Bivalent Boosters for Young Children Are Elusive. The Search Is On for Ways to Improve Access.
It’s Theo’s* first time in the snow. Wide-eyed, he totters outside holding his father’s hand. Sarah Holmes feels great joy in watching her 18-month-old son experience the world, “His genuine wonder and excitement gives me so much hope.”
In the summer of 2021, two months after Theo was born, Holmes, a behavioral health provider in Nebraska lost her grandparents to COVID-19. Both were vaccinated and thought they could unmask without any risk. “My grandfather was a veteran, and really trusted the government and faith leaders saying that COVID-19 wasn’t a threat anymore,” she says.” The state of emergency in Louisiana had ended and that was the message from the people they respected. “That is what killed them.”
The current official public health messaging is that regardless of what variant is circulating, the best way to be protected is to get vaccinated. These warnings no longer mention masking, or any of the other Swiss-cheese layers of mitigation that were prevalent in the early days of this ongoing pandemic.
The problem with the prevailing, vaccine centered strategy is that if you are a parent with children under five, barriers to access are real. In many cases, meaningful tools and changes that would address these obstacles are lacking, such as offering vaccines at more locations, mandating masks at these sites, and providing paid leave time to get the shots.
Children are at risk
Data presented at the most recent FDA advisory panel on COVID-19 vaccines showed that in the last year infants under six months had the third highest rate of hospitalization. “From the beginning, the message has been that kids don’t get COVID, and then the message was, well kids get COVID, but it’s not serious,” says Elias Kass, a pediatrician in Seattle. “Then they waited so long on the initial vaccines that by the time kids could get vaccinated, the majority of them had been infected.”
A closer look at the data from the CDC also reveals that from January 2022 to January 2023 children aged 6 to 23 months were more likely to be hospitalized than all other vaccine eligible pediatric age groups.
“We sort of forced an entire generation of kids to be infected with a novel virus and just don't give a shit, like nobody cares about kids,” Kass says. In some cases, COVID has wreaked havoc with the immune systems of very young children at his practice, making them vulnerable to other illnesses, he said. “And now we have kids that have had COVID two or three times, and we don’t know what is going to happen to them.”
Jumping through hurdles
Children under five were the last group to have an emergency use authorization (EUA) granted for the COVID-19 vaccine, a year and a half after adult vaccine approval. In June 2022, 30,000 sites were initially available for children across the country. Six months later, when boosters became available, there were only 5,000.
Currently, only 3.8% of children under two have completed a primary series, according to the CDC. An even more abysmal 0.2% under two have gotten a booster.
Ariadne Labs, a health center affiliated with Harvard, is trying to understand why these gaps exist. In conjunction with Boston Children’s Hospital, they have created a vaccine equity planner that maps the locations of vaccine deserts based on factors such as social vulnerability indexes and transportation access.
“People are having to travel farther because the sites are just few and far between,” says Benjy Renton, a research assistant at Ariadne.
Michelle Baltes-Breitwisch, a pharmacist, and her two-year-old daughter, Charlee, live in Iowa. When the boosters first came out she expected her toddler could get it close to home, but her husband had to drive Charlee four hours roundtrip.
This experience hasn’t been uncommon, especially in rural parts of the U.S. If parents wanted vaccines for their young children shortly after approval, they faced the prospect of loading babies and toddlers, famous for their calm demeanor, into cars for lengthy rides. The situation continues today. Mrs. Smith*, a grant writer and non-profit advisor who lives in Idaho, is still unable to get her child the bivalent booster because a two-hour one-way drive in winter weather isn’t possible.
It can be more difficult for low wage earners to take time off, which poses challenges especially in a number of rural counties across the country, where weekend hours for getting the shots may be limited.
Protect Their Future (PTF), a grassroots organization focusing on advocacy for the health care of children, hears from parents several times a week who are having trouble finding vaccines. The vaccine rollout “has been a total mess,” says Tamara Lea Spira, co-founder of PTF “It’s been very hard for people to access vaccines for children, particularly those under three.”
