On Human Gene Editing, seizing control of human inheritance
December 5, 2015 5:57 AM   Subscribe

Last April, motivated by rumors of a Chinese paper published the next month that physically demonstrated the technical feasibility of editing human germline DNA with CRISPR by successfully modifying human embryos, a coalition of well regarded scientists assembled to address this fundamentally new ability and they called for an international summit. It was to be billed as a new Asilomar Conference on Recombinant DNA for a new age in order to lead a new global conversation on questions of whether and how to control human inheritance, which could only be dreamed of 40 years ago. This is a fundamental departure from the non-inheritable gene engineering with CRISPR covered on the blue recently. Thus, from December 1-3, the International Summit on Human Gene Editing, held as a collaborative effort between U.S. National Academy of Sciences and National Academy of Medicine, the Chinese Academy of Sciences, and The Royal Society, met to discuss the future of this technology and has come out with a clear consensus statement.

This is the relevant section of the consensus statement, briefly, they have ruled out either a ban or a moratorium on the modification of human embryos that are destined to become people, however they also stated that altering the DNA of human embryos for clinical purposes was unacceptable for any currently proposed project and called for the careful individual consideration of any future proposals as the technology continues to advance.
"...Gene editing might also be used, in principle, to make genetic alterations in gametes or embryos, which will be carried by all of the cells of a resulting child and will be passed on to subsequent generations as part of the human gene pool. Examples that have been proposed range from avoidance of severe inherited diseases to ‘enhancement’ of human capabilities. Such modifications of human genomes might include the introduction of naturally occurring variants or totally novel genetic changes thought to be beneficial.

Germline editing poses many important issues, including: (i) the risks of inaccurate editing (such as off-target mutations) and incomplete editing of the cells of early-stage embryos (mosaicism); (ii) the difficulty of predicting harmful effects that genetic changes may have under the wide range of circumstances experienced by the human population, including interactions with other genetic variants and with the environment; (iii) the obligation to consider implications for both the individual and the future generations who will carry the genetic alterations; (iv) the fact that, once introduced into the human population, genetic alterations would be difficult to remove and would not remain within any single community or country; (v) the possibility that permanent genetic ‘enhancements’ to subsets of the population could exacerbate social inequities or be used coercively; and (vi) the moral and ethical considerations in purposefully altering human evolution using this technology.

It would be irresponsible to proceed with any clinical use of germline editing unless and until (i) the relevant safety and efficacy issues have been resolved, based on appropriate understanding and balancing of risks, potential benefits, and alternatives, and (ii) there is broad societal consensus about the appropriateness of the proposed application. Moreover, any clinical use should proceed only under appropriate regulatory oversight. At present, these criteria have not been met for any proposed clinical use: the safety issues have not yet been adequately explored; the cases of most compelling benefit are limited; and many nations have legislative or regulatory bans on germline modification. However, as scientific knowledge advances and societal views evolve, the clinical use of germline editing should be revisited on a regular basis."
Leading up to the summit, there has been a fascinating and unusually wide disagreement in the literature about the ethical and social implications of human gene editing.
Geneticist Jennifer Doudna co-invented a groundbreaking new technology for editing genes, called CRISPR-Cas9. The tool allows scientists to make precise edits to DNA strands, which could lead to treatments for genetic diseases … but could also be used to create so-called "designer babies." Doudna reviews how CRISPR-Cas9 works — and asks the scientific community to pause and discuss the ethics of this new tool. A TED talk that would make a good introduction to the technology, what it can do, and what many are concerned about.

Pollack, an American biologist who now studies the intersections between science and religion had this to say: Eugenics lurk in the shadow of CRISPR, (Published in Science)

Henry Miller, whose role as the medical reviewer for the first genetically engineered drugs to be evaluated by the FDA was instrumental in the wisely rapid licensing of genetically engineered human insulin as well as human growth hormone that saved thousands of lives in the 90s, had this to say: Germline gene therapy: We're ready, (Published in Science)

George Church, a Harvard researcher at the center of Synthetic Biology who is on the boards of just about every major company involved in CRISPR research and is thus better placed than anyone on Earth to know what the state of the art is, has this to say: Perspective: Encourage the innovators (Published in Nature)

A collection of researchers working on making non-heritable edits to the human genome have this to say in Nature: Don’t edit the human germ line: Heritable human genetic modifications pose serious risks, and the therapeutic benefits are tenuous. They are however opposed by their colleagues who have this: Germline edits: Heat does not help debate and this: Germline edits: Trust ethics review process to say. (Published in Nature)
Also relevant:
Where in the world could the first CRISPR baby be born? A look at the legal landscape suggests where human genome editing might be used in research or reproduction.

Human-embryo editing poses challenges for journals: Ethical concerns complicate publishing process.

Why human gene editing must not be stopped in The Guardian
posted by Blasdelb (67 comments total) 56 users marked this as a favorite
 
If it's okay to edit the genes of other organisms, why not humans?
posted by Faint of Butt at 6:03 AM on December 5, 2015 [2 favorites]


For the same reason it's socially acceptable to kill and eat other organisms, but not humans. Humans are just animals, but we're still pretty picky - and rightfully so - about what happens to us. We might not care too much if your CRISPR'd dog has a slightly mangled genome (and we probably care a lot less about an animal we're planning on eating, and just forget about plants), but humans, and to a lesser extent other species in possession of higher degrees of consciousness, are considered more ethically tricky because of said consciousness. Similarly, we're not really worried about race relations between members of an animal species, while with humanity that's definitely a concern.

Also, when it comes to genetic modifications, we have to worry about the survival of the species. It'd be a tragedy if an accumulation of mutations from CRISPR-ing a species lead it to just collapse and die, but it would mean the end of humanity if we did that to ourselves. We don't want to end up like Gros Michel banana, after all.
posted by Punkey at 6:19 AM on December 5, 2015 [10 favorites]


There are many valuable areas of research (e.g. hemophilia) that can serve as important benchmarks before we start making permanent changes.
posted by CheeseDigestsAll at 6:20 AM on December 5, 2015


Just as a bit of a glossary for those who might be new to the terminology:
Germline cells: The germ line is represented by the sex cells (eggs, sperm, and the stem cells that make them) that are used by sexually reproducing organisms to pass on genes from generation to generation. Egg and sperm cells are called germ cells, in contrast to the other cells of the body that are called somatic cells.

