First Human Embryos Edited in U.S.

Researchers have demonstrated they can efficiently improve the DNA of human embryos.
https://www.technologyreview.com/s/608350/first-human-embryos-edited-in-us/

The first known attempt at creating genetically modified human embryos in the United States has been carried out by a team of researchers in Portland, Oregon, MIT Technology Review has learned.

The effort, led by Shoukhrat Mitalipov of Oregon Health and Science University, involved changing the DNA of a large number of one-cell embryos with the gene-editing technique CRISPR, according to people familiar with the scientific results.

Until now, American scientists have watched with a combination of awe, envy, and some alarm as scientists elsewhere were first to explore the controversial practice. To date, three previous reports of editing human embryos were all published by scientists in China.
 

Ygggdrasil

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Notably, the article suggests that Mitalipov (an expert in working with human embryos who previously performed some of the pioneering experiments on generating human stem cells by cloning) has significantly improved upon previously published efforts at germline gene editing:
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.
Of course, it is hard to compare the studies as the research has not yet been published in a peer-reviewed journal.
 
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Ygggdrasil

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The paper describing these experiments has just been published in Nature: https://www.nature.com/nature/journal/vaop/ncurrent/full/nature23305.html

Abstract:
Genome editing has potential for the targeted correction of germline mutations. Here we describe the correction of the heterozygous MYBPC3 mutation in human preimplantation embryos with precise CRISPR–Cas9-based targeting accuracy and high homology-directed repair efficiency by activating an endogenous, germline-specific DNA repair response. Induced double-strand breaks (DSBs) at the mutant paternal allele were predominantly repaired using the homologous wild-type maternal gene instead of a synthetic DNA template. By modulating the cell cycle stage at which the DSB was induced, we were able to avoid mosaicism in cleaving embryos and achieve a high yield of homozygous embryos carrying the wild-type MYBPC3 gene without evidence of off-target mutations. The efficiency, accuracy and safety of the approach presented suggest that it has potential to be used for the correction of heritable mutations in human embryos by complementing preimplantation genetic diagnosis. However, much remains to be considered before clinical applications, including the reproducibility of the technique with other heterozygous mutations.
 
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Call me old fashioned, but I'm ANTI-genetic engineering in general, especially in humans. Umm, if there's some kind of genetic engineering that will make a crop resistant to disease or bug or freezing temperatures, say, I may bend a bit, but in general, genetics and natural selection go hand in hand, like peas and carrots. Meaning that it was designed (haha) to not be designed, it works the way it works as a self-organized process. If you want to start mucking around with the works, you are likely to create an abomination, especially with human genetic engineering. As an artificial intelligence and robotics researcher, I say leave the intelligence engineering to electronics, and leave genetics out of it...

 
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We have been "mucking around" with evolution for the last 10,000 years. Selective breeding is a much slower process, but it still transformed the animals and plants we use massively over time.

This is how a wild banana looks like:

319px-Inside_a_wild-type_banana.jpg

Source

This is a watermelon from the 17th century:

Pasteques%2C_extrait_d%27un_tableau_de_Giovanni_Stanchi.jpg

Source

With the wild type of everything, we would still be groups of farmers, because there would be no food surplus to go beyond that.
 
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With the wild type of everything, we would still be groups of farmers, because there would be no food surplus to go beyond that.
To start, I did say in my post #4 that I was perhaps friendly in some capacity even to genetically modified crops, conservatively. What you are talking about in you post isn't genetic engineering, it's "artificial selection" . Even so, artificial selection is actually a misnomer, because artificial selection is actually natural selection in disguise, it's just being naturally selected by human cognition and consciousness to craft an environment beneficial to the master species. But it's still natural selection.

Genetic engineering is a whole different ballgame. In fact, I don't really like the idea of genetic engineering on any animal species, much less humans. If you're gonna experiment with it, keep it out of Kingdom Animalia.
 