Seventeen states have passed laws that give pharmacists authority to vaccinate as young as six months. Under federal law, the minimum age in other states is three. Even in the states that allow vaccination of toddlers, each pharmacy chain varies. Some require prescriptions.
It takes time to make phone calls to confirm availability and book appointments online. “So it means that the parents who are getting their children vaccinated are those who are even more motivated and with the time and the resources to understand whether and how their kids can get vaccinated,” says Tiffany Green, an associate professor in population health sciences at the University of Wisconsin at Madison.
Green adds, “And then we have the contraction of vaccine availability in terms of sites…who is most likely to be affected? It's the usual suspects, children of color, disabled children, low-income children.”
It can be more difficult for low wage earners to take time off, which poses challenges especially in a number of rural counties across the country, where weekend hours for getting the shots may be limited. In Bibb County, Ala., vaccinations take place only on Wednesdays from 1:45 to 3:00 pm.
“People who are focused on putting food on the table or stressed about having enough money to pay rent aren't going to prioritize getting vaccinated that day,” says Julia Raifman, assistant professor of health law, policy and management at Boston University. She created the COVID-19 U.S. State Policy Database, which tracks state health and economic policies related to the pandemic.
Most states in the U.S. lack paid sick leave policies, and the average paid sick days with private employers is about one week. Green says, “I think COVID should have been a wake-up call that this is necessary.”
Maskless waiting rooms
For her son, Holmes spent hours making phone calls but could uncover no clear answers. No one could estimate an arrival date for the booster. “It disappoints me greatly that the process for locating COVID-19 vaccinations for young children requires so much legwork in terms of time and resources,” she says.
In January, she found a pharmacy 30 minutes away that could vaccinate Theo. With her son being too young to mask, she waited in the car with him as long as possible to avoid a busy, maskless waiting room.
Kids under two, such as Theo, are advised not to wear masks, which make it too hard for them to breathe. With masking policies a rarity these days, waiting rooms for vaccines present another barrier to access. Even in healthcare settings, current CDC guidance only requires masking during high transmission or when treating COVID positive patients directly.
“This is a group that is really left behind,” says Raifman. “They cannot wear masks themselves. They really depend on others around them wearing masks. There's not even one train car they can go on if their parents need to take public transportation… and not risk COVID transmission.”
Yet another challenge is presented for those who don’t speak English or Spanish. According to Translators without Borders, 65 million people in America speak a language other than English. Most state departments of health have a COVID-19 web page that redirects to the federal vaccines.gov in English, with an option to translate to Spanish only.
The main avenue for accessing information on vaccines relies on an internet connection, but 22 percent of rural Americans lack broadband access. “People who lack digital access, or don’t speak English…or know how to navigate or work with computers are unable to use that service and then don’t have access to the vaccines because they just don’t know how to get to them,” Jirmanus, an affiliate of the FXB Center for Health and Human Rights at Harvard and a member of The People’s CDC explains. She sees this issue frequently when working with immigrant communities in Massachusetts. “You really have to meet people where they’re at, and that means physically where they’re at.”
Equitable solutions
Grassroots and advocacy organizations like PTF have been filling a lot of the holes left by spotty federal policy. “In many ways this collective care has been as important as our gains to access the vaccine itself,” says Spira, the PTF co-founder.
PTF facilitates peer-to-peer networks of parents that offer support to each other. At least one parent in the group has crowdsourced information on locations that are providing vaccines for the very young and created a spreadsheet displaying vaccine locations. “It is incredible to me still that this vacuum of information and support exists, and it took a totally grassroots and volunteer effort of parents and physicians to try and respond to this need.” says Spira.
Kass, who is also affiliated with PTF, has been vaccinating any child who comes to his independent practice, regardless of whether they’re one of his patients or have insurance. “I think putting everything on retail pharmacies is not appropriate. By the time the kids' vaccines were released, all of our mass vaccination sites had been taken down.” A big way to help parents and pediatricians would be to allow mixing and matching. Any child who has had the full Pfizer series has had to forgo a bivalent booster.
“I think getting those first two or three doses into kids should still be a priority, and I don’t want to lose sight of all that,” states Renton, the researcher at Ariadne Labs. Through the vaccine equity planner, he has been trying to see if there are places where mobile clinics can go to improve access. Renton continues to work with local and state planners to aid in vaccine planning. “I think any way we can make that process a lot easier…will go a long way into building vaccine confidence and getting people vaccinated,” Renton says.
Michelle Baltes-Breitwisch, a pharmacist, and her two-year-old daughter, Charlee, live in Iowa. Her husband had to drive four hours roundtrip to get the boosters for Charlee.
Michelle Baltes-Breitwisch
Other changes need to come from the CDC. Even though the CDC “has this historic reputation and a mission of valuing equity and promoting health,” Jirmanus says, “they’re really failing. The emphasis on personal responsibility is leaving a lot of people behind.” She believes another avenue for more equitable access is creating legislation for upgraded ventilation in indoor public spaces.
Given the gaps in state policies, federal leadership matters, Raifman says. With the FDA leaning toward a yearly COVID vaccine, an equity lens from the CDC will be even more critical. “We can have data driven approaches to using evidence based policies like mask policies, when and where they're most important,” she says. Raifman wants to see a sustainable system of vaccine delivery across the country complemented with a surge preparedness plan.
With the public health emergency ending and vaccines going to the private market sometime in 2023, it seems unlikely that vaccine access is going to improve. Now more than ever, ”We need to be able to extend to people the choice of not being infected with COVID,” Jirmanus says.
*Some names were changed for privacy reasons.
For decades, women around the world have made the annual pilgrimage to their doctor for the dreaded but potentially life-saving Papanicolaou test, a gynecological exam to screen for cervical cancer named for Georgios Papanicolaou, the Greek immigrant who developed it.
The Pap smear, as it is commonly known, is credited for reducing cervical cancer mortality by 70% since the 1960s; the American Cancer Society (ACS) still ranks the Pap as the most successful screening test for preventing serious malignancies. Nonetheless, the agency, as well as other medical panels, including the US Preventive Services Task Force and the American College of Obstetrics and Gynecology are making a strong push to replace the Pap with the more sensitive high-risk HPV screening test for the human papillomavirus virus, which causes nearly all cases of cervical cancer.
So, how was the Pap developed and how did it become the gold standard of cervical cancer detection for more than 60 years?
Born on May 13, 1883, on the island of Euboea, Greece, Georgios Papanicolaou attended the University of Athens where he majored in music and the humanities before earning his medical degree in 1904 and PhD from the University of Munich six years later. In Europe, Papanicolaou was an assistant military surgeon during the Balkan War, a psychologist for an expedition of the Oceanographic Institute of Monaco and a caregiver for leprosy patients.
When he and his wife, Andromache Mavroyenous (Mary), arrived at Ellis Island on October 19, 1913, the young couple had scarcely more than the $250 minimum required to immigrate, spoke no English and had no job prospects. They worked a series of menial jobs--department store sales clerk, rug salesman, newspaper clerk, restaurant violinist--before Papanicolaou landed a position as an anatomy assistant at Cornell University and Mary was hired as his lab assistant, an arrangement that would last for the next 50 years.
Papanikolaou would later say the discovery "was one of the greatest thrills I ever experienced during my scientific career."
In his early research, Papanikolaou used guinea pigs to prove that gender is determined by the X and Y chromosomes. Using a pediatric nasal speculum, he collected and microscopically examined vaginal secretions of guinea pigs, which revealed distinct cell changes connected to the menstrual cycle. He moved on to study reproductive patterns in humans, beginning with his faithful wife, Mary, who not only endured his almost-daily cervical exams for decades, but also recruited friends as early research participants.
Writing in the medical journal Growth in 1920, the scientist outlined his theory that a microscopic smear of vaginal fluid could detect the presence of cancer cells in the uterus. Papanikolaou would later say the discovery "was one of the greatest thrills I ever experienced during my scientific career."
