by Dan Ariely
Modified mosquito larvae would later be moved to James’s field site, which consists of five pairs of cages, each with a control cage housing a population of wild mosquitoes and a treatment cage where modified mosquitoes mix with locals. Each cage is guarded by multiple layers of mesh—protection against escapees—which researchers must carefully navigate through as they add new test subjects to the experiment.
The strict protocol is an attempt to avoid past errors. Developing countries have long made a convenient location for First World field trials, but a cavalier attitude toward the local environment has led to backlash that derailed entire research programs. Perhaps no field is more fraught with abuses—both real and perceived—than genetically modified organisms.
Poison in the Wells
In 1969, for example, the World Health Organization and the Indian government teamed up to study genetic control of three mosquito species: Culex fatigans, which spreads filariae (parasites that cause elephantitis); A. aegypti, which spreads dengue and yellow fever; and malaria-spreading Anopheles stephensi. The US government funded some of the research.
In 1972 a scientist anonymously published an article in India’s National Herald alleging that researchers had been placing mosquitoes treated with thiotepa—described as a mustard gas derivative that causes birth defects and cancer in animals—in village drinking wells. The scientists in charge of the project issued a timid rebuttal and rebuffed subsequent interview requests from the press. Then in 1974 the Press Trust of India ran a story with the incendiary headline “WHO Works for U.S. Secret Research in India.” The article alleged that the mosquito project was being used to test the practicality of using A. aegypti as a biowarfare agent. India was being used to test “chemicals or methods not permitted in sponsoring countries,” the account ran, also charging that A. aegypti was being studied because “its eggs (unlike those of other mosquitoes) can be dried, put on a piece of paper in an envelope and mailed to any part of the country where they can hatch.” Although the investigators strenuously denied the allegations, the public relations debacle prompted the WHO to abandon the program.
Since then, investigators have been terrified of conducting field trials of genetically modified (GM) organisms, says Stephanie James (no relation to Anthony), director of the Grand Challenges in Global Health initiative at the Foundation for the National Institutes of Health. “There was a real psychological barrier. They knew they couldn’t afford to mess up.”
“All my career I’ve been told you’ll never get people to agree to do this,” Anthony James told me. At the 2005 inaugural dinner for Grand Challenges grant recipients, he consulted Jim Lavery, who specializes in the science of community engagement at Toronto’s Center for Global Health Research at St. Michael’s Hospital. “GM freaks people out,” James said. “So how do you involve the community?”
Lavery suggested choosing a location where dengue was a significant public health issue and control methods were failing, in a country with a stringent, sophisticated regulatory structure capable of assessing the risks and benefits of a genetically modified, dengue-fighting mosquito. That way locals would be comfortable that the effort would not endanger or exploit them. He and the mosquito field-trial veteran Thomas Scott of U.C. Davis helped Anthony James assemble an international team of mosquito ecologists, anthropologists, and ethicists long before he had enough mosquitoes to test.
By 2006 Tapachula was the frontrunner for these trials. Mexico had national laws on genetically modified organisms and had signed the Cartagena Protocol on Biosafety—the international framework for importing them. Experience with the medfly meant the Tapachula community wasn’t “freaked out” by the idea of modifying an insect, Lavery says.
“At first the request for land sounded strange,” said Martimiano Barrios Matute, leader of the farming community where the experiment is based. Why would anyone want to build large cages and fill them with man-made mosquitoes? The community was also confused about what transgenic mosquitoes could do. Could escapees hurt them or their fields? Would their sterility be transferred to other insects?
James and his group addressed the community’s concerns and purchased the land to build the cages through the traditional communal land-ownership program in the area. And they continue to engage the locals as the experiment continues.
In a weekly town hall gathering in the Casa de la Cultura on Tapachula’s historic main square, Ramsey, the project’s field site manager, described the project to an audience of community leaders, thirty men and five women. It was hard to tell that she was an American expatriate as she held the room transfixed; she was animated, gesturing, and joking.
When she concluded, the audience cautiously asked questions. One man asked if he could visit the mosquito cages. Another wanted to know what happens if mosquitoes escape. A young woman asked why people are against transgenics. An elderly man from a mountain village asked whether malaria and dengue are different. Ramsey answered them all, then smiled and shook hands as she left.
“Now that we understand, even more so do we like the project,” said Barrios Matute, a slender soy farmer with gold-capped teeth. “It will benefit not only Rio Florido but all around Rio Florido and Mexico and other parts of the world.”
The Great Escape
While all this slow scientific and community work was going on in Mexico, Alphey was quietly taking a dramatically different approach. Last November he arrived at the annual meeting of the American Society of Tropical Medicine and Hygiene with a surprising story to tell. Beginning in September 2009, Alphey said, Oxitec had been releasing genetically modified mosquitoes on Grand Cayman Island in the Caribbean. (The mosquitoes are similar to the ones being tested in Tapachula, but not identical—in the Cayman strain, both male and female mosquitoes die as larvae.) Between May and October of 2010, Oxitec released more than 3 million male mosquitoes, he revealed, which cut the indigenous A. aegypti population by 80 percent. The data have been submitted for publication.
Alphey defended his gung-ho approach, saying that Oxitec leaves outreach largely to the governments because they understand the cultural sensitivities. On Grand Cayman, outreach involved one five-minute spot on the local nightly news broadcast and a pamphlet that described the mosquitoes as sterile, avoiding any mention of genetic modification. There were no public meetings or opportunities for residents to voice concerns.
Alphey justified his actions at the Atlanta meeting. “In terms of publicity, we were only doing it in the Cayman Islands,” he said. “We only need the community, people on the island, to know about it.”
Mark Q. Benedict, a molecular biologist at the University of Perugia in Italy and a consultant to the Gates Foundation, says Oxitec has broken no laws and calls the Cayman trials “courageous” for testing technology bound to attract “attention, both good and bad.” Benedict says confused and conflicting media reports created the impression of “the lone scientist who rushes out with his bucket of mosquitoes and throws them into the environment without any oversight. That is not happening.” Oxitec works with both local and national governments to gain approval before any field test.
Still, the Cayman release has provoked strong emotions—distrust, disappointment, and frustration—from many of Alphey’s colleagues, environmental groups, and the public. “The international community was taken by surprise that this release had happened,” says Bart Knols, a medical entomologist at the University of Amsterdam and managing director of MalariaWorld. “Now the outside world perceives Oxitec as secretive, which makes the public wonder why. It breeds suspicion.”
This is promising technology, Knols says. “If some party messes up badly and misinforms the public, the risk is that other GM trials will suffer.” Now, because of Oxitec, he adds, “we have the same problems as the WHO had in India in 1976.”
Other experts say the company is preying on countries with minimal bureaucracy and regulations. In the Cayman Islands, Oxitec conducted its trials in a place with a “streamlined reg
ulatory structure,” says Stephanie James, where the ink was barely dry on a biosafety bill that has yet to become law.
Malaysia was next. Amid protests from twenty-plus nonprofit organizations, Oxitec launched a trial in an uninhabited area last December. A follow-up in a nearby village is pending. Even with a newly minted National Biosafety Board that monitors modified organisms and the 2009 Malaysian Biosafety Act regulations, many feel that Malaysia lacks the experience to monitor the experiment, says Gurmit Singh, chair of the nonprofit Center for Environment, Technology and Development, Malaysia.
Anthony James slumped in a chair as we discussed the situation but, always diplomatic, said flatly, “That’s the difficulty of working with corporations. I can’t control corporate partners.” He added, “If it blows up, I told you so. If not, you got lucky.” James said that Oxitec’s approach would be impossible in Mexico, adding that he is confident his team’s community engagement activities have “set a standard for testing genetically modified organisms.”
