Update on clinical studies of human gene editing

The January 22 edition of The Wall Street Journal carried an article the essential message of which was, “the Chinese are ahead of us in gene editing.”  Specifically, more human clinical trials are active in China than in the US using gene editing in some form to treat people with specific diseases.  Some of these trials use the “hot, new” CRISPR-Cas9 approach to gene editing.  Almost all of the active ones are in China, although one has recently been approved by regulators to begin in the U.S., at the University of Pennsylvania.  That one appears not yet to be recruiting patients.  In most of these “CRISPR” trials, cells are removed from a patient’s body, altered in the laboratory to make them more likely to treat the disease in question (in this case read: attack a cancer), and injected back into the patient.  They are thus variations on a 30-or-so-year-old approach of using cells that have been modified in some way to treat cancer.

The difference here is that the cells have their genes edited, and that raises potential safety risks, such as, what happens if the wrong genes are “edited,” and the altered cells go nuts and do something undesirable?  Because of this, human trials of gene editing in the U.S. are closely regulated, including having to pass scientific and safety review by the “RAC” (that’s for “Recombinant DNA Advisory Committee,” in case the acronym made any of you think of the Spanish Inquisition…then again, I have had researchers who have had to go through it suggest that the analogy is apt…).

The RAC was established back in the late 1970’s when drugs started being made with recombinant DNA, and trials of gene therapy using genes inserted into viruses were conducted.  A famous case of that work going awry raised concerns about oversight, and slowed things down substantially.  And as it stands now, the U.S. regulatory process for this work is cumbersome.  In China, not so much—a local ethics review board looks at a proposal, and off they go.  The WSJ makes it sound like informed consent for the Chinese studies may be a bit thin, too.  U.S. experts are quoted as saying not that we need less regulation, but that they (the Chinese) need more, to bring them back to our speed.

Perhaps so.  My point here is that this work is going on.  Examples like those cited here seem to me to fall under the existing regulatory regime for human trials, and don’t pose the same sort of ethical issues as the potential for inherited gene edits—that is, editing embryos and babies.  That’s a different kettle of fish.

One Chinese CRISPR trial appears not to alter cells outside the body, but actually try to administer the genetic material to make an edit to a cervical cancer-causing gene.  That poses similar safety concerns to other gene therapy approaches, including some with “zinc finger” editing technology, like a currently-active U.S. study to treat hemophilia, a disorder in which someone has a genetic flaw that makes them susceptible to excessive bleeding and the goal is to repair the offending gene.

In considering this work, I think it’s important to distinguish use of the gene-editing approach for incremental steps to treat human disease, like the cell therapy approaches, or true “gene therapy” approaches in which a “corrected” gene is administered to a patient, from the more problematic possibility of editing individuals in ways that can be inherited.  The latter is what worries me.  I wrote about this last November 9 and November 16.   And yes, the current Chinese work should be more closely regulated.  Doubt we have any control over that.

An FDA blog post from a year ago (by the former FDA Commissioner) provides a useful, brief discussion of the FDA’s approach to regulating various applications of genetic editing.  Worth reading.

Is Your Polygenic Risk Score a Good Thing?

Back in October, Jon Holmlund wrote a blog entry regarding the popular company 23andMe and their collection of your health-related information along with your genetic material. I missed the significance of that relationship at the time. It took a recent article in Technology Review by my favorite technology writer Antonio Regalado to raise my ethical antennae. In his article, he explains the nexus of big data mining of genetic data and health information (such as is collected by 23andMe) and its future potential use to select embryos for IVF, selecting not only against polygenic diseases such as type 1 diabetes but potentially for non-diseases such as height, weight or even IQ.

Yikes.