At this time, cervical cancer was the number one cancer killer of American women but physicians were skeptical of these new findings. They continued to rely on biopsy and curettage to diagnose and treat the disease until Papanicolaou's discovery was published in American Journal of Obstetrics and Gynecology. An inexpensive, easy-to-perform test that could detect cervical cancer, precancerous dysplasia and other cytological diseases was a sea change. Between 1975 and 2001, the cervical cancer rate was cut in half.
Papanicolaou became Emeritus Professor at Cornell University Medical College and received numerous awards, including the Albert Lasker Award for Clinical Medical Research and the Medal of Honor from the American Cancer Society. His image was featured on the Greek currency and the US Post Office issued a commemorative stamp in his honor. But international acclaim didn't lead to a more relaxed schedule. The researcher continued to work seven days a week and refused to take vacations.
After nearly 50 years, Papanicolaou left Cornell to head and develop the Cancer Institute of Miami. He died of a heart attack on February 19, 1962, just three months after his arrival. Mary continued to work in the renamed Papanicolaou Cancer Research Institute until her death 20 years later.
The annual pap smear was originally tied to renewing a birth control prescription. Canada began recommending Pap exams every three years in 1978. The United States followed suit in 2012, noting that it takes many years for cervical cancer to develop. In September 2020, the American Cancer Society recommended delaying the first gynecological pelvic exam until age 25 and replacing the Pap test completely with the more accurate human papillomavirus (HPV) test every five years as the technology becomes more widely available.
Not everyone agrees that it's time to do away with this proven screening method, though. The incidence rate of cervical cancer among Hispanic women is 28% higher than for white women, and Black women are more likely to die of cervical cancer than any other racial or ethnicities.
Whether the Pap is administered every year, every three years or not at all, Papanicolaou will always be known as the medical hero who saved countless women who would otherwise have succumbed to cervical cancer.
Science Has Given Us the Power to Undermine Nature's Deadliest Creature: Should We Use It?
Lurking among the swaying palm trees, sugary sands and azure waters of the Florida Keys is the most dangerous animal on earth: the mosquito.
While there are thousands of varieties of mosquitoes, only a small percentage of them are responsible for causing disease. One of the leading culprits is Aedes aegypti, which thrives in the warm standing waters of South Florida, Central America and other tropical climes, and carries the viruses that cause yellow fever, dengue, chikungunya and Zika.
Dengue, a leading cause of death in many Asian and Latin American countries, causes bleeding and pain so severe that it's referred to as "breakbone fever." Chikungunya and yellow fever can both be fatal, and Zika, when contracted by a pregnant woman, can infect her fetus and cause devastating birth defects, including a condition called microcephaly. Babies born with this condition have abnormally small heads and lack proper brain development, which leads to profound, lifelong disabilities.
Decades of efforts to eradicate the disease-carrying Aedes aegypti mosquito from the Keys and other tropical locales have had limited impact. Since the advent of pesticides, homes and neighborhoods have been drenched with them, but after each spraying, the mosquito population quickly bounces back, and the pesticides have to be sprayed over and over. But thanks to genetic engineering, new approaches are underway that could possibly prove safer, cheaper and more effective than any pesticide.
One of those approaches involves, ironically, releasing more mosquitoes in the Florida Keys.
The kill-switch will ensure that the female offspring die before they reach maturity and thus, be unable to reproduce.
British biotech company Oxitec has engineered male mosquitoes to have a genetic "kill-switch" that could potentially crash the local population of Aedes aegypti, at least in the short-term. The modified males that are being released are intended to mate with wild females.
Males don't bite; it's the female that's deadly, always seeking out blood to gorge on to help mature her eggs. After settling her filament-thin legs on her prey, she sinks a needlelike proboscis into the skin and sucks the blood until her translucent belly is bloated and glowing red.
The kill-switch will ensure that the female offspring die before they reach maturity and thus, be unable to reproduce. In some experiments using genetically modified mosquitoes, the small number of females that survived were rendered unable to bite. The modification prevented the proboscis, the sickle-like needle that pierces the skin, from forming properly. But this isn't the case with Oxitec's mosquitoes; in the Oxitec release, the females simply die off before they can mate.
