I think both these analogies are really bad, and will contribute more to confusion than understanding. [This is an entry to the 2019 Adversarial Collaboration Contest by Nita J and Patrick N.]. Top of the line stuff will always be more expense or rare than what is available to everyone, due to a bottleneck in the expertise for it. Sorry, what is the argument? This argument gets laid out in the final chapter of the book “The Revolutionary Phenotype” by Dr. Gariepy in which he also describes the emergence of genetic layers and the evolution of sex. Fair question. Common chronic diseases, such as Alzheimer’s, type 2 diabetes, and cardiovascular disease, likely require a more nuanced approach, as gene expression, governed by factors such as diet and lifestyle, plays a significant role in disease pathogenesis. We’ve found ways to open closed-up arteries and replace failed joints and fix rotted-out teeth. Regardless, I think you’re right that this collaboration suffers from a lack of a unified message. Making these types of edits successfully would therefore require inhibition of P53; however, cells could become more vulnerable to tumorigenic mutations and the development of cancer as a result. I don’t want to detract from the authors’ work — they clearly put a lot of research and thought into the essay. Every somatic cell in the human body contains nearly identical genetic material, but skin cells, muscle cells, bone cells, and nerve cells exhibit different properties due to different sets of genes being turned on or off. Also in the “if I were dictator” category – incentivize people to provide a large control group. Also, rich people already use their status and wealth to obtain better genetics for their children — mate selection. There’s also plenty of research on the value of diversity/disadvantages of group think. In this manner, malaria acts as a selective evolutionary pressure maintaining the occurrence of the sickle cell variant in the gene pool. There’s no reason to assume a large percent of cancers are not susceptible to this imagined therapy because their primary etiology is epigenetically-based, not genetically-based. Indeed, this is the safest and most effective way to go. Additionally, in vitro studies have demonstrated that CRISPR techniques exhibit better correction efficiencies and fewer off-target effects than TALEN. As always, trade-offs exist, and the idea of the “perfect specimen” is a fallacy. Eloi is certainly something to think about. Germline editing may therefore provide a more expedient option for the prevention of some genetic diseases such as sickle cell disease or cystic fibrosis. How does gene expression contribute to disease risk? I’d tend to think anyone claiming (2) was protesting too much, but there’s a related concept they might mean: 3) If a pair of genes are closely linked because they physically interact with each other, and matching sets have a fitness advantage, then changing a non-standard version of one of the genes to the more common version may stop it from interacting with its partner, revealing an unexpected deleterious phenotype. Maybe the original title of this collaboration was different, but I think discussing the applicablity of genome editing against cancer does little to answer the titular question. Eventually people will calm down and accept it like they do with things like rock and roll and divorce. But going after all mutations is IMO excessive. Completely agree. One of the most compelling arguments against CRISPR gene editing, namely the potential for misuse, can also be considered the most compelling argument for CRISPR gene editing. If you need millions of dollars in equipment and a team of skilled professionals, it’s hard for a black market to arise. Moreover, the use of CRISPR can speed up the manufacturing of CAR T cells and drive down costs of such therapies from hundreds of thousands of dollars to a few hundred dollars. Bear in mind that in many developed countries, the government pays for most health care. There’s huge pressure to make the tech cheaper. 2. Modern CRISPR technology is not affected by such hurdles, however, as it does not rely on the use of viral vectors. Cigarette smoke has been shown to promote both demethylation of metastatic genes in lung cancer cells as well as regional methylation of other specific genes via modulation of enzymatic activities. At least, not that we’ve observed or have evidence to support. Even intended cuts can have unexpected consequences. Even with dealing with just disease there is a sort of on the one hand and on the other hand thing going on which isn’t very useful if you don’t give any quantitative estimates. CRISPR also offers the additional possibility of removing parts of a gene, providing extra value over standard viral gene therapy, which only allows for insertion of genes. To even attempt to answer something like this is hugely speculative and probably a waste of time. However, since the pathological mutation for sickle