Pre-implantation genetic diagnosis (PGD) already is used to select for particular embryos for IVF implantation that do not have genetic patterns such as cystic fibrosis or Down syndrome. Diseases that result from multiple genes (polygenic disorders) presently defy current PGD methods used to detect future diseases. Using Big Data analysis of health information compared against linked genetic data, scientists are getting better at accurate polygenic risk scores, statistical models which may more accurately ‘guess’ at an embryo’s future risk for not only juvenile diabetes but also later-in-life diseases (such as heart disease, ALS or glaucoma) or other less threatening inheritable traits (such as eye color, height or IQ) that result from multiple genes (and perhaps even environmental factors). There is confidence (hubris?) that with enough data and enough computing power, we can indeed accurately predict an embryo’s future health status and all of his or her inheritable traits. Combine that further with all of the marketing data available from Madison Avenue, and we can predict what type and color of car that embryo will buy when he or she is 35.

Ok, maybe not the color…

Seriously, companies such as Genomic Prediction would like to see IVF clinics eventually use their expanded statistical models to assist in PGD, using a proprietary technique they are calling Expanded Pre-implantation Genomic Testing (EPGT). Consider the following two quotes from Regalado’s article:

I remind my partners, “You know, if my parents had this test, I wouldn’t be here,” says [founding Genomic Prediction partner and type 1 diabetic Nathan] Treff, a prize-winning expert on diagnostic technology who is the author of more than 90 scientific papers.

For adults, risk scores [such as calculated by 23andMe] are little more than a novelty or a source of health advice they can ignore. But if the same information is generated about an embryo, it could lead to existential consequences: who will be born, and who stays in a laboratory freezer.

Regalado’s last comment is dead-on – literally. Who will be born and who stays in the freezer is another way of saying “who lives and who dies”.

Technologies such as EPGT are poised to take us further down the bioethical slope of choosing which of our children we want to live and which we choose to die. For the sake of driving this point home, let’s assume that the technology becomes essentially 100% accurate with regard to polygenic risk scoring and we can indeed determine which embryo will have any disease or trait. Since we already permit the use of single gene PGD to prevent certain genetic outcomes, should there be any limit to polygenic PGD? For instance:

(A) Should this technology be used to select against immediate life threatening illnesses only or also against immediate mentally or physically permanently crippling diseases that don’t cause death directly?

(B) Should this technology be used to select against later-in-life diseases that are life threatening at the time or also against mentally or physically crippling diseases that don’t cause death directly? (Would it make a difference if the disease occurred as a child, teenager or adult?)

(C) Should this technology be used to select against non-disease inheritable traits that society finds disadvantageous (use your imagination here)?

(D) Should this technology be used to select for inheritable traits that society finds advantageous (a slightly different question)?

Depending upon your worldview, until recently, answering Questions A through D used to be the purview of God or the random result of chance. Are we ready (and capable) to assume that responsibility? Make your decision as to where you would draw the line then review this short list of famous scientists and see how many on that short list your criteria would permit to be born.

Are you happy with that result? Would you call it good?

It would be nice to get this right since it now appears to be our call to make…

More about gene therapy and human gene editing

To my post of last week, add the case of a 44 year-old man who has received gene therapy for an inherited metabolic disease called Hunter’s syndrome. This is another example of a form of gene editing as true therapy.  That is, an existing individual is given a construct intended to edit his genes to introduce a gene that makes an enzyme that is lacking in the disease, and that causes terrible problems.  In this case, as part of a clinical trial, the construct, using a so-called “zinc finger” technique, is intended to introduce the gene into only about 1% of the patient’s liver cells.   If successful, the damage already done by the disease won’t be affected, but it’s progress may be arrested, with the potential to avoid having to have repeated, costly treatment with the missing enzyme protein itself.

Cool idea–and well within the current regulatory ethical regime.  The edit would not be inherited, and unborn humans don’t have to be sacrificed to develop the technique.  The adult patients are capable of giving informed consent.  Trials in children would come later, controlled by accepted ethical experimentation on children in clinical trials.