Somatic cells: A somatic cell is any cell of the body except sperm and egg cells, representing the vast majority of cells in the body.

CRISPR/Cas9: The CRISPR/Cas system is a prokaryotic immune system that confers resistance to foreign genetic elements such as plasmids and phages, and provides a form of acquired immunity. CRISPR spacers recognize and cut these exogenous genetic elements in a manner analogous to RNAi in eukaryotic organisms. CRISPRs are found in approximately 40% of sequenced bacteria genomes and 90% of sequenced archaea. The CRISPR/Cas system has been used for gene editing (adding, disrupting or changing the sequence of specific genes) and gene regulation in species throughout the tree of life. By delivering the Cas9 protein and appropriate guide RNAs into a cell, the organism's genome can be relatively cheaply cut at any desired location. CRISPR has a number of potential applications including altering the genetic blueprint of humans and livestock, and manipulating the genes of food crops.
posted by Blasdelb at 6:23 AM on December 5, 2015 [6 favorites]


So the Eugenics Wars are still on?
posted by blue_beetle at 6:34 AM on December 5, 2015 [14 favorites]


I think that we need to focus on the important aspects of this, such as, how does this help me join the Avengers?
posted by Halloween Jack at 6:39 AM on December 5, 2015 [6 favorites]


Interestingly, Dr. Francis Collins, the deeply Evangelically Christian director of the American NIH (National Institutes of Health) that funds most health related research in the US, may need to revise his very restrictive guidelines in light of the new statement that clearly demonstrates him to be wrong about the current state of the global scientific conversation.
posted by Blasdelb at 6:39 AM on December 5, 2015 [2 favorites]


There was also recently a fascinating exchange between Professor George Church and NIH Director Francis Collins published in STAT:
Collins: The ethical arguments against human germline engineering are significant. A most compelling one is that medical research should always seek to balance benefits and risks, with individuals who are participating in research giving fully informed consent. But the individuals whose lives are potentially affected by germline manipulation could extend many generations into the future. They can’t give consent to having their genomes altered from what nature would have made possible.

Church: Parents do not get consent from future generations to make mutations in gametes via excessive time at high altitude, or to alter young minds with rules, tools, and schools. Each of these can be transmitted to multiple generations (some without changing DNA, some harder to reverse than DNA changes).

Collins: There’s also a concern about human hubris. Who gets to decide what’s an improvement on the genome?

Church: This is similar to asking, “Who currently gets to decide about many interventions during child development?” such as fetal surgery, genetic counseling, vaccines and education. The answer is physicians, parents, and society. The term “hubris” seems dismissive rather than encouraging deep exploration of exemplary cases.

Collins: Many of the scenarios being discussed aren’t about correcting a disorder caused by misspelling of a single gene. For that, preimplantation genetic diagnosis already offers a practical and much less ethically challenging option for most couples seeking to avoid the birth of a child with a serious genetic disorder. Instead, futurists dream about changing traits that someone decides could be improved, such as intelligence, height, or risk of some common chronic illness. All of those are complex multigene situations in which the environment plays critical roles, and no single genetic change would be expected to have much benefit.

Church: “Multigene situations” do not prevent single-gene changes from being very significant. For example, alterations in growth hormone genes have large impacts on height in humans. Changes in other specific genes can positively affect learning, memory, anxiety, and problem solving in mice. In humans, single gene variants can protect against chronic Alzheimer’s disease, AIDS, and coronary artery disease. Safety and efficacy, case by case, should determine FDA acceptance, not unproven a priori biases about single vs. multiple gene impacts.

Collins: Evolution has been working toward optimizing the human genome for 3.85 billion years. Do we really think that some small group of human genome tinkerers could do better without all sorts of unintended consequences?Church: Those billions of years were spent optimizing the human genome for environments and goals very different from those found in modern times. Humans are not optimally adapted for desk work, high-rise megacities, or space travel. A small group of human tinkerers did indeed optimize, for modern needs, IR8 rice, border collies, and many other forms of life. We will eventually address unintended consequences, if any, not via prejudicial bans lacking end points, but by encouraging experiments — as was done with in vitro fertilization, medications from recombinant DNA, and genetically modified crops.

Collins: There are also issues of equity and justice. Who would have access to this kind of human germline engineering? Do we want to accept the scenario that only those with financial resources get to “improve” the genomes of their children?Church: We do not need to accept a scenario in which costs stay fixed. Cellphones have dropped in price such that even remote, poor villages can afford them — and services such as GPS and computer searches are free. The cost of DNA sequencing has dropped over 3 million fold and seems to be continuing downward. If we encourage creativity in genome engineering, then the huge drop in cost that accompanied CRISPR is likely just a start.

Collins: A more subtle but significant concern is whether the application of germline manipulation would change our view of the value of human life. If genomes are being altered to suit parents’ preferences, do children become more like commodities than precious gifts?Church: The trend away from children as commodities can be compatible with germline alterations. Past expectations of needing large numbers of children to replace those lost to infection and genetic disease is giving way to expectations of long, high-value lives. The old “one size fits all” medicine is giving way to personalized medicine in which each child is precious and unique. “Parents’ preferences” have, for ages, influenced their descendants’ genetics (via mate choice), their initial religion, language, hometown, and occupation. But increasingly, parents accept that their children are not “gifts” to be owned. The better the launch, the further the child may go from the parent.

Collins: If there was a truly compelling argument that only human germline engineering could alleviate the suffering of many people, then I would say we might consider trying it under closely controlled circumstances. But the fact that there is a profound paucity of compelling cases, and that the ethical counterarguments are so significant, makes me conclude that the balance of the debate leans overwhelmingly against human germline engineering.