The modified mosquitoes are the second genetically engineered insect to be released in the U.S. by Oxitec. The first was a modified diamondback moth, an agricultural pest that doesn't bite humans. But with the mosquitoes, there are many questions about the long-term effects on wild ecosystems, other species in the food chain, and human health. With the Keys initiative, there has been vociferous opposition from environmental groups and some local residents, but some scientists and public health experts say that genetically modified insects pose less of a risk than the diseases they carry and the powerful, indiscriminant pesticides used to combat them.
Oxitec spent a decade developing the technology and engaging in a massive public education campaign before beginning the field test in April. Eventually, the company will release 750,000 of the insects from six locations on three islands of the Florida Keys. Although the release has been approved by the Environmental Protection Agency, the Florida Department of Agriculture and Consumer Services, and the Florida Keys Mosquito Control District, the company was never able to obtain unanimous approval among local residents, some of whom worry that the experiment could cause irreversible damage to the ecosystem.
The company has already begun distributing multiple blue and white boxes containing the eggs of thousands of the mosquitoes which, when water is added, will hatch legions of modified males.
There are a number of techniques available to genetically engineer animals and plants to minimize disease and maximize crop yields. According to Kevin Gorman, chief development officer for Oxitec, the company's mosquitoes were altered by injecting genetic material into the eggs, testing them, then re-injecting them if not enough of the new genes were incorporated into the developing embryos. "We insert genes, but take nothing away," he says.
Gorman points out that the Oxitec mosquitoes will only pass the kill-switch genes on to some of their offspring, and that they will die out fairly quickly. They should temporarily lessen diseases by reducing the local population of Aedes aegypti, but to have a long-term effect, repeated introductions of the altered mosquitoes would have to take place.
Critics say the Oxitec experiment is a precursor to a far more consequential, and more troubling development: the introduction of gene drives in modified species that aggressively tilt inheritance factors in a decided direction.
Gene Drives
Gene drives coupled with the recent development of the gene-editing technique, CRISPR-Cas9, promise to be far more targeted and powerful than previous gene altering efforts. Gene drives override the normal laws of inheritance by harnessing natural processes involved in reproduction. The technique targets small sections of the animal's DNA and replaces it with an altered allele, or trait-determining snippet. Normally, when two members of a species mate, the offspring have a 50 percent chance of receiving an allele because they will receive one from each parent. But in a gene drive, each offspring ends up getting two copies of a desired allele from a single parent—the modified parent. The method "drives" the modified DNA into up to 100 percent of the animals' offspring.
In the case of gene drive mosquitoes, the modified males will mate with wild females. Upon fertilization of the egg, the offspring will start off with one copy of the targeted allele from each parent. But an enzyme, called Cas9, is introduced and acts as a kind of molecular scissors to cut, or damage, the "wild" allele. Then the developing embryo's genetic repair mechanisms kick in and, to repair the damage, copy the undamaged allele from the modified parent. In this way, the offspring ends up with two copies of the modified allele, and it will pass the modification on to virtually all of its progeny.
There is some debate among researchers and others about what constitutes a gene drive, but leaders in the nascent field, such as Andrea Crisanti, generally agree that the defining factor is the heritability of a change introduced into a species. A gene drive is not a particular gene or suite of genes, but a program that proliferates in a species because it is inherited by virtually all offspring.
An illustration of how gene drives spread an altered gene through a population.
Mariuswalter, CC BY-SA 4.0 <https://creativecommons.org/licenses/by-sa/4.0>, via Wikimedia Commons
Of the experts who spoke with Leaps.org for this article, there was disagreement on whether the Oxitec mosquitoes carry a gene drive, but Gorman says they don't because they carry no inheritance advantage. The mosquitoes have baked-in limitations on their potential impact on the tropical ecosystem because the kill-switch should only temporarily affect the local population of Aedes aegypti. The modified mosquitoes will die pretty quickly. But modified organisms that do carry gene drives have the potential to spread widely and persist for an unknown period of time.
Since it has such a reproductive advantage, animals modified by CRISPR and carrying gene drives can quickly replace wild species that compete with them. On the other hand, if the gene drive carries a kill-switch, it can theoretically cause a whole species to collapse.
