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Featured First Human Embryos Edited in U.S.

  1. Aug 6, 2017 #26

    Ygggdrasil

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    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).

    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.

    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.
     
  2. Aug 6, 2017 #27

    BillTre

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    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.
     
  3. Aug 6, 2017 #28

    Ygggdrasil

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    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.
     
  4. Aug 6, 2017 #29
    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.
    The development of glasses technology does not have nearly the serious consequences that genetic engineering could have.
    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
    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?
    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.
     
  5. Aug 6, 2017 #30

    Ygggdrasil

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    Nuclear weapons. See sometimes two wrongs do make a right :)
     
  6. Aug 6, 2017 #31
    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.
     
    Last edited: Aug 6, 2017
  7. Aug 6, 2017 #32
    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.
     
  8. Aug 6, 2017 #33
    This thread is getting interesting. It really is one of the quintessential-form ethics debates.

    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..

    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/Endless-Forms-Most-Beautiful-Science/dp/0393327795

    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..
     
    Last edited: Aug 6, 2017
  9. Aug 6, 2017 #34

    Fervent Freyja

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    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.
     
  10. Aug 7, 2017 #35

    mfb

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    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?
    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.
    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.
     
  11. Aug 7, 2017 #36
    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.
     
  12. Aug 7, 2017 #37

    mfb

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    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?
    I don't see the relation to life-threatening diseases.
     
  13. Aug 7, 2017 #38
    Of course not, that would be throwing the baby out with the bath water.

    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.
     
  14. Aug 7, 2017 #39
    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?
     
  15. Aug 7, 2017 #40
    That is my point precisely.
    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.
     
  16. Aug 7, 2017 #41

    Buzz Bloom

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    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.
     
  17. Aug 7, 2017 #42

    Ygggdrasil

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    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).
     
  18. Aug 7, 2017 #43

    jim mcnamara

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    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)
     
  19. Aug 7, 2017 #44
    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.
     
  20. Aug 7, 2017 #45

    Ygggdrasil

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    I have not heard of this concern. Do you have a reference discussing this possibility?
    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.
    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).
    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.
     
  21. Aug 7, 2017 #46

    jim mcnamara

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    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.

    4H006_Ophi-reti_AT_GM_MX.jpg

    The fern is small, too.
     
  22. Aug 8, 2017 #47

    Buzz Bloom

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    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
     
  23. Aug 8, 2017 #48
    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 lets 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 lets 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.
     
  24. Aug 8, 2017 #49

    Buzz Bloom

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    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'.
    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
     
  25. Aug 8, 2017 #50

    mfb

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    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?
     
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