do you really think you will be among the ones allowed at the top? Protip: if you were you wouldn't be here right now. We will all likely be denied access to the best technology and will quickly fall behind within a couple generations.
I of course have no sources to back this up (how would one even get such data?) but I suspect billionaires have better things to do than go e-slumming with those of us with fewer than 30 cars.
Billionaires? Perhaps. But aren't most of us on here taking a quick break from our Silicon Valley-like software engineering jobs that put us in or near the highest income 1% of the United States, and firmly within the highest income 1% of the world? I'm sure any significant medical advance that is remotely scalable will be available to most of us if our competitiveness and survival depends on it.
In my class just Monday, we watched a film titled Gattaca, which tells the story of a society fueled by eugenics, where most births are in-vitro modified babies, and there is clear discrimination against those with "imperfect" genes. It's crazy how close these things are to reality.
I hated that movie. It's nice to think that you could overcome a heart condition through willpower, but the flip side of that is that if someone has a heart condition and doesn't overcome it then it's their fault. In reality life is just biologically unfair and disease or infirmity isn't actually a moral failing.
I don't think they ever confirm he has the heart condition, just when they screen him as an infant there is "~99% chance" he has it. Part of the plot is that the main character and others like him are never given a chance at anything in life because genetics have become viewed as destiny. They have futuristic advanced medical technology that probably could give everyone a good, meaningful life. He lives at the best time in history to survive a heart condition and yet he can't even get into daycare because the insurance won't cover him.
The society in Gattaca has used their advanced technology to imprison themselves and eliminate social mobility rather than expand it.
No. Birth defects aren't contagious and are not often fatal. Also -- where do you draw the line between "defect" and "cosmetic enhancement"? It will become a race to the bottom.
How would genetic editing be a race to the bottom? If anything it would be a race to the top. If every generation got smarter, healthier and more attractive thanks to procedures like this humanity would be better for it. This would probably be true even if only a minority of people can afford it. If we had orders of magnitues more of genius level intellects pushing the boundaries of technology and science, humanity would be better for it. I just don't see where this would be harmful if it works as intended.
>If we had orders of magnitues more of genius level intellects pushing the boundaries of technology and science, humanity would be better for it. I just don't see where this would be harmful if it works as intended.
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.
>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.
That is partly because most people are not Einstein, MLK, Carl Sagan. If using genetic techniques and most people become as smart and wise as those names the world WILL be a better place, no?
> Birth defects aren't contagious and are not often fatal.
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?
What is advantageous in keeping anything that is guaranteed to need life long treatment to simply stay alive and is genetically accurately identified in our gene pool (eg cystic fibrosis, not mild myopia) ? Technology for this is already available (and even parental testing could already help diminishing incidence) yet I doubt it's common.
Wasn't there a HN post/thread a week or so ago about some scientist having a (new-ish) theory about DNA and the role specific genes play? If there's enough doubt that there's still room for other theories, is CRISPR really a good idea?
I remember they used to say that...when the world was flat :)
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.
Evolution made us, then we discovered it, and now we can directly code it.
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!
> 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.
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.
Well this is exciting, but hopefully it will advance beyond "genetic disease". Or maybe in the future we will be able to expand our definition of that term, to include all genetic predispositions to suboptimal traits? (e.g. slow observation-decision loop, hedonism, sentimentalism/too-much-empathy, neuroticism, etc.)
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.
Wait, being empathic is now a negative trait? I'd hope we would want our first generation of superhumans to be too empathic, or else they might exterminate all of us of inferior breed.
You would want that, but that choice may not be possible. There are some known genes where you choose between social skills or memory. You cannot have both as it is the same gene.
In addition to the factors mentioned in the sibling comment, empathy can often lead one to make the wrong decision. (Where by "wrong" I mean any decision other than the one best supported by one's rational analysis.)
We already have a clear division in health along socioeconomic lines, but delivberately encoding our inequalities into our DNA is a future I could skip.
I don't think the modest raise in IQ would be worth a society that considers children as products they can alter to specification. Bill McKibben in Enough wrote eloquently about the existential dread that could happen if we somehow managed to select for musical skill for example. It's one thing to deal with your talent or lack of it in terms of the randomness of normal life, another thing to realize you are little more than a racehorse that has been bred because your parents want you to be something.
This is the real shit right here. There's going to be gene-ism against older generations with inferior genetics, talk of "cutting them off" of government health programs because their fragile bodies are too expensive to maintain...
Seems like a more socially acceptable form of Eugenics since society seems to value advanced science more than it does traditional mate selection based on desired physical traits.