In a separate note, on a separate topic, Nature Biotechnology is editorializing that inherited gene editing is way behind mitochondrial replacement therapy (MRT), the “3-parent baby” approach to treating genetic problems, and will likely have limited use in the future.  Why?  Because it is likely that preimplantation genetic diagnosis (PGD) after in vitro fertilization (IVF) will be preferred to identify and give birth to babies unaffected by serious genetic disorders.  The journal editors argue that gene editing would be preferred only in those few cases where PGD cannot avoid passing on a disease–for example, in cases where it is known that all embryos from a fertilizing couple would be affected. Otherwise, the gene editing would not be worth the trouble.

MRT, on the other hand, has been studied more and is closer to being used to treat unborn humans who have diseases that MRT could treat.  Thing is, those diseases are also rare, on the order of 1000 cases per year in the US, and technically, gene editing would probably not be too useful for those.

There is a lot of talk about using a mix of gene editing and PGD to eliminate certain genetic disease from the human prospect.  I recently wrote about the Chinese government working on this.  To achieve the goal absolutely, every born human would have to be a product of IVF.

And the risk of some of the disorders is low enough that the absolute risk in any one “natural” pregnancy would be low.  So why go to the trouble of trying to eliminate the risks utterly?  (I think that’s a rhetorical question.)

The title of the editorial in question is “Humans 2.0.”  Indeed.

There’s gene therapy and there’s gene therapy

I’ve seen a number of different things described in the general press as “gene therapy.” But they are indeed different.  It’s important to be specific.

For one, there’s the situation where a set of mature human cells are obtained from the person to be treated and genetically altered outside the body to make them into a potentially useful treatment, then re-administered (by vein) to the patient.  Such is the case with so-called “CAR-T” therapy, which is well handled by current regulatory structures.  Main ethical issues: common human subject research concerns, regulation of the quality of the cells, and whether the treatment, which can be dramatically effective, is worth the high price.

Then there are situations where a diseased tissue is altered to make it normal, like the recent report of how a mutation in the skin of a boy was altered, and the repaired skin grafted back on, to spread over most of his body and replace the defective skin.  Again, way cool, well dealt with by current ethical and regulatory structures.

Or, similarly, Spark Therapeutics’ LUXTERNA, which is a gene injected into the eye to repair a defective gene causing blindness, literally restoring some sight, recently recommended for approval by an advisory committee to FDA.   Truly a gene made into a therapy.

Where the ethical issues get thorny is when one speaks of possibly editing a gene in a person–likely an unborn person very early in development; i.e., and embryo–in a way that can be inherited over generations.  I and others have discussed this recently on this blog.  See for example my post of last month (October 5).  Adherents say that there are serious diseases demanding cures, and that those who would counsel caution are obstructionists who fret too much about enhanced Olympic athletes.  (Example here, but subscription required.)  But the ethical issues are several: How safe and reliable will the technique be, and how much testing should be required before trying to birth “edited” babies?  How many embryos will have to be destroyed to perfect the approach?  How can we know whether there will be unforeseen long-term effects, after several generations?  How much should we care about that?  How will discrimination be avoided?  What are the implications for control of human reproduction–no more babies from sex? And who will decide and control that?

And–where, short of the Olympics, will it all end?  Should we try to edit genes that are known to increase cancer risk, to eliminate them from the human race?

The Hastings Center recently convened journalists to discuss some of the ethical issues with gene editing.  But even then, they are more concerned about whether there is a parental duty to “edit” the next generation.  Precautionary deliberations appeared to be limited to environmental concerns from the use of “gene drive” to spread genetic modifications rapidly through entire plant or animal species.  (Fair enough, but I’d extend the precautions to humans, where “gene drive” is not an issue.)  And, helpfully, the Hastings symposium did ask, will general press coverage necessarily be biased because reporters’ sources are the very scientists who tend to be enthusiasts?  In any event, the Center should not only do more public education events, but should make much more of the detailed content from such symposia available to the public for free, online, much as the Presidential bioethics commissions do.  As it is, we are left with their brief press releases, usually.  Thin gruel, IMHO.