Church: The historical paucity of compelling cases articulated for human flight, personal computers, stem cells, etc., reflect the lack of imagination of the opinion leaders of the day. We need only one compelling argument to initiate a new social norm — even when the market is small (as for orphan drugs). For germline modification, we have at least three compelling cases: 1) mitochondrial diseases; 2) families in which post-natal remedies are inadequate and both parents are fully afflicted (20 percent of the world’s marriages involve close relatives); and 3) scenarios in which treating (and possibly pre-screening) single germ cells is safer than treating millions of somatic cells, since each cell adds to the collective risk of developing cancer.
Just, wow do we live in the future.
posted by Blasdelb at 6:52 AM on December 5, 2015 [23 favorites]


The George Church piece is so troubling. "If we don't do it, the black market will" is not an adequate ethical argument to pursue a line of treatment. He mentions athletic doping and other unregulated uses of medical treatment and yet doesn't once mention the trouble we get into with regulated but revenue-focused medicine already. We have a nation of people begging doctors for medicines they have seen on a shiny commercial on TV, and those doctors are willing to overprescribe; we have a massive legal narcotic problem; we recall hundreds of adulterated or mislabled medicines a year. Can we honestly say we have an ethical culture in medicine that can handle germline editing once it is in the wilderness of the free market?

On the other hand, I see a profitable uptick in disaster book and movie plotlines! "A simple edit saved them when they were babies...but now they are bursting into flames, one by one. Who can avoid the grip...of the CRISPER!"
posted by mittens at 6:53 AM on December 5, 2015 [12 favorites]


This is the way the world will end, not with a bang but with a CRISPR...
posted by Devonian at 6:59 AM on December 5, 2015 [5 favorites]


Being dumb sucks. I hope they fix all the dumb genes.
posted by todayandtomorrow at 7:06 AM on December 5, 2015


CRISPR supposedly makes gene editing ridiculously easy. How long until The Island of Dr Moreau (or many other science fictions) becomes a reality?
posted by eye of newt at 7:07 AM on December 5, 2015 [2 favorites]


I find the issue of consent an interesting one to consider further, and to not be waved away by saying, "Parents do not get consent from future generations to make mutations in gametes via excessive time at high altitude, or to alter young minds with rules, tools, and schools." Children who reach adulthood can and do now hold their parents responsible for the choices they made in raising them. This can be as simple as resenting religious instruction or homeschooling, or as complicated as gender-assignment of intersex babies. I think consent should be carefully considered in this light.

Another issue would be one of access. IVF is prohibitively expensive for many, if not most, now, and is not covered by insurance. Access to genetic therapies such as CRISPR editing are likely to be an out-of-pocket expense, and thus only available to those with significant wealth. This could have follow-on societal effects, exacerbating disparities in health and longevity already evident.
posted by Existential Dread at 7:10 AM on December 5, 2015 [6 favorites]


Another issue would be one of access. IVF is prohibitively expensive for many, if not most, now, and is not covered by insurance. Access to genetic therapies such as CRISPR editing are likely to be an out-of-pocket expense, and thus only available to those with significant wealth. This could have follow-on societal effects, exacerbating disparities in health and longevity already evident.
At least currently, any attempt to modify human embryos intended for a successful pregnancy would indeed require all of the justifiably expensive and technically difficult aspects of IVF for each embryo individually as a necessary prerequisite in addition to the added cost and challenge of designing the targeted CRISPR systems involved.
posted by Blasdelb at 7:19 AM on December 5, 2015 [1 favorite]


Thanks for putting together a great series of links, Blasdelb. I was lucky enough to attend BEINGS 2015 this summer, which was yet another attempt to bring together scientists and bioethicists to talk about these issues (broader than just CRISPR) and begin to write policy recommendations. A presentation of some of the wide range attendee perspectives here. (Also, Margaret Atwood kicked Stephen Pinker's ass.)
posted by hydropsyche at 7:38 AM on December 5, 2015 [3 favorites]


the fact that, once introduced into the human population, genetic alterations would be difficult to remove

*shudder*
posted by tunewell at 7:42 AM on December 5, 2015 [3 favorites]


CRISPR supposedly makes gene editing ridiculously easy. How long until The Island of Dr Moreau (or many other science fictions) becomes a reality?

CRISPR is really not the best technology to use for this - it's used more for single gene deletions and insertions. We've been making chimeras by fusing embryos for something like a hundred years. The future for human-hybrid monsters is bright and well established!
posted by maryr at 7:45 AM on December 5, 2015 [3 favorites]


hydropsyche:
"(Also, Margaret Atwood kicked Stephen Pinker's ass.)"
Heh, I found this by Pinker, who can be such a pompous ass, but figured it wasn't worth being in the FPP:
Germline editing should be treated like any other medical procedure, weighing benefits against harms. It should not be banned out of a nebulous terror about tampering with a sacrosanct entity called “the human germline” — a concept which is biological nonsense. We affect the genetic makeup of our offspring, and the species, every time we choose one sex partner over another. And each of us introduces dozens of mutations into our own germlines by exposing ourselves to everyday radiation and chemical mutagens. Genetic editing would be a droplet in the maelstrom of naturally churning genomes.

What are the potential benefits? There are several scenarios in which germline editing could benefit parents who carry disease genes. It could be used when both parents are homozygous for the disease, when in vitro fertilization doesn’t produce enough viable and unaffected embryos for preimplantation genetic diagnosis, or if future data shows that babies who undergo the procedure have compromised longevity or health. The principal harm of germline editing is the risk of producing a sick or deformed child. Frankly, I suspect that this risk will always be unacceptable, so most of this discussion is moot. But suppose safety could be ensured. Should we fear the prospect of parents genetically enhancing their babies, the outcome the prohibitionists dread?

This is highly unlikely — a relic of the early 1990s, when people thought there was “a gene for” this or that talent. We now know that heritable psychological traits, such as intelligence and personality, are the product of hundreds or thousands of genes, each with a tiny effect. And many genes have multiple effects, some of them harmful, such as an increased risk of neurological disease or cancer.With each enhancement providing a trifling benefit and a non-negligible risk, and with the editing process itself imposing risks, it’s unlikely that today’s morbidly risk-averse helicopter parents will take a chance at enhancing a child. They won’t even feed their babies genetically modified applesauce! Add these risks to the expense and tribulation of IVF compared to good old-fashioned sex, and one can conclude that widespread genetic enhancement is too unlikely a possibility to worry about.
posted by Blasdelb at 7:47 AM on December 5, 2015


God, schmod, I want my monkey-man!
posted by Faint of Butt at 7:50 AM on December 5, 2015


All of this cheap posturing and talk!!!!!

