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Daily News Blog

11
Feb

Biotech Fixes for Pesticide Failures Continue Treadmill of Increased Toxic Chemical Use

(Beyond Pesticides, February 11, 2022) A team of researchers has proffered a potential, biotechnical, way forward in the quest to reduce the scourge of malaria, which affects many people across the world. Their work uses the relatively new “Crispr” technique to address, and reverse, the growing problem of mosquito resistance to the pesticides that currently dominate control strategies for the insects that spread the disease. This innovation nevertheless raises concern about both the introduction of new, genetically altered organisms into the environment without sufficient information on the implications, and continued, intensive pesticide use. Beyond Pesticides recognizes, as do the researchers, that malaria-borne mosquitoes pose a serious public health problem; however, it advocates for alternatives to chemical approaches to managing the spread of the disease, and asserts that successful management strategies will contend with the underlying conditions that exacerbate that spread. In 2020, Executive Director Jay Feldman said, “We should focus on the deplorable living conditions, and inequitable distribution of wealth and resources worldwide that give rise to squalor, inhumane living conditions, and the poor state of development that, together, breed insect-borne diseases like malaria.”    

Malaria, which is spread by female Anopheles mosquitoes infected with a Plasmodium parasite, causes illness in more than 200 million people annually, and is lethal to more than 400,000, many of whom are children. (There are five types of Plasmodium that cause malaria.) Roughly half of the global population, across more than 100 countries and territories, is at risk of contracting the disease. Those areas at greatest risk include large swaths of Africa and South Asia, parts of Central and South America, the Caribbean, Southeast Asia, the Middle East, and Oceania. 

Beyond Pesticides wrote in 2020, “In such regions, primary control strategies for these mosquito vectors during the past couple of decades have been the insecticidal treatment of bed nets (known as ITNs), and indoor residual spraying (IRS) of insecticides on walls, floors, ceilings, and eaves prior to the intensive malaria transmission season.” However, Anopheles mosquitoes are increasingly developing resistance to at least two of the four insecticides most commonly used — pyrethroid insecticides and DDT — meaning that such controls are becoming far less effective. (Over the past two decades, deltamethrin and λ-cyhalothrin (synthetic pyrethroids), and DDT have been used for IRS, but other classes of insecticides, such as carbamates and organophosphates, are increasingly being added to the IRS “arsenal.”)

It is important to note the toxicity and persistence of DDT. It has been linked to cancer in humans and is acutely toxic to fish and marine invertebrates. Intensive global use of DDT (which was banned in the U.S. in 1972 in recognition of its extreme harms) has resulted in rapid development of resistance in some regions (as has the overuse of synthetic pyrethroids and DDT alternatives). The stability and persistence of DDT, and its decades-long use, now manifest in its presence everywhere, from the open oceans to Himalayan glaciers — even in Arctic polar bear populations Antarctic penguin colonies.

A 2020 Daily News Blog article and another in 2021 detail the rise of resistance to mosquito pesticides and the need to shift to alternative management strategies. Research in Kenya back in 2015 pointed to rapidly developing resistance in Anopheles gambiae to pyrethroids and DDT. A June 2020 research study revealed a dramatic increase in resistance to these insecticides across sub-Saharan Africa, where malaria is spread by A. gambiae. This widespread resistance means that the tools on which antimalarial public health measures have heavily relied are working less and less well. This subject study was conducted by a team out of the University of California San Diego and the Tata Institute for Genetics and Society in India; the study paper was published on January 12 in Nature Communications.

The Crispr gene editing used in this research allows the identification and alteration of a specific bit of DNA inside a cell. The team used Drosophila melanogaster (the common fruit fly) rather than mosquitoes in its lab experiments because of the greater base knowledge and protocols related to Drosophila (as compared with Anopheles). The research experiment replaced an insecticide-resistant gene mutation (kdr) that confers resistance to pyrethroids and DDT, the insecticides commonly used against Anopheles, with the normal form of the gene — thus restoring, temporarily, the efficacy of the insecticides.

