by Alexis Girard and Arnaud Girard…….

“We’re guinea pigs in their science experiment,” said Dick Nalley. Like many of his neighbors in Key Haven, he has dotted his front yard with angry placards. The government, you see, together with a British biotech company called Oxitec, plans to release three million genetically modified mosquitoes into their small island neighborhood, 5 miles northeast of Key West. The ultimate goal is to test this new tool for stopping the propagation of the Aedes aegypti mosquito, which carries dengue, chikungunya, and Zika.

A 2013 Survey of Key Haven residents conducted by local mosquito control staff had concluded that over 90% of them were not opposed to the release. Either the survey was flawed or the residents changed their minds. This week, The Blue Paper is taking a look at the rights of people to refuse being involved in scientific experiments against their will.

Officially, Key Haven residents have nothing to worry about. The Food and Drug Administration reviewed Oxitec’s 140-page environmental assessment and concluded: “the probability of adverse impacts on humans or other animal health is negligible or low.”

“This could have a huge benefit for Key West,” says Michael Doyle, director of the county’s Mosquito Control District.  “With traditional tools,” which, in Monroe County, include insecticide, larvaecide, a helicopter, and a nearly 16 million dollar annual budget, “we eradicate only 50% of the Aegypti,” says Doyle.  According to Oxitec, their genetic mutation strategy eradicates up to 90% of the targeted mosquito.

This is how it’s supposed to work:  In its mosquito farms, Oxitec raises millions of Aedes aegypti mosquitoes which are bred with a defective lethal gene.  They stay alive only because their food is laced with an antibiotic [tetracycline].  When the adult males are released (at a ratio of 10 for every one wild male mosquito) they mate with wild females and pass that lethal gene onto their offspring. The larvae, without the benefit of tetracycline, die before reaching adulthood. In various areas infected with dengue, Oxitec claims to have successfully reduced the number of mosquitoes, boasting 90% eradication in Panama and Brazil and 80% in the Cayman Islands.

But, for many Key Haven residents, Oxitec is just a sorcerer’s apprentice and they are being forced by their government into becoming designated volunteers in an experiment that includes their blood, a Frankenstein mosquito, and a sinister third party: the dengue virus.

Some residents’ concerns don’t check out.  Many claim there’s been no peer review of Oxitec’s work.  In fact, both the Pasteur Institute in Paris and the University of Colorado have recreated the Oxitec procedure in their labs.  With some divergence as to the actual level of success, both found the process was effective in reducing the number of mosquitoes.  The fear that Oxitec mosquitoes would survive and reproduce by exposure to tetracycline in the environment such as in human trash or cat food was dismissed by researchers at the Pasteur Institute.

However, some concerns which might seem as though borrowed from a B-movie plot, actually do find an echo in the scientific world. Could the genetic modification of the mosquito cause a mutation of the dengue or Zika virus, turning it into a super virus?

According to Dr. Jan Medlock, a professor at Oregon State University, the genetic manipulation of the Aedes aegypti could impact the human viruses it carries. In 2009, Medlock and three other scientists published their research on The Impact of Transgenic Mosquitoes on Dengue Virulence to Humans and Mosquitoes. In a mathematical model, adapted to an epidemic situation, they found that there was a definite risk that the transgenic mosquito could trigger an evolutionary response by the dengue virus: the mutation could increase the virulence of dengue fever in humans.

While their analysis did not focus on Oxitec’s gene modification strategy specifically, it did consider similar genetically engineered mosquito eradication methods. In simple terms, the new gene could cause the virus to adapt to the changes in its host and mutate into a more dangerous form of the disease. In a telephone interview this week Dr. Medlock indicated, however, that he believed that the chances of such a mutation are very remote.

“It is frustrating,” says Dr. Medlock, “after what happened elsewhere, that Oxitec has not done a better job with consent this time.” In Malaysia and the Cayman Islands, Oxitec and the local governments it worked with didn’t tell residents about trials involving millions of GM Mosquitoes until a month after they were released.

