Let’s Talk Human Engineering

Experts continue to discuss the logistics and ethical considerations of editing human genomes at a historic meeting in Washington, DC. 

By | December 3, 2015

Researchers gather in the National Academy of Sciences auditorium for first day of the Human Gene Editing Summit on December 1.JEF AKSTMore than 400 scientists, bioethicists, and historians from 20 countries on 6 continents have gathered this week in Washington, DC, for the Human Gene Editing Summit. The attendees are a veritable who’s who of genome editing: Jennifer Doudna of the University of California, Berkeley, Emmanuelle Charpentier of Max Planck Institute for Infection Biology, and Feng Zhang of the Broad Institute of MIT and Harvard—the three discoverers of the CRISPR-Cas9 system’s utility in gene editing—plus dozens of other big names in genome science. Cal Tech’s David Baltimore along with the heads of the four national societies hosting the meeting (US National Academy of Sciences, US National Academy of Medicine, Chinese Academy of Sciences, and the U.K.’s Royal Society) provided opening remarks on Tuesday (December 1). And as I sat stage right in the NAS auditorium, I noticed the unmistakable rear profile of Harvard Medical School’s George Church three rows in front of me.

Church was scheduled to speak at a session later that afternoon about the application of CRISPR and other new precision gene editing techniques to the human germline—a hot-button topic since April, when a Chinese group published it had successfully modified the genomes of human embryos, and the National Institutes of Health (NIH) said it would not fund such research. Then in September, the U.S./U.K.-based Hinxton Group, an international consortium of scientists, policy experts, and bioethicists, said it supported the use of genetic editing in human embryos for limited applications in research and medicine.  

But the debate continues, as opponents of the technology’s use in the human germline cite the near-term feasibility of “designer babies.” Three different speakers referenced a particularly chilling work of literature, starting with Baltimore, who chaired the Summit Planning Committee. “Aldous Huxley, in his book Brave New World, imagined a society built on selection of people to fill particular roles in society with environmental manipulation to control the social mobility and behavior of the population,” he said in his opening remarks on Tuesday morning (December 1). “The warning implicit in his book is one that we should take to heart as we face the prospect of this new and powerful means to control the nature of the human population.”

Some speakers said the controversy surrounding gene editing was reminiscent of the hubbub over recombinant DNA in the 1970s, when researchers first learned how to cut and paste genetic code, albeit very inefficiently (with a one-in-a-million chance of introducing desired DNA in a desired location). Some even drew parallels between the Human Gene Editing Summit and the 1975 Asilomar Conference on ensuring the safety of recombinant DNA techniques and other biotechnology, where a group of experts wrote regulatory guidelines that still affect the development of new technologies today.

But later sessions on the science underlying the new gene-editing techniques engendered excitement that overshadowed much of the concern expressed in earlier talks. Precision gene editing is cheap, efficient, and easy to use, said Charpentier; it can edit multiple genes at once, and it can make specific changes to the epigenome in addition to the DNA sequence. “It’s a very powerful technology.”

There’s still plenty of room for improvement, however. While CRISPR’s precision represents a vast improvement on the crude methods of the past, it still has off-target effects that pose problems for patient safety and the efficiency of CRISPR research. But researchers are already working on the problem. As Zhang attended the summit in DC, Science was releasing his group’s demonstration of one option to improve the specificity of the system: alter Cas9’s charge so it binds less tightly to mismatched DNA.

Researchers at the summit also discussed the need to continue exploring other CRISPR systems, a natural component of bacterial defense against viral infections. In the last few months, scientists have uncovered four new Cas proteins that may expand the gene editing toolbox. Charpentier and others added that they must begin to develop and refine efficient delivery methods to bring the CRISPR components to their target genes in the nucleus of the cell.

Once the kinks are worked out, the question will be: “How if at all do we as a society want to use this capability?” Baltimore said. When it comes to editing somatic cells, Harvard Medical School’s George Daley predicted the “imminent” use of CRISPR/Cas9 in gene therapies, which are rapidly approaching the market. Researchers could edit the HIV receptor gene CCR5 to make T cells that are resistant to infection, for example, or correct mutated genes that are causing disease—therapies that are already progressing through clinical trials based on other, less-efficient, gene-editing techniques.