Ygggdrasil

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It's valid to question the extent to which the research reported yesterday in Nature actually represents genetic engineering. The cells that the researchers modified contained one normal copy of the MYBPC3 gene (from the mother) and one mutated copy (from the father). Because MYBPC3 encodes a protein that helps to maintain heart muscle, mutation of MYBPC3 is associated with an increased risk of heart failure and sudden death.

When the researchers introduce CRISPR-Cas9 into the embryos containing the mutation, they stimulated cells to repair the faulty, paternal copy of the MYBPC3 gene using the normal copy from the maternal chromosome using the cell's natural DNA repair mechanisms. No DNA that is not normally present in human cells was introduced (in fact, the research suggests that it may be more difficult than expected to use CRISPR to introduce foreign DNA into human embryos). There are few safety concerns from the gene "edits" they introduced because the normal MYBPC3 sequence introduced into the paternal chromosome is present in >99% of humans.

This is not "genetic engineering" in the GATTACA and designer baby sense. This is genetic engineering to cure disease. Is hip replacement surgery unnatural? Is prescribing glasses to fix one's vision unnatural? Yes, CRISPR could be used to potentially "enhance" humans (though we are very far away from knowing how to do that for most traits we are interested in), but all technologies have good uses and potentially bad uses (though not everyone agrees that genetic enhancement is a step too far).
 
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BillTre

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Is prescribing glasses to fix one's vision unnatural?
Interestingly, Ian Malcolm is wearing glasses in the video above!
In a a society without glasses, he could well be dead or economically marginalized.
 

BillTre

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Before I had kids, I didn't want a boy and a girl (which is what I got) but a clone and a recombinant.

Sadly the technology was not (and still isn't) available and I'm stuck with the old fashioned reproductive products.
 

OCR

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Look at the (partial) abstract again... and pay attention to the key words...
Genome editing has potential for the targeted correction of germline mutations. Here we describe the correction of the heterozygous MYBPC3 mutation in human preimplantation embryos with precise CRISPR–Cas9-based targeting accuracy and high homology-directed repair efficiency by activating an endogenous, germline-specific DNA repair response...
In the sense of common usage... IMO .
This is not "genetic engineering"... it's repairing something that "should NOT have been" broken, and I'm all for it !

Carry on... that's ALL, from me.
 
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Sure, this isn't GATTACA... but it certainly opens that door.
 
T

thejosh

Before I had kids, I didn't want a boy and a girl (which is what I got) but a clone and a recombinant.

Sadly the technology was not (and still isn't) available and I'm stuck with the old fashioned reproductive products.
I would like to point out that that is a really savage remark for a father to say before I argue my point @BillTre, I hope your kids never get to view that post.:wideeyed::))

1.Anyway, nature already corrects such errors naturally since a person born with such characteristics usually does not live long enough to reproduce thus the trait will eventually be lost - naturally.
2.I think the issue here is that unfortunately we have not completely figured out what - for example- the full purpose of most genes are and so to tamper with these genes would result in unpredictable effects, whether in the immediate/long term phenotype or genotype. Although there are some obvious benefits of the idea, the fact remains that we are messing around with what we have not fully understood and although we would like to be able to achieve such a feat the consequences of failure are completely unpredictable and probably not worth it HEAR me out - FOR NOW- since we have not completely grasped the functions, uses etc - what I am effectively saying is we should be cautious and take our time in understanding what we are diving into since a serious mutation/side effects caused by these corrections could result in catastrophic results causing the whole thing to be more harmful than helpful.
3.Glasses are physical objects that we put in front of our damaged/weakened eyes , yes to correct BUT the difference is that if the glasses stop working you can take them off and throw them away but if your DNA becomes unstable due to tampering........:)) :sorry::wideeyed::oops::frown:
4.Humans make errors:
come on be realistic don't become a sad statistic.:woot:
 

jim mcnamara

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@thejosh
Your point in #1 is not correct - traits that are recessive and potentially deleterious like nearsightedness, Sickle Cell disease are not "lost" from a population and do not automatically disappear. There are a variety of reasons but you might want to get and read a book on Population Genetics. Try this youtube video might help. Please do not post things that are misleading or incorrect.

