First Human Embryos Edited in U.S.

[Greg Bernhardt]

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]

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.

 

[Ygggdrasil]

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.

 

[DiracPool]

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...

 

[mfb]

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:

Source

This is a watermelon from the 17th century:

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.

 

[DiracPool]

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 going to experiment with it, keep it out of Kingdom Animalia.

 

[Ygggdrasil]

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 https://www.physicsforums.com/insights/dont-fear-https://www.physicsforums.com/insights/dont-fear-crispr-new-gene-editing-technologies-wont-lead-designer-babies/-new-gene-editing-technologies-wont-lead-designer-babies/ 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).

 

[BillTre]

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]

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]

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.

 

[Lord Crc]

Sure, this isn't GATTACA... but it certainly opens that door.

 

[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.

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...
4.Humans make errors:
come on be realistic don't become a sad statistic.

 

[jim mcnamara]

@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.

 

[fresh_42]

@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]

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.

They have heard it several times and have no problem with it.
They are not so fragile as you seem to think.

 

[Ygggdrasil]

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...

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.

 

[Ygggdrasil]

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.

Nearsightedness may be a side effect of too much time spent indoors see: http://www.nature.com/news/the-myopia-boom-1.17120

 

[jim mcnamara]

@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]

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.

 

[Telemachus]

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]

@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]

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 going to 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?

 

[Isaac0427]

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.

 

[Isaac0427]

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?

 

[mfb]

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?

 

[Ygggdrasil]

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.

Current guidelines around gene editing deal with this problem by limiting gene edits to only those introducing alleles already prevalent in the population. This restriction is also good from a safety perspective since there is much less risk when introducing common alleles to an embryo than when working with very rare alleles (such as ones that could potentially protect against Alzheimer's or heart disease).

Exactly! Once you can "fix" babies with heart problems, you can fix babies with intellectual problems, or height problems. IMO, that is just wrong.

The genetics of the heart problem associated with the MYBPC2 mutation are very well known. At the moment, the genetics of traits like intelligence and height are not well understood enough for us to be able to reliably enhance these traits through gene editing.

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

Yet the same technologies have also given us nuclear energy, vaccines, and fertilizers. Regarding the last point, here's a nice piece from Radiolab about Fritz Haber, whose Nobel-prize winning work on the Haber-Bosch process for synthesizing ammonia allowed the world to feed itself, but who also helped the Nazis develop chemical weapons:
http://www.radiolab.org/story/180132-how-do-you-solve-problem-fritz-haber/

Technologies can do either good or evil. I think it's better to regulate the people using the technologies than to ban the technologies altogether.

 

[BillTre]

This technology is not being developed in a vacuum.

Many more experiments (probably thousands) are being done on lots of other animals and on lots of genes that you have probably never heard about.
This is creating an increasing amount of knowledge about possible direct and indirect effects of changing particular genes in different situations. Although not all of this is directly related to human genome manipulation, any realistic changes that might be made in the near future would not be done in such a blind manner as it is often portrayed.

Furthermore, the situations where this might first be tried, would be more extreme life threatening cases, where inaction also carries negative consequences.

Personal examples can be useful.
I can think of several (currently ill-defined) things in my own genome that might be worth changing:

1. Whatever underlies my needing to use glasses after 50 years old (not such a big deal since glasses work well).
   
2. My autoimmune disease that has killed off my thyroid gland (I now take artificial thyroxin). This may be a genetically inherited condition (or predisposition) since my Mom, one of my sisters, and another relative had this. Along with that my sister got thyroid cancer which may or may not be linked. This is a condition that I would like to be able to eliminate form the line of my progeny going down through future generations.
   
3. My allergies (very annoying and very likely genetically inherited).
   
4. Color blindness (from my wife's side of the family), which prevented my some (who inherited it) from being a Navy or Air Force flier.

For these examples, my order of priorities (based on my own perceived life impact) would be: 2, 3, 4, 1.
Taking any action on this ordering, in the real world, would then be influenced by lots of other issues (some technical) including:

• how much knowledge is there on the underlying causative genetics,
  
• what is know about the genes influence on other biological aspects in the body,
  
• how well can the changes be made (and potentially unmade),
• there are probably others that a more careful consideration would reveal (@Ygggdrasil probably could fill in more!).

In the long run (in a Science Fictiony way), as more knowledge and technical capability is developed, both greater and more subtle effects could be more confidently engineered into people, but that would probably take longer that films like Blade Runner would have you believe.