Two cases of genetics ethics issues

There is an ongoing NIH-sponsored database effort called the Genotype-Tissue Expression (GTEx) project the goal of which is to collect data on genetics–not just DNA gene sequences, but also gene activity, looking at “expression,” which is reflected in the RNA that is transcribed from genes–in a wide range of human tissues.  The tissues are obtained from deceased voluntary organ donors.  The ethical issues are not unique, but representative of the challenges that our bioinformatics age present.  Organ donors’ consent to donate a broader range of tissues is not documented in advance, nor is it assumed, but, like organs, the tissue specimens must be collected soon after death to prevent decay from compromising their usefulness.  That means that consent for the tissue donation has to be obtained from grieving survivors, immediately after a loved one’s death that is often unexpected and shocking, and duress is unavoidable.  The donation request comes out of the blue and donors’ survivors often don’t recall what they agreed to.  The genetic expression information is usually not provided to the donors’ families, a situation that seems to be less tenable with the passage of time and the increase in genetic research.  And there is the persistent issue of minority representation (the information could be valuable to help improve the health of minorities on a population basis), and the resurgent issue of whether the donors’ survivors ought to benefit from any financial gains that might come from the research.

Read a brief story about it here.

A story about the company 23andme includes an observation that its 2 million customers constitutes “the largest genetic study the world has ever known.”  You can get a kit in the mail, send some saliva, and get back information about genes that might be associated with a number of traits, many trivial, like earwax consistency.  With only limited FDA-approved exceptions for rare, clearly understood genetic diseases, you can’t get much health-related information from the company.  FDA’s concern about such information being misleading, with potentially harmful consequences, almost sunk the company in 2013.  But the data is still valuable to researchers, and to drug companies trying to use it to discover new drugs.  So 23andme asks its customers for health information online, and drug companies can pay them, not for the actual data, which 23andme keeps to itself, but for results of analyses 23andme does on the data. I don’t know what sort of consent process is applied, but I’m guessing that an IRB was not involved.  By the way, 23andme’s is now adding its own attempts to become a drug company in its own right, using drug development ideas that might spring from the genetic information it has for its customers.

Human gene editing marches on

Nature has recently carried two new reports of human gene editing.  In one, embryos donated from an IVF clinic had a gene critical to very early development altered, to study what happens when you do that, and try to understand early human development more than we now do.  In the other, scientists studied editing of an abnormal recessive gene, specifically the one causing a type of blood disorder called thalassemia, by using cloning to create a new embryonic version of an adult with the disease.  (This made it technically easier to start in the laboratory with an embryo that has the disease, because it is genetically recessive, meaning that both copies of the gene are abnormal.)  This follows earlier publication of similar work to edit dominant mutation-causing genes, in which the embryos arose because of new IVF, done in the lab, by the scientists, using donated eggs fertilized with sperm from a male donor who carried the abnormal gene.

In all three cases, the main biologic approach, and the main ethical issues, are the same.  The main differences were which genes were being edited, and how the embryos were obtained.

This prompted Nature to run an editorial to say that it is “time to take stock” of the ethics of this research.  Read the editorial here.  The key points:  This is important work that should be undertaken thoughtfully.  Accordingly, donors of any embryos or cells should be fully informed of the planned research.  Only as many embryos should be created as are necessary to do the research.  Work on embryos should be preceded by work on pluripotent, or “reprogrammed,” stem cells, and if questions can be fully answered by work with those cells, then it may not be necessary to repeat the studies on whole, intact human embryos, and if that is not necessary, perhaps it should not be done.  Finally, everything should be peer reviewed.

I agree that editing work in non-totipotent cells should be at all times favored over work on intact embryos, but if one holds that an embryo is a human being that should have the benefits of protections afforded human research subjects, then Nature’s ethical principles are rather thin, little more than an extension of animal use provisions for studies in which early humans are the raw materials for the development of new medical treatments.

