CRISPR Technology Poses Hopes — and Threats

DIFFICULT MORAL QUESTIONS: Exercising control over the ‘language’ of DNA could be perhaps the most godlike power humans have ever practiced.

(photo: Pixabay/CC0)

Q. Some friends recently were speaking about the dangers of genetic engineering. I’ve heard good things and bad things about that this new science. But aren’t we in danger of throwing the baby out with the bathwater? Thank you. —Caitlin, Arizona

A. Imagine you are a caveman communicating with complex grunts. Your neighbor shows you a copy of the Oxford Shorter dictionary together with an English grammar book and signs that the combined information is going to change everything … that humans will now be able to cooperate flexibly in large groups; knowledge will be able to accumulate; sciences develop; cultures perpetuate themselves; and the libraries, O the libraries! You grunt your approval.

We’re at an analogous point today with genetic engineering.

Our DNA is itself a kind of language. This “genetic code” provides instructions for making proteins, large molecules necessary for carrying out most all cellular activity, including the building, repairing and regulating of our tissues, organs and organ systems. Our genetic code is contained on the DNA that resides in every cell of our body.

By now most everyone has heard of the revolutionary system for DNA editing called CRISPR-Cas9 (see shorter or longer videos). Older genetic engineering techniques, which have been with us for decades, were laborious, time consuming, imprecise and costly. CRISPR is simple, fast, razor-exact and cheap.

If CRISPR is what Caitlin means by the “new science,” I fully agree that it poses hopes and threats for the future of humanity. It’s important for everyone to understand what’s going on with it, and why we need to be careful going forward.


CRISPR in Bacteria

The CRISPR system was first observed in nature in bacteria, which possess a sophisticated molecular defense mechanism for identifying enemy viruses and disabling them.

When a virus infects a cell, it injects its DNA into the cell. In nature, CRISPR allows a bacterium to make a record of the viral DNA for future identification.

When the virus appears again, the bacterium, with its DNA database, detects the viral DNA. The bacterium produces an RNA sequence that matches that of the invading virus. This “guide RNA” then unites with an enzyme called Cas9 that acts as a tiny pair of molecular scissors.

When the matching sequence of the guide RNA binds to its target sequence within the viral genome, Cas9 cuts the viral DNA thus disabling the virus.

Scientists found that they could hijack this system for their own purposes. Not only can CRISPR Cas9 be used to cut viral DNA, it can be used for cutting any DNA at specifically targeted locations.

The system acts as a kind of programmable sentinel. Technicians create a synthetic guide RNA that corresponds to a specific sequence of DNA that they are interested in editing. Then they attach the guide to a Cas9 enzyme. The sentinel will now seek out that specific corresponding sequence of DNA.

When it finds the sequence, it binds to it and follows its further programming. It might cut out the specific DNA sequence thus disabling the related gene. Or a new sequence of DNA might be introduced at the site of the cut. Or if the scissor mechanisms are deactivated, Cas9 might be used to transport things like enzymes to very precise regions of the genome.


Uses of CRISPR

Next to miracle working and the forgiveness of sins, exercising control over the “language” of DNA is perhaps the most godlike power humans have ever practiced. Evolution changes genetic codes over millions of years. We are on the verge of doing it overnight.

CRISPR Cas9 is already being used in remarkable ways as a prophylactic against disease and a catalyst for necessary resources.

For example, research is being done to create malaria-resistant mosquitoes; to improve disease resistance in crops; and to decrease disease susceptibility and increase production in livestock; (even to bring extinct species — e.g., the woolly mammoth — back to life).

But it’s greatest hope lies in the healing of human disease.

Whether a sickness is caused by abnormalities in the genome, or is amenable to correction through genetic manipulation, most diseases, including some of our most daunting, such as cancer, are potentially (but not yet) treatable with CRISPR derived therapies: by silencing disease causing genes, repairing defective ones, programming genes to recognize and attack unhealthy cells, or turning genes on and off or adjusting their levels of activity to maximize disease resistance; research into all these is underway.

For example, research is being done to identify genes responsible for brain diseases such as Alzheimer’s and Parkinson’s; to understand genetic disorders such as sickle cell disease, cystic fibrosis and hemophilia; to make immune cells more effective at targeting and destroying cancer cells; to cause mutations that increase resistance to the HIV virus; to create a new generation of treatments for heart disease, blood disorders and blindness; even to make pig organs more compatible for human transplantation. (Think of a world that had an unlimited supply of transplantable organs!)


Dangers of CRISPR

But with the exercise of great power, comes the need for seasoned moral virtue, of which the scientific community is in short supply. And so, predictably, there is virtually no outcry against the lethal experimentation on human embryos taking place for “perfecting” CRISPR techniques.

China with its permissive oversight of biomedicine was the first to use CRISPR to edit the DNA of human embryos in 2015. Westerners at first gasped, then said, “How about us?” Thus, in early 2016, scientists in London gained regulatory permission to use CRISPR to genetically modify human embryos; but with this caveat: that the researchers must destroy the lab subjects after seven days!

The most promising and at the same time threatening CRISPR research is being done in reproductive medicine.

Gene editing, as suggested above, could potentially one day wipe out heritable diseases, first in individuals, then blood lines and finally populations.

If techniques of this sort could be perfected without immoral research or the intention to use them for immoral purposes (e.g., IVF), then support for the research would not only be licit, but it seems to me morally required.

A problem is that when unscrupulous fertility experts think about “designer children” they see only dollar signs; give the people what they want, they say. So if parents want to introduce desirable traits in some children or suppress undesirable ones in others, or eliminate children altogether, so be it.

Almost weekly there are announcements about advances in this dubious field of CRISPR research.


Unintended Evils

Even if we were able to eliminate every form of objectively immoral research, CRISPR is still so young that nobody can yet guarantee off-target effects won’t take place where the system inadvertently targets sites not intended, causing mutations that alter our biology in unforeseen ways. This together with imprecise edits and the variable efficacy of edits all pose unforeseen and unforeseeable safety risks, to individuals, yes, but also to the human race.

Thus great patience and restraint is needed to eliminate these dangers.


Need for Public Policy

As I’ve recently argued, we also need sensible legislation prohibiting unethical forms of research and guiding legitimate forms to serve human good.

But there is great resistance to this among scientists and their ethicists. When they came together from all ends of the globe in 2017 under the auspices of the National Academies of Sciences, Engineering and Medicine to discuss germ-line editing (DNA edits that are passed on to progeny), the most they could agree upon was summed up in the typically toothless maxim “caution does not mean prohibition” (see comprehensive report).

Many people ask why scientists are so willing to consent to immoral research.

Because like you and me, they are sinners, and sinners have always been tempted to do illicit things that promise them gain.

Rightly expressed, humanity’s power over nature can result in triumphs for human good (look at S. Yamanaka’s pioneering research into cellular reprogramming).

But in the hands of the covetous, it too often turns out to be — quoting C.S. Lewis — “a power by some men over other men with Nature as its instrument.”

Since crossing forbidden lines in science will always be a temptation, statesmen need to use their rightful authority to limit science’s capacity to cross those lines.