When it comes to germline editing—the more ethically vexing application of CRISPR and other precision gene editors—Daley described a spectrum of moral acceptability. Most researchers and clinicians agree that “designer babies,” with parents able to select detailed physical traits, improve intelligence, or extend the lifespan of their children, is unethical and crosses an unspoken line. At the same time, many strongly support the eventual use of CRISPR to correct disease-causing mutations in embryos. Regulation of the technology, whether it be through governmental guidance or legislation, will likely land somewhere in the middle.

Despite the challenges that lie ahead, the researchers gathered at the Human Gene Editing Summit, which continues through today (December 3), are excited to see what the future holds. “We could be on the cusp of a new era in human history,” Baltimore said. “Although gene editing is in its infancy today, it is likely that the pressure to use gene editing will increase in time, and the actions we take now will guide us into the future.” 

Update (December 4): Members of the Organizing Committee for the International Summit on Gene Editing yesterday released their official report from the meeting. While they support the integration of CRISPR and other precision gene editing techniques for somatic cellbased gene therapies that are “intended to affect only the individual who receives them,” they conclude that [i]t 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.”

Editor’s note (December 31): After this article was published, George Church contacted The Scientist to discuss the way the media and prize-awarding committees have portrayed contributions to CRISPR

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Avatar of: nslavov

nslavov

Posts: 9

December 3, 2015

Successful germline engineering requires (1) a technology for editing DNA safely and (2) knowledge of what to edit and how to edit based on understanding the underlying biology. We are approaching (1), which is the easier part; we do not have (2), and we are far from achieving it for most desired "edits".   A huge hurdle to germline engineering is that, beyond a few simple cases, our understanding does not allow achieving desired effects while avoiding unintended consequences. Unlike DNA sequencing, silicon chips and DNA editing, our understanding of complex combinatorial multi-gene interactions has made very little progress over the last few decades. Until we made more progress and understand gene interactions and the respective health outcomes better, germline engineering is akin to medieval quack therapies based the technology to bleed patients and feed them various concoctions but with very limited understanding of the medical consequences. We can fix the unintended consequences later and then fix the unintended consequences from the fixing, and we will keep trying!    Nikolai Slavov 
Avatar of: PastToTheFuture

PastToTheFuture

Posts: 69

December 3, 2015

It's all about context.

Human Gene editing like this relates to survival. I assume that is the purpose of it. Anytime you mention human survival, moral instincts far older than intellect, suddenly come to attention. Ethics are fine, but they speak to the mind. If you do not have a moral context for this technology, if you cannot speak to the heart, you could end up with a battle over this technology as nasty as the one about abortion. Maybe worse.

So why do you want to do this? Genes are about adapting to one's environment to survive. Well, that certainly is rapidly changing. Am I to assume that you have a detailed understanding of how that is changing and how you can adapt genetically? Of course, humanity's primary method of adaptation is strategic, so I'll assume you have a clear understanding of that as well.

Then again, CRISPR is simply not likely to be the method used. Look at the cost equation - genetic analysyis, germ cloning, CRISPR technology, gentic analysis of result, then implantation. Heck, there is a far cheaper way to do it and it has been done already. ... and the moral and ethical issues are less ... For all its amazing potential, CRISPR is a technology that I see being very rarely used for humans in the future. 

Besides, what do you want to accomplish with it? Remove some viral genes. Good idea. Maybe fix an inherited disease. Good idea. Create a new genetic sequence... Well now, that is another issue. Besides the cautions obviously required, why. What do you want to make? I've asked a lot of people and no one has had an answer. ... I sort of lean towards biologicla BlueTooth, but that's another story. 

Well, we're talking genes here, Heredity, the Second Forbidden Question in Science (just ask James Watson). I mean, come on, you've obviously thought of the social implications of this. What about race then? Also, the ecological implications are obvious too, aren't they. Humans left our last stable ecology when we started agriculture and cities. We need a new stable ecology to survive in. We will need to adapt genetically and strategically. Can CRISPR help us with that? 