Included was a link to the journal’s policies for considering for publication any reports of experimentation on living organisms.  Those policies include this paragraph regarding modification of the human germline:

“In deciding whether to publish papers describing modifications of the human germline, we will be guided by safety considerations, compliance with applicable regulations, as well as the status of the societal debate on the implications of such modifications for future generations. We have established an editorial monitoring group to oversee the consideration of these concerns. (The monitoring group includes the Editor-in-Chief of Nature publications, the Nature Editorial Director, the Head of Editorial Policy, Nature Journals and the Executive Editor, Life Sciences.) This group will also seek advice from regulatory experts to ensure that the study was conducted according to the relevant local and national regulations. In this evaluation, we will be strongly guided by the guidance issued by the International Society for Stem Cell Research: Guidelines for the Conduct of Human Embryonic Stem Cell Research (http://www.isscr.org/home/publications/guide-clintrans ).”

I want to be reassured by their invoking “the status of the societal debate on the implications of such modifications for future generations,” but the weaknesses are first, that debate is just not very robust, and “society” is generally in a position of accepting, more or less uncritically, the ongoing technical push; and second, that the ones considering the status of the issues will more or less naturally view them through the relatively narrow researchers’ scope I describe above.  To be sure, the goals at a minimum appear to be to ensure that the research is not reckless, that it meets technical standards, that obtaining and creation of embryos is relatively limited in scope, and that nobody, for now, is trying to bring gene-edited embryos to human pregnancy, much less birth.  At least, not until the scientists and regulators tell us they think it’s time to try that.

Is Obfuscation Ever Helpful in Science or Ethics?

Obfuscation and science would seem to be polar opposites. The scientific method hinges upon correctly identifying what one starts with, making a single known alteration in that starting point, and then accurately determining what one ends up with. Scientific knowledge results from this process. Accidental obfuscation in that three-step process necessarily limits the knowledge that could potentially be gleaned from the method. Peer review normally identifies and corrects any obfuscation. That is its job. Such peer review can be ruthless in the case of intentional obfuscation. It should be. There is never any place for intentionally misrepresenting the starting point, the methods or the results.

Until now?

In an excellent article in Technology Review, Antonio Regalado describes the current status of research where human embryonic stem cells “can be coaxed to self-assemble into structures resembling human embryos.” The gist of the article is that the scientists involved are excited and amazed by the stem cells’ ability to self-organize into structures that closely resemble many features of the human embryo. Perhaps more importantly, per Regalado:

“…research on real human embryos is dogged by abortion politics, restricted by funding laws, and limited to supplies from IVF clinics. Now, by growing embryoids instead, scientists see a way around such limits. They are already unleashing the full suite of modern laboratory tools—gene editing, optogenetics, high-speed microscopes—in ways that let them repeat an experiment hundreds of times or, with genetic wizardry, ask a thousand questions at once.”

This blog has reported on Synthetic Human Entities with Embryo-like Features (SHEEFs) before (see HERE and HERE for starters). The problem from a bioethical standpoint is this: is what we are experimenting upon human, and thus deserving protections as to the type of research permitted that we presently give to other human embryos? Answering that ethical question honestly and openly seems to be a necessary starting point.

Enter the obfuscation. Consider just the following three comments from some of the researchers in the article:

When the team published its findings in early August, they went mostly unnoticed. That is perhaps because the scientists carefully picked their words, straining to avoid comparisons to embryos. [One researcher] even took to using the term ‘asymmetric cyst’ to describe the [amniotic cavity-like structure] that had so surprised the team. “We have to be careful using the term synthetic human embryo, because some people are not happy about it,” says [University of Michigan professor and lab director Jianping] Fu.

“I think that they should design experiments to focus on specific questions, and not model everything,” says Insoo Hyun, professor and ethicist at Case Western University. “My proposal is, just don’t make the whole thing. One team can make the engine, another the wheels. The less ambiguous morally the thing is that you are making, the more likely you can do your research unimpeded.”

“When Shao presented the group’s work this year, he added to his slides an ethics statement outlined in a bright yellow box, saying the embryoids ‘do not have human organismal form or potential.’”