This makes many people uneasy in an age of mass extinctions, when animals and ecosystems are already under extreme stress due to climate change and the ceaseless destruction of their habitats. Ecosystems are intricate, delicately balanced mosaics where one animal's competitor is another animal's food. The interconnectedness of nature is only partially understood and still contains many mysteries as to what effects human intervention could eventually cause.
But there's a compelling case to be made for the use of gene drives in general. Economies throughout the world are often based on the ecosystem and its animals, which rely on a natural food chain that was evolved over billions of years. But diseases carried by mosquitoes and other animals cause massive damage, both economically and in terms of human suffering.
Malaria alone is a case in point. In 2019, the World Health Organization reported 229 million cases of malaria, which led to 449,000 deaths worldwide. Over 70 percent of those deaths were in children under the age of 12. Efforts to combat malaria-carrying mosquitoes rely on fogging the home with chemical pesticides and sleeping under pesticide-soaked nets, and while this has reduced the occurrence of malaria in recent years, the result is nowhere near as effective as eradicating the Anopheles gambiae mosquito that carries the disease.
Pesticides, a known carcinogen for animals and humans, are a blunt instrument, says Anthony Shelton, a biologist and entomologist at Cornell University. "There are no pesticides so specific that they just get the animal you want to target. They get pollinators. They get predators and parasites. They negatively affect the ecosystem, and they get into our bodies." And it's not uncommon for insects to develop resistance to pesticides, necessitating the continuous development of new, more powerful chemicals to control them.
"The harm of insecticides is not debatable," says Shelton. With gene drives, the potential harm is less clear.
Shelton also points out that although genetic modification sounds radical, people have been altering the genes of animals since before recorded history, through the selective breeding of farm and domesticated animals. While critics of genetic modification decry the possibility of changing the trajectory of evolution in animals, "We've been doing it for centuries," says Shelton. "Gene drives are just a much faster way to do what we've been doing all along."
Still, one might argue that farms are closed experiments, because animals enclosed within farms don't mate with wild animals. This limits the impact of human changes on the larger ecosystem. And getting new genes to work their way through multiple generations in longer-lived animals through breeding can take centuries, which imposes the element of time to ascertain the relative benefits of any introduced change. Gene drives fast-forward change in ways that have never been harnessed before.
The unique thing about gene drives, Shelton says, is that they only affect the targeted species, because those animals will only breed with their own species. Although the Oxitec mosquitoes are modified but not imbued with a gene drive, they illustrate the point. Aedes aegypti will only mate with its own species, and not with any of the other 3,000 varieties of mosquito. According to Shelton, "If they were to disappear, it would have no effect on the fish, bats and birds that feed on them." But should gene drives become widely used, this won't always be true of animals that play a larger part in the food chain. This will be especially true if gene drives are used in mammals.
One factor, cited by both proponents of gene drives and those who want a complete moratorium on them, is that once a gene drive is released into the wild, animals tend to evolve strategies to resist them. In a 2017 article in Nature, Philip Messer, a population geneticist at Cornell, says that gene drives create "the ideal conditions for resistant organisms to flourish."
Sometimes, when CRISPR is used and the Cas9 enzyme cuts an allele soon after egg fertilization, the animal's repair mechanism, rather than creating a straight copy of the desired allele, inserts random DNA letters. The gene drive won't recognize the new sequence, and the change will slip through. In this way, nature has a way of overriding gene drives.
In caged experiments using CRISPR-modified mosquitoes, while the gene drive initially worked, resistance has developed fairly rapidly. Scientists working for Target Malaria, the massive anti-malaria enterprise funded by the Bill and Melinda Gates Foundation, are now working on developing a new version of a gene drive that is not so vulnerable to genetic resistance. But cage conditions are not representative of complex natural ecosystems, and to figure out how a modified species is going to affect the big picture, ultimately they will have to be tested in the wild.
