Special Edition: What Parents Need to Know about the Recent CRISPR Trisomy 21 Research

People have asked me about the recent clustered regularly interspaced palindromic repeats (CRISPR)/Cas9 study where scientists successfully removed the third copy of chromosome 21 in cell lines that model Trisomy 21. While this area is absolutely not my area of expertise, I have read the original, peer-reviewed research. I learned a lot. Given others’ requests of my opinion and our interested position as a family with an individual that has Down syndrome, I feel compelled to offer some measured thoughts. So here is a special edition of the blog.

Before offering the limited and measured thoughts, I will simply list some factual highlights and observations. Pardon the points where the terminology is still thick.

• While the research was published back in February, the press has picked up considerably within this last week or so.

• CRISPR is a powerful genome-editing technology that has been around for a while.

• I learned that, “While most genes on HSA21 maintain functionality in each copy, a small subset exhibits parent-of-origin-dependent silencing.” Which basically means that any of the three copies can likely be eliminated without issue, but the combination of instructions left will be slightly different depending on which copy is removed. This technique always eliminated the same, targeted copy so that the effect would be obvious and measurable if it worked.

• The technique to eliminate the extra copy relies on suppressing natural repair mechanisms for messed up DNA. Basically, our bodies don’t want wacky copies of DNA to be propagated when cells divide. Since CRISPR intentionally hacks apart pieces of DNA, these checking and repair mechanisms need to be tuned so that the hacked apart DNA (the third chromosome) is packaged for deletion and not passed on at all during cell division.

• The scientists showed that their strategy for selecting pieces of DNA to remove from the third chromosome + tuning the natural checks and repair mechanisms led to clean removal in some of the cells.

• They demonstrated that the rescued cells, the scientific way for saying “returned to typical state”, functioned differently that the trisomic, non-altered cells. (The different, more typical, functions are due in large part to normalized protein expression, so the cells build all their pieces in an expected way.)

• I learned that though its called Trisomy 21, the genetic information from the extra chromosome results in other genes throughout the genome being expressed in different amounts, both more and less.

• The phenotype (or the way that a cell ends up functioning) was so affected back to typical in the rescued cells that Reactive Oxygen Species (ROS), which are a big deal for those with Down syndrome, was drastically reduced. The health implication for reducing ROS to normal levels is immense.

• The scientists outline a number of hurdles before this technique would ever be tried in humans. First, the experiments were done in a dish. Second, if I understand correctly, fewer than 20% of the trisomic cells became the rescued, disomic cells. Definitely a considerable feat, but there is a ways to go in efficiency. Third, every person with Down syndrome is different, so figuring out which copy to target in each individual would be non-trivial. Fourth, as is typical with new technologies, we don’t have any data on how this technique would play out long term.

Okay, so now the tricky part, the evaluation. It is doubtful that this technique will advance to clinical implementation in our lifetimes. So no matter how intense the atmosphere feels right now, we need to recognize the strong science for what it is and the need for careful ethical consideration for what it is. The way people have been talking about this technique suggests that we are capable of getting rid of individuals with Down syndrome tomorrow or next year. That’s not the case. Does this article demonstrate the potential for correcting the number of chromosomes in someone, someday? Yes, there is potential. Will medical science go there? I have no idea. Should we go there? There are ethicists, theologians, physicians, and affected individuals who have more elevated positions for this discussion.

Do we love our people with Down syndrome? Undoubtedly. Do we wish that we could fix the medical conditions that they often have? You bet. Would “rescuing” their cells to be able to function and, therefore develop, typically change who they are fundamentally? I truly don’t know how to think about that. The potential outcome of the technique is restoration of typical cellular function, so growth, aging, and even cognitive ability would theoretically become typical. Would that change who a person is? That’s the part that I can’t figure out how to answer while respecting that the third copy changes so much of development. Do I wish that this technique was being used to address a more clear cut situation, like a lethal triplication? 100%; we wouldn't have to ask and answer hard questions as it seems like that situation would just be beneficial.

If this assessment sounds wishy-washy, you’re not wrong. I wanted to read the science and share what I learned so that more people could think about their responses in a more informed way than the headlines and some social media blurbs and comments seem to be enabling. I don’t know exactly where to land on it, and I am, sheepishly, glad I won’t need to decide for my child. I will keep learning who she is and supporting her in every way I can. I trust that you will do the same for your people, even as we embrace curiosity….