Industry has and is delivering to the waters above and below ground, therefore the cultivated fields and therefore the bodies of all species on Earth, a dose of mutagenic chemicals untested, untried, unapproved for safety of the genome, much less the entire biome. With a system of checks, so cunningly betrayed by legal language, we and ours are utterly compromised, fifty years, a hundred years ago. If a chemical isn't destined for the plate, lungs, or skin of humans, (it used to be middle aged white men,) then it poses no danger, even if when it does arrive. Because then no industry looks back unless someome with a considerably large, hired foot, kicks them soundly in the ass. We are plagued with mutagens, that will carry on for many generations to come, and then the chemical cures dispensed by these same industries or allied industries, are so profitable, no one of them will find the root cause for which they bear responsibility.

So now comes designer genetic cures for some of the damage, that should not be taking place, in any case. When do my great grand children have to carry papers identifying their intelectual mutations that equip them for engineering schools, or space academies?
posted by Oyéah at 7:54 AM on December 5, 2015


All these posturing, eloquent hawkers. One protects a theology, one protects a budding industry.
posted by Oyéah at 7:57 AM on December 5, 2015 [2 favorites]


maryr: "CRISPR is really not the best technology to use for this - it's used more for single gene deletions and insertions. We've been making chimeras by fusing embryos for something like a hundred years. The future for human-hybrid monsters is bright and well established!"
This actually now has a recent caveat! Two months ago George Church published a paper demonstrating how his lab took a pig cell line and removed each of the 62 porcine endogenous retroviruses (PERVS) found in their genomes using CRISPR to eliminate one of the especially terrifying prospects of animal to human organ transplantation. The pig cells are still absurdly antigenic, but presumably he is working on that next.
Genome-wide inactivation of porcine endogenous retroviruses (PERVs)
The shortage of organs for transplantation is a major barrier to the treatment of organ failure. Although porcine organs are considered promising, their use has been checked by concerns about the transmission of porcine endogenous retroviruses (PERVs) to humans. Here we describe the eradication of all PERVs in a porcine kidney epithelial cell line (PK15). We first determined the PK15 PERV copy number to be 62. Using CRISPR-Cas9, we disrupted all copies of the PERV pol gene and demonstrated a >1000-fold reduction in PERV transmission to human cells, using our engineered cells. Our study shows that CRISPR-Cas9 multiplexability can be as high as 62 and demonstrates the possibility that PERVs can be inactivated for clinical application of porcine-to-human xenotransplantation.
posted by Blasdelb at 8:03 AM on December 5, 2015 [3 favorites]


When do my great grand children have to carry papers identifying their intelectual mutations that equip them for engineering schools, or space academies?

Gattaca is not a documentary.
posted by maryr at 8:04 AM on December 5, 2015 [3 favorites]


Gattaca is not a documentary.

True. It's more like a proof of concept.
posted by Thorzdad at 8:15 AM on December 5, 2015 [8 favorites]


Ha ha ha and I misspelled intellectual. Rich.
posted by Oyéah at 8:41 AM on December 5, 2015 [2 favorites]


porcine endogenous retroviruses (PERVs)

Heh. Yes I chuckled.
posted by Pyrogenesis at 8:45 AM on December 5, 2015


I'm okay with racks that grow slabs non-conscious pork chops and baby back ribs. That's for my carnivorous offspring to deal with--a matter of taste. I have some trouble with other versions of this. Patenting, for example.

A company owning the patented gene complex that reshuffles genes that provide a reliable immunity to a certain version of cancer. A patented process that increases one's intellectual ability. The patented process that produces an individual with extremely powerful muscles and blazing reflexes. Owning the patented genes that prevent aging.

These would be okay, yeah?

Skinner smiles from his grave.
posted by mule98J at 8:48 AM on December 5, 2015 [3 favorites]


My misgivings about marketing of medicine aside, I would way rather replacement kidneys become standard of care for CKD and ESRD, than see yet another shopping-center dialysis place open up. Those places depress the hell out of me...always in the strip malls next to the tanning salons, liquor stores and payday loans, like a little museum of vice and its consequences.
posted by mittens at 8:50 AM on December 5, 2015 [2 favorites]


"A company owning the patented gene complex that reshuffles genes that provide a reliable immunity to a certain version of cancer. A patented process that increases one's intellectual ability. The patented process that produces an individual with extremely powerful muscles and blazing reflexes. Owning the patented genes that prevent aging."
For better or worse, the Supreme Court has already determined that DNA sequences found in nature cannot be patented, no matter how much effort you put into annotating them, two years ago: Association for Molecular Pathology v. Myriad Genetics. However, if specific advantageous edits to DNA were to become something that would be a marketable thing and that thing were patentable, would the patentability of it necessarily be bad? The goal of patents is to ensure that advances that would otherwise become trade secrets can be publishable, and thus examined by the whole world, that all patented advances become the collective property of all mankind within 20 years, that the advances can still provide a return on the investment necessary to create them.

If we were to decide that being able to market specific traits to prospective parents would be an ok thing, and I've got my reservations too, wouldn't private patents be an ideal way to fund the research necessary to make that happen?
posted by Blasdelb at 9:02 AM on December 5, 2015


"Humans are not optimally adapted for desk work."

But some could be genetically engineered to be, praise science.
posted by one_bean at 9:03 AM on December 5, 2015 [3 favorites]


The goal of patents is to ensure that advances that would otherwise become trade secrets can be publishable, and thus examined by the whole world, that all patented advances become the collective property of all mankind within 20 years, that the advances can still provide a return on the investment necessary to create them.

Why just look at how it's working in the prescription drug world! It truly is the best of all possible worlds.
posted by one_bean at 9:07 AM on December 5, 2015 [3 favorites]


"Humans are not optimally adapted for desk work."

But some could be genetically engineered to be, praise science.


And we will call them Gammas. (The CEOs are Alpha Pluses.) Ford be praised!
posted by Rangi at 9:11 AM on December 5, 2015 [5 favorites]


wouldn't private patents be an ideal way to fund the research necessary to make that happen?