This last comment seems to contradict the very emphasis of the linked article. As Regalado nicely points out: “The whole point of the structures is the surprising, self-directed, even organismal way they develop.”

Honestly, at this point, most are struggling to understand whether or not the altered stem cells have human organismal form or potential. I suspect everyone thinks they must or else researchers would not be so excited to continue this research. The value of the research increases the closer a SHEEF gets to being human. If our techniques improve, at what point does a SHEEF have the right to develop as any other normal embryo? Said differently, given their potential, and particularly as our techniques improve, is it right to create a SHEEF to be just the engine or the wheel?

Having scientists carefully picking their words and straining to avoid comparisons is not what scientists should ever be doing. Doing so obfuscates both science and ethics. Does anyone really think that is a good thing?

Questioning whether genes in human embryos were in fact successfully edited

Nature reports that the editing of a gene in human embryos–reported earlier in August and discussed recently on this blog–has been questioned by a different group of scientists.

Read a fuller, general-public-level description here.

The questioning scientists doubt a specific claim of the initial work; namely, that a faulty gene in human sperm was edited through a corresponding gene in the human egg fertilized by that sperm, yielding a normal embryo.  This was reported to underlie a remarkably high rate of success in the gene editing process in a group of these embryos.  They’ve submitted a paper with their findings, for publication.

The initial scientists say “balderdash,” the other folks don’t know what they are talking about.  Well, they’re more sophisticated in their wording than that, and there is a legitimate difference of scientific opinion here.  It will have to be adjudicated by reviews of the actual data.

But in the meantime doubts have been raised about the reliability of the initial report.  Nobody’s claiming fraud, just misinterpretation.

We should watch that space for more.

Search and destroy—or at least, select

This week’s issue of Nature carries a feature article on the explosion of preimplantation genetic diagnosis (PGD) in China.  Because women are having children later in life, partly because of relaxation of the old one-child policy; because Chinese culture sees it as a duty to seek to bear healthy children; because some Chinese want to try to enable their kids to exploit some features of life–reproductive technology, specifically in vitro fertilization, is exploding, and embryos are selected for the absence of certain diseases.  Embryos with genes that transmit such diseases have oblivion as their fate, but the Chinese hope that all children born there are born are free of the burdens of some truly bad diseases, and if they have those diseases, they won’t be born.  Retinoblastoma.  Huntington’s disease.  Brittle-bone disease (osteogenesis imperfecta).  (That’s the disease that Alec, the kid on the Shreiners Hospital for Children ads, has–you know, “we’ll send you this adowable wuv-to the wescue bwanket.”  I love those ads.) Polycystic kidneyShort-rib polydactyly syndrome.

Deafness.  Maybe the Chinese think that deaf people have no reason to live, kind of like Randy Newman’s short people.

The Asian gene that makes it hard to metabolize alcohol.  Without that gene, it’s possible to drink at a business lunch.  Important for career success.

The central government’s 5-year plan puts a high priority on using PGD to optimize the population.  Not too many people object.

Folks in the West wonder why the US can’t get with the program the way the Chinese do.

Chinese physician-scientists speak of eliminating all 6000 known disease-causing genes from the population.  “We just do them one-by-one until we get the whole set,” one Chinese geneticist is quoted as saying.

The article says further: “The Chinese word for eugenics, yousheng, is used explicitly as a positive in almost all conversations about PGD. Yousheng is about giving birth to children of better quality.”

The Chinese are also busily aborting babies with Down syndrome.  In this case, of course, Down syndrome is identified by prenatal diagnosis, when not only fertilization has occurred, but there is a pregnancy.  As in Iceland, as CBS recently reported.  If you abort such a baby in China, “nobody scolds you,” they say.  In Iceland, they “don’t look at abortion as murder.”  They “look at it as a thing that we ended.”  There are one or two Down syndrome births per year in Iceland, CBS reports  Abortion after 16 weeks is legal there for a “fetal deformity,” like Down syndrome.  The abortion rate in Iceland after a prenatal Down syndrome diagnosis is “nearly 100 percent,” compared with an estimated 67 percent in the US, 77 percent in France, and 98 percent in Denmark, according to CBS.  I didn’t see a rate for China in the Nature article.  But they sold over a million Down syndrome diagnosis kits last year, it says.

