Aldous Huxley’s novel, “Brave New World” (written in 1931!), envisioned a future with genetically-modified human beings. In 2018, a rogue Chinese scientist performed the first gene-editing of human babies, producing two apparently healthy twin girls. He was also subsequently indicted and fined by the Chinese government, and also censured by the international scientific community. Nevertheless, in the area of genetic engineering, science is catching up with last century’s science-fiction.
The technology behind current gene-editing is known as CRISPR, which stands for Clustered Regularly Interspaced Short Palindromic Repeats. That somewhat-inscrutable acronym is representative of the problem with trying to understand and explain gene-editing: lots of unfamiliar concepts and terminology.
CRISPR, technically CRISPR+cas9, has been described as a pair of “DNA scissors,” which is, in fact, a pretty good description of what it does. Most people understand that DNA is what carries the genetic code for a living organism, even if they don’t know that DNA stands for deoxyribonucleic acid.
These molecular scissors break the double helix of DNA at a precise point, allowing either the removal of a gene (a sequence of the base pairs that make up DNA), or the addition of a new one (a little iffy, since we don’t quite fully understand the effects of adding genetic material to DNA). For example, in the case of the twin Chinese girls, the researcher was attempting to remove a gene, which produces a protein used by some strains of the HIV virus to enter cells. This would make the resulting children HIV-resistant (their father was HIV-positive).
CRISPR-based gene editing is basically chemistry. In fact, you can buy a do-it-yourself CRISPR kit for as little as $169 at the-odin.com. Of course, these kits edit the genes of the familiar E. Coli bacterium, not humans. But for a couple of Benjamins, you get a kit which will let you “make a genome mutation (K43T) to the rpsL gene changing the 43rd amino acid, a Lysine(K) to a Threonine(T), thereby allowing the bacteria to survive on Strep media, which would normally prevent its growth.”
Of course, removing genes is not without potential problems. There is some experimental evidence that the CCR5 gene removed in the Chinese twins “is a suppressor for cortical plasticity and hippocampal learning and memory.” In other words, removing CCR5 may improve the memory function of these children. In addition to the fact that a single gene may affect more than one thing, CRISPR has an additional problem, known as “off-target editing.” The molecular scissors are positioned by what is called “guide RNA”, a sequence of 20 base pairs that will bind to a particular location on a DNA strand. This matching isn’t perfect, and so unintended locations may be affected.Fortunately, it’s possible to screen for these effects, and a number of methods, which significantly reduce off-target editing have been developed.
The “in vitro” use of CRISPR has gotten a lot of attention, as such experiments result in genetically-modified babies. “In vivo” application of CRISPR is also possible: modifying the genes of a living human by removing some of their cells, editing the DNA in those cells, and then reinjecting them to fight the disease. These are much safer than in vitro edits, since the results can be extensively checked before being introduced into the body (the Chinese researcher did perform tests on the modified embryos as they developed, but any negative results would have had far greater consequences).
Clinical trials of a CRISPR-based gene therapy for thalassemia, a disease which affects the oxygen-carrying capacity of the blood, are now underway. The initial test subject was found free of the effects of the disease for nine months following treatment. In a related trial, the same therapy was applied to a subject with sickle-cell anemia, who has now been crisis-free for four months.
If you’d like to know more about this topic, check out the Netflix documentary Unnatural Selection, which includes four hour-long episodes that investigate various perspectives on gene-editing technology, from biohackers in their garages to ethicists in the ivory tower. A related documentary produced by Dan Rather is Human Nature. Unfortunately, it isn’t available for streaming, but you can see a list of upcoming screenings at WonderCollaborative.org.
If you don’t have the time, and just want a quick visual recap of what I’ve tried to explain, there’s a two-minute video and a more in-depth video on YouTube from the Mayo Clinic.
It’s important you understand this new technology, even if it doesn’t directly impact your business, (though CRISPR is already at work in agriculture, since it works much faster than selective breeding of crops). The effects of CRISPR will be far-reaching and life-changing—and potentially catastrophic if misused. Next month, I’ll be writing about the gene drive, a scary-amazing effect of CRISPR technology.