cell disease has already been clearly identified, correction of the mutated gene using CRISPR may offer a more straightforward approach. Decades? When does this sort of meddling become hubris? -1 You have not addressed the evolutionary argument against gene editing. Joseph Fletcher, one of the founders of bioethics, wrote in 1971, “Man is a maker and a selector and a designer, and the more rationally contrived and deliberate anything is, the more human it is.” The establishment of gene editing guidelines should include input from scientists, policy makers, and the public and incorporate the most current knowledge available in order to prevent misuse and realize potential. It’s quite another to make that susceptibility more broad. Designer babies become possible, but they’re very expensive. Conventional gene therapies, which attempt to insert healthy copies of genes into cells using viruses, faced many early setbacks, including the tragic death of 18-year-old Jesse Gelsinger in 1999 during a gene therapy trial for ornithine transcarbamylase deficiency. Ethical & Social topics for Group Discussion, Creative & Abstract Topics for Group Discussion, General Interest Topics for Group Discussion. Human generations are long; human lifespans are longer. 2. Delivery is, IMO, the biggest challenge, and there is no Amazon Prime for CRISPR. For a while. I see a lot of control groups being dissolved, after the treated group seemingly do a lot better, suggesting that trade-off between ‘withholding treatment to be surer that the treatment works’ vs ‘treating people with poor evidence’ is shifting to the latter. I would also mention prime editing (published October 2019 here: https://www.nature.com/articles/s41586-019-1711-4). Still, thanks! What’s the difference between a cure, a therapy with persistent impacts, and ‘playing god’? I guess somewhere there is going to be a statistic that the same percentage of people is dying of cancer as 30 years ago, which ignores the fact that people have to die of something and simultaneous advances in different disease areas will tend to keep the death stats balanced. But if someone tried to take the knowledge we have today and use it to genetically engineer children with higher IQs, there would probably be a lot of unintended consequences – we simply don’t understand enough about those genes to do it safely at this point. Many in the scientific community have decried the work. More than likely though, there will be several local maximum genomes that optimize for different traits. It is, as you say, a complex topic. While sometimes considered controversial, gene editing has been used as a last resort to cure some diseases. (Not a literal peacock tail, of course; but e.g. It’s one thing for some humans to have an error that creates genetic susceptibility to certain diseases. In the 1970s, scientists first began to establish distinctions between somatic and germline genome modifications; somatic edits only affect a single individual while germline edits can be passed down over generations. The major worry among scientists revolves around the long-term consequences of germline modification, meaning genetic changes made in a human egg, sperm, or embryo. Unfortunately, these studies often fail to employ random sampling, and 96 percent of subjects included in GWAS have been people of European descent. Doudna intones, “Someday we may consider it unethical not to use germline editing to alleviate human suffering.” What was unthinkable just a few years ago will soon enter clinical praxis. EMT can be triggered by genetic changes, but also very much by the environment, even in a genetically normal cell. Epigenetic changes control the expression of genes through various mechanisms and are influenced by diet, exercise, lifestyle, sunlight exposure, circadian rhythms, stress, trauma, exposure to pollutants, and other environmental factors. Also the microenvironmental discussion ignores the subtle interplay between the cancer cells themselves and the tumor infiltrating immune cells. I specifically mean that (in the U.S.) policy for newborns born to opioid-addicted (or any other drug that causes harm to developing fetuses) mothers is case-by-case, and mothers are frequently allowed to retain custody despite permanent damage done in vitro. This seems like it should be one of the most interesting technological issues to keep an eye on, because yes, in theory it should be possible to make not-quite-superhumans-but-really-impressive-humans by simply going through and replacing every rare variant with a common one. I feel like this entry, moreso than the others thus far, has suffered from a degree of blatant “one author writes one paragraph, the next author writes the next paragraph, et cetera”. Yeah, and the link goes to a report that excitedly describes recent advances. In other words, the same oncogenic mutation that is adaptive for cancer in altered tissue is not advantageous to cancer in healthy, homeostatic cells. Researchers