Follow the links and read both articles in full.

And go back and read Mark McQuain’s fine post of this past Tuesday, August 15, and the Time magazine article to which he linked.  The most telling statement of that article, in my opinion: “I worry that in our haste to make people healthy, we are in fact making the people we want.”

Precisely.  Beyond the concern of killing unborn humans lies the conceit that we know what people we want.  That those choices will always appear benign, or praiseworthy.  That we don’t have to worry about being told what people we want.  That the group of people doing the choosing won’t be very narrow indeed.

Perhaps it is time to start a society of free-range humans.

 

CRISPR and Identity

Dr. Joel Reynolds, a postdoctoral fellow at The Hastings Center recently wrote a very poignant essay in Time magazine arguing that our increasing ability to edit our own genetic code risks eventually eliminating the very genetic code that results in people like his younger brother Jason, who was born with muscle-eye-brain disease, resulting in muscular dystrophy, hydrocephalus, cerebral palsy, severe nearsightedness and intellectual disability. In answering his question – “What, precisely, are we editing for?” – he makes the case that editing the code that resulted in Jason effectively eliminates Jason. I encourage you to read the short article, as any further summary on my part does not do it justice.

How much change of my genetic code would alter my identity? This is an important ethical question as scientists seek to use our growing genetic knowledge to alter our genetic code. Using preimplantation genetic diagnosis (PGD) to eliminate diseased segments of genetic code also eliminates the rest of the genome since a completely disease-free human embryo is selected for implantation and the disease-carrying embryo is destroyed/killed. Obviously, the identity of the implanted embryo is completely different from the destroyed embryo. No identity preservation here.

CRISPR-Cas9 (CRISPR) is held out as the beginning of future techniques to successfully remove and replace sections of our human genetic code. Diseases that are caused by point mutations would seem to be ideal challenges for CRISPR, where removing a single nucleotide effectively cures the individual of the disease, and, at least on cursory consideration, leaves the identity of the individual intact (after all, we would only be changing one nucleotide in the individual’s 3.2 billion nucleotide sequence in their unique genetic code).

Color blindness is one such example, one that I “suffer” from. If my parents had the ability to change my genetic code just after conception to eliminate my color blindness, it seems that I would be the same man I am today, absent the need to have my wife select my ties and socks. However, other life experiences could have been available were my color vision intact, such as F-14 fighter pilot and/or completion of the NASA astronaut selection program, both requiring normal color vision. Likely, I would have been someone with the same identity but certainly with very different life experiences.

At the more serious end of diseases with point mutations is Tay-Sachs disease, where a defective enzyme fails to prevent the build up of toxic fatty deposits in the brain and spinal cord, and, in the infantile form, results in mental impairment, severe sensory pain and pre-mature death. If I had the infantile form of Tay-Sachs disease and my parents changed my genetic code, is my identity different? Am I just the same “me” experiencing a tremendously different life experience or am I a different “me”? If I am a different “me”, is it just because we hold cognitive ability/behavior/function critical to one’s identity? One can lose the function of the nerves in one’s leg and not consider this a challenge to one’s identity. Sustain an injury to one’s brain and the challenge to one’s identity is stronger. Dr Reynold’s makes a similar case in describing his brother Jason as he actually was, compared to how he could have been had the prayers for healing been answered or genetic editing been available. To paraphrase, a “corrected” Jason is no longer Jason.

None of the forgoing discussion considers the human soul as it relates to identity or whether alterations in the human genome affects the human soul (or vice versa?). Those issues will have to wait for another blog post. For now my question is this: How much of my genetic code can I change and still be me?