If you could protect children in Africa from malaria by genetically transforming the entire mosquito population, would you do it? That’s the dilemma posed by a new technology known as gene drive, evolutionary ecologist James Collins from Arizona State University in Tempe told a session at the annual meeting of the American Association for the Advancement of Science in February held in Boston.
Based on CRISPR, the up-and-coming genome-editing technology, gene drives bias the inheritance of a trait, such as resistance to a parasite, causing it to spread through a population. But because of the possible unintended consequences of transforming the genetics of an entire population, the National Academies of Sciences, Engineering, and Medicine last year said extensive testing should precede any release into the environment.
Collins became involved in gene ethics after realizing that its implications could touch his own research. At Arizona State, his lab studies how ecology and evolution shape species. Currently, amphibians are globally declining. Under two National Science Foundation grants, Collins heads an international team of 26 investigators that is studying how pathogens are invading populations and leading to this decline.
Tracing the pathogen’s steps and being able to predict the next wave of amphibian deaths poses a difficult ethical question for Collins. With gene drive technology, researchers may be able to save these species by introducing a gene that is resistant to the pathogen, but is manipulating nature ever okay? The issue also raises the question of whether humans are a part of nature. After his talk at AAAS, Collins discussed the ethics of gene drives with SciCom’s Yasemin Saplakoglu.
Editor’s note: A shorter version of this piece appeared online at Science.
How do gene drives work?
You take out a gene and substitute or cause a substitution of another one. As a consequence of that modification, you bias the inheritance of that trait.
Should we be looking at how the environment might be affected by gene drives?
Absolutely; this is a manipulation of nature. We don’t know how it would affect population dynamics and ecosystems. In some cases, the purpose of gene drives would be to reduce population sizes of an organism, which could influence processes like pollination and transmission of parasites. In other cases, we would use gene drives to weed out disease by driving the population that carries that disease to extinction.
What is the worst-case scenario of releasing these organisms?
Eliminating an organism or reducing its numbers greatly. By eliminating one plant species, you cause the proliferation of others, and this leads to a series of changes in the ecosystem. We need to understand the system well enough so that we can take ethical concerns into account as we make decisions.
Who gets to make these decisions?
Social scientists are trying to come up with better ways to sample human populations to get a better sense of what’s tolerable and what’s not tolerable in terms of their release. If you release [modified mosquitoes] in Town A, the mosquitoes may not have any problem flying to Town B, even though Town B is not interested in having them. They’ll go anyway.
The U.S. Food and Drug Administration approved the release of genetically modified male mosquitoes in certain areas of Florida. When these altered male mosquitos mate with Zika-carrying female mosquitoes, their Zika-carrying offspring will die. If that technology is acceptable, why be so cautious about gene drives?
The advantage of these other technologies is that they are effective only as long as you’re releasing modified male mosquitoes. When you stop the manipulation, the population would bounce back to normal levels. You have a control over the system that is yet to be demonstrated for gene drives; once you alter the genes in these populations, they just keep changing.
"This is a manipulation of nature. We don’t know how it would affect population dynamics and ecosystems."
So, it would get out of control.
It’s not so much that it would be out of control, it’s that you couldn’t have, right from the start, the sort of control that you would have using these other approaches for altering mosquito populations.
How did you get involved with gene drives?
I was drawn into it by colleagues at the Wilson Center for Science Policy in Washington D.C. who were looking for someone who understood ecological and evolutionary arguments and had a policy background. By that time I had spent five years working at the National Science Foundation. I also had an interest in ethical issues, and so they brought me in to help organize some workshops in synthetic biology.
What kind of workshops?
The question had to do with what might be the ecological and evolutionary ethical consequences of the synthetic biology work that people were doing. One of the examples was gene drives.
How do gene drives play into your own research at Arizona State University?
We work on the evolution of infectious diseases, specifically in amphibians. We are particularly interested in the way in which infectious diseases can cause extinction in amphibian populations. There was some hope that this gene drive technology might be applicable in amphibians to alter their biology in order to make them more resistant to the infectious fungus, called “chytrid” fungus, which could kill them. But I don’t see that as a real option, at least in the immediate future.
What is the most surprising discovery your lab has made?
The most satisfying discovery was one that we made about five years ago working with Karen Lips and colleagues at the University of Maryland. We found that chytrids were clearly responsible for the decline and extinction of amphibian species in Panama. This was the first and clearest demonstration that this infectious fungus caused the decline. As opposed to other cases where you see the appearance of a pathogen and then the decline of individual species but you don’t have evidence that the pathogen was in the populations before their decline, in our case we had data showing that the pathogen was not in these populations to begin with. So, it entered the population and caused their decline.
Did humans introduce the fungus?
We don’t know how it got in. In fact, the data on how this pathogen is moved is diverse and uncertain at the moment. One hypothesis is that bullfrogs are moving the pathogen around, but we need more evidence to understand this.
So that was five years ago. What have you been doing in your lab since?
We’ve mostly been working on trying to understand the variations in environmental conditions under which this pathogen will live, such as variations in temperature. There’s also work we’ve been doing at more of a meta-analysis level, synthesizing a wide variety of papers to try to understand where the pathogen lives and identify areas where it absolutely doesn’t. A couple of my grad students are working now to understand why this pathogen doesn’t seem to be causing declines in parts of Arizona as it does in other places.
What are you hoping to find out?
We are hoping that we can understand what larger climatic variables might be driving success and failure, in terms of the existence of this pathogen on these hosts. Also, what are some of the microclimatic circumstances that allow these animal hosts to have this pathogen on them that sometimes cause death and other times don’t.
Your research also looks at the natural way in which genes evolve and change throughout time. Is the parallel between human-induced gene drives and natural gene evolution an idea you’re interested in?
I’m interested in understanding the population dynamics of the host and pathogen in the natural field, as opposed to gene drives, which is more from the point of view of science policy right now. Ben Minteer [professor of environmental ethics and conservation at Arizona State University] and I have written a number of papers in this area called ecological ethics. We are very interested in the conditions under which nature gets manipulated. What’s the distinction between natural systems and systems that are not natural? Are humans in nature, or are we out of nature?
So would studying climate and microenvironments be necessary groundwork for gene drive research?
The potential of using gene drives for initially controlling emerging infectious diseases like malaria or dengue is an epidemiological story. The amphibian decline story is an epidemiological story as well. So there’s a real connection between the two—one doesn’t have an application as far as technology is concerned, but the other potentially does.
How would the gene drive technology actually protect amphibians from such pathogens?
The results from Panama showed that this pathogen was moving to Panama through Costa Rica in a wave-like pattern. We got to the point where we could predict where the next communities of amphibians were that were likely to be affected by this pathogen if the pattern held up. In one case, our prediction was dead on. Indeed, the pathogen showed up and began to cause declines. We then made a prediction for another spot. But then the question becomes, as a scientist, do you just document this as part of understanding host-pathogen biology, or is there in some sense an ethical obligation to try and conserve those species?
Is there?
One answer is, sure. In the interest of conservation biology, some say these animals should be pulled out and saved. Indeed that’s the answer that is taken by folks from the Atlanta Zoo. They went in and removed species, and that’s still being done in other cases.
Another answer is: there’s no evidence yet that this pathogen is being moved around by humans, so just let it go. This is a natural system, let it go. The notion of ecological ethics is much about how we adjudicate both of those positions and how we reason our way through acting in one way as opposed to another.
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© 2017 Yasemin Saplakoglu. Watch Yasemin’s writing evolve at https://www.yaseminsaplakoglu.com.