have been investigating the possible insertion of wild-type, “anti-sickling” genes using viral vectors in affected patients as therapy. Since this is a hypothetical, we can offer hope – you found a cure! Instead of a nicely sculpted foot grinding down on a slightly misshapen face forever, let’s assume there’s a normal course of technological development. Here’s what I think they get wrong, though– in a scenario like this a shortage of evidence shouldn’t mean “eh, seems OK, go ahead” which is more or less what the authors say in their conclusion. Because those epigenetic changes are driven by pre-existing genetic ‘programming’ that was already present and got activated inappropriately and lead to cancer. The government already spends unbelievable amounts of money on attempting to make people more productive through schooling. I’ve not personally worked with CRISPR before, but my sense is that – similar to other molecular biology techniques – there’s a huge difference between single-gene editing and wholesale changes to more than one gene. We’ve been selecting more prosocial, more obedient, more agreeable children essentially forever, until we decided every child is a special little snowflake. If you imagine your genetic code as the hardware of a computer, epigenetics is the software that runs on top and controls the operation of the hardware. The really competitive ones line up overnight and pull strings to get their kids into the most exclusive preschool. What would it really mean to ‘play God’ in the way most people imagine the term to mean? I think that’s why issues around fertility, childbirth, and abortion are so fraught: because they touch on something very primal, almost sacred. I very little concern with fixing those – not none, because I can imagine somethign with unpleasant side effects that’s actually a net benefit. Is it really that easy from a technical standpoint? This is incorrect, it’s not what linkage means. Editing a single SNP is shockingly easy; it would be completely feasible for an ordinary fertility clinic to do so (maybe not literally right now, but it will be soon.) Why would they converge? In response to the international furor, China began redrafting its civil code to include regulations that would hold scientists accountable for any adverse outcomes that occur as the result of genetic manipulation in human populations. This is what I think is a little misleading. A minority of those who opt for riskier or more marginal/aesthetic edits will unfortunately have children with some form of (potentially novel) disability. Dr. To account for the discrepancy between genetic predisposition and disease manifestation, in 2005, cancer epidemiologist Dr. Christopher Wild proposed the concept of the exposome, which encompasses “life-course environmental exposures (including lifestyle factors) from the prenatal period onwards” and accounts for factors such as socioeconomic status, chemical contaminants, and gut microflora. As the custodians of such powerful technology, we must take care to use it in an ethical and responsible manner. People will generally want to make their children successful in their current environment, and will do so if they can. The most oft-cited example discrediting this theory is that of giraffes elongating their necks by stretching to reach the treetops and then passing on this trait of long necks to their progeny. The ones that are disadvantageous tend to get rid of themselves, but with lots of suffering as it happens. If a more efficacious means of doing this comes along why shouldn’t the government also want to spend hundreds of thousands of dollars per child effecting it? Human germline modification could also theoretically allow for the installation of genes to confer protection against infections, Alzheimer’s, and even aging. About one percent of the population is naturally immune to HIV due to a CCR5 gene mutation, which prevents the expression of a cell surface receptor that HIV binds to in order to gain entry into host cells. Additionally, most traits are influenced not only by genetics but also environmental factors, and monozygotic twin studies demonstrate that genes alone cannot predict whether physical traits will be expressed. Gene editing - Pros and Cons Gene editing was not even a term few years back but now the technology is at full swing with more scientific research and experiments being done in various countries. Jennifer Doudna offers the following visual: “Imagine trying to correct an error in a news article after the newspapers have been printed and delivered, as opposed to when the article is still just a text file on the editor’s computer.” Germline editing may therefore provide a more expedient option for the prevention of some genetic diseases such as sickle cell disease or cystic fibrosis. Whether it’s even possible to use it against complex multigenic diseases we’re still struggling to understand is not clear. Given the sources of genetic information used to