Oh, then there is the elephant in the room. It's not just that we need to adapt to a new ecology, also what we are calling Human Progress is the removal of Natural Selection. While at the same time we've gone to smaller families and older parents. Kablooy. It's the shelf life of the human genome and cheap genetic sequencing has revealed it. If you pick any "at risk" group with health problems and do a genetic sequencing on them, guess what, you find that around 50% of the problem is due to "de novo" mutations. Sorry, CRISPR can never keep up. 

So, you need to solve the problems of natural genetic deterioration, the heredity problem and the problem of genetic adaptation to a new ecology. ... along with a number of other problems, like figuring out just what that new ecology is. I know, read "Transition To A New Human Ecology" at Amazon. It explains it all and why CRISPR is not near as economical as an alternative. Plus, as a freeby bonus, it includes a complete moral context so that it can talk to the head and the heart so people don't start that embarassing frothing at the mouth. The dangers are greater than you know, but the potentials are as great as human aspiration.

 

 

Avatar of: Ferez

Ferez

Posts: 12

December 4, 2015

The CrispoR/Cas9 concern is a non-issue! It is rendered so by the collection of contemporary debates on similar issues in the Physical and Life Sciences, the record of Humankind in dealing with all the positive and negative dimensions of the historical progression of civilization and the many evolutionary answers to these issues that have always existed! Not only does the current biotechnolgy revolution, but also such things as mitochondrial and chloroplast biogenesis, Dr. Barbara MccLintock's mobile eukaryotic genome, trans species integrants of Azotobacter plasmids and Circulating Tumor DNAs in humans have reduced the similar concerns of Recombinant DNA expressed at Asilomar to superstitions. The continuing CrispR/Cas9 debate distracts from the historical obligations of humankind to those millions who with an errant turn of the genetic dice will come down with intractable diseases. Diseases with pathologies that have consequences worse than those inflicted by Death Camps and that cost hundreds of trillions of dollars per annum - in perpetuity!

Because all of these contemporary methods, including OMICs (CrispR/Cas9) and Stem cell therapies, are retrospective therapeutic interventions they are not preemptive of the mutational causes of diseases states, will not stop new cases from arising and do not go far enough! These preemptive therapies can be developed by systematizing and controlling the networks of genes maintaining the human genome through a combination of Evolutionary and Mouse Genetics with OMICs.

The Crispr/Cas9 debate distracts from the primary obligation of Humankind to ameliorate the condition of those millions who will come down with cancers, neurodegenerative and developmental diseases - for which immune based methods are only a distant hope that have yet to emerge from the the great Evolutionary Adaptabilities that are put in play!  Again they will do nothing to prevent new cases! All of the concerns of this meeting have been as reasonably met in History as is possible! The participants should set aside this very public Angst and concentrate their efforts on the more immediate necessities! They will find that their concerns have been addressed before in the links that are copied below.

Respectfully yours,

Ferez S. Nallaseth, MS, PhD

(1) Do we want this - gene editing on human embryos? Do we have the right to deny recourse?

https://www.linkedin.com/pulse/do-we-want-gene-editing-human-embryos-have-right-nallaseth-ph-d-?trk=mp-reader-card

(2) Allelic variation - CrispR-Cas9 Vs genocide: concerns balanced with human costs!

https://www.linkedin.com/pulse/allelic-variation-crispr-cas9-vs-genocide-concerns-nallaseth-ph-d-?trk=mp-reader-card

(3) Darwin could not possibly have known! 140 years on we do and can!

https://www.linkedin.com/pulse/20141208002114-48493309-darwin-could-not-possibly-have-known-140-years-on-we-do-and-can?trk=mp-reader-card

 

 

Avatar of: PastToTheFuture

PastToTheFuture

Posts: 69

Replied to a comment from Ferez made on December 4, 2015

December 5, 2015

Uh, that was pretty complicated, but I think what you were saying is that we should treat the symptoms of the inevitable diseases... I really think that we can prevent them using artificial selection. Phreventitive medicine is better than curative.