The technique used is known as a “gene drive” — a type of biotechnology that “overrules the laws of heredity to spread a trait through a population more quickly than . . . would happen naturally, forcing that gene into a population’s offspring. In this case, the change essentially reboots the gene pool to what it was before the insects evolved resistance to a particular pesticide.” The gene drive used by the team uses a “guide RNA” molecule that tells the Crispr system to delete the unwanted gene variant — in this case, the one that causes resistance to these insecticides — and to replace it with the normal, or “native” gene variant (which does not exhibit pesticide resistance).

Thus, the Drosophila’s vulnerability to the chemicals’ lethality is restored, the normal variant gets copied, and all offspring inherit it. The authors write, “This successful proof-of-principle opens up numerous possibilities including targeted reversion of insecticide-resistant populations to a native susceptible state or replacement of malaria transmitting mosquitoes with those bearing naturally occurring, parasite-resistant alleles.”

The researchers began with a population of fruit flies in which 83% had the pesticide-resistant gene variant and 17% had the normal/native version. With the Crispr intervention, that ratio was reversed to 17% with the resistant allele and 83% with the normal version — in 10 generations. How to account for that 17% that continue to resist the pesticides? As Wired magazine coverage of the study notes, “Lab tests of gene drives have shown that it’s possible to spread a desired genetic trait through several generations. But studies have also found that resistance to gene drives can emerge because some mosquitoes don’t inherit the desired trait. In the wild, resistance is almost certain to occur, meaning that gene drives would probably still leave behind some mosquitoes that could bite humans and transmit disease.”

The authors posit that, because both fruit flies and Anopheles have two-week life cycles, it would take a few months to “re-jigger” the genetics of a population of Anopheles so as to restore vulnerability to pesticides. But the scientists agree that a single use of a gene drive on a population of Anopheles is not a long-term solution, because even if a local population of mosquitoes could be eliminated, insects “can travel halfway around the world, pop up in a new place, and establish a new population. A gene drive . . . might need to be applied seasonally, especially if multiple resistant genes are present within a population or new ones arise.”

Senior study author Ethan Bier, PhD commented, “This technology . . . offers a solution to the conundrum we’re facing now, which is that there hasn’t been a new category of insecticides developed for over 30 years. If you can go on using the ones you’ve got by re-sensitizing the mosquitoes to those, I think that would be an enormous benefit.” The team proffers the idea that employing this technology could both effectively control the spread of malaria and ultimately allow reductions in the amounts of insecticide used to manage local insect populations. Underscoring Beyond Pesticides’ point about resistance (see below), Dr. Bier added, “This is no silver bullet. You never win when you try to play the evolutionary game with insects.” His team is now working on translating the fruit fly gene drive into lab mosquitoes.

Other researchers are pursuing solutions that do not involve use of pesticides. In the summer of 2021, a research group out of the Polo GGB lab in Italy announced success in using the Crispr technique to introduce a mutation into female Anopheles that prevents the insects from biting, and therefore, from spreading the Plasmodium parasite that causes malaria. Another strategy is to genetically engineer mosquitoes to kill the malaria parasite they host. Yet another focuses on eradicating mosquitoes themselves via making mosquitoes infertile. “By using a gene drive to render males or females infertile,” Wired writes, “you could conceivably crash an entire population of mosquitoes.”

Beyond those, after three decades of research, the pursuit of a vaccine is finally yielding some benefit. Last October, the World Health Organization (WHO) recommended limited use of the world’s first malaria vaccine for use in children living in sub-Saharan Africa and other regions with moderate to high transmission rates of Plasmodium falciparum, the deadliest of the parasites that cause malaria. The recommendation opens the door to approval of a broader rollout of the vaccine program.