determine “wild-type” sequences, we may be using information that is relevant to one demographic but not another. You did some searching and have found this same virus has been endemic in human populations for over five hundred years, we just didn’t know until now that many people we thought just had weak immune systems were actually infected by this virus. Any edits to a gene belonging to a linked pair may therefore inadvertently cause an edit in its neighboring partner. That’s what I was pushing back against. My impression (mainly from reading _The Emperor of All Maladies_) is that the reason cancer progress is so slow is that most of the targeted treatments work only on a really narrow set of cancers, so instead of scientists producing a generic cure for cancer, they (with great effort and expense) produce a cure or near-cure (long term remission) for one tiny subset of cancer cases at a time. No, never bothered to actually read that; but I might have picked it up indirectly from there. I’m not so sure that this is comparable. Does this mean germline removal of certain genetic abnormalities might reverse problems we accidentally created? Fact that phenotype is heavily influenced by both genetics and enviornment does nothing to show that human enhancements wouldn’t have a massive effect. The better we get at keeping alive people who suffer from genetically-driven diseases (which are only a subset of all disease, of course) to the point where they’re able to survive to pass on their genes to the next generation, the more we enrich for those genes and perpetuate that disease. Currently the selection doesn’t move the probability estimates much but it will improve and even a 2% reduction in risk for depression would be a huge benefit. When necessary, the CRISPR defense system will slice up any DNA matching these genetic fingerprints. Categories: APA (edition "APA 6") Health Care and Life Sciences. To succinctly summarize, genes themselves are not driving tumor formation; rather inappropriate gene expression is increasing the risk of tumor development. I think it’s a bad idea to go around making this change to ALL humans. It’s hard to talk dispassionately about it — and that applies to “germline” human editing. For example, the APOE gene, which encodes for the production of a protein known as apolipoprotein E, comes in three genetic forms- APOE2, APOE3, and APOE4 with the last being associated with an increased risk of developing Alzheimer’s disease (AD). I know that’s putting words in their mouths, but I think it’s justified otherwise why include it in the discussion? Inappropriate DNA methylation has been referred to as a “hallmark of cancer,” along with uncontrolled cell growth and proliferation. All Rights Reserved. Let’s go with a boring hypothesis. Physical Education should not be mandatory in schools! The biotech company CRISPR Therapeutics recently announced the results of a phase I clinical trial in which CRISPR technology was used to treat a patient with sickle cell disease, although the efficacy and safety of the intervention have not yet been evaluated. If you change a variant that occurs in 0.1% of the population into a variant that occurs in 90% you are not going to break anything. Also in the “if I were dictator” category – incentivize people to provide a large control group. I wonder at what point it becomes no different from using donor egg and sperm, or adopting. Was that a bad thing? It then moves to survey proposals that have been advanced to construct mechanisms of governance for overseeing research with genome editing in humans. Another problem with CAR-T is that they often don’t work as well in solid tumors, where the tumor microenvironment often excludes newly infiltrating T-cells. Challenges still exist, as human immunodeficiency virus (HIV) inserts itself into the host genome and mutates rapidly, making complete eradication of the disease very difficult. 0 Comments . I know it’s a hard topic and I may not have done any better but I don’t think this really got at the important enhancement issues which dominate costs and benefits. If you have a nonviable fetus that would have been rejected naturally, should you implant it in an artificial womb and develop it to maturity? https://www.futurity.org/crispr-multiple-genes-2132952/. The people that gene edit will have more fit babies and those in turn will be more likely to gene edit. Sickle cell anemia is a disease inherited in an autosomal recessive pattern—two copies of the problematic gene variant are necessary for disease expression. How reliable is our understanding of gene-disease links? ridiculous slimness, or height, or some such – yes, of course all babies are born by C-section, because of what this requires of female hips, but slimness is so much healthier …). In October 2018, the world’s first genetically edited babies were born, twin girls given the pseudonyms Lulu and Nana; Chinese scientist He Jiankui used CRISPR technology to edit the CCR5 gene in