For Key Haven residents consent is the crux of the matter. Under Article 7 of the International Covenant on Civil and Political Rights, “no one shall be subjected without his free consent to medical or scientific experimentation.”  “It’s a basic right of people,” says Medlock. The treaty, which originated in the United Nations, was ratified by the U.S. in 1992.

So how is Oxitec getting away with not having to obtain formal individual consent? When we reviewed Oxitec’s application with FDA, we found it had been filed with the FDA’s Center for Veterinary Medicine. In other words, the experiment in Key Haven is being processed as the approval of an “animal drug.” As for any drug involving only animals, no human consent is required.

Oxitec has been releasing millions of mosquitoes in open air experiments in residential neighborhoods, at times unbeknownst to residents. In Brazil, Oxitec adopted a more transparent method: One of the promotional slogans, spread throughout poor neighborhoods read, “Let these mosquitoes into your home. These mosquitoes are our friends.” How Brazilians were supposed to make the difference between a male transgenic mosquito and a dangerous carrier of hemoragic dengue before inviting them in is not explained.

Oxitec claims that: “Informed consent is a process for getting permission before conducting a healthcare intervention on a person. Our approach is emphatically not a healthcare intervention and we make no healthcare claims. Our aim is to control the mosquito population.” They go further: “FDA also sees this as an intervention for mosquitos with no human health claims – that is why it is being regulated as an animal drug and not a human drug.”

The UN treaty, however, is not limited to healthcare research but also includes any “scientific experiment.” The controversy about secret releases of millions of mosquitoes by Oxitec brought some harsh words from Anthony James, administrator of a 19.7-million-dollar transgenic mosquito testing program funded by the Bill and Melinda Gates Foundation.

“It’s my blood,” says Key Haven resident John Murphy. In fact, blood is an indispensable element of the Aedes egypti reproductive cycle.  The female mosquito (the only one that bites) cannot grow eggs without the protein and iron she finds in blood.  When she pumps up that special supper, she also injects her saliva into her prey’s bloodstream. That is when she passes on any virus she may be carrying.

As per Oxitec’s own admission, the experiment can only be carried out inside a residential neighborhood like the Key West / Key Haven area. Michael Doyle indicates that in less inhabited areas of the Keys, like Big Pine, the percentage of Aedes egypti can be as low as only 1% of the total mosquito population. For Mr. Murphy, unquestionably, the true subject of the experiment is that symbiotic relationship between Aedes egypti, humans, and the blood and viruses they share.

When it comes to “consent,” like Oxitec, FDA’s track record is quite murky.

In 1977 a US Senate subcommittee met to investigate the military’s testing of biological weapons simulants sprayed from aircraft over unsuspecting civilian populations in San Francisco, New York, and Key West. The FDA allowed the use of a placebo, that turned out to be a dangerous pathogen, in biological weapons research.

The exchange between senators and military brass make for interesting reading.

Senator Schweiker: the other question is, do you know exactly when the Florida test in Key West, the Monroe County area, was conducted? All I have is the year 1952[…]

Lt. Colonel Carruth: I do not have the exact date of that test. We could not find the report. We found only fragmentary data.

Senator Schweiker:  The other statistics. I want to bring out […] is disturbing in view of the Alabama figure [an increase to three times the normal rate of pneumonia] relates to the Key West test.  A lot depends on when the test was conducted. Because the Florida State health records show that the 1953 is the only year in which Monroe County’s rate of pneumonia […] exceeded the state-wide rate.

Senator Kennedy: I want to know what justification there was for this endangering of the public health and the disregard for individual human rights. 

In the end the Senate found that, “consent forms were largely inadequate” and “the FDA had inappropriately given up its responsibility for assuring that drug test subjects were fully protected.”

In the face of growing opposition, Monroe County is now preparing for a non-binding referendum on the Oxitec question. However, under federal guidelines community consent cannot replace individual consent.

So why does the Key Haven trial seem so important to Oxitec? The answer may be money.  A lot of money. Until recently Oxitec’s website opened up with a presentation showing some alarming numbers about the world-wide impacts of dengue fever; with 390 million dengue infections a year.  It followed with the fact that there was “no known vaccine” for dengue fever.  Immediately thereafter came a description of the great financial prospects for Oxitec on the stock market and the opportunity for investors to get very rich – very soon.

Since then however French pharmaceutical company Sanofi, in association with the Pasteur Institute and a research center in Delhi, India has perfected a dengue vaccine. By April of 2015, Sanofi was already engaged in a program aimed at vaccinating one million school children in the Philippines. Dingvaxia is approved for all 4 serotypes of dengue fever. Not good for Oxitec shares.

Oxitec trials in the developing world have also been overrun by controversy. In Panama, in spite of triumphant statements by Oxitec, its government partner, the Gorgas Institute, called the results of the trial “inconclusive”: $620,000 was spent to reduce the number of mosquitoes in a neighborhood of only 200 families.

In the 2010 trial in the Cayman Islands, Oxitec ended up releasing three times more mosquitoes than projected. 25 transgenic males were released for every 1 wild male mosquito to achieve an 80% reduction in the mosquito population.

In Northeast Brazil the overlapping of the release of Oxitec transgenic mosquitoes with a Zika epidemic is a source of much controversy as to the safety of the Oxitec protocol. Could the transgenic mosquito have caused the “evolutionary response” described in Dr. Medlock’s mathematic model? Could the transgenic mosquitoes have helped the Zika virus mutate from the benign head-ache and skin rash to the nightmarish head-shrinking virus it is today. There is no definitive response to those questions, but the languishing uncertainty doesn’t help Oxitec.

Blue Paper columnist, Dr. Martha Huggins, also pointed out that Oxitec’s credibility is overshadowed by the presence of multi-millionaire Ronildo Pereira Medeiros as a member of  the United Kingdom’s Oxitec board of advisors for Brazil.  Madeiros has been embroiled in highly publicized bribery scandals, and could be perceived as a man who would bend scientific truths for profit.

With a cheap vaccine at the gate and rumors of impropriety running wild on the net, Oxitec desperately needs a bonafide success story in the developed world, preferably in the US. It needs the stamp of approval from the FDA. Key West, with sporadic dengue outbreaks, and its affluent island suburb of Key Haven would be a perfect fit.

In August of 2015 Oxitec was bought out, for 160 million, by Intrexon, a biopharmaceutical company. Success in Key Haven could be publicized worldwide and held up against the highest standards. Transgenic mosquito programs could finally be sold with government backing and financial grants backed by big brother, USA.

“The British scientific establishment is acting like the last bastion of colonialism,” said Dr. Helen Wallace, of GeneWatch, using the rest of the world “as a private lab.”

Obtaining the consent of residents is not impossible.  In 2012, in Queensland, Australia, a controlled release of mosquitoes carrying Wolbachia [a disease that kills wild mosquitoes] did just that. Renowned mosquito expert, Dr. Scott O’Neil and his team obtained the written consent of every resident who would participate in a neighborhood release; the few who objected were excluded from the experiment as were their adjacent neighbors.

“Nobody asked us if we wanted to be a part of what is –  clear and simple- a medical experiment,” said Key Haven resident John Murphy.  Ultimately the issue in Key Haven is not just whether the Oxitec process is safe or efficient or if people believe it is safe but rather whether they have an inalienable right to say “no” to a scientific experiment involving their blood regardless of their motives for refusing to do so.

Consent of patients is not a medical “safeguard,” it is about a basic human right.  Under the 1992 treaty, it doesn’t matter if the FDA concludes the risks are “low or negligible.” Article 4 of the treaty prohibits any regulatory infringement on the basic human right to say, “I don’t want to be part of your experiment.”

With possibly one of the highest percentages of lawyers per square yard in Florida, could Key Haven be more trouble than it’s worth? Or perhaps Oxitec needs to follow the advice of Jack Nicholson in A Few Good Men: “You have to ask nicely.”

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Key Haven residents are not alone: A change.org online petition was recently published by Cayman Island residents opposing a new release, without consent, of millions more of Oxitec’s GM mosquitoes there aimed at combatting the Zika virus.