 

[Ygggdrasil]

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.

Relating to this point, I posted a link to a recent analysis from researchers at Stanford supporting your concern: https://www.physicsforums.com/threads/omnigenetic-model-for-complex-traits.922051/

Essentially, they hypothesize that all genes expressed inside a cell are interconnected in their function such that changing one gene may have many unintended consequences on a variety of different traits. Definitely cause for concern when considering altering the human genome.

While we may be have the technology very soon to safely edit genes in human embryos, it may be a while before we know what genes to edit in order to safely change some of the traits @BillTre cares about.

 

[Isaac0427]

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.

I do support avoiding life-threatening conditions. But at what cost? This is allowing the development of a technology that could potentially produce a world like that in GATTACA. You may say that it is not going to happen-- but 200 years ago the same thing could be said about multiple countries having an arsenal that is capable of single-handedly blowing up the world ten times.

Do you also fear an army of humans with glasses?

The development of glasses technology does not have nearly the serious consequences that genetic engineering could have.

Science lead to the discovery/invention of some things that can be used to kill others. How exactly is this related to this topic?

Read what I wrote after that-- it explains why it is related. Just like how America and Russia took science too far in developing a nuclear arsenal that can blow up the world ten times, what stops some government from deciding to make a new generation of hyperintellegent humans with increased muscle strength in order to win a war/assume more power? That's what we could be opening the door up to here.

Although, there is then this

Current guidelines around gene editing deal with this problem by limiting gene edits to only those introducing alleles already prevalent in the population. This restriction is also good from a safety perspective since there is much less risk when introducing common alleles to an embryo than when working with very rare alleles (such as ones that could potentially protect against Alzheimer's or heart disease).

which is wonderful in theory. We have a ban on the use of chemical weapons too. That doesn't stop a rogue government from using them. Knowing the world as it is, if one country did what I mentioned above, then other countries would follow suit in order to compete. How long after that does GATTACA start happening?

Yet the same technologies have also given us nuclear energy, vaccines, and fertilizers. Regarding the last point, here's a nice piece from Radiolab about Fritz Haber, whose Nobel-prize winning work on the Haber-Bosch process for synthesizing ammonia allowed the world to feed itself, but who also helped the Nazis develop chemical weapons:
http://www.radiolab.org/story/180132-how-do-you-solve-problem-fritz-haber/

Technologies can do either good or evil. I think it's better to regulate the people using the technologies than to ban the technologies altogether.

I understand this, too. However, in my opinion, we must weigh out the pros and cons. While there are a lot of life-saving things this technology can provide, we must ask ourselves if the possible consequences (i.e. something like GATTACA or an international race on who can breed the best hyperintellegent super-strong human army to fight in wars) are worth it.

Call me crazy for thinking of those as possibilities, but crazier things have happened.

 

[Ygggdrasil]

what stops some government from deciding to make a new generation of hyperintellegent humans with increased muscle strength in order to win a war/assume more power?

Nuclear weapons. See sometimes two wrongs do make a right :)

 

[Telemachus]

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?

But we have nuclear plants that produce lots of energy and don't produce greenhouse gases, and also the knowledge that made nuclear weapons some day will perhaps produce fusion nuclear plants, which would mean limitless clean and cheap energy for everyone. Knowledge and science are just tools, you can use a hammer to build a house, and you can also use it to bang on someones head. We shouldn't stop the progress in science just because there is danger of getting it to the wrong hands, we must just do it with caution and responsibility, because this progress might bring solution for so many problems. Otherwise, how many research areas should we cut just because there is danger?

If science is done for the pursuit of progress and under a strong ethical basis, we must go ahead. But we must also be certain on doing it under those lines, otherwise it will be used as a tool of those in power to preserve the statu quo and expand their areas of domination. Ethics must be important for a scientist if he doesn't want his research to be used against humanity. And also politics, because politics is the game of power and powerful people, and at the last, many times we are just working for those people while we don't even realize of it. And I really wouldn't want to wake up one day to see that something I did is being used to kill people somewhere around the world. And you don't even have to work on genetics, nor nuclear research to serve to those ends! there are so many ways to contribute to it that I can't even imagine.

 

[Isaac0427]

But we have nuclear plants that produce lots of energy and don't produce greenhouse gases, and also the knowledge that made nuclear weapons some day will perhaps produce fusion nuclear plants, which would mean limitless clean and cheap energy for everyone. Knowledge and science are just tools, you can use a hammer to build a house, and you can also use it to bang on someones head. We shouldn't stop the progress in science just because there is danger of getting it to the wrong hands, we must just do it with caution and responsibility, because this progress might bring solution for so many problems. Otherwise, how many research areas should we cut just because there is danger?

A fair point, though I still think every situation must be judged. As I said in post 29, the pros and cons must be judged. And that judgement process is tricky; for me, it is very fuzzy around nuclear weapons/nuclear power, chemical weapons/fertilizer and biological weapons/vaccines-- with those I don't know how the pros and cons weigh out (although hindsight is 20/20). However, with genetic engineering I see more of a clear line: yes, it can save many lives, but, while every life is precious and we should do what we can for all of them, I fear that the possible imminent threats to our entire society and world that genetic engineering poses are just too much.

Again, I completely see where you all are coming from, but I think negative implications need to be considered far more thoroughly before further research on this continues.

 

[DiracPool]

This thread is getting interesting. It really is one of the quintessential-form ethics debates.

Essentially, they hypothesize that all genes expressed inside a cell are interconnected in their function such that changing one gene may have many unintended consequences on a variety of different traits. Definitely cause for concern when considering altering the human genome.

I think Ygggdrasil hit on the main point here...

My undergraduate degree is in biology. I was fascinated with it. I had a molecular biology teacher in 1990 who said that he started out as a physicist but he switched to biology because he thought the biophysics of energy and metabolic cycles of the cell were much more interesting and complex than the solid state physics he was doing at the time.

And that's the point. They are complex. Very complex. There's no magic bullet, like mfb alluded to..

yes, I support removing it from embryos, with the potential to remove it from the gene pool completely over time.

It doesn't work like that. "Most" everything in cellular and systems biology is connected in a very complicated way. Embryos form the body plan initially with homeobox genes and then the cells further differentiate down the line. But this is a complex orchestration that is highly reliant on certain genes being differentiated at certain times and expressing transcription factors that orchestrate the differentiation of other cells, etc. etc. This is the science of "Evo-devo" and relates the epigentic development of the organism, which also involves the environmental conditions the organism is developing in. For the layperson, Sean "B." Carroll (not the popular physicist) has a great book on the subject called "Endless forms most beautiful."

https://www.amazon.com/dp/0393327795/?tag=pfamazon01-20

So, there's two things going on here. The first is how we deal with say, nearsightedness, and other genetic anamolies that require some sort of "correctedness," such as Steven Hawking (ALS) with a wheelchair, for these individuals to survive and reproduce in the gene pool. The other is how do we find the gene(s) that cause these maladies and how do we eradicate them in vitro before we plant the zygote in the womb? The answer is that, in the first case, we are "artificially selecting" a genetic blood line by operating on a phenotype whereas in the second case were doing it by operating on a genotype.

If you are lumping those two together as the same thing in your ethics assessment of the theme of this thread, please think a little more about that..

 

[Fervent Freyja]

While I appreciate your trust in scientists, IMO that trust is misplaced.

You are dealing with a common bias called focalism, among others, regarding this topic. You may simply need to spend a few more years learning before you truly understand the real purpose and benefits that science has given us.

 

[mfb]

This is allowing the development of a technology that could potentially produce a world like that in GATTACA.

As Ygggdrasil mentioned already, it is not. It is one step such a technology would need, but that also applies to computers, for example.
Did stopping a research branch because you don't like what it could find out ever work?

for me, it is very fuzzy around nuclear weapons/nuclear power, chemical weapons/fertilizer and biological weapons/vaccines-- with those I don't know how the pros and cons weigh out (although hindsight is 20/20)

While we don't have an alternate history for direct comparison, nuclear weapons probably reduced the number of casualties of the second world war, and without them the Cold War might have become WW 3. No countries with nuclear weapons fought a war against each other, and we live in the most peaceful time of human history.
And then we have nuclear power, of course. Without nuclear power we would burn more coal, leading to millions of additional deaths and a faster climate change.

Fertilizer feeds billions. We went from "nearly everyone is extremely poor and famines are widespread" to a world where extreme poverty and famines are very rare, and fertilizer had a big contribution to it.

How many have been killed by biological weapons?
Smallpox alone killed millions every year.

