The Mosquito

by Timothy C. Winegard

  Given that the mosquito is far and away our biggest killer, there are many that argue along Malthusian lines against trying to eradicate mosquito-borne disease. Both humans and mosquitoes are part of the global ecology and biosphere, existing within a natural and animate system of checks and balances. Creating a disturbance in the force by eradicating our top predator is playing a dangerous game of Russian roulette. From a Malthusian worldview, given the limitations and sustainability of resources, the repercussions of unbridled human population growth might well lead to unimaginable suffering, starvation, disease, and catastrophic death—a Malthusian check by and of itself.

  Alternatively, if it is equality and justice for all we are seeking, it is hard not to appreciate the urgent logic of the counterargument—the unconditional and absolute eradication of the mosquito and her diseases from the face of the earth. Currently, four billion people in 108 countries around the world are at risk from mosquito-borne disease.* As our ancestors can attest, our battle with the mosquito has always been a matter of life and death. At this moment, with disease vectors crisscrossing the globe at record rates, even as our species overshoots the ecological carrying capacity of the planet, it’s beginning to look as though our history-shaping confrontation with the mosquito is coming to a head.

  Rachel Carson wrote that our attitude toward plants and animals is a singularly narrow one, that “if for any reason we find its presence undesirable or merely a matter of indifference, we may condemn it to destruction forthwith.” She could not have anticipated the arrival of CRISPR gene-editing technology, though, which dramatically speeds up the meaning of “forthwith,” and even changes the parameters and definition of the phrase “condemn to destruction.” By tinkering in a lab, we can now trespass and intrude on natural selection and biological design to impose extinction on any undesirable or indifferent species.

  Since its discovery by a team at the University of California Berkeley, led by biochemist Dr. Jennifer Doudna in 2012, the revolutionary gene-altering innovation known as CRISPR has shocked the world and altered our preconceived notions about our planet and our place on it.* The front pages of widely read magazines and journals are currently consumed by the topic of CRISPR and mosquitoes. First successfully used in 2013, CRISPR is a procedure that snips out a section of DNA sequencing from a gene and replaces it with another desired one, permanently altering a genome, quickly, cheaply, and accurately. Think of it as “cutting and pasting” genes at will.

  In 2016, the Gates Foundation investment toward CRISPR mosquito research totaled $75 million, the largest single sum backing gene-drive technology. “Our investments in mosquito control,” outlines the foundation, “include nontraditional biological and genetic approaches as well as new chemical interventions aimed at depleting or incapacitating disease-transmitting mosquito populations.” These genetic approaches include the use of CRISPR machinery to eradicate mosquito-borne diseases, most notably malaria. In an article titled “Gene Editing for Good: How CRISPR Could Transform Global Development,” published by Foreign Affairs in Spring 2018, Bill Gates summarized the tangible benefits of using CRISPR technology and the specific areas of research targeted and funded by his (and his wife, Melinda’s) foundation:

  But, ultimately, eliminating the most persistent diseases and causes of poverty will require scientific discovery and technological innovations. That includes CRISPR and other technologies for targeted gene editing. Over the next decade, gene editing could help humanity overcome some of the biggest and most persistent challenges in global health and development. The technology is making it much easier for scientists to discover better diagnostics, treatments, and other tools to fight diseases that still kill and disable millions of people every year, primarily the poor. It is also accelerating research that could help end extreme poverty by enabling millions of farmers in the developing world to grow crops and raise livestock that are more productive, more nutritious, and hardier. New technologies are often met with skepticism. But if the world is to continue the remarkable progress of the past few decades, it is vital that scientists, subject to safety and ethics guidelines, be encouraged to continue taking advantage of such promising tools as CRISPR.

  It’s not difficult to see why. A team of biologists at Berkeley reported that CRISPR chews through Zika, HIV, and other diseases “like Pac-Man.”

  The strategic target and goal of the Gates Foundation is, and has always been, the extermination of malaria and other mosquito-borne diseases, not to bring the mosquito—which is harmless when flying solo, untethered from a hitchhiking microorganism—to the brink of extinction. Of the more than 3,500 mosquito species, only a few hundred are capable of vectoring disease. Prefabricated genetically modified mosquitoes rendered incapable of harboring the parasite (a hereditary trait passed down their bloodline) just might end the timeless scourge of malaria. But, as Dr. Doudna and the Gates Foundation are acutely aware, CRISPR gene-swapping technology also has the potential to unleash darker, more sinister genetic blueprints with perilous and dangerous possibilities. CRISPR research is a global phenomenon, and neither Doudna nor the foundation has a monopoly on its limitless designs, its instruments of implementation, or its operational execution.

  CRISPR has been dubbed the extinction drive, machine, or gene, as this is precisely what it can accomplish—the extermination of mosquitoes by way of genetic sterilization. This theory has been floating around the scientific community since the 1960s. CRISPR can now put these principles into practice. To be fair, the mosquito altered our DNA in the form of sickle cell and other genetic malarial safeguards; perhaps it is time to return the favor. Designer male mosquitoes, which have been genetically modified with domineering “selfish genes” using CRISPR, are released into mosquito zones to breed with females to produce stillborn, infertile, or only male offspring. The mosquito would be extinct in one or two generations. With this war-winning weapon, humanity would never again have to fear the bite of a mosquito. We would awaken to a brave new world, one without mosquito-borne disease.

