[WSF18] “Rewriting” DNA with CRISPR brings both promises and perils



Is CRISPR the cure-all some think it is?

AiPT! Science was out in full force for New York City’s recent World Science Festival — keep checking back all week for more coverage, with the tag WSF18!

Every year, the World Science Festival is held in New York City, bringing lectures, panel discussions, and other events to the public, all held by leading scientists in their fields. Sure, other popular conventions occasionally have science panels, but rarely are they as well-vetted as these are. That’s important because some of the topics in these discussions could make huge impacts on our lives.

On Thursday, May 31, 2018, the Festival hosted a panel discussion titled “Rewriting Life: The Promise and Peril of Editing Your DNA,” which was largely about CRISPR, a new genetic editing technology.

Panel members, from left to right: Neville Sanjana, Samuel Sternberg, Fred Gould, Josephine Johnston, and moderator Lesley Stahl. Photo: World Science Festival/Greg Kessler

Editing DNA the easy way, with CRISPR/Cas9

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is often compared to a word processor’s Search & Replace function: It exploits the behavior of a naturally occurring bacterial enzyme, called Cas9, to find specific sequences in the A-T-C-G nucleotides of DNA strands and replace them with a different sequence, in a way that’s a lot easier and faster than previous genetic modification technologies. CRISPR sequences are built to describe the targets, and Cas9 is used to execute the cutting and pasting.

Gene modification has been possible since the 1990s, of course, but back then geneticists had to do a lot more engineering to build their own “DNA scissors” from scratch, even with the help of the enzymes and ligases already available. The almost automatic slicing and insertion capabilities of Cas9 were discovered while researching the adaptive immune systems of bacteria.

There is a lot of promise here, as the panel was enthusiastic to point out. However, there are also some perils they touched upon, as well.

The promises

Each of the panelists was asked what they thought the greatest promise of CRISPR technology might be. Sam Sternberg, from Columbia University, initially gave a very generic answer about how it will give us “more creative ways to solve problems”. Fred Gould, professor of agriculture at North Carolina State University, gave a more specific answer — we can push malaria-resistance in mosquitos to a wider range of species, greatly reducing the worldwide risk of infection.

NYU’s Neville Sanjana talked of what scientists call “Genetic Model Organisms,” which are used in fundamental research. Right now, such models are currently limited to mice and a few other species, but with CRISPR, the idea of what can constitute a model (something that that has enough similarities to people for experimentation purposes) could become much wider.

Josephine Johnston, a lawyer for The Hastings Center, brought up the point that CRISPR is not facing the same set of outdated regulations from the U.S. Agriculture Department that apply to older genetic technologies regarding the use of “pests”. Of course, it will still face some regulation, in a more appropriate form. It just won’t be as inconvenient.

Crops can be made more resistant to diseases, requiring less use of fungicides and pesticides.

Throughout the discussion, other promising ideas were put forward. Most of these also apply to the pre-CRISPR days of gene modification, but remember: CRISPR makes it easier to see these through.

  • The most obvious would be the eradication of many forms of heritable diseases: sickle-cell anemia, many retinal diseases, and even some skin and blood cancers.
  • The idea that treatments for these diseases could be administered through a single dose, instead of a long and complicated schedule of drugs.
  • Crops can be made more resistant to diseases, requiring less use of fungicides, pesticides, etc.
  • Hornless bulls could be bred in many more species than have already been produced through selective breeding.
  • Designer pets could be produced without the negative consequences of inbreeding.
  • The conservation of bio-diversity would benefit, in general. We can fix genetic issues directly in the effected species, without interbreeding them with other populations to filter those problems out.
  • The panelists also imagined a fantasy in which the woolly mammoth could be resurrected. We’ve already constructed a map of their genes. We can use an elephant as a base, and make the necessary changes to that. Welcome to Woolly Park!
  • A possible advantage specific to CRISPR is a library of CRISPR/Cas9 variations, available for scientists to utilize and customize, much like software code repositories.

It is worth noting, however, that CRISPR might not be able to solve all of our problems. It’s hard to predict what impact it will make on autism, since that encompasses a wide spectrum of poly-genetic diseases. CRISPR is better at handling disorders with only a few, well understood targets.

The potential perils

The panel members were actually quite hesitant to talk much about the perils, at first. Some might assume this was due to pressure from their sponsors, but perhaps there’s just not much to worry about? The moderator, 60 Minutes correspondent Lesley Stahl, was able to probe them with the right questions, to get the reality of the situation out. Among the perils mentioned:

  • CRISPR can make mistakes, which are referred to as “off-target results”. However, there are procedures in place to monitor and mitigate these issues, as research progresses.
  • Even if the correct gene is changed, it could have unintended consequences in the expression of genes (phenotype) elsewhere in the body. It might be worth pointing out, however, that this type of issue is conceivably a lot worse with currently-accepted gene modification technologies, such as mutation breeding, and everyone seems to be okay with those.
  • There is, of course, the general anti-GMO paranoia, in some people, which the panel referred to as a “cultural problem,” in getting CRISPR widely adopted.
  • Regulation of this technology does need to be ironed out. There is fear among some folks in the public that this could lead to a new form of eugenics. The panel certainly agreed that state-sponsored eugenics programs are bad things, no doubt! They also explained how voluntary genetic modification of embryos, to avoid a disease or deafness, might be a lot more palatable to most people. We already do heart surgery on infants who need it — maybe we can avoid more traumas by fixing them in utero, before the baby is even born.
  • The panel also imagined a future in which companies would engineer pathogens to target their competitors’ crops, bringing about a new era of germline corporate warfare.
  • The potential threat of “garage tinkering” does not seem realistic to the panel, yet, as the technology is still quite difficult for the average person to work with. This could change in the distant future, however.
  • The word “bioweapons” was mentioned, early on, as an aside, and not really elaborated on.
Regulation of this technology does need to be ironed out.

If that seems like a long list to panic over, remember — every single gene-related technology we have today has also had its long list of potentially harrowing dangers and disasters associated with it, and none of them have ever been realized. It turns out that scientists’ track record for addressing these types of perils is pretty solid.

Conclusions

CRISPR is a victory for conducting basic research. Its discoverers did not set out to revolutionize gene editing; they were studying immune systems in bacteria, and happened to hit upon it. These are the reasons funding fundamental research is important.

At the end of the event, Stahl stated that “there is an element of idealism” in all the panelists do. The history of science shows us we are generally good at keeping the perils of gene technology at bay, by understanding the risks and being sensible about approaching them.

Check out the whole panel for yourself!