Avatar of: jeenious

jeenious

Posts: 43

January 15, 2016

We would do well to have much more dialogue concerning benefits of learning how to gene edit, if only for benefit of better informing innocent, benign medically productives spin-offs.

Surely pre-fertilization management of conceptions would surely be far preferable to zygote altering procedures.

But even after fertilization it's less difficult to condemn procedures that prevent  development that will be certain to result in hideously deformation or uncorrectable brain abnormalities, or pre-dispositions of babies to suffer horridly or die early and miserable deaths.

At some level hardly anyone would agree that we should make it a goal to produce superior athletes, geniuses or desirable personalities.  But if we could prevent births of infants highly predisposed to develop cancers, type one diabetes, schizophrenia, violent behavior... how different is that from doing surgical or chemotherapy on those born with likelihood of having these problems.  If it is not "playing God" to treat such problems after they are manifest, how much worse is it to prevent such genes from being allowed to play a part in fertilization feforehand.

Yes, it's scary.  And, yes, its hard to find commonalities of agreement on where to draw the lines.  But the study of what goes on with genes and reproductions needs to advance.  And the dialogue needs to be engaged in, as broadly as possible, and indefinitely.

Avatar of: jeenious

jeenious

Posts: 43

January 15, 2016

We would do well to have much more dialogue concerning benefits of learning how to gene edit, if only for benefit of better informing innocent, benign medically productive spin-offs.

Surely pre-fertilization management of conceptions would be far preferable to zygote altering procedures, if that could be managed.  But that is only feasible for motivated volunteers.

But even after fertilization it's less difficult to condemn procedures that prevent  development that will be certain to result in hideous deformations or uncorrectable brain abnormalities, or pre-dispositions of babies to suffer horridly, or to die early and miserable deaths.

At some level hardly anyone would agree that we should make it a goal to produce superior athletes, geniuses or desirable personalities.  But if we could prevent births of infants highly predisposed to develop cancers, type one diabetes, schizophrenia, violent behavior... how different is that from doing surgical or chemotherapy procedures to intercede in such problems only after they are manifest.

If it is not "playing God" to treat such problems after they present, then how much worse is it to prevent such genes from being allowed to play a part in fertilizations feforehand, or if that is not feasible, to intrude as necessary to correct them, if we can in a zygote.

Yes, the whole subject is scary.  And, yes, its hard to find commonalities of agreement on where to draw the lines.  But the study of what goes on with genes and reproductions needs to continue to be advanced.  And the dialogue about where it is ethical and reasonable and human to venture... this dialogue needs to be engaged in, as broadly as possible, and indefinitely.

Avatar of: jeenious

jeenious

Posts: 43

January 15, 2016

We would do well to have much more dialogue concerning benefits of learning how to gene edit, if only for benefit of better informing innocent, benign medically productive spin-offs.

Surely pre-fertilization management of conceptions would be far preferable to zygote altering procedures, if that could be managed.  But that is only feasible for motivated volunteers.

But even after fertilization it's less difficult to condemn procedures that prevent  development that will be certain to result in hideous deformations or uncorrectable brain abnormalities, or pre-dispositions of babies to suffer horridly, or to die early and miserable deaths.

At some level hardly anyone would agree that we should make it a goal to produce superior athletes, geniuses or desirable personalities.  But if we could prevent births of infants highly predisposed to develop cancers, type one diabetes, schizophrenia, violent behavior... how different is that from doing surgical or chemotherapy procedures to intercede in such problems only after they are manifest.

If it is not "playing God" to treat such problems after they present, then how much worse is it to prevent such genes from being allowed to play a part in fertilizations feforehand, or if that is not feasible, to intrude as necessary to correct them, if we can in a zygote.

Yes, the whole subject is scary.  And, yes, it's hard to find commonalities of agreement on where to draw the lines.  But the study of what goes on with genes and reproductions, and how we might humanely and mercifully intercede appropriately and in appropriate ways... needs to continue to be advanced.  And the dialogue about where it is ethical and reasonable and humane to venture... this dialogue needs to be engaged in, as broadly as possible, and indefinitely.

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