  An alternative to erecting a mosquito exhibit in the extinct-species wing of museums is simply to make them harmless, a strategy supported and funded by the Gates Foundation. With “gene drive” technology, explained Gates in October 2018, “essentially, scientists could introduce a gene into a mosquito population that would either suppress the population—or prevent it from spreading malaria. For decades, it was difficult to test this idea. But with the discovery of CRISPR, the research became a lot easier. And just last month, a team from the research consortium Target Malaria announced that they’d completed studies where mosquito populations were fully suppressed. To be clear: The test was only in a series of laboratory cages filled with 600 mosquitoes each. But it’s a promising start.” Dr. Anthony James, a molecular geneticist at the University of California Irvine, who self-admittedly “has been obsessed with mosquitoes for 30 years,” CRISPR’d a species of Anopheles mosquito to make it incapable of spreading malaria, by eliminating the parasites as they are processed through the mosquito’s salivary gland. “We added a small package of genes,” explains James, “that allows the mosquitoes to function as they always have, except for one slight change.” They can no longer harbor the malaria parasite. The Aedes breed is more difficult to tackle since it transmits a handful of diseases that include yellow fever, Zika, West Nile, chikungunya, Mayaro, dengue, and other encephalitides. “What you need to do is engineer a gene drive that makes the insects sterile,” James said of the Aedes breed. “It doesn’t make sense to build a mosquito resistant to Zika if it could still transmit dengue and other diseases.” We have reached the point in history where we can choose life-forms to eradicate nearly as easily as we order items from a menu, pick a bingeworthy show on Netflix, or click to buy anything on Amazon.

  We have valid, although yet unknown, reasons to be careful what we wish for. If we eradicate disease-vectoring mosquito species, such as Anopheles, Aedes, and Culex, wo
uld other mosquito species or insects simply fill the ecological niche and occupy the zoonotic gap, continuing the transmission of disease? What effect would eliminating mosquitoes (or any other animals for that matter, or reintroducing long-extinct species) have on the balance of the force and Mother Nature’s biological equilibrium? What would happen if we exterminate species that play an essential but unrecognized role in global ecosystems? Where would it end? As we are just beginning to ask these morally fraught and biologically ambiguous questions, no one really knows the answers.

  The only human disease to have been completely exterminated is the variola virus or smallpox. During the twentieth century, before it was condemned to extinction and entrusted to history, smallpox killed an estimated 300 million people. The disease was targeted for eradication by the WHO, not only because of its lethal nature, but also because it could not hide. Humans were the sole host, and the virus could not survive independently for more than a few hours at most. The last natural case of this legendary killer was reported in Somalia in 1977. The 3,000-year cycle of smallpox transmission had been forever stamped out. At the same time, however, the still unidentified HIV was slowly making its global rounds out of Africa. One deadly disease was replaced with another. For polio and numerous parasitic worms, including filariasis, the end is also near. But these too are being replaced by other new emerging diseases such as Ebola, Zika, West Nile, and others. Since 2000, for instance, the newfangled mosquito-borne Jamestown Canyon virus, a milder West Nile copycat first isolated in Jamestown, Colorado, in 1961, has spread across North America as far afield as Newfoundland.

  With CRISPR, we as a species now have the ability to effect premeditated extinction on any organism we choose. We also have the capacity to bring extinct species back to life, so long as ancient DNA is viable. In February 2017, a team of Harvard scientists announced that “the Wooly Mammoth will be back from extinction in two years.” Did I not already watch this movie as a kid? Back then, it was sci-fi and we called it Jurassic Park. Hollywood has a dramatic flair for exploiting and capitalizing on our scientific marvels gone awry and our hubris-driven technological miscalculations. The consequences of abusing or misusing CRISPR technology, short of velociraptors terrorizing Times Square or Piccadilly Circus and T. rex window shopping down Main Street USA or the Champs-Élysées, are real. “We can remake the biosphere to be what we want, from woolly mammoths to nonbiting mosquitoes,” counsels Henry Greely, professor of law and the director of the Center for Law and the Biosciences at Stanford University. “How should we feel about that? Do we want to live in nature, or in Disneyland?” We as a species are faced with an unprecedented moral dilemma, with repercussions that are immeasurable and almost certainly unintended. The tsunami of cataclysmic change would occur in every sector of civilization. Science fiction would become reality, if it has not already.

  According to Dr. Thomas Walla, professor of biology in tropical ecology and my colleague at Colorado Mesa University, “the technology is so easy, cheap, and widespread that graduate students will be able to experiment with new CRISPR applications in the lab with relative ease. The launch of CRISPR might well have unhinged Pandora’s Box.” With CRISPR, the DNA building blocks of any organism, including humans, can be rearranged endlessly. “What are the unintended consequences of genome editing?” Doudna asked herself. “I don’t know that we know enough,” she answered. “But people will use the technology whether we know enough about it or not. It seemed incredibly scary that you might have students who were working on such a thing. It’s important for people to appreciate what this technology can do.” Revolutionary, yes, but frightening at the same time. As J. Robert Oppenheimer, head of the Manhattan Project, lamented after the first successful atomic test in July 1945, “I remembered the line from the Hindu scripture, the Bhagavad-Gita; Vishnu is trying to persuade the Prince that he should do his duty and, to impress him, takes on his multi-armed form and says, ‘Now I am become Death, the destroyer of worlds.’”

