The Double Helix Waltz

Is gene editing a marvel or a monstrosity?

A couple of my friends and I were talking about the release of genetically modified mosquitos in Florida this spring. Our responses were all quite different and I suspect there’s wisdom in each of them. Let’s start with the story which got us talking about GMOs (Genetically Modified Organisms) in the first place. Genetically modified versions of the mosquito Aedes Aegypti have been released in Brazil, Panama and India and have successfully reduced the number of said mosquitos. Male mosquito eggs were released which had been gene edited in such a way that their daughters did not live to adulthood. Since adult females are the ones who bite and impact the size of the next generation, the overall number of Aedes Aegypti individuals, and thus the number of bites, decreased.

My first friend, who is a doctor, immediately latched onto this being a fantastic development. For one thing, she has really bad reactions to mosquito bites herself. But what she focused on in the case of the Florida release was that the reduction in the number of Aedes Aegypti would reduce the number of cases of dengue fever, Zika and chikungunya. These are common diseases in warmer parts of the US.

The second of my friends is a scientist who has actually worked on the ethics of genetically modified organisms, specifically on CRISPR. This friend didn’t say whether or not she thought the mosquito release was a good idea. Rather, upon seeing the horror on my face she countered our doctor friend’s observation with the point that there might be ramifications for the food chain if most of a given species were eliminated.

However, my horror, while added to by thoughts of disrupted food chains, was far deeper. Messing around with the genes which determine the lifespan of a animal and releasing it into the wild sounds terrifying to me. Could it somehow spread into other species? The doctor shook her head and said she saw no way that could happen, because as she rightly pointed out, that hereditary line will die out before it can reproduce, by design. It won’t get passed to the next generation. And indeed, in the places where these modified mosquitos have been released the mosquito numbers climbed back up to their prerelease numbers a few weeks after the intended plummet in numbers. But natural systems don’t always play out as we expect.

So was my worry and shock about the release of genetically modified mosquitos out of proportion or reasonable caution? As often is the case, it turns out the answer isn’t a simple yes or no. And the first thing to unravel is that I’ve been muddled about what a GMO actually is, and perhaps you have too. I’d often argued with anti-GMOers that we’ve been modifying animals and plants genomes for thousands of years, so genetic modifications are nothing new. While it is true that carrots, tomatoes, tea, dogs, horses and cows are all domesticated species that differ, genetically, from their wild ancestors they are not GMOs. GMOs genes have been directly altered by introducing, modifying or removing genes. Deliberately and at the gene level. Thus GMOs do not include creatures created with selective breeding, crossbreeding, nor cloning.This new appreciation for the definition of GMOs pushed back on my comfort with them.

On the other hand, in researching this article I’ve also learned about the enormous benefits that are possible with GMOs. In the food category alone, there are such remarkable benefits that about 90% of corn, soybeans and sugar beets on the market today are GMOs. The engineered crops have higher yields, longer shelf lives and are bred to be resistant to diseases and pests. Some taste better and others have higher nutrient quantities. Disease and pest resistance are, on the surface, a win win for farmers and the environment since less pesticide is needed. GMOs may well be better for the environment than conventionally grown crops. There are also applications for livestock, such as a genetically engineered salmon that reaches maturity at 18 months rather than 3 years.

The same kind of gene manipulation is in trial for several diseases in humans, especially hereditary diseases. Genetic engineering allows the alteration of genes can such as cutting out mutated, disease causing genes and inserting healthy ones. There have been promising results in cases of advanced cancer, thalassemia, and cystic fibrosis. There is ongoing research exploring using gene editing to cure other diseases like childhood blindness, muscular dystrophy, and Huntington’s disease, as well as treating both AIDS and COVID-19 and other influenzas. That’s a pretty amazing list.

This has been made more feasible by the technological advance of CRISPR, an acronym for clustered regularly interspaced short palindromic repeats. Working with various enzymes, CRISPR can recognize, and cleave, modify, or replace specific strands of DNA. The applications for this are endless, from curing diseases to designer babies. If you think that sounds like science fiction, you’d be right that it sounds fantastical but it isn’t fiction. The first CRISPR genome-edited babies were born in October 2018, amid great secrecy. Their dad was HIV positive and CRISPR was used to remove the CCR5 gene from his sperm before fertilization took place in the hopes of conferring genetic resistance to HIV to the twins.

However, the work leading to the birth of the genetically modified twin girls has been broadly and vehemently condemned as irresponsible and against guidelines for the use of CRISPR on human embryos. The researcher in charge of this experiment was indeed suspended from his job, and sentenced to 3 years in prison. In addition, there are questions surrounding the necessity of gene manipulation in this particular case because HIV positive fathers routinely sire HIV negative babies.

The case of the twins also exposed the reasons we need to be cautious about messing with the human genome. These girls are capable of passing on their genetic mutations to their progeny. And because the field of editing the genes of humans is so new, we don’t know the potential negative or long term consequences of the procedure nor of altering humanity’s DNA. One of the key worries is that CRISPR may not be as precise as one would like and may edit genes unintentionally and / or may only partially edit some cells - call mosaicism. There is evidence that the twins have mosaicism, meaning, among other possible consequences they may not even be HIV resistant. It is possible that the gene editing they did receive will make them more susceptible to West Nile Virus and possibly the flu.

Unintended consequences of gene editing have also arisen in a study exploring the use of CRISPR to repair a mutation that can cause hereditary blindness. This study found that CRISPR can cause serious side effects - prompting the ejection of large chunks of genetic material. In the blindness study roughly 1/2 of the specimens were compromised. Some by so much that entire chromosomes were ejected by the parent cells, including the units in which human DNA is found. This is wholesale big impact consequence, in a situation where even tiny changes can have dramatic consequences.

So where do we stand on this dance floor with regard to gene editing? Gene editing offers amazing potential - to whirl us away on a wave of joy by reducing our needs for pesticides, by reducing nutritional deficiencies, and by curing all kinds of diseasess. And at least in terms of the disease research, it feels fairly well monitored, even safe that we are designing the dance steps towards these cures. Great care and consideration is being taken with modifications to the human genome. Quite rightly. But there are many more cases of genetically modified plants and animals, some of which are already in commerce. And in the non-human examples we are not being nearly as careful. Man made genetic modifications have already leaked into the wild in a number of cases and have even cross-pollinated with other strains demonstrating the ability of human-engineered genes to evolve and thrive.

There’s no putting that genie back in its bottle. While the likelihood that one of these edited genes will lead to disaster may be very small, the potential consequences and the unpredictability of the technology are too large for me to want to contribute to that risk. So while I’m in favor of gene editing research continuing, I am still uncertain that we are ready to commodify it. Luckily, it is easy enough to avoid supporting GMO foods by buying organic. For both in the UK and the US organic labeling prohibits the use of GMOs. Fill up my dance card with organics please.