Ideal? That's the very dynamic that has utterly broken medicine.
posted by mittens at 9:26 AM on December 5, 2015 [4 favorites]


I'm just going to leave this here: a homogeneous humanity would be rather boring and shallow, and likely would not last long on this planet (all things considered). So I sincerely hope that human gene modification / tinkering / whatever is approached with the utmost caution, leaning on the side of "dont fucking do it".

I know this is intellectually shallow compared to above commentary, but it doesn't take a masters degree to understand that present cultural undercurrents and manual, non-evolutionary human gene modification make for a truly dangerous combination.
posted by JoeXIII007 at 9:42 AM on December 5, 2015 [1 favorite]


But some could be genetically engineered to be, praise science.

Wouldn't be cost effective. IVF costs $10k-$20k per implantation currently, and obviously not every implantation results in a pregnancy. Add into that the costs of genome sequencing and the CRISPR editing (not to mention post-CRISPR sequencing to confirm the edits were done correctly) and you've probably added six figures of cost and reduced the number of viable embryos significantly. May as well just force wild-type humans (ha, I love that expression) to suffer from decades of desk work.

Patents are an interesting question. In an ideal world, patents would incentivize research investment by private companies by allowing those companies a 20 year monopoly on the technology. Patents generated by public research dollars are assigned (essentially "owned") by the nonprofit institute or for-profit company that performed the research, with certain 'march-in' rights reserved by the federal govt. A number of issues have caused the problems evident in today's medical landscape: the extremely high cost of drug R&D + regulatory approval; sketchy pharma behavior in marketing to doctors through high-priced junkets and getaways; the long length of time to get a drug to market which can extend beyond the life of the patent; and a lack of single-payer negotiation on drug prices (see: Canada).

For CRISPR and Cas9, method patents are already applied for and in some cases granted. From my cursory review of the patent literature, it appears that Professor Doudna's filings are recent enough that they have yet to be reviewed by the various patent offices. The genes themselves, if they are naturally occuring, would not be eligible for patent protection, as Blasdelb points out. I'm not a geneticist, so I'm not familiar with the feasibility of engineering novel genes, but engineered protein design is a mature field, so I'd imagine that novel genes could be developed and perhaps then patented. It's hard to say what the effects of such a patent would be.
posted by Existential Dread at 9:43 AM on December 5, 2015 [2 favorites]


"The genes themselves, if they are naturally occuring, would not be eligible for patent protection, as Blasdelb points out. I'm not a geneticist, so I'm not familiar with the feasibility of engineering novel genes, but engineered protein design is a mature field, so I'd imagine that novel genes could be developed and perhaps then patented. It's hard to say what the effects of such a patent would be."
Engineered proteins are totally patentable as novel inventions, just like any other new machine someone might design, my understanding is that its generally the protein itself that is protected. Patents for the editing process or say the guide RNA that directs the CRISPR system to do its thing wouldn't have, at least directly, creepy implications but I suppose a patent on an inheritable engineered protein meant to be expressed by human cells could get super creepy depending on how that patent would end up getting interpreted.

It would be totally conceivable to take a sequence for a human protein, express it in a microbe, and then use directed evolution techniques or rational protein design to generate a novel protein that then does what the human one did but better in some way or with some new function. That novel, and theoretically patentable, protein could then be inserted into embryos using homologous recombination guided by a CRISPR system. If, or perhaps when, this happens, what exactly would a company/non-profit/whatever own the intellectual property of for those 20 years? Certainly not the child itself, but still,

...creepy
posted by Blasdelb at 11:01 AM on December 5, 2015 [1 favorite]


Ha ha ha, you have no idea how many discussions at work contain with "We can just get a [SUBSTRATE]ase from industry and engineer it to be heat-stable" like that is an approach that has ever worked for us. *sigh* Guys, it is not as trivial as you think. Remember [PROJECT MARYR WORKED ON FOR TWO FUCKING YEARS]? *grumble grumble* Yeah, yeah, I'll go run more assays
posted by maryr at 11:09 AM on December 5, 2015 [7 favorites]


Well, I guess compared to the average MeFite I'm a gung ho transhumanist.

The passage above from Stephen Pinker is very important to keep in mind in this debate. The human genome is pretty well honed (so is pretty much any genome for that matter), and the idea that we could just flip a few genes and make people better/faster/stronger is pretty unrealistic.

At the same time, there are well known diseases that could, from what I understand, be edited out pretty easily. This includes the one that has killed/almost killed several members of my family, so I always get a bit miffed when people apprently find these questions so easy. I don't like the idea of consigning people to suffering due to gut feelings about the sacredness of the genome. Don't get me started on people who seem to think that people with such diseases have an important outlook on life.
posted by Alex404 at 11:20 AM on December 5, 2015 [4 favorites]


You and me both Alex404. Bring it on.
posted by Justinian at 11:22 AM on December 5, 2015 [1 favorite]


I think the first limitation should be to focus on curing disease in preference to other modifications. There are lots of potentially unexpected side effects to enhancing humans. For example, if you tweaked the genes related to producing HGH and you raised a generation that was a foot taller, that of how that would affect everything from food consumption to the size of airline seats.
posted by CheeseDigestsAll at 11:24 AM on December 5, 2015


To be clear, my problem with Stephen Pinker is not that he wants to cure diseases. Curing diseases is great, and genetic engineering is obviously a promising way to do so. My problem with Pinker is that he doesn't think bioethicists even have a place in the conversation. He is firmly convinced that a) nothing bad will ever come of manipulating the human genome and/or b) anything bad that does come of manipulating the human genome will be minor and totally worth it because of all the good it will do. In either case, he thinks we shouldn't even discuss the ethics of research and that placing any kind of ethical restrictions on research is actually ethically wrong. As a biologist who tries to do ethical research and thinks that it is helpful to have guidelines for ethical research, that really pisses me off.
posted by hydropsyche at 11:32 AM on December 5, 2015 [5 favorites]


You know that thing where bananas are at risk of being 99% wiped out because we selectively bred one single specific type of banana that has no resistance to a certain type of pathogen? That happens so often with modern large-scale farming, because no one thinks it's more valuable to maintain genetic diversity than to ensure a consistent product.