I know very little about this topic, but let me shoot: isn't this method for improving competitiveness misguided and shortsighted? How about working on emotional intelligence, better education and talent management, better food in schools, better child care, more support for disadvantaged families - there is so much we can do... Or is it just not about improving society, but individuals (with deep pockets)?
I'm eager to see the long-term results of the gene editing procedures.
>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.
"Now Mitalipov is believed to have broken new ground both in the number of embryos experimented upon and by demonstrating that it is possible to safely and efficiently correct defective genes that cause inherited diseases."
Seems a little early for such a claim based on embryos that only developed for a few days.
Evolutionary logic is like a massive legacy codebase without any tests. Fuck with it at your own risk. You could definitely get lucky and improve functionality but you'll never know what you'll be breaking.
I think enough people recognize the ethical issues inherent in designer babies enough that we are in no danger of reaching that point. I think the tech could have great applications in livestock and curing genetic defects.
Because we've already done it with plenty of other animals, even cloned them and let them grow to maturity. Never heard of Dolly?
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.
CRISPR is coming. I seriously think with CRISPR we could see several trillion dollar companies. From cancer and aids cures to fundamentally altering what it means to be human, this is all within the near grasp of CRISPR ( if what i've been reading is to be believed ).
Gilead managed to demonstrate how curing a major disease does not result in such a spectacular outcome (of the trillion dollar scale). They did very well by curing HepC, briefly, and now they're eroding back down after just a few boom years. The same would occur with curing HIV/AIDS. There would be a brief boom derived from sales in some developed nations (most nations would receive the cure extremely inexpensively, as with HepC). It might get a company to a couple hundred billion market cap short-term, nowhere near a trillion dollar outcome however. Further, attempting to charge a lot for the HIV/AIDS cure (such that you could get to a trillion dollar market cap), would result in a far worse PR outcome than what Gilead & Co. saw with HepC drugs; calls for nationalization would be overwhelming. Nations such as India and China would simply ignore all patents and proceed to copying the cure - few would support any economic counter/consequence against that move.
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.
Well said, I would only disagree with the treatment of Gilead and pharma in general. The moral outrage is against greed. Even when the cost-benefit relation works to other (similarly overpriced) treatments, their margins are way too excessive from the patients' pov imo, because 1. manufacturing cost next to nothing 2. pharma spends way more on marketing than r&d [1]
what you describe just shows that the old business model - pill in exchange for money - starts to show its limitations in the globalized world. Facebook would never get where it is now if it charged $10/year in Africa and $100/year in US. The pharma company who figures out that new business model would become that trillion dollar company.
There is no new business model that will derive a lot more money. There's a finite amount of global income available in a given year and it's not expanding at a rapid clip.
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?
Perhaps I am up too late and don't completely understand where your question is coming from... but there's a lot of hope available in biology because DNA is one of the most successfully widely deployed technologies of the last 4 billion years. It's had hundreds of trillions of years being battletested in production environments. It's cheap to copy, replicate and eventually it will be cheap to modify and write. Literally everyone is (badly?) programmed with DNA-- and CRISPR isn't the last word on genome engineering. There will absolutely be changes that large chunks of the population will demand, far and beyond the demand for vaccines.
For each trillion dollars of company, you'll need a billion people to pay $1k each.
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.
100 million paying 10k is much more likely. And 1 trillion is in market value, not revenue. Imagine if you could sell a therapy such as a seasonal cure for "common cancer". Drugs can be insanely profitable and there are already several drug makers in the hundreds of billions of market cap.
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?
How much would an insurance company pay to fix high cholesterol, diabetes, cancer etc? I know people spending close $10,000 a year on cholesterol medication. Diabetics' insulin can cost $500 (I don't know how long this lasts), plus the other blood monitoring costs and costs of other complications. Cancer treatment is not cheap but I don't know how to look up the costs.
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).
CRISPR likely won't be the ultimate cure you think it is. There are many diseases that aren't linked to a single gene. Even if you could edit the genome through magic, if you don't know what change to make then you can't do anything.
I don't think there's any need for a cui bono line of thinking. There are biologists who have nothing to gain who thought this paper was lousy. For example, every single biologist in my department that I spoke to, and every biologist I've found online who had something to say on the matter.
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.
Good point... but how would you describe it? It's not exactly lay-press, but it's still a secondary source. It's written for an educated audience, but not necessarily in this field.
What would you call them in this case? Science press?
Still - not enough room in an article like this for too many details.
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.