Alphey is undeterred. Earlier this year Oxitec launched a six-month trial in a poor suburb of Juazeiro, Bahia, in northern Brazil, which is plagued by mosquitoes and dengue year-round. Later this year Alphey plans to return to Grand Cayman to pit the Tapachula and Cayman strains of transgenic mosquitoes against the local mosquitoes to see which lives longer, flies farther, and is better at mating with local females. Mosquito-control officials in Panama and the Philippines have shown interest, as have the authorities in Florida.
Permanent Spread
Of course, many groups oppose the release of any transgenic organisms, no matter how thoughtfully the scientists explain themselves beforehand. Janet Cotter, a senior scientist at Greenpeace Research Laboratories, warns that “Oxitec’s release of GM mosquitoes is extremely risky. There’s no such thing as one hundred percent sterility, so there are going to be some fertile females that will be released, and we don’t know the implications of that.”
Some people wonder if it is ethical—or safe—to eliminate an organism, even in just a small geographic area. Proponents argue that A. aegypti is an invasive species that has evolved to exploit a solely human niche. “Urban A. aegypti is not part of any significant food chain,” says Phil Lounibos, a mosquito ecologist at the Florida Medical Entomology Laboratory. Yet Lounibos doubts whether eliminating A. aegypti would stop dengue transmission permanently. “A previous campaign to eradicate this species from the Americas in the 1950s and 1960s, when it was the primary vector of urban yellow fever, failed miserably,” he says. The invasive Asian tiger mosquito—another good dengue vector—readily occupies niches vacated by A. aegypti. Moreover, both the Cayman and Tapachula mosquito strains, even if successful, are not permanent. Migration of mosquitoes from neighboring regions into Tapachula could foil eradication attempts and mandate frequent releases of the modified males to keep the population in check.
James and his collaborators have been developing a self-sustaining but more controversial solution. It uses a “gene drive system,” which promotes the spread of dengue-resistance genes through a wild mosquito population, blocking the replication of at least one form of the dengue virus, known as type 2. Unlike the Tapachula mosquitoes, which die soon after release, mosquitoes outfitted with a gene drive will persist in the environment. James says field trials for gene drive systems are still a few years away.
“Something that spreads genes through populations is going to have much more difficult regulatory hurdles,” James says, “so I’m happy to take something that is self-limiting, not sustainable, like [the Tapachula strain] and have that be our first shot.”
Undersecretary of Health Domínguez Zárate views the genetically modified approach as “low cost and high creativity.” “If dengue was something with less importance, then why modify something from nature?” he asks. “We need to respect nature as much as we can.” Still, the costs of dengue outweigh the potential environmental risks, he says. “It’s worth the gamble.”
SY MONTGOMERY
Deep Intellect
FROM ORION
ON AN UNSEASONABLY warm day in the middle of March, I traveled from New Hampshire to the moist, dim sanctuary of the New England Aquarium, hoping to touch an alternate reality. I came to meet Athena, the aquarium’s forty-pound, five-foot-long, two-and-a-half-year-old giant Pacific octopus.
For me, it was a momentous occasion. I have always loved octopuses. No sci-fi alien is so startlingly strange. Here is someone who, even if she grows to one hundred pounds and stretches more than eight feet long, could still squeeze her boneless body through an opening the size of an orange; an animal whose eight arms are covered with thousands of suckers that taste as well as feel; a mollusk with a beak like a parrot and venom like a snake and a tongue covered with teeth; a creature who can shape-shift, change color, and squirt ink. But most intriguing of all, recent research indicates that octopuses are remarkably intelligent.
Many times I have stood mesmerized by an aquarium tank, wondering, as I stared into the horizontal pupils of an octopus’s large, prominent eyes, if she was staring back at me—and if so, what was she thinking?