So um, good luck, human race!
posted by showbiz_liz at 11:51 AM on December 5, 2015 [3 favorites]


You know that thing where bananas are at risk of being 99% wiped out because we selectively bred one single specific type of banana that has no resistance to a certain type of pathogen? That happens so often with modern large-scale farming, because no one thinks it's more valuable to maintain genetic diversity than to ensure a consistent product.
What edible bananas are is often breathlessly reported by the media but not often well understood. The homogeneity of bananas are an inherent part of what makes bananas edible, if bananas had sex, we couldn't eat them.

Modern bananas are a really cool application of genetics that has practically invented the world's most popular fruit, turning a starchy thing with giant spiky seeds into something so perfect that it convinced Kirk Cameron that the fruit was made by his God. It turns out that you can breed two types of wild inedible banana trees with different even numbers of chromosomes together to create a new tree with an odd number of chromosomes incapable of producing viable sex cells - making a sterile banana tree that doesn't produce seeds or get starchy. Banana trees don't need to have sex to make offspring so long as there are humans around to propagate them asexually from offshoots, but Cavendish bananas are going to eventually go extinct at the current rate because we suddenly run into the problem of having created a sweet tree that we can't easily diversify having imposed the sterility that makes bananas edible. Thus hobbled banana trees incapable of competing in evolutionary arms races with their pathogens get outpaced, but so long as banana research is funded and maintain appropriate economic structures capable of handling the biological challenges we can compete for them through careful quarantine and by switching out the type of banana we eat every 60-100 years.

Of course we could also figure out what molecular weapons banana trees need to fight current diseases and then use genetic engineering to arm them.
posted by Blasdelb at 12:23 PM on December 5, 2015 [9 favorites]


This is highly unlikely — a relic of the early 1990s, when people thought there was “a gene for” this or that talent. We now know that heritable psychological traits, such as intelligence and personality, are the product of hundreds or thousands of genes, each with a tiny effect. And many genes have multiple effects, some of them harmful, such as an increased risk of neurological disease or cancer.With each enhancement providing a trifling benefit and a non-negligible risk, and with the editing process itself imposing risks, it’s unlikely that today’s morbidly risk-averse helicopter parents will take a chance at enhancing a child.

This "relax, we'll never make genetic superhumans because it's way too hard" seems naive or disingenuous given how much CRISPR itself seems like an implausible plot device from a science-fiction novel.
posted by straight at 12:33 PM on December 5, 2015 [3 favorites]


Church: This is similar to asking, “Who currently gets to decide about many interventions during child development?” such as fetal surgery, genetic counseling, vaccines and education. The answer is physicians, parents, and society. The term “hubris” seems dismissive rather than encouraging deep exploration of exemplary cases.

This is the kind of smart-stupid answer that to me confirms the existence of false consciousness. I'd love to tell him he's the one in need of an educational intervention.
posted by polymodus at 1:30 PM on December 5, 2015 [1 favorite]


Metafilter: if bananas had sex, we couldn't eat them.
posted by sammyo at 2:40 PM on December 5, 2015 [3 favorites]


Has the argument been presented that we need legitimate research to keep up with the pirates? That is, someone will do the science and engineering (ahem, that Chinese cloning factory in the news). Without a stable community of the most ethical scientists keeping the state of the art published and the widest range of doctors understanding and being involved in the process we'll get super humans from the dark alleys of the research community.

It's going to happen. Just by who and how.
posted by sammyo at 2:46 PM on December 5, 2015 [5 favorites]


There already are gene-edited cattle on the ground. Ideally, we want to make the edits in the germ line so that they're heritable. The big question is how the regulators will rule. Cloned animals cannot enter the food chain in the US, so it's better-than-even odds that gene-edited animals will be problematic.
That happens so often with modern large-scale farming, because no one thinks it's more valuable to maintain genetic diversity than to ensure a consistent product.
That is not an accurate description of modern animal breeding. Diversity is very commonly discussed by both farmers and scientists. Clearly consistency is important, but the value of heterozygosity in livestock populations is well understood.
posted by wintermind at 2:50 PM on December 5, 2015 [1 favorite]


"Has the argument been presented that we need legitimate research to keep up with the pirates? That is, someone will do the science and engineering (ahem, that Chinese cloning factory in the news). Without a stable community of the most ethical scientists keeping the state of the art published and the widest range of doctors understanding and being involved in the process we'll get super humans from the dark alleys of the research community."
George Church has been, somewhat controversially, making this exact point here and elsewhere. It probably wouldn't be in China, whose scientific community has been very conspicuously a part of this global conversation and is if anything more effectively self-policing than many western communities. For example the Huang lab at Sun Yat-sen University in Guangzhou does gene-function research and is very much not a cloning factory, but it probably would be somewhere.
posted by Blasdelb at 3:39 PM on December 5, 2015


Dear Lord, they did not just use 'Crisper' and 'human embryos' in the same sentence, did they?
posted by sexyrobot at 7:34 PM on December 5, 2015


polymodus, I don't understanding your ascribing "false consciousness" to Dr. Church. I took his point to be "Hey, the same people making other choices about medicine will be making the call when it comes to gene editing. And, btw, 'hubris' is a pejorative word to throw around and unhelpful in moving the discussion forward." How is he wrong on any of that or proof that he is poerating under some sort of illusion about the true nature of things (that apparently you have access to...unhubristically of course)?

Hubris is always negative. And it isn't just pride or excessive arrogance--it is the pride that goeth before the fall--since the Greek tragedies hubris has been used to describe those who sow the seeds of their own downfall in their arrogance.

The most visible use of hubris in recent years in the academy is as the title of Kershaw's first volume of his two-part Hitler biography. That is what the word hubris is all about. Lobbing it at people who spend a ton of time explaining what they are doing in science, while being at the forefront of their fields, as Church is... that is just head-shakingingly wrong to me.

I suppose it could also be a little bit of a shot across the bow to Collins, who is an evangelical Christian as well as the head of the NIH. Maybe hubris, which was also about offending the gods, sounded a little bit too much like an injection of Collins' religiosity in something that should ave no "gods" involved.

But maybe you are using false consciousness in a novel way?
posted by Cassford at 11:07 PM on December 5, 2015


Faint of Butt: "God, schmod, I want my monkey-man!"