It doesn't work like that. "Most" everything in cellular and systems biology is connected in a very complicated way. Embryos form the body plan initially with homeobox genes and then the cells further differentiate down the line. But this is a complex orchestration that is highly reliant on certain genes being differentiated at certain times and expressing transcription factors that orchestrate the differentiation of other cells, etc. etc.

I don't see how this is related to my point of the effect of well-studied, single point mutations leading to potentially lethal diseases where the vast majority of the population has a gene without this mutation. Of course you cannot do that with every possible genetic disease, but with some you can.

 

[Lord Crc]

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?

That the recipient of the "fix" cannot consent on any level. Consider gender "fixing" done on babies, gender (re)assignment, and how many of those persons suffer later in life due to the choice the doctors made for them.

 

[mfb]

That the recipient of the "fix" cannot consent on any level.

That applies to babies as well, and parents have some responsibility until the child is an adult. Okay: Do you want to get rid of modern medicine applied to anyone who is not an adult yet?

Consider gender "fixing" done on babies, gender (re)assignment

I don't see the relation to life-threatening diseases.

 

[Lord Crc]

That applies to babies as well, and parents have some responsibility until the child is an adult. Okay: Do you want to get rid of modern medicine applied to anyone who is not an adult yet?

Of course not, that would be throwing the baby out with the bath water.

I don't see the relation to life-threatening diseases.

Are you implying this technology will only ever be used for life-threatening diseases? If so, I think history has shown that's a very naive view.

 

[Lord Crc]

I guess my point is, GATTACA was hypothetical. Now it is a possible future we can chose.

Before there was no line to draw. Now we have to draw it somewhere.

Some of you seem to want to reserve it for life-threatening issues. Why not for say meromelia or similar?

 

[Isaac0427]

Are you implying this technology will only ever be used for life-threatening diseases? If so, I think history has shown that's a very naive view.

That is my point precisely.

As Ygggdrasil mentioned already, it is not. It is one step such a technology would need, but that also applies to computers, for example.

But it is a huge step towards such technology. The comparison to computers doesn't make sense at all, though. There is a clear difference between how computers would contribute to a world like GATTACA and how genetic engineering would.

 

[Buzz Bloom]

Sure, this isn't GATTACA... but it certainly opens that door.

While there are a lot of life-saving things this technology can provide, we must ask ourselves if the possible consequences (i.e. something like GATTACA or an international race on who can breed the best hyperintellegent super-strong human army to fight in wars) are worth it.

That doesn't stop a rogue government from using them. Knowing the world as it is, if one country did what I mentioned above, then other countries would follow suit in order to compete. How long after that does GATTACA start happening?

I personally do not think Gattaca is a good example of bad effects from genetic manipulation. I have started a thread in the SciFi forum to discuss this.

https://www.physicsforums.com/threads/bad-society-from-human-genetic-manipulation.922106/​

 

[Ygggdrasil]

There is a clear difference between how computers would contribute to a world like GATTACA and how genetic engineering would.

Can I ask for clarification? You reference GATTACA as an example of the threats of genetic engineering, yet all your examples have to do with the danger of armies of super-human soldiers (not the subject of GATTACA). Along the lines of @Buzz Bloom's comments, can you clarify what aspects of the society portrayed by GATTACA you see as most threatening to society? It seems to me that many of the issues brought up by GATTACA could have policy and regulatory solutions that do not involve completely banning the technology. (Following your arguments, a ban would not actually work since some rouge countries or scientists that do not agree with the ban will continue the research anyway).

With regard to the comment about computers vs genetic engineering, if you are worried about super-intelligent beings causing widespread disruptions to society, I see the threat from artificial intelligence as more imminent than the threat from genetic engineering. (I do support continuing AI research, however).

 

[jim mcnamara]

Can we leave the realm of Science Fiction in fiction? Yes, there can be moral lessons in Uncle Tom's Cabin or Gattaca. Simply regarding stuff like that as THE model for this issue is way less than scientifically illuminating, to be polite.

Once you understand what @Ygggdrasil is trying to say, you get the idea that using a simple map to find your way in an extremely complex and potentially dangerous endeavor is not trivial. And it involves Biomedical Ethics. Gattaca does NOT explain it, nor do superhuman powers. This is not a comic strip endeavor. To continue do comic book analysis is, well, very devoid of good sense.