human embryos with the aim of conferring resistance to HIV. Any edits to a gene belonging to a linked pair may therefore inadvertently cause an edit in its neighboring partner. At that point, there will be people offering designer babies, and the most ambitious-for-their-kids people will provide a ready market. The major worry among scientists revolves around the long-term consequences of germline modification, meaning genetic changes made in a human egg, sperm, or embryo. One thing you mentioned briefly are CAR T cells. Could anyone have predicted how democracy would work out on the national scale without adopting it? You don’t need to sequence the whole genome if all you’re looking at is one or a defined set of genes. Not always. Eternal youth? Indeed, why worry about a potentially pathogenic gene if it is never expressed? Actually, what you break is the presence of that new mutation that’s in fact advantageous, but since we don’t know how, we get rid of it. It would be bizarre if somehow a bunch of random epigenetic ‘mutations’ all happened to create an EMT-like state in cancer cells. Discussions of heritable enhancements in particular raise fears of a possible return to eugenics. Correction to the above: 3. Why shouldn’t future generations be healthier, happier, longer-lived, nicer, smarter and more attractive? Minor quibble with your point (minor because you are very correct, it is a complex topic and no short comment is going to completely cover it). Is it just because we don’t want to mess with DNA? Most mutations are disadvantageous, but most != all. Has democracy been used beneficially and responsibly in all cases? 1. Another point to consider is the fact that the CCR5 mutation that confers HIV immunity more commonly appears in Caucasians and may make individuals more susceptible to infections that are common in Asia. The Conversation, provided principles and recommendations to guide the governance of human genome editing, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Public License, Centre for the Fourth Industrial Revolution, Schwab Foundation for Social Entrepreneurship. Personally I expect: “Even if we do make the changes we want to make, there’s still question about whether it will do what we want and not do things we don’t want.”, Nevertheless, a slight increase in cancer risk might be a worthwhile trade-off for many patients with genetic diseases, such as the aforementioned SCIDs, which affect 1 in 50,000 people globally. As previously mentioned, the first genetically edited babies were born in October 2018 after Chinese scientist Dr. The death rate from cancer in the US has fallen 26% since 1991. We have the ability to change, add or delete genes in human embryos, adults and plants alike. But isn’t the deliberate harm of gestating fetuses intended for delivery already permitted? If you grew up with the standard genetic kit that makes you a dutiful, diligent, verbally and mathematically inclined workaholic, you might very well decide to scrap all that and make kids who are designed to turn out cool. He, a married couple with the pseudonyms Mark and Grace consented to in vitro fertilization with additional CRISPR treatment to provide immunity to HIV for their offspring. I mean, half our kids used to die before they turned five, now a kid dying that young is a rare terrible tragedy. My main concern is that I hope our reach and our grasp advance at roughly the same rate. The question “can gene editing eliminate disease?” is like the question “do quarks cause consciousness?” I mean, maybe? Weak can never forgive, forgiveness is the attribute of the ... Human beings should be treated as 'ends' and not as 'means', Population Growth - Boon or Bane to India's growth. While more precise than traditional gene therapy, CRISPR nonetheless sometimes results in unintended edits, which may be especially problematic for certain gene targets. Nevertheless, many consider mainstream germline gene editing an inevitability. 1. In biology, those organisms that are most suited to their environment exhibit the highest fitness, a measure that accounts for both survival and reproduction. Either the message has been garbled or someone got the wrong end of the stick. There’s a stronger norm against medical providers causing harm than not preventing it. But I don’t know anyone who would suggest that repeat activation of a normal physiological process of wound healing would lead to tumorigenesis through epigenetic factors alone. The question “can gene editing eliminate disease?” is like the question “do quarks cause consciousness?” […] I don’t know that the authors realised the enormity and complexity of the question they were taking on. Chinese authorities suspended all of He’s research activities, saying his work was “extremely abominable in nature” and a violation of Chinese law. Alice and Bob just happen to take a vacation in Brazil where they get pregnant for each of their kids, and their kids just happen to be extremely athletic and