No. No monkey man for you.
posted by schmod at 8:11 AM on December 6, 2015 [1 favorite]


I guess you all missed the memo. If you are hearing about it, it is done, it has been in the works for at least a decade. China is doing exactly what it wants to, we are either leading or following suit. Death spiral.
posted by Oyéah at 9:07 AM on December 6, 2015


Interesting that we were just discussing non-sexual monoculture bananas, because they are in the news today.
posted by eye of newt at 10:39 AM on December 6, 2015


At the same time, there are well known diseases that could, from what I understand, be edited out pretty easily.

This is where the heartbeat hits the wall, so to speak. I happen to have stumbled into a very good health plan, which put me in line for a stem cell transplant, and several other front-line medical procedures, all of which were extremely expensive, and without which I would not be alive today. From this perspective, it wasn't (the availability of) the medical procedure, but the insurance structure, that saved my life. I don't believe my case represents a broad demographic.

My (layman's) view doesn't fault the advancement of science. If the argument is that the patenting process empowers research, then my question would be: how could we link these advancements to those individuals who may benefit from them? Shall we define them by their health insurance? If the procedure was like, say, a vaccination that anybody could afford to choose, then perhaps the patenting issues would be inconsequential.

Research is one organ of our economic system--a many-legged creature with no soul. It sucks up megabucks the way we humans breathe air. That's the nature of the beast. Somebody has to pay to keep it operating. We do not live in the Star Trek universe. I'm in a position to see cancer vaccinations on the medical horizon, but I just saw "too big to fail" demonstrate how our economic system defines the consumer. Without some revision, it seems to me that every time we add another leg to the creature we make it that much harder to attach human (as well as economic) value.

Maybe the individual researcher ought to have some agency other than as a gunslinger for the corporation. I can't imagine how that might work. That argument, perhaps, belongs on another page in the Blue.

Hang on, I gotta go Chiquita my banana.
posted by mule98J at 12:22 PM on December 6, 2015


Research is one organ of our economic system--a many-legged creature with no soul. It sucks up megabucks the way we humans breathe air.

Big pharmaceutical companies are spending far more on marketing than research.
posted by mittens at 1:02 PM on December 6, 2015 [1 favorite]


I think as this technology gets better, there's going to be more fighting about it. Right now everyone agrees that we don't know enough to do the things people want with it. But the time is going to come when we can genetically enhance children, and half of us are going to, and the other half will not. Then, not now, is when it gets hairy.
posted by corb at 2:27 PM on December 6, 2015


Oyéah: I guess you all missed the memo. If you are hearing about it, it is done, it has been in the works for at least a decade. China is doing exactly what it wants to, we are either leading or following suit. Death spiral.
In this case the Chinese scientific establishment has communicated super clearly that what it wants is to meaningfully contribute to and then follow a global consensus. Casually racist knee-jerk Sinophobia like this should have no place here.
Oyéah: All these posturing, eloquent hawkers. One protects a theology, one protects a budding industry.
And all that this pathetically paralyzing cynicism protects is the position of a head firmly wedged up its cognate ass, wiggling around, at worst harmless to anyone or anything.
posted by Blasdelb at 4:58 PM on December 6, 2015 [1 favorite]


Read again, no Sinopbobia. It would be a mistake to think china lines up behind consensus. I don't mind that China is an independent entity. But we are a competitive species which cooperates at times and then shifts loyalty to survival mode when deemed necessary. Genetic research is a well funded race, egged on by acute need in some quarters, and then all sorts of the usual in others.

It is irresistibly tempting stuff that carries innate promise. Just like everything else that should be sacred, the integrity of billions of years of evolution is negotiable.
posted by Oyéah at 6:23 PM on December 6, 2015


But the time is going to come when we can genetically enhance children

I feel like I may be over-grarring in the thread at this point, so forgive me if this is totally irrational, but doesn't it seem like the problem is exactly the opposite? It's not that genetically enhancing children is an automatic evil...it's that we're going to have the ability to bring the tragedy of birth defects to an (almost) end, worldwide...but we probably won't do it. Again, I point to Church up there at the top, who mentions consanguineous marriage...but those are the couples who will not be able to afford genetic treatment for their children, any more than they are able to afford proper maternal/fetal care right now. We are already screwing up access to so much basic medicine, that holding out the promise of science-fiction medicine almost seems cruel. Poor kids will continue to be born with genetic defects, will continue to suffer and die.

Which isn't the researchers' fault, I should say. My grar is not with them, except when they have painfully idealized versions of health care that don't take into account what happens when business enters the mix, which is why I think the Church quotes bug me so much, as they seem premised on a world very different from the one I live in.
posted by mittens at 6:26 PM on December 6, 2015 [2 favorites]


It's not that genetically enhancing children is an automatic evil...it's that we're going to have the ability to bring the tragedy of birth defects to an (almost) end, worldwide...but we probably won't do it.

I think your point is totally valid, and for me is the real concern about these technologies. At the same time, I am generally an optimist about technology, so although I wouldn't dismiss your points, I can at least play devil's advocate.

Ignoring the fact that these technologies will probably only get cheaper with time, it's important not to forget that promoting the health of a population isn't just an act of charity, but also just makes economic sense. The reason why we have healthcare is because after all the resources that have gone into training an adult human to be a productive member of modern society, it doesn't make sense to let them die of preventable diseases.

Being able to edit out diseases from the germ line makes way more economic sense than waiting for the disease to hit the carrier. Of course wealthy people, or at least citizens of wealthy countries, will have access to this stuff first. Over time though I see no reason why this can't make it to all corners of the world.

So yah, as far as your point about us screwing up the availabilty of medicine is concerned... on the whole, I'm not inclined to agree. In some sense it all comes down to free market capitalism. I personally think that moderated capitalism is doing a reasonably good job of spreading wealth around the world, and will continue to do so, provided it doesn't destroy the environment, which is the only thing that scares me when I think about the future.
posted by Alex404 at 12:48 AM on December 7, 2015


-CRISPR: Safe and Effective?
-MIT, Broad scientists overcome key CRISPR-Cas9 genome editing hurdle
-Using CRISPR genome editing to define the ~2000 essential human genes
-Open Season Is Seen in Gene Editing of Animals
Dr. Whitelaw has changed three genes in domesticated pigs vulnerable to African swine fever, which can devastate herds, to resemble those from wild pigs that are resistant to the disease. He is now breeding them to put them to the test.

With a tool called Talens, Recombinetics says it has created gene-edited pigs that can be fattened with less food and Brazilian beef cattle that grow large muscles, yielding more meat that may also be more tender. Others are working on chickens that produce only females for egg-laying and cattle that produce only males, since females are less efficient at converting feed to muscle.

Chinese researchers have produced meatier cashmere goats that also conveniently grow longer hair for soft sweaters, miniature pigs lacking a growth gene to be sold as novelty pets and bulky beagles lacking a muscle-inhibiting gene, an edit that could make for faster dogs.

Using the most powerful of the new tools, called Crispr-Cas9, in pursuit of treatments for human disease, researchers are also altering pigs in hopes of making them grow human organs and creating “gene drives” that would ensure that the edit to make mosquitoes malaria-proof, for instance, would spread through the whole population...

Today’s chickens, for instance, produce nearly 80 percent more meat for the same amount of feed as the chickens of the 1950s; if chicken breeders had had access to genome technology over that time, said John Hickey, a quantitative geneticist and a co-author of the paper, farmers would have been able to achieve that increase and also be able to grow chickens on half the land.

Others say the technology could benefit human health. The National Science Foundation is underwriting an effort to create dairy cattle that can resist a parasite that causes sleeping sickness in sub-Saharan Africa, a blight often treated with an antimicrobial drug that ended up making its way into the meat consumed by humans.

Several projects underway to edit genetic resistance to a variety of diseases in livestock could theoretically reduce the overuse of antibiotics, which has made it harder to treat human bacterial infections. With funds from the United States Department of Agriculture, Bhanu Telugu, a University of Maryland researcher, is trying to design pigs so they can no longer serve as a reservoir for the flu virus. He argues for genome editing on behalf of animal health, too. “If we know we can eliminate the disease and we don’t, it is in my mind animal cruelty,” he said.
uplift! (and/or planet of the apes, pinky and the brain, mrs. frisby and the rats of NIMH ;)
posted by kliuless at 9:06 PM on December 7, 2015 [1 favorite]


Zheng's going to speak at an alumni event I was wanted to go to on Thursday, but I have to go to my company Holiday party instead, argl.
posted by maryr at 8:21 AM on December 8, 2015


Motherboard: Someone Will Eventually Use CRISPR to Try to Make a Dragon or Unicorn
"Basic physics will almost certainly combine with biological constraints to prevent the creation of flying dragons or fire-breathing dragons—but a very large reptile that looks at least somewhat like the European or Asian dragon (perhaps even with flappable if not flyable wings) could be someones target of opportunity," [Greely and Charo] write.
posted by Rangi at 8:31 AM on December 8, 2015


Would you please stop making my eyes roll? I am getting a headache. I may go stick my head in the crisper.
posted by maryr at 3:15 PM on December 8, 2015


so someone asks: "How long do you think it will probably take for someone to create babies who will grow up to be significantly smarter than any non-genetically engineered human has ever been? Is the answer closer to 10 or 30 years?"

and hsu responds:
IF gene editing continues to improve at this rate, then the main bottleneck will be the sample size of good (cognitive, genotype) data sets necessary to extract the genetic architecture. IF we can get to ~ millions (very plausible in 5-10 years), then we can extract SNPs accounting for most of the genetic variance. Editing would then allow many SDs of improvement. So 10 years is not impossible, and in 30 years the super-geniuses would be adults ... But who will have the guts to try it? There could easily be a decade or two lag between when it first becomes possible and when it is actually attempted.

More modest advances are likely via IVF selection (driven by self-interested parents), which then raise confidence levels in our ability to do genomic prediction. Plenty of parents want to make sure their kid is above average, or to select against negative fluctuations. Not so many want a historical super-genius via a riskier path.
some say (for example ;) nurture > nature when it comes to intelligence, that "advances in education can influence average intelligence significantly more than either genetic engineering, genetic screening, etc." and while i think that's true at the group level over the near term, i wonder about individuals on the margin who display phenotypic 'genius' -- glial cells? -- and whether they can be selected for (whatever!) over the long run... beyond (simple!) assortative mating :P

in any event, ramez naam, for one, doesn't worry too much about a gattaca-like future: "in general, parents are risk averse when their children are involved. Using gene editing to reduce the risk of disease is quite different than taking on new risks in an effort to boost a trait like height or IQ. That's even more true when it takes dozens or hundreds of genetic tweaks to make even a relatively small change in those traits – and when every genetic tweak adds to the risk of an error."

anyway that just makes me more intrigued by 'open season' on gene editing in other animals, plants, etc. where other species have their genomes directed/mutated for (SCIENCE) better or worse. that is, while animal experimentation for human convenience is as morally fraught as ever, the calculus still remains -- if perhaps shifting somewhat -- that if it lowers human suffering then some amount of animal suffering would be acceptable.

it strikes me tho that with the bad may come some good; individual animals by paying the price -- think of the life of the rats of NIMH -- stand to reap benefits for their group as a whole to the extent that selected traits -- strength, constitution, dexterity, intelligence, wisdom, charisma -- are viewed as desirable (by whom? us or others of their species?) so maybe the relevant question might be more like: 'how long do you think it will probably take for someone to create mice who are significantly smarter than any non-genetically engineered mouse has ever been?'

but then where do the boundaries -- "mice with the human DNA had brains that were noticeably larger" -- lie? i keep thinking about freeman dyson's admonition: "Now, after three billion years, the Darwinian interlude is over. It was an interlude between two periods of horizontal gene transfer. The epoch of Darwinian evolution based on competition between species ended about ten thousand years ago, when a single species, Homo sapiens, began to dominate and reorganize the biosphere... And now, as Homo sapiens domesticates the new biotechnology, we are reviving the ancient pre-Darwinian practice of horizontal gene transfer, moving genes easily from microbes to plants and animals, blurring the boundaries between species. We are moving rapidly into the post-Darwinian era."
posted by kliuless at 5:25 PM on December 8, 2015




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