Not long ago, a question like this would have seemed foolish, if not crazy. How can an octopus know anything, much less form an opinion? Octopuses are, after all, “only” invertebrates—they don’t even belong with the insects, some of whom, like dragonflies and dung beetles, at least seem to show some smarts. Octopuses are classified within the invertebrates in the mollusk family, and many mollusks, like clams, have no brain.
Only recently have scientists accorded chimpanzees, so closely related to humans that we can share blood transfusions, the dignity of having a mind. But now, increasingly, researchers who study octopuses are convinced that these boneless, alien animals—creatures whose ancestors diverged from the lineage that would lead to ours roughly 500 to 700 million years ago—have developed intelligence, emotions, and individual personalities. Their findings are challenging our understanding of consciousness itself.
I had always longed to meet an octopus. Now was my chance: senior aquarist Scott Dowd arranged an introduction. In a back room, he would open the top of Athena’s tank. If she consented, I could touch her. The heavy lid covering her tank separated our two worlds. One world was mine and yours, the reality of air and land, where we lumber through life governed by a backbone and constrained by jointed limbs and gravity. The other world was hers, the reality of a nearly gelatinous being breathing water and moving weightlessly through it. We think of our world as the “real” one, but Athena’s is realer still: after all, most of the world is ocean, and most animals live there. Regardless of whether they live on land or water, more than 95 percent of all animals are invertebrates, like Athena.
The moment the lid was off, we reached for each other. She had already oozed from the far corner of her lair, where she had been hiding, to the top of the tank to investigate her visitor. Her eight arms boiled up, twisting, slippery, to meet mine. I plunged both my arms elbow deep into the 57-degree water. Athena’s melon-sized head bobbed to the surface. Her left eye (octopuses have one dominant eye, just as humans have a dominant hand) swiveled in its socket to meet mine. “She’s looking at you,” Dowd said.
As we gazed into each other’s eyes, Athena encircled my arms with hers, latching on with first dozens, then hundreds, of her sensitive, dexterous suckers. Each arm has more than two hundred of them. The famous naturalist and explorer William Beebe found the touch of the octopus repulsive. “I have always a struggle before I can make my hands do their duty and seize a tentacle,” he confessed. But to me, Athena’s suckers felt like an alien’s kiss—at once a probe and a caress. Although an octopus can taste with all of its skin, in the suckers both taste and touch are exquisitely developed. Athena was tasting me and feeling me at once, knowing my skin, and possibly the blood and bone beneath, in a way I could never fathom.
When I stroked her soft head with my fingertips, she changed color beneath my touch, her ruby-flecked skin
going white and smooth. This, I learned, is a sign of a relaxed octopus. An agitated giant Pacific octopus turns red, its skin gets pimply, and it erects two papillae over the eyes, which some divers say look like horns. One name for the species is devil fish. With sharp, parrotlike beaks, octopuses can bite, and most have neurotoxic, flesh-dissolving venom. The pressure from an octopus’s suckers can tear flesh (one scientist calculated that to break the hold of the suckers of the much smaller common octopus would require a quarter ton of force). One volunteer who interacted with an octopus left the aquarium with arms covered in red hickeys.
Occasionally an octopus takes a dislike to someone. One of Athena’s predecessors at the aquarium, Truman, felt this way about a female volunteer. Using his funnel, the siphon near the side of the head used to jet through the sea, Truman would shoot a soaking stream of salt water at this young woman whenever he got a chance. Later she quit her volunteer position for college. But when she returned to visit several months later, Truman, who hadn’t squirted anyone in the meantime, took one look at her and instantly soaked her again.
Athena was remarkably gentle with me—even as she began to transfer her grip from her smaller outer suckers to the larger ones. She seemed to be slowly but steadily pulling me into her tank. Had it been big enough to accommodate my body, I would have gone in willingly. But at this point I asked Dowd if perhaps I should try to detach from some of the suckers. With his help, Athena and I pulled gently apart.
I was honored that she appeared comfortable with me. But what did she know about me that informed her opinion? When Athena looked into my eyes, what was she thinking?
