The Brown family at the Grand Tetons (2019). Clockwise from left, Christine, Kevin, Keagan, Connor, and Kellen.
But Christine Brown knew none of this when the hospital called saying that standard newborn screening of her son Connor had come back positive for PKU. It was urgent that they visit a special metabolic clinic the next day, which was about a three-hour drive away.
“I was told not to go on the Internet,” Christine recalls, “So when somebody tells you not to go on the Internet, what do you do? Even back in 2005, right.” What she saw were the worst examples of retardation, which was a common outcome from PKU before newborn screening became routine. “We were just in complete shell shock, our whole world just kind of shattered and went into a tail spin.”
“I remember feeding him the night before our clinic visit and almost feeling like I was feeding him poison because I knew that breast milk must have protein in it,” she says.
“Some of my first memories are of asking, ‘Mommy, can I eat this? There were yes foods and no foods.'"
Over the next few days the dedicated staff of the metabolic clinic at the Waisman Center at the University of Wisconsin Madison began to walk she and husband Kevin back from that nightmare. They learned that a simple blood test to screen newborns had been developed in the early 1960s to detect PKU and that the condition could be managed with stringent food restrictions and vigilant monitoring of Phe levels.
Everything in Your Mouth Counts
PKU can be successfully managed with a severely restricted diet. That simple statement is factually true, but practically impossible to follow, as it requires slashing protein consumption by about 90 percent. To compensate for the missing protein, several times a day PKU patients take a medical formula – commonly referred to simply as formula – containing forms of proteins that are digestible to their bodies. Several manufacturers now add vitamins and minerals and offer a variety of formats and tastes to make it more consumer friendly, but that wasn't always the case.
“When I was a kid, it tasted horrible, was the consistency of house paint. I didn't think about it, I just drank it. I didn't like it but you get used to it after a while,” recalls Jeff Wolf, the twang of Appalachia still strong in his voice. Now age 50, he grew up in Ashland, Kentucky and was part of the first wave of persons with PKU who were identified at birth as newborn screening was rolled out across the US. He says the options of taste and consistency have improved tremendously over the years.
Some people with PKU are restricted to as little as 8 grams of protein a day from food. That's a handful of almonds or a single hard-boiled egg; a skimpy 4-ounce hamburger and slice of cheese adds up to half of their weekly protein ration. Anything above that daily allowance is more than the body can handle and toxic levels of Phe begin to accumulate in the brain.
“Some of my first memories are of asking, ‘Mommy, can I eat this? There were yes foods and no foods,’” recalls Les Clark. He has never eaten a hamburger, steak, or ribs, practically a sacrilege for someone raised in Stanton, a small town in northeastern Nebraska, a state where the number of cattle and hogs are several-fold those of people.
His grandmother learned how to make low protein bread, but it looked and tasted different. His mom struggled making birthday cakes. “I learned some bad words at a very young age” as mom struggled applying icing that would pull the cake apart or a slice would collapse into a heap of crumbs, Les recalls.
Les Clark with a birthday cake.
Courtesy Clark
Controlling the diet “is not so bad when you are a baby” because that's all you know, says Jerry Vockley, Director of the Center for Rare Disease Therapy at Children's Hospital of Pittsburgh. “But after a while, as you get older and you start tasting other things and you say, Well, gee, this stuff tastes way better than what you're giving me. What's the deal? It becomes harder to maintain the diet.”
First is the lure of forbidden foods as children venture into the community away from the watchful eyes of parents. The support system weakens further when they leave home for college or work. “Pizza was mighty tasty,” Wolf' says of his first slice.
Vockley estimates that about 90 percent of adults with PKU are off of treatment. Moving might mean finding a new metabolic clinic that treats PKU. A lapse in insurance coverage can be a factor. Finally there is plain fatigue from multiple daily dosing of barely tolerable formula, monitoring protein intake, and simply being different in terms of food restrictions. Most people want to fit in and not be defined by their medical condition.