 
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fresh_42

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@thejosh
Your point in #1 is not correct - traits like recessive potentially deleterious like nearsightedness, Sickle Cell d are not "lost" from a population ...
... which in my opinion only proves, that we already uncoupled us (in parts) from the usual evolutionary processes. And sickle cell disease can even be an evolutionary advantage, as it can prevent people from the worst versions of malaria (https://www.ncbi.nlm.nih.gov/pubmed/22372205?dopt=Abstract). The nearsightedness, as I see it, is a side effect of our too big heads, but I'm not sure - it simply fits into optical physics and the fact that it usually starts during growth. Of course and fortunately we do not deselect all genetic disadvantages, but we still obey evolutionary processes. (Sorry, only found a Time Magazine article on a quick search to support this position.)

So @thejosh's position #1 is only partly wrong and #2,#3 and #4 are - in my opinion - valid arguments. So the question is not so much about correct medical studies, but rather whether we want to do it and which risks are connected by it. I see post #12 as an attempt to describe those risks.
 

BillTre

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I would like to point out that that is a really savage remark for a father to say before I argue my point @BillTre, I hope your kids never get to view that post.:wideeyed::))
They have heard it several times and have no problem with it.
They are not so fragile as you seem to think.
 

Ygggdrasil

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2.I think the issue here is that unfortunately we have not completely figured out what - for example- the full purpose of most genes are and so to tamper with these genes would result in unpredictable effects, whether in the immediate/long term phenotype or genotype. Although there are some obvious benefits of the idea, the fact remains that we are messing around with what we have not fully understood and although we would like to be able to achieve such a feat the consequences of failure are completely unpredictable and probably not worth it HEAR me out - FOR NOW- since we have not completely grasped the functions, uses etc - what I am effectively saying is we should be cautious and take our time in understanding what we are diving into since a serious mutation/side effects caused by these corrections could result in catastrophic results causing the whole thing to be more harmful than helpful.
This is absolutely correct, and many scientists would agree with this point. This mainly is a concern, however, regarding trait enhancement (i.e. introducing rare alleles into the population). In the case of repairing mutations that cause genetic disease, such as the Nature paper correcting the MYBPC2 mutation, the researchers are replacing a rare allele with a very common allele, so the risks of unintended side effects are minimal. For this reason, when the National Academies released guidelines for potential gene editing therapies, they stressed limiting edits to introducing alleles already prevalent in the population (i.e. replacing disease alleles with normal ones).

3.Glasses are physical objects that we put in front of our damaged/weakened eyes , yes to correct BUT the difference is that if the glasses stop working you can take them off and throw them away but if your DNA becomes unstable due to tampering........:)) :sorry::wideeyed::oops::frown:
This is a good point, and it's worse. When you edit an embryo's DNA, not only do you change that unborn individual's DNA (bringing up issues with consent), but you are also affecting that individual's children, and their children's children, etc. This is one reasons why there needs to be very broad discussions of the topic so societies can make informed decisions about these technologies and their implications.

This is not "genetic engineering"... it's repairing something that "should NOT have been" broken, and I'm all for it !
Although I agree with the argument, for the sake of discussion, I'll play devil's advocate. What constitutes broken? There are some clear examples of mutations that lead to disease (e.g. the MYBPC2 mutation repaired in the Nature paper), but other cases might be more borderline. If we can understand the genetics of autism, should genes that predispose toward autism be considered broken or should society strive for greater acceptance of neurodiversity? This point is especially important for editing of embryos as embryos cannot give consent as to whether they want particular traits edited from their genomes. Similarly, if we start to understand the genetics of intelligence, would having predisposition toward below average intelligence be considered a genetic flaw requiring correction? These are all very tough issues that society (not just scientists) should consider as these technologies move toward the clinic.
 