Co-authors of a 2011 study that addressed the use of DDT in malaria prevention captured the conundrum of pesticide-oriented solutions to malarial spread: “Overall, community health is significantly improved through all available malaria control measures, which include IRS with DDT. Is DDT ‘good’? Yes, because it has saved many lives. Is DDT safe as used in IRS? Recent publications have increasingly raised concerns about the health implications of DDT. Therefore, an unqualified statement that DDT used in IRS is safe is untenable. Are inhabitants and applicators exposed? Yes, and to high levels. Should DDT be used? The fact that DDT is ‘good’ because it saves lives, and ‘not safe’ because it has health and environmental consequences, raises ethical issues.” (There is no current and legitimate science that would defend DDT use as “safe.”)

The central issue, as Beyond Pesticides sees it, is that developing genetic engineering techniques to enable continued use of toxic pesticides is effort misplaced. Deployed, such strategies would not only cause collateral health and environmental harms from the continued use of pesticides, but also, could have unanticipated organismic and/or ecosystem impacts. As a professor of health law and ethics at Boston University, George Annas, JD, MPH (who authored a code of ethics for gene drive research), has said, “A lot of people think we shouldn’t use insecticides at all. The idea of using heavy-duty genetic editing so that we can continue using insecticides isn’t going to appeal to everyone. . .[C]onvincing the public to release genetically modified mosquitoes just to keep using insecticides, which come with a host of negative health and environmental effects, could be a hard sell.”

Mr. Annas is not the first ethicist to raise concern about unintended consequences of releasing gene drive technology into the wild, including a resurgence of resistance. According to Wired, he would like to see researchers work on some way to stop, or recall, a gene drive if an unsavory outcome develops. He said, “I’m not saying we’re going to develop a super mosquito, but that’s not out of the realm of possibility. A gene drive might make things worse and you certainly don’t want to do that.”

Beyond those concerns, as Beyond Pesticides has repeatedly identified, the pursuit of chemical fixes — whether for crop pests or for containing disease vectors — is ultimately a fool’s errand. In 2020, we wrote: “Resistance to pesticides is nearly inevitable. Development of resistance is an entirely normal, adaptive phenomenon: organisms evolve, ‘exploiting’ beneficial genetic mutations that give them survival advantage. For nearly a century, human response to this has been primarily a chemical ‘chasing’ of such evolutionary changes — developing a compound that kills the offending organism (whether pest or weed or bacterium or fungus) for a while. Organisms nearly inevitably change to become resistant to that particular chemical assault, whereupon people — the chemical industry, researchers, applicators, farmers, public health workers, clinicians, et al. — have typically moved on to the next chemical ‘solution.’”

In 2017, Pesticide Action Network North America (PANNA) concurred, noting, “This highlights the problem of relying on insecticide-based strategies for vector control… Ultimately, disease vectors and parasites develop resistance to the insecticide and it becomes almost ineffective in the long run.” The sustainable solutions to containing the spread of malaria lie not in the use of more and different chemicals, but in nontoxic approaches that respect nature and ecological balance. More sustainable (and effective) approaches would include habitat modification, improved sanitation, and use of natural controls, such as larviciding with Bt (Bacillus thuringiensis).

Beyond Pesticides has chronicled that the most successful mosquito management programs combine multiple strategies and focus, as well, on community education — but also, require significant government commitment and political will. In 1991, Vietnam reduced malaria deaths by 97% and malaria cases by 59% when it switched from malaria eradication attempts using DDT to a DDT-free malaria control program. A program in Kenya uses livestock as bait, introduces biological controls, and distributes mosquito nets in affected areas. Management strategies to combat malaria cannot be successful if they are entirely chemical because such approaches ignore the underlying conditions that exacerbate disease spread.

Even if malaria is not a local concern in the U.S., most people are concerned about the diseases mosquitoes can transmit, including West Nile virus, Eastern Equine Encephalitis, and Zika fever. Learn more about mosquito management at Beyond Pesticides’ resources on Mosquito Management and Insect-Borne Diseases, and Public Health Mosquito Management Strategy for Decision Makers and Communities.

Source: https://www.wired.com/story/could-crispr-flip-the-switch-on-insects-resistance-to-pesticides/

All unattributed positions and opinions in this piece are those of Beyond Pesticides.

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