Jeff Wolf was one of those who dropped out in his twenties and thirties. He stopped going to clinic, monitoring his Phe levels, and counting protein. But the earlier experience of living with PKU never completely left the back of his mind; he listened to his body whenever eating too much protein left him with the “fuzzy brain" of a protein hangover. About a decade ago he reconnected with a metabolic clinic, began taking formula and watching his protein intake. He still may go over his allotment for a single day but he tries to compensate on subsequent days so that his Phe levels come back into balance.
Jeff Wolf on a boat.
Courtesy Wolf
One of the trickiest parts of trying to manage phenylalanine intake is the artificial sweetener aspartame. The chemical is ubiquitous in diet and lite foods and drinks. Gum too, you don't even have to swallow to receive a toxic dose of Phe. Most PKUers say it is easier to simply avoid these products entirely rather than try to count their Phe content.
Treatments
Most rare diseases have no treatment. There are two drugs for PKU that provide some benefit to some portion of patients but those drugs often have their own burdens.
KUVAN® (sapropterin dihydrochloride) is a pill or powder that helps correct a protein folding error so that food proteins can be digested. It is approved for most types of PKU in adults and children one month and older, and often is used along with a protein-restricted diet.
“The problem is that it doesn't work for every [patient's genetic] mutation, and there are hundreds of mutations that have been identified with PKU. Two to three percent of patients will have a very dramatic response and if you're one of those small number of patients, it's great,” says Vockley. “If you have one of the other mutation, chances are pretty good you still are going to end up on a restricted diet.”
PALYNZIQ® (pegvaliase-pqpz) “has the potential to lower the Phe to normal levels, it's a real breakthrough in the field,” says Vockley. “But is a very hard drug to use. Most folks have to take either one or two 2ml injections a day of something that is basically a gel, and some individuals have to take three.”
Many PKUers have reactions at the site of the injection and some develop anaphylaxis, a severe potentially life-threatening allergic reaction that can happen within seconds and can occur at any time, even after long term use. Many patients using Palynziq carry an EpiPen, a self-injection devise containing a form of adrenaline that can reverse some of the symptoms of anaphylaxis.
Then there is the cost. With the Kuvan dosing for an adult, “you're talking between $100,000 and $200,000 a year. And Palynziq is three times that,” says Vockley. Insurance coverage through a private plan or a state program is essential. Some state programs provide generous coverage while others are skimpy. Most large insurance company plans cover the drugs, sometimes with significant copays, but companies that are self-insured are under no legal obligation to provide coverage.
Les Clark found that out the hard way when the company he worked for was sold. The new owner was self-insured and declined to continue covering his drugs. Almost immediately he was out of pocket an additional $1500 a month for formula, and that was with a substantial discount through the manufacturer's patient support program. He says, “If you don't have an insurance policy that will cover the formula, it's completely unaffordable.” He quickly began to look for a new job.
Hope
It's easy to see why PKUers are eager for advances that will make managing their condition more effect, easier, and perhaps more affordable. Synlogic's efforts have drawn their attention and raised hopes.
Just before Thanksgiving Jerry Vockley presented the latest data to a metabolism conference meeting in Australia. There were only 8 patients in this group of a phase 2 trial using the original version of the company's lead E. coli product, SYNB1618, but they were intensely studied. Each was given the probiotic and then a challenge meal. Vockley saw a 40% reduction in Phe absorption and later a 20% reduction in mean fasting Phe levels in the blood. The product was easy to use and tolerate.
The company also presented early results for SYNB1934, a follow on version that further genetically tweaked the E. coli to roughly double the capacity to chop up the target proteins. Synlogic is recruiting patients for studies to determine the best dosing, which they are planning for next year.
“It's an exciting approach,” says Lex Cowsert, Director of Research Development at the National PKU Alliance, a nonprofit that supports the patient, family, and research communities involved with PKU. “Every patient is different, every patient has a different tolerance for the type of therapy that they are willing to pursue,” and if it pans out, it will be a welcome addition, either alone or in combination with other approaches, to living with PKU.
Author's Note: Reporting this story was made possible by generous support from the National Press Foundation and the Fondation Ipsen. Thanks to the people who so generously shared their time and stories in speaking with me.
The Aedes aegypti mosquito, which can carry devastating diseases, was recently engineered by a biotech company to have a genetic "kill switch" intended to crash the local population in the Florida Keys.
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.