Because there are so many unknowns, such testing is just too dangerous to undertake, according to environmentalists such as Dana Perls of the Friends of the Earth, an international consortium of environmental organizations headquartered in Amsterdam. "There's no safe way to experiment in the wild," she says. "Extinction is permanent, and to drive any species to extinction could have major environmental problems. At a time when we're seeing species disappearing at a high rate, we need to focus on safe processes and a slow approach rather than assume there's a silver bullet."
She cites a number of possible harmful outcomes from genetic modification, including the possible creation of dangerous hybrids that could be more effective at spreading disease and more resistant to pesticides. She points to a 2019 paper in Scientific Reports in which Yale researchers suggested there's evidence that genetically modified species can interbreed with organisms outside their own species. The researchers claimed that when Oxitec tested its modified Aedes aegypti mosquitoes in Brazil, the release resulted in a dangerous hybrid due to the altered animals breeding with two other varieties of mosquito. They suggested that the hybrid mosquito was more robust than the original gene drive mosquitoes.
The paper contributed to breathless headlines in the media and made a big splash with the anti-GMO community. However, it turned out that when other scientists reviewed the data, they found it didn't support the authors' claims. In a short time, the editors of Nature ran an Editorial Expression of Concern for the article, noting that of the insects examined by the researchers, none of them contained the transgenes of the released mosquitoes. Among multiple concerns, Nature found that the researchers didn't follow the released population for more than a short time, and that previous work from the same authors had shown that after a short time, transgenes would have faded from the population.
Of course, unintended consequences are always a concern any time we interfere with nature, says Michael Montague, a senior scholar at Johns Hopkins University's Center for Health Security. "Unpredictability is part of living in the world," he says. Still, he's relatively comfortable with the limited Florida Keys release.
"Even if one type of mosquito was eliminated in the Keys, the ecosystem wouldn't notice," he says. This is because of the thousands of other species of mosquito. He says that while the Keys initiative is ultimately a test, "Oxitec has done their due diligence."
Montague addressed another concern voiced by Perls. The Oxitec mosquitoes were developed so that the female larvae will only hatch in water containing the antibiotic tetracycline. Perls and others caution that, because of the widespread use of antibiotics, the drug inevitably makes its way into the water system, and could be present in the standing pools of water that mosquitoes mate and lay their eggs in.
It's highly unlikely that tetracycline would exist in concentrations high enough to make any difference, says Montague. "But even if it did happen, and the modified females hatched out and mated with wild males, many of their offspring would inherit the modification and only be able to hatch in tetracycline-laced water. The worst-case scenario would be that the pest control didn't work. Net effect: Zero," he says.
As for comparing GMO mosquitoes with insecticides, Montague says, "We 100 percent know insecticides have a harmful effect on human health, whereas modified [male] mosquitoes don't bite humans. They're essentially a chemical-free insecticide, and if there were to be some harmful effect on human health, it would have to be some complicated, convoluted effect" that no one has predicted.
It's not clear, though, given the transitory nature of self-limiting genetically modified insects, whether any effects on the ecosystem would be long-lasting. Certainly in the case of the Oxitec mosquitoes, any effect on the environment would likely be subtle. However, there are other species that are far more important to the food chain, and humans have been greatly impacting them for centuries, sometimes with disastrous effects.
The world's oceans are particularly vulnerable to the effects of human actions. "Codfish used to dominate the North Atlantic ecosystem," says Montague, but due to overfishing, there were huge changes to that ecosystem, including the expansion of their prey—lobsters, crabs and shrimp. The whole system got out of balance." The fish illustrate the international nature of the issues related to gene drives, because wild species have few boundaries and a change in one region can easily spread far and wide.
On the other hand, gene drives can be used for beneficial purposes beyond eliminating disease-carrying species. They could also be used to combat invasive species, fight crop-destroying insects, promote biodiversity, and give a leg up to endangered species that would otherwise die out.
Today nearly 90 percent of the world's islands have been invaded by disease-carrying rodents that have over-multiplied and are driving other island species to extinction. Common rodents such as rats and mice normally encounter a large number of predators in mainland territories, and this controls their numbers. Once they are introduced into island ecosystems, however, they have few predators and often become invasive. Because of this, they are a prevalent cause of the extinction of both animals and plants globally. The primary way to combat them has been to spread powerful toxicants that, when ingested, cause death. Not only has this inhumane practice had limited impact, the toxicants can be eaten by untargeted species and are toxic to humans.