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Ygggdrasil

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jim mcnamara

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@Ygggdrasil - nearsightedness (myopia) has been far more prevalent among Navajos than in the general US population. They lived almost completely outside up until about 30 years ago. I have seen it attributed to Founder Effect because of the mass movement off the Reservation with subsequent fatalities. Very like the low genetic diversity in modern cheetahs due to some (AFAIK) unspecified die off. It may well be possible that there is some kind of environmental response related to eye use that you cited. Ex: https://ehp.niehs.nih.gov/122-a12/


The Long Walk of the Navajo, also called the Long Walk to Bosque Redondo, refers to the 1864 deportation of the Navajo people by the government of the United States of America.
https://www.nlm.nih.gov/nativevoices/timeline/332.html
 

Buzz Bloom

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This point is especially important for editing of embryos as embryos cannot give consent as to whether they want particular traits edited from their genomes.
Hi @Ygggdrasil

I am not sure I understand your logic here. The impression I am getting is that you are using the following syllogism.
Premise 1. All humans have the right of consent regarding whether or not to accept some proposed medical intervention.
Premise 2. A human embryo is a human.
Conclusion. Therefore a human embryo has the right of consent regarding whether or not to accept some proposed medical intervention.​
If this is your intended logic, then I take issue with both of the premises.
Regarding (1): Young children do not have the right of consent. Their parents have this right, although sometimes a court judge may overrule this right.
Regarding (2): This is a theological assumption that is not generally agreed to by a large part of the population.

Regards,
Buzz

Edit jmc 8/5/2017 18:01 MDT - add a an @ to Ygggdrasil.
 
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They have heard it several times and have no problem with it.
They are not so fragile as you seem to think.
It kind of shocked me the first time I've read what you say, but after thinking of it, I think a clone will be much easier to educate than a child with other genes. One would know more exactly what to do with that kid to make it better based on personal experience than with a child whose DNA is completely unique.
 

Ygggdrasil

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@Ygggdrasil - nearsightedness (myopia) has been far more prevalent among Navajos than in the general US population. They lived almost completely outside up until about 30 years ago. I have seen it attributed to Founder Effect because of the mass movement off the Reservation with subsequent fatalities. Very like the low genetic diversity in modern cheetahs due to some (AFAIK) unspecified die off. It may well be possible that there is some kind of environmental response related to eye use that you cited. Ex: https://ehp.niehs.nih.gov/122-a12/
Sure, as the Nature news piece I linked to mentioned, there is evidence for both genetic and environmental factors playing a factor in myopia (as in the case of most traits). For example, the piece cites twin studies from the 1960s showing that myopia has a genetic component. However, there is also strong evidence for an environmental component. For example:
East Asia has been gripped by an unprecedented rise in myopia, also known as short-sightedness. Sixty years ago, 10–20% of the Chinese population was short-sighted. Today, up to 90% of teenagers and young adults are. In Seoul, a whopping 96.5% of 19-year-old men are short-sighted.

Other parts of the world have also seen a dramatic increase in the condition, which now affects around half of young adults in the United States and Europe — double the prevalence of half a century ago.
One of the clearest signs came from a 1969 study of Inuit people on the northern tip of Alaska whose lifestyle was changing2. Of adults who had grown up in isolated communities, only 2 of 131 had myopic eyes. But more than half of their children and grandchildren had the condition. Genetic changes happen too slowly to explain this rapid change — or the soaring rates in myopia that have since been documented all over the world
These observational studies are backed up by more recent randomized clinical trials experiments where increasing the time spent outdoors lessened the incidence of myopia in children compared to a control group (see the Nature piece for a more detailed description of the experiments). So, in some populations (such as the Navajo), genetics will the be primary cause of myopia, but for many other populations, environmental effects seem to be a major factor.