  While this type of genetic manipulation used on humans could eradicate disease, biological disorders, or essentially any traits deemed “undesirable,” it could also be harnessed for eugenics, biological WMDs, other depraved purposes, or the eradication of “undesirables,” emulating the script of the 1997 movie Gattaca. In February 2016, the US director of national intelligence, James Clapper, warned Congress and President Barack Obama in his annual report that CRISPR should be regarded as a viable and potential WMD. “Just as gene drives can make mosquitoes unfit for spreading the malaria parasite,” warns David Gurwitz, professor of human molecular genetics and biochemistry at Tel Aviv University, “they could conceivably be designed with gene drives carrying cargo for delivering lethal bacterial toxins to humans.” While zoonotic animal vectors, including the mosquito, can be genetically driven to terminate the spread of pathogens, they could also be manipulated to become supercharged delivery systems for these same diseases. Although we have unlocked the secrets of this technology, we have only scratched the surface of its potential. The downside to CRISPR is pretty much the definition of dystopia.

  In 2016, the Chinese conducted the first human CRISPR trials, quickly followed by the United States and Great Britain in early 2017. “Everything is possible with CRISPR,” says geneticist Hugo Bellen at Baylor College of Medicine. “I’m not kidding.” Within the whirlwind of CRISPR genetic reprogramming, there are currently over 3,500 CRISPR human gene-drive experiments under way in laboratories all over the world. While we can remove mosquitoes, we can also remodel humankind. Like any other species, we are the product of millions of years of sophisticated evolution. Now, with CRISPR, we are taking matters into our own hands.

  On November 26, 2018, at the Second International Summit on Human Genome Editing, He Jiankui, a Chinese geneticist, announced to the world that he had defied government regulations and guidelines and successfully CRISPR’d the embryos of twin girls, bestowing on one of them, Nana, complete immunity to HIV, while her twin sister, Lulu, was given only partial immunity.* His declaration has stirred up a hornet’s nest of controversy, condemnation, criticism, and, most importantly, questions and international dialogue over the future use of CRISPR. Leading geneticists and biologists, including Jennifer Doudna, were appalled by the revelation and issued panning responses that included: “Irresponsible”; “If true, this experiment is monstrous”; “We’re dealing with the operating instructions of a human being. It’s a big deal”; “I unequivocally condemn the experiment.” An article in Nature stated that his Chinese colleagues were especially disenchanted, and reproaches were “particularly acute in China, where scientists are sensitive to the country’s reputation as the Wild West of biomedical research.”

  In his “2018 Year in Review” or annual “wrap-up,” Bill Gates weighed in on He Jiankui’s rogue “CRISPR baby” creations, affirming that “I agree with those who say this scientist went too far.” In his hopeful and inspiring vision of the future, however, Gates added, “But something good can come from his work if it encourages more people to learn and talk about gene editing. This might be the most important public debate we haven’t been having widely enough. The ethical questions are enormous. Gene editing is generating a ton of optimism for treating and curing diseases, including some that our foundation works on (though we fund work on altering crops and insects, not humans). . . . I am surprised that these issues haven’t generated more attention from the public. Today artificial intelligence is the subject of vigorous debate. Gene editing deserves at least as much of the spotlight as AI.” For better or for worse, it is widely accepted and acknowledged that CRISPR will soon take center stage and dominate the spotlight, if it has not already.

  By the time this book is published, I can promise and safely predict that genetically modified CRISPR “designer babies” will have caused a storm of controversy and debate and a flood of international moral and legal soul-searching. As Harvard University geneticist Dr. George Church declared, with
CRISPR “the genie is already out of the bottle.” Many embroiled in its research and debate want to stuff it back in as quickly as possible. If Dr. He Jiankui’s announcement turns out to be true and his results authenticated, this window of opportunity might have already closed.

  The idea that we can control these unimaginably complex genetic encodings and ecosystems is like believing we can control the weather. Yes, we can affect it, but we can also certainly make it worse. We have no reason whatsoever to believe that we can engineer a perfectly desired outcome or fabricate a flawlessly designed product 100% of the time. It only takes one mistake, slipup, inadvertent human error to set us on a disastrous orbit or flight path. The recent uptick in natural disasters, or Malthusian checks, including emerging or reemerging diseases, devastating hurricanes, tsunamis, wildfires, droughts, and earthquakes, reminds us that we are relatively helpless and are not quite as clever or omnipotent as we often believe. We are one of an estimated 8–11 million species that share our planet.* We are no different from any other organism of Darwin’s evolutionary design engaged in the continuous struggle of survival of the fittest. Nature always has a way of bringing us, and our Homo sapiens “wise man” hubris, back down to earth.