The Genetic Biocontrol of Invasive Rodents program (GBIRd), an international consortium of scientists, ethicists, regulatory experts, sociologists, conservationists and others, is exploring the possible development of a genetically modified mouse that could be introduced to islands where rodents are invasive. Similar to the Oxitec mosquitoes, the mice would carry a modification that results in the appearance of only one sex, and they would also carry a gene drive. Theoretically, once they mate with the wild mice, all of the surviving offspring would be either male or female, and the species would disappear from the islands, giving other, threatened species an opportunity to revive.
GBIRd is moving slowly by design and is currently focused on asking if a genetically engineered mouse should be developed. The program is a potential model for how gene drives can be ethically developed with maximum foresight and the least impact on complex ecosystems. By first releasing a genetically engineered mouse on an island — likely years from now — the impact would naturally be contained within a limited locale.
Regulating GM Insects
While multiple agencies in the U.S. were involved in approving the release of the Oxitec mosquitoes, most experts agree that there is not a straightforward path to regulating genetically modified organisms released into the environment. Clearly, international regulation is needed as genetically modified organisms are released into open environments like the air and the ocean.
The United Nations' Convention on Biological Diversity, which oversees environmental issues at an international level, recently met to continue a process of hammering out voluntary protocols concerning gene drives. Multiple nations have already signed on to already-established protocols, but the United States has not and, according to Montague, is not expected to. "The U.S. will never be signatory to CBD agreements because agricultural companies are huge businesses" that may not see them as in their best interests, he says. Bans or limitations on the release of genetically modified organisms could limit crop yields, for example, thereby limiting profits.
Even if every nation signed on to international regulations of gene drives, cooperation is voluntary. The regulations wouldn't prevent bad actors from using the technology in nefarious ways, such as developing gene drives that can be used as weapons, according to Perls. An example would be unleashing a genetically modified invasive insect to destroy the crops of enemy nations. Or the releasing of a swarm of disease-carrying insects. But in this scenario, it would be very hard to limit the genetically modified species to a specific environment, and the bad actors could be unleashing disaster on themselves.
Because of the risks of misuse, scientists disagree on whether to openly share their gene drive research with others. But Montague believes that there should be a universal registry of gene drives, because "one gene drive can mess up another one. Two groups using the same species should know about each other," he says.
Ultimately, the decision of whether and when to release gene drives into nature rests with not one group, but with society as a whole. This includes not only diverse experts and regulatory bodies, but the general public, a group Oxitec spent considerable time and resources interacting with for their Florida Keys project. In the end, they gained approval for the initiative by a majority of Keys residents, but never gained a total consensus.
There's no escaping the fact that the use of gene drives is a nascent field, and even geneticists and regulators are still grapping with the best ways to develop, oversee, regulate, and control them. Much more data is needed to fully ascertain its risks and benefits.
Experts agree that the Oxitec venture isn't likely to have a noticeable effect on the larger ecosystem unless something truly catastrophic goes wrong. But following the GMO mosquitoes over time will give scientists more real-world data about the long-term effects of genetically altered species. If the release doesn't work, nothing about the ecosystem will change and Aedes aegypti will continue to be a menace to human health. But if something goes horribly wrong, it could hinder the field for years, if not forever.
On the other hand, if the Oxitec mosquitoes and other early initiatives achieve their goals of reducing disease, increasing crop yields, and protecting biodiversity, in the words of Anthony Shelton, "Maybe, 25 to 50 years from now, people will wonder what all the fuss was about."
Correction: The original version of this article mistakenly stated that the modified Oxitec mosquitoes would not be able to form a proper proboscis to bite humans. That is true for some modified mosquitoes but not the Oxitec ones, whose female offspring die off before they reach maturity. Additionally, the Oxitec release was not approved by the FDA and CDC, as originally stated. The FDA and CDC withdrew their role and passed the oversight to other regulatory entities.