In literature it is okay, even encouraged, to use fictive models based partially on sets of assumptions outside of Science. Science Fiction and Fantasy (note the equivalence) has had a really great run in fiction and entertainment. But. We do not do that here on PF. Entertainment is not a good model, particularly for this issue. And the argument that you have to rely on this kind of model because it is 'what I understand' is pure baloney. Scientists who get the whole picture are able to carry on good discussions on this topic without basing discussions on TV shows and movies. DiracPool tried. If you cannot participate on a reasonable level, that's okay. There are discussions on PF for which the best I can ever hope to be is in readonly mode, too. Just lurk and maybe learn, too.

Can we please stop with the hoo-ha? This thread has wonderful potential, IMO.

Thanks
(The cranky old guy who can and will lock this thread)

 

[thejosh]

One of the main problem with genetic engineering is even if we were able to insert and correctly apply a different base, chromosome or some other part of DNA, if we were able to successfully accomplish this feat and come up with the desired phenotype, one of the biggest problems is the fact that we cannot control mutations, which would result in the "normal" genes effectively -lets say- swapping over with the newly introduced gene, now if this were to happen the effect would be unpredictable.
Consider that we improved -lets say- a rodent to have stronger bones , yes.
Now the rodent seems to be okay but we cannot see what's happening to its genetic make-up. If this rodent reproduces with a normal rat and produces a baby with a degenerative disease, let's say haemophilia , chances are that we would be unable to pinpoint exactly where the error in its genetic makeup occurred. We would not be able to tell whether the error occurred due to natural causes or as a result of our "tampering."
Worse still if the degenerative disease occurs further down the rat's bloodline.This could then be an autosomal recessive mutation or-again- it could be a natural reason (this is purely just an example so excuse the use of haemophilia and the rodents etc.)
As you can see from my example- genetic engineering is a very touchy and difficult to understand concept.We do not even know what most genes do or how they affect an animal, whether or not the gene affects the immediate or future phenotype of a species.
If your still not convinced that genetic engineering is a touchy topic listen to this:
The more complex an organism the more chromosomes it has right?
eg a human has 23 pairs of chromosomes whilst a fruitfly has 4
But guess which animal has the largest amount of chromosomes.
You didn't guess it- a SNAIL!
Weird isn't it?Why you ask.We simply do not know, so how can we engineer something we do not understand, it's like building a house with dark matter- simply unattainable until we get the understanding behind the works.

 

[Ygggdrasil]

One of the main problem with genetic engineering is even if we were able to insert and correctly apply a different base, chromosome or some other part of DNA, if we were able to successfully accomplish this feat and come up with the desired phenotype, one of the biggest problems is the fact that we cannot control mutations, which would result in the "normal" genes effectively -lets say- swapping over with the newly introduced gene, now if this were to happen the effect would be unpredictable.

I have not heard of this concern. Do you have a reference discussing this possibility?

Consider that we improved -lets say- a rodent to have stronger bones , yes.
Now the rodent seems to be okay but we cannot see what's happening to its genetic make-up. If this rodent reproduces with a normal rat and produces a baby with a degenerative disease, let's say haemophilia , chances are that we would be unable to pinpoint exactly where the error in its genetic makeup occurred. We would not be able to tell whether the error occurred due to natural causes or as a result of our "tampering."
Worse still if the degenerative disease occurs further down the rat's bloodline.This could then be an autosomal recessive mutation or-again- it could be a natural reason (this is purely just an example so excuse the use of haemophilia and the rodents etc.)

This is why one performs controlled studies with large numbers of animals. One can compare the rate at which bad outcomes occur in the group of animals that underwent gene editing to the rate at which these outcomes happen in a control group which received no treatment or a placebo treatment. The FDA and other regulatory bodies would require these types of controlled trial in both animals and humans to be performed before any medical treatment is approved for use.

As you can see from my example- genetic engineering is a very touchy and difficult to understand concept.We do not even know what most genes do or how they affect an animal, whether or not the gene affects the immediate or future phenotype of a species.

The functions of many genes are not well understood, but that does not mean it is impossible to engineer them. As stated previously, current guidelines limit gene editing to replacing rare, disease alleles with alleles that are prevalent in the population. Because we are changing DNA sequences to sequences that exist in ~7 billion healthy people with varying genetic backgrounds, we can be reasonably sure that the edit will not have any harmful side effects (as long as no "off-target" mutations occur). Furthermore, these technologies will undergo extensive testing to make sure that no unanticipated side effects accompany the treatment (see above).

