It’s a Fine Line Between Utopia and Gattaca
In a previous piece, we talked about why scientists and innovators around the world are so excited about CRISPR, a powerful new gene editing technology. The tool was first published 2012, but it still regularly makes headlines. Less than a month ago researchers in Portland, Oregon announced the first successful use of CRISPR in human embryos in the US. One of the pioneers of CRISPR, Jennifer Doudna, just recently released a memoir. It’s a technology that stands poised to change the course of our future, so much so that experts tend to agree that the question is not if CRISPR will be widespread someday, but rather when.
As a neuroscientist who studies Alzheimer’s Disease, I am endlessly fascinated by the potential use of CRISPR to edit the human genome. We can already use CRISPR in our lab to create human cell lines with the mutations we want, which we can then grow in a dish for study. The natural next step is to explore the possible outcomes if we can use CRISPR to edit a living, breathing person. Right now we have technology that could tell me if I have genes that put me at risk for Alzheimer’s Disease, like a copy of APOE-ε4, which increases an individual’s risk somewhat but doesn’t itself cause the disease. I’ve always told myself I don’t want to know. At best I’d be learning of a risk, not a guarantee or even a course of action. But what if I could edit that gene so that I wouldn’t pass it on to future generations? Could I help to reduce the risk of that horrible illness for future generations of my family? That’s some action I can see myself taking.
This proper scientific miracle is known as editing the human germline. The germline refers to the cells in our body that are capable of reproduction – your eggs, your sperm, even zygotes (the earliest stage of becoming a human). Unlike some current procedures like gene therapy, in which a mutation in some somatic cells (i.e. cells that are not members of the fruitful germline) can be repaired and reintroduced into your body, the use of CRISPR in the human germline implies that we would be making edits that would be passed down to our children, and to their children, and to their children’s children, and so on. We would essentially be manufacturing a mutation, just like the disease mutations that evolved naturally and now run in our families. The only difference is that this would be a mutation we actually want.
In the hypothetical Alzheimer’s Disease scenario I mentioned, we could edit the germline to get rid of the APOE-ε4 gene copy, reducing the risk of this disease in future generations. For some other diseases in which genes have been identified as not only conferring risk but actually causing the disease – such as Huntington’s Disease – this kind of therapy becomes that much more appealing. In that Alzheimer’s scenario I’m playing with the odds. For a family with Huntington’s in their DNA, it goes beyond reducing risk; they could be eliminating the disease entirely from future generations.
This future world in which we can delete devastating illnesses from the human genome is what I will call Utopia. To be clear, we aren’t exactly knocking at Utopia’s door right now. We need to do a lot more research before we can guarantee CRISPR will be safe to use in humans. Furthermore, we also need to have a significantly better understanding of the cause of each disease we want to erase. Based on current knowledge, there is not going to be one readily identifiable gene that causes every illness. A very large proportion of them will be caused not only by genes but also the environment. If genes don’t play as big a role in a disease as environment to begin with, CRISPR may not be the answer. So Utopia won’t be totally free from problems, but it’s a leap in a beautiful direction.
This prophylactic approach to combatting genetic illness enjoys some degree of precedent in our society. We have been using genetic screening to diagnose conditions like Down’s syndrome during pregnancy for years, and the results of this practice are quantifiable. Although the average number of diagnoses has risen as women choose to have children later in life, the number of children actually born in the United States with the condition has largely remained unchanged because the majority of pregnancies in which such a diagnosis is made are terminated. The use of CRISPR to edit the human genome could likewise be used to prevent the inheritance of Down’s syndrome, by way of prenatal editing versus termination. In this regard, we as a society have already begun to answer the question of whether or not we would take advantage of the ability to edit our children’s genomes before they are born; if we hadn’t placed a premium on genetic normalcy (for want of a better term), we would have more children with Down’s syndrome in our country today.
As I subtly intimated in the title of this piece, the utopian world in which CRISPR has arrived to eradicate the unwanted genetic features of our species is a fragile hypothetical scenario. There are many ways in which a haphazard roll out of CRISPR as a therapeutic tool could set us on track towards a modern day Gattaca. In this 1997 Oscar-nominated flop-turned-cult classic, reproductive science has progressed to a point where parents can select the traits of their children – an oddly prescient scenario for a film universe whose technology as a whole hasn’t evolved much past the late 90’s. The ability to select the traits of ones children raises the potential dystopian rise of genetic discrimination, which threatens to expand the growing divide between upper and lower socioeconomic classes. These sort of social consequences will be explored in an upcoming third part of this CRISPR series. For now, we’re going to stick with the more clinical questions related to the ethics of editing the human germline.
Consider this most basic description I gave of CRISPR’s potential clinical use – eradication of unwanted genetic traits – in the context of Down’s syndrome screening practices. As I mentioned, the majority of pregnancies that receive this diagnosis are terminated, indicating a trend towards labeling Down’s syndrome as an unwanted genetic trait by the general public. However, there are many who would consider this to be an ableist point of view, or a prejudicial attitude against a person with a physical, intellectual, or other form of disability. That people without Down’s syndrome would consider a third copy of the 21st chromosome (the genetic cause of this condition) to be an unwanted genetic variation is born out of the assumption that the quality of life for a person with Down’s syndrome is inherently less than that of a person with just the standard two copies of that chromosome. It is true that there are multiple medical complications associated with having Down’s syndrome that will make life harder. However, it is also true that many people with firsthand experience with Down’s syndrome see the condition in a very positive light, and would not want to necessarily reverse it given the opportunity.
The same is true for many other conditions generally considered to be a handicap by able populations, such as deafness. It is not uncommon for deaf individuals to turn down cochlear implant surgery, which would restore the ability to hear, in favor of retaining their current lifestyle. Deaf culture describes the unique life experience of individuals in the deaf community who take pride in their deafness, which they view as an identity rather than a disability.
If we decide that we want to use CRISPR to edit the human genome, we are going to have to ask ourselves some very hard questions. Many scientific experts agree that strict regulations should be in place with regard to how we can use this powerful tool, but how do we draw those lines? Do we allow for the correction of any perceived disability, including ones that have developed their own thriving culture like deafness? Do we limit the use of gene editing to only life-threatening conditions? If so, how strictly do we view a condition as life-threatening? For example, a patient diagnosed with Huntington’s Disease could live a healthy life into their 40s before their nervous system degenerates, but that time will definitely come. A child with Down’s syndrome on the other hand will have evident symptoms of the condition from the time of birth, and maybe none appear immediately life-threatening. However, that child is at a significantly higher risk than the rest of the population to develop Alzheimer’s Disease in their 40s. If a high risk for early neurodegeneration merits the use of genetic editing, Down’s syndrome falls squarely into a group of allowable corrections with the likes of Huntington’s Disease and Alzheimer’s Disease, despite the fact that the actual patient population in question here, as well as their families, have already expressed that eliminating Down’s syndrome is not so obviously the right choice.
The conversation about how we use CRISPR in humans is going to be long and difficult, but it is worthy of intense scrutiny. Remember that editing the human germline means editing a gene in perpetuity. It is not as simple as allowing people to make their own decision on a case-by-case basis, because patients would essentially be granting consent to change not only their own genome, but for every generation that follows them. What is the future of medical consent if those in question have not even been conceived yet, let alone born or grown to adulthood? It is clear at this point that CRISPR could, and likely will, be an evolutionary game-changer. The question remains: how will it change the future of humanity?