the smartest kids in their class and unusually tall and very healthy. Some people seem to desire diversity of skin color, gender, etc, but within a monoculture with very restrictive allowed opinions. However, the accumulation of genetic mutations is not sufficient to cause cancer; the tumor microenvironment must be taken into account. Nobody can know everything, but some of these explanations were a little too tailored for easy public consumption which sacrificed accuracy. If a mistake is made in the process and a new disease inadvertently introduced, these changes will persist for generations to come. Nevertheless, interracial marriage rates remain relatively modest. For many, the thought of controlling our own genetic destinies seems to be a very slippery slope, conjuring up dystopian images of Frankenstein or Brave New World. I guess a minor crusade of mine is getting more people to recognize how much of cancer biology is just hijacking physiological processes for pathological ends. Memes. This week we will explore the methods and impacts of gene editing on humans and plants. How should society move forward with gene editing technology? In other words, a cell pre-programmed to be a differentiated skin cell that reverses its programming is likely doing so because of genetic, not epigenetic, changes. In breast cancer alone, we’ve seen the introduction of trastuzumab and other HER2-targeting therapies, letrozole, palbociclib, and (insert other new drugs I’m forgetting). I think in many ways controversial philosophical questions are not very analogous to difficult empirical ones…, This doesn’t really relate so much to the post as opposed to the subject in general (except insofar as I think it’s relevant that the post didn’t mention this), but, to repeat what I said on an earlier thread…, The possibility that scares me isn’t people using gene editing to enhance their children — I mean, greater capabilities are a good thing — but to make their children more things-their-parents-want-but-that-are-not-in-fact-better. Which, in my experience, progressives tend to present as being unequivocally in favor of diversity*, even though the actual results seem largely a wash. That makes it cheaper still. Sorry if you were being purposefully coy and I’m outing you, but Kaczynski makes this argument fairly compellingly in Industrial Society and Its Future, so that might be where you got it from. The use of gene editing to mold favorable traits, such as eye or hair color, likely exposes individuals to unnecessary risks and does not constitute medical necessity. Unless I’m missing something here, the theory that cancer is driven by genetic changes (often introduced by environmental factors, yes) is still sound in a world where lots of hypomethylation is present in the cell. If you imagine your genetic code as the hardware of a computer, epigenetics is the software that runs on top and controls the operation of the hardware. Testing indicated that gene editing did not successfully alter both copies of the CCR5 gene in one of the twins, however. While the death of Jesse Gelsinger marked a somber moment for the field, gene therapy also experienced successes when researchers from Paris treated two young infants who suffered from a fatal form of severe combined immunodeficiency disease (SCID), an inherited disorder characterized by low levels of T cells and natural killer cells, which leaves affected patients incredibly susceptible to infection. Human genomes were not meant to be experimented and altered is what ethics and religious values have been denouncing about. Whether it’s driven by chemokine signalling, costimulatory molecules, or messing around with tumor vasculature, the cancer cells themselves are the ones playing the immune system to make it change to a pro-tumor response. b) With plenty of unintended consequences. That is a very creative way of thinking and you are probably right in some cases. I don’t think it’s possible to be egalitarian about this either. An illegal-but-available designer baby industry would find a huge pool of customers here. Advantages and Disadvantages of Recruitment agencies. I don’t think this would become universal — I think many if not most parents would realize this is a bad idea. While gene editing has been used in laboratory experiments on individual cells and in animal studies for decades, 2015 saw the first report of modified human embryos. Incidentally, this probably means that in the medium run, genetic editing will be egalitarian in outcomes. Cancers are front and center among the conditions gene editing therapies are targeted to treat. (Even though, in that novel, there weren’t any notable unintended consequences – the main value of “control naturals” was as a source of novel mutations, some potentially advantageous.). When only the father is HIV-positive, as in this case, sperm washing alone is usually sufficient to reduce transmission of the virus.
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