Hi @YgggdrasilI am not sure I understand your logic here. The impression I am getting is that you are using the following syllogism.
Premise 1. All humans have the right of consent regarding whether or not to accept some proposed medical intervention.
Premise 2. A human embryo is a human.
Conclusion. Therefore a human embryo has the right of consent regarding whether or not to accept some proposed medical intervention.​
If this is your intended logic, then I take issue with both of the premises.
Regarding (1): Young children do not have the right of consent. Their parents have this right, although sometimes a court judge may overrule this right.
Regarding (2): This is a theological assumption that is not generally agreed to by a large part of the population.
Both are very good points. As I mentioned previously, I bring these arguments up mostly as a devil's advocate to illustrate some of the important ethical questions that others have brought up with regard to germline gene editing. I have no problem with research on embryos (for example, in the future, cloning an individual's cells to generate genetically identical embryonic stem cells for clinical uses). However, when generating embryos that will become a person, I think scientists and physicians have a responsibility to exercise caution in performing any procedures that carry risks of harming the embryo. While embryos do not have personhood under law, embryos destined for implantation probably should have some sets of rights to consider. Clinical research operates on the principle of informed consent, though we recognize that this is not always possible (e.g. in the case of research on children). Thus, when the subject cannot give informed consent, special precautions should be taken to manage the risks involved (e.g. having an Institutional Review Board scrutinize the proposed procedures with the interests of the unborn children in mind).
 

Fervent Freyja

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Genetic engineering is a whole different ballgame. In fact, I don't really like the idea of genetic engineering on any animal species, much less humans. If you're gonna experiment with it, keep it out of Kingdom Animalia.
Dirac, I understand your fears, but I also have faith in science and that the people who study it will protect society.

My little brother is 25 years old and has stage C right and left-sided heart failure with moderately severe COPD, which were caused by his individual genetic syndrome. When will he die? Will it really be within the next 10 years? I love who he is, but I don't want him to die, but what if the mutation in his NSD1 gene, normally responsible for producing a single protein that turns on and off a few genes that mainly affect growth and development, could have been altered/replaced/improved? How could that have changed who he is, when he already makes a little from his other copy, just not enough of it on this one? He really wants a permit to drive, but his intellectual disability and seizures bar him. Will he ever really be apart of college football, find love, or have a child- the things he talks about, before he dies? Could he have had that otherwise? I don't want to change who he is, but I do want him to have what he wants: simple opportunities that are given to most humans, so much that he has been denied. And I want him to live. I see nothing but goodness in genetic engineering for future people.

All I needed to do was help him make more histones. When will he die?
 
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Look at the (partial) abstract again... and pay attention to the key words...


In the sense of common usage... IMO .
This is not "genetic engineering"... it's repairing something that "should NOT have been" broken, and I'm all for it !

Carry on... that's ALL, from me.
Respectfully, I disagree. What stops someone from saying that average intelligence, height, attractiveness, etc. are "broken" traits, and that a baby should not be born with them? What is to stop this from being a method to fix all "imperfect" traits that people have.

Perfect humans due to genetic modifications... that reminds me of something...
Sure, this isn't GATTACA... but it certainly opens that door.
Exactly! Once you can "fix" babies with heart problems, you can fix babies with intellectual problems, or height problems. IMO, that is just wrong.
 
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Dirac, I understand your fears, but I also have faith in science and that the people who study it will protect society.
While I appreciate your trust in scientists, IMO that trust is misplaced. I don't mean this in a bad way, of course, as someone who wants to be a scientist, but here's a reminder of some of the things scientists have given us:
-Nuclear weapons
-Biological weapons
-Chemical weapons

What's next? An army of genetically modified humans?

Governments are never afraid to have scientists go one step too far and use technology that should never have been used to acquire power. If some government wants the smartest and strongest people in the world, can you say for certainty that they won't use science to achieve that goal?
 
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Exactly! Once you can "fix" babies with heart problems, you can fix babies with intellectual problems, or height problems. IMO, that is just wrong.
Avoiding life-threatening conditions is wrong? That is an easy, clear distinction: Is the rare genetic condition likely to kill the person? If yes, I support removing it from embryos, with the potential to remove it from the gene pool completely over time.

We fix things all the time. Most of the medical sector is about fixing things. Do you want to get rid of modern medicine? If not, where exactly do you see the difference? If yes, I think further discussion is pointless.
but here's a reminder of some of the things scientists have given us:
-Nuclear weapons
-Biological weapons
-Chemical weapons
Science lead to the discovery/invention of some things that can be used to kill others. How exactly is this related to this topic?
What's next? An army of genetically modified humans?
Do you also fear an army of humans with glasses?
 

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