If your still not convinced that genetic engineering is a touchy topic listen to this:
The more complex an organism the more chromosomes it has right?
eg a human has 23 pairs of chromosomes whilst a fruitfly has 4
But guess which animal has the largest amount of chromosomes.
You didn't guess it- a SNAIL!
Weird isn't it?Why you ask.We simply do not know, so how can we engineer something we do not understand, it's like building a house with dark matter- simply unattainable until we get the understanding behind the works.

It is well known that the size of a genome does not correlate with the complexity of the species. This seeming inconsistency, termed the C-value paradox, is due to the fact that most animal genomes contain a lot of non-coding DNA (only 2% of the human genome encodes protein), most of which is "junk DNA" (e.g. repetitive DNA derived from transposons or endogenous retroviruses). There is a lot of functional non-coding DNA, and there are still many unanswered questions about the functions of non-coding DNA sequences, but only about 10% of the non-coding DNA appears to be evolutionary conserved.

 

[jim mcnamara]

In terms of chromosome number, n, ferns win. What they win I'm not sure. Many fern species have a large n and are polyploid. Ophioglossum reticulata has 1260 chromosomes. I think it wins against all fern contenders. So chromosome number and polyploidy do tell not us much. Except that changing chromosome number is a good way to isolate a newly emerging species from other members of the genus. So it is good evolutionary isolation mechanism to allow a population to differentiate genetic traits without having those changes swamped by genes from cousins.

The fern is small, too.

 

[Buzz Bloom]

but we cannot see what's happening to its genetic make-up

Hi josh:
Part of the technology about genetics is that the research leads to more and more understanding of what the genes do, although we have a long road ahead since this research is only a few decades old. When the eventual gene function database gets large enough then there will be opportunities to "see what is happening to" the genetics of an embryo conceived with a mutated egg or sperm. Today's technology includes the ability to extract a cell from a embryo, and also let this cell multiply sufficiently for a DNA analysis to be performed. The gene function database permits the possibility of detecting a ovum or sperm mutation in an embryo. A mutation to a a non-germ cell in the embryo itself (or later fetus or born child) after fertilization does lead to any inheritance of the mutation.

Regards,
Buzz

 

[thejosh]

immediate or future

even if we were able to insert and correctly apply a different base

Worse still if the degenerative disease occurs further down the rat's bloodline.

how can we engineer something we do not understand

What I was trying to put across is the issue of mutations which would arise in the event that we successfully cracked the problem of how to correctly apply different phenotype traits.This is in the event that we venture into putting relatively foreign genes into an organisms DNA which would effectively increase the risk of mutations coming about and producing maybe even new genetic diseases.(This is where we are trying to go right , since not all genetic diseases are cured by common genes) Ok so let's say we have normal genes W and R. when these mutate together it produces the mutation E but E is recessive and is easily gotten rid of eventually and does not cause much harm.Now let's say we replaced R with S, if W and S mutate together they now produce something quite different T, which has unpredictable effects on the organism. Realising this we must take into account that mutations can occur at any period of an organisms life or not at all so experimental breeding would not solve the issue since mutations are unpredictable. Its like predicting if an organism will get cancer, we can make vague estimates that are often incorrect since cancer can only be risk assessed.this is looking forward past the issue of where to put the correct genes on what chromosomes etc that are the main issues of concern RIGHT NOW, my post was looking a wee bit further than that.

 

[Buzz Bloom]

mutation E

Hi @thejosh:

I think I am finally mostly getting the complicated example you are describing, but it took me a while to decide that your phrase "mutation E" was intended to mean the phenotype E was produced by the combination of mutations to both normal genes W and R. Let us call these mutated versions of W and R: W' and R' respectively. Thus phenotype E is produced by W' and R'.

Now let's say we replaced R with S

As I understand what the genetic repair would be in this example, we do not replace R with S, nor do we replace R' with S. What we do is replace R' with R and also W' with W. With this repair, what is the next mutation in your example?

Regards,
Buzz

 

[mfb]

Ok so let's say we have normal genes W and R. when these mutate together it produces the mutation E

What do you mean by "mutate together"?

What this thread is about: We have variants W and R, where 98% of the world population have WW, 2% have WR and 0.01% have RR. The last one leads to some disease. The method described here changes RR to WW.

Assuming the edit changes nothing else: What exactly could be harmful?