Science Policy For All

Because science policy affects everyone.

Posts Tagged ‘mosquitos

Genetically Modified Animal Vectors to Combat Disease

leave a comment »

By: Sarah L Hawes, PhD

Mosquito larvae: ©ProjectManhattan via Wikimedia Commons

Diseases transmitted through contact with an animal carrier, or “vector,” cause over one million deaths annually, many of these in children under the age of five. More numerous, non-fatal cases incur a variety of symptoms ranging from fevers to lesions to lasting organ damage. Vector-borne disease is most commonly contracted from the bite of an infected arthropod, such as a tick or mosquito. Mosquito-borne Zika made recent, regular headlines following a 2015-2016 surge in birth defects among infants born to women bitten during pregnancy. Other big names in vector-borne disease include Malaria, Dengue, Chagas disease, Leishmaniasis, Rocky Mountain spotted fever and Lyme.

Vaccines do not exist for many of these diseases, and the Centers for Disease Control (CDC) Division of Vector-Borne Diseases focuses on “prevention and control strategies that can reach the targeted disease or vector at multiple levels while being mindful of cost-effective delivery that is acceptable to the public, and cognizant of the world’s ecology.” Prevention through reducing human contact with vectors is classically achieved through a combination of physical barriers (i.e. bed nets and clothing), controlling vector habitat near humans (i.e. dumping standing water or mowing tall grass), and reducing vector populations with poisons. For instance, the Presidential Malaria Initiative (PMI), initiated under President Bush in 2005, and expanded under President Obama, reduces vector contact through a complement of educating the public, distributing and encouraging the use of bed nets, and spraying insecticide. Now a 600 million dollar a year program, PMI has been instrumental in preventing several million Malaria-related deaths in the last decade.

But what if a potentially safer, cheaper and more effective solution to reduce human-vector contact exists in the release of Genetically Modified (GM) vector species? Imagine a mosquito engineered to include a new or altered gene to confer disease resistance, sterility, or to otherwise impede disease transmission to humans. Release of GM mosquitos could drastically reduce the need for pesticides, which may be harmful to humans, toxic to off-target species, and have led to pesticide-resistance in heavily-sprayed areas. Health and efficacy aside, it is impossible to overturn or poison every leaf cupping rainwater where mosquitos breed. GM mosquitos could reach and “treat” the same pockets of water as their non-GM counterparts. However, an insect designed to pass on disease resistance to future generations would mean persistence of genetic modifications in the wild, which is worrisome given the possibility of unintended direct effects or further mutation. An elegant alternative is the release of GM vector animals producing non-viable offspring – and this is exactly what biotech company Oxitec has done with mosquitos.

Oxitec’s OX513A mosquitos express a gene that interferes with critical cellular functions in the mosquitos, but this gene is suppressed in captivity by administering the antibiotic tetracycline in the mosquitos’ diet. Release of thousands of non-biting OX513A males into the wild results in a local generation of larvae which, in the absence of tetracycline, die before reaching adulthood. Release of OX513A has proven successful at controlling mosquito populations in several countries since 2009, rapidly reducing local numbers by roughly 90%. Oxitec’s OX513A line may indeed be a safe and effective tool. But who is charged with making this call for OX513A and, moreover for future variations in GM vector release?

Policy governing use of genetically modified organisms must keep pace with globally available biotechnology. Regulatory procedures for the use of GM vector release are determined by country, and there is a high degree of international policy alignment. The Cartagena Protocol on Biosafety is a treaty involving 170 nations currently (the US not included) that governs transport of “living modified organisms resulting from modern biotechnology” with potential to impact environmental or human health. The World Health Organization (WHO) and the Foundation for the National Institutes of Health (FNIH) published the 2014 guidelines for evaluating safety and efficacy of GM mosquitos.

Within the US, the 2017 Update to the Coordinated Framework for the Regulation of Biotechnology was published this January in response to a solicitation by the Executive Office of the President for a cohesive report from the Food and Drug Administration (FDA), Environmental Protection Agency (EPA), and US Department of Agriculture (USDA). Separately, biotech industry has been given fresh guidance on whether to seek FDA or EPA approval (in brief):  if your GM product is designed to reduce disease load or spread, including vector population reduction, it requires New Animal Drug approval by FDA; if it is designed to reduce pest population but is un-related to disease, it requires Pesticide Product approval by EPA under the Federal Insecticide, Fungicide, and Rodenticide Act.

Thus, for a biotech company to release GM mosquitos in the US with the intent of curbing the spread of mosquito-borne disease, they must first gain FDA approval. Oxitec gained federal approval to release OX513A in a Florida suburb in August 2015 because of FDA’s “final environmental assessment (EA) and finding of no significant impact (FONSI).” These FDA assessments determined that the Florida ecosystem would not be harmed by eliminating the targeted, invasive Aedes aegypti mosquito. In addition, they affirmed that no method exists for the modified gene carried by OX513A to impact humans or other species. Risks were determined to be negligible, and include the accidental release of a few, disease-free OX513A females. For a human bitten by a rare GM female, there is zero risk of transgene transfer. There is no difference in saliva allergens, and therefore the response to a bite, from GM and non-GM mosquitos. In addition, as many as 3% of OX513A offspring manage to survive to adulthood, presumably by spawning in tetracycline-treated water for livestock. These few surviving offspring will not become a long-term problem because their survival is not a heritable loop-hole; it is instead analogous to a lucky few mosquitos avoiding contact with poison.

Solid scientific understanding of the nature of genetic modifications is key to the creation of good policy surrounding the creation and use of GMOs. In an updated draft of Guidelines For Industry 187 (GFI 187), the FDA advises industry seeking New Animal Drug Approval to include a molecular description of the intentional genetic alteration in animals, method for alteration, description of introduction to the animal, and whether the alteration is stable over time/across generations if heritable, and environmental and food safety assessments. Newer genomic DNA editing techniques such as CRISPR offer improved control over the location, and thus, the effect of genetic revisions. In light of this, the FDA is soliciting feedback from the public on the GFI 187 draft until April 19th, 2017, in part to determine whether certain types of genetic alteration in animals might represent no risk to humans or animals, and thus merit reduced federal regulation.

Following federal clearance, the decision on whether to release GM vectors rests with local government. Currently, lack of agreement among Florida voters has delayed the release of OX315A mosquitos. Similar to when GM mosquito release was first proposed in Florida following a 2009-2010 Dengue outbreak, voter concern today hinges on the perception that GM technology is “unproven and unnatural.” This illustrates both a healthy sense of skepticism in our voters, and the critical need to improve scientific education and outreach in stride with biotechnology and policy. Until we achieve better public understanding of GM organisms, including how they are created, controlled, and vetted, we may miss out on real opportunities to safely and rapidly advance public health.

Have an interesting science policy link?  Share it in the comments!

Written by sciencepolicyforall

February 16, 2017 at 9:46 am

Science Policy Around the Web – August 5, 2016

leave a comment »

By: Fabrício Kury, MD

Genetic engineering

‘Gene drive’ organisms should be tested in field trials, not widely released, experts say

While the Zika virus shows spread into the US, with mosquito-borne transmission having been reported in Miami, the scientific community is eager to kick-start the use of the new biotechnology called Gene Drive. This technique allows for the creation of genes that cheat the trial of chance and get passed on to nearly 100% of the offspring. This way, it is possible to alter the genome of entire populations of species, for example, by making populations of Aedes mosquitoes unable to transmit the Zika or Malaria viruses — if not plainly kill all the Aedes.

The danger of Gene Drive is our lack of knowledge about the impact of drastic alterations in the behavior or biology of one species, and also the consequences from the quick removal of a pervasive species from an ecosystem. The slow progress of Zika into the U.S. through warmer and wetter edges such as Florida and Puerto Rico seems like a window of opportunity for attacking the spread of the disease while it is still relatively isolated. However, the National Academies of Sciences, Engineering and Medicine call for tightly controlled experiments before wide use of the gene drive. As MIT Media Lab professor Kevin Esvelt put it, “there is a nontrivial chance that [the genes] will spread from a single organism released into a wild population into most or all members of the local population — and very possibly into every population of the target species around the globe.” (Ike Swetlitz, STAT news)

Technology and Healthcare

Why lawmakers are trying to make ransomware a crime in California

Ransomware is a type of malware (a “virus”) that can make money for a hacker very quickly. The ransomware program encrypts files in the target computer, then demands a ransom, usually to be paid in cryptocurrency (the most popular is Bitcoin) which can be hard to track, to release the key that decrypts the files. Hospitals are perfect targets for ransomware attacks because they are often big institutions, are mostly unprepared to defend themselves against cybercrime, and hold precious data in its computers. Most often, ransomware makes the system of computers functionally “locked inside a black box” or completely unable to be used, creating mounting losses and outright risks that outweigh the price of the ransom.

This includes the medical data that is kept private inside those computers and becomes locked behind the ransomware’s military-grade encryption. Other times, the cyberattack consists of “kidnapping the privacy” of the patients. Here the hacker makes a copy of the data and requests a ransom not to release it to the public. In 2015 alone, 113 million patients had some or all of their health records stolen, and the hospital hacks showed increase of 600%. It has been called “The Year of the Hospital Hack.” Moreover, according to the FBI, ransomware as a broader industry is on the rise. In the first three months of 2016, victims of ransomware lost more than $209 million, compared to $25 million in the entire 2015. (Jazmine Ulloa, Los Angeles Times)

Affordable Care Act Effects

How I Was Wrong About ObamaCare

The strategy implemented by the Patient Protection and Affordable Care Act (PPACA, “ObamaCare”) for the purpose of controlling health care costs is one that strives for paying for healthcare by value provided instead of service provided. The promoted understanding, as summarized by former health policy advisor to the Obama administration Dr. Ezekiel Emanuel, 2011, is that such force will pressure the health care industry to undergo vertical consolidation into Integrated Delivery Systems. These systems, whose likes could be named as Kaiser Permanente, Geisinger Health Care System, and Intermountain Healthcare, are consolidations of all types of providers (physician, imaging, therapy, nursing, surgery, home care, specialty care etc.) and strives to be at least internally coordinated to provide the best value per cost, since its payment is not completely tied to the number of procedures or services performed.

Two PPACA-derived value-based reimbursed programs were launched in 2012 — the smaller and more cautious Pioneer Accountable Care Organizations, reserved for groups of providers with more experience in integrated health care delivery, and the larger and more ambitious Shared Savings Program Accountable Care Organizations. Their data has been released along the past year. The data shows that, along the first performance year of the Medicare Shared Savings Program, 58 ACOs generated $705 million in savings, feat which earned them $315 in bonuses as per the program’s workings, leaving net $260 million in savings to CMS. In April this year, the first study of the official CMS claims data indicated that the better savings were among the ACOs classified as small groups of providers. This is understood as evidence against the “Kaiserification” of healthcare as envisioned by Dr. Emmanuel, since the savings come not from having all providers as employees of a big conglomerate, but instead in giving more autonomy and power to the health care provider at the forefront of the contact with the patient. (Bob Kocher, Wall Street Journal)

Have an interesting science policy link?  Share it in the comments!

Written by sciencepolicyforall

August 5, 2016 at 11:00 am

Science Policy Around the Web – February 2, 2016

leave a comment »

By: Agila Somasundaram, Ph.D.

Map representing scientific collaborations from 2005 to 2009 using data from Scopus. International cooperation. Credit: Computed by Olivier H. Beauchesne and Scimago Lab

Science Policy on a Global Scale

Global science engagement

The American Association for the Advancement of Science (AAAS) will have its annual meeting in Washington DC, from 11 to 15 February 2016. World leaders in science and policy will discuss major challenges, such as food security and health, facing the global community. Dr. Geraldine Richmond, President of the AAAS, says that nations need to employ ingenious ways to find solutions to the ever-increasing demands for food, energy, water, and a healthy environment, which are complex and interconnected problems. Dr. Richmond emphasizes the importance of international research partnerships and innovative approaches that assimilate perspectives and lessons from all over the world, including the developing countries. Such ‘Global Science Engagement’ will be the focus of this year’s AAAS meeting. Dr. Richmond cautions that isolationist views that undervalue international initiatives are unwise. For example, the United States spends billions of dollars providing clean drinking water to its people, but 90 percent of that water is flushed down the drain. Valuable lessons could be learnt from countries such as Namibia where recycled water has been consumed since 1969 with no adverse health consequences. Diversity in opinions, ideas, and experiences is essential to furthering creativity and innovation that is required to solve complex global problems. But scientists in developing countries face difficulties connecting with their peers in more advanced nations, for e.g. due to limited journal access, and people in the United States who are interested in global engagement have limited ways to do so. While commending the efforts of AAAS and other scientific societies in facilitating international engagements, Dr. Richmond calls for more efforts and commitment to strengthen such collaborations. (Geraldine Richmond, Science)

Zika Virus

New Weapon to Fight Zika: The Mosquito

The Zika virus is rapidly spreading in the Americas, and has been linked to a severe defect in brain development, microcephaly, in babies. The Zika virus is spread by mosquitoes, mainly the Aedes aegypti species, which also transmits deadly infections such as chikungunya, yellow fever and dengue fever. Efforts to develop vaccines against the virus are underway, but it may take many years, even a decade, before an effective vaccine can be given to the public. Experts argue that new methods are needed since the traditional ones, involving insecticides and reducing stagnant water to prevent mosquito breeding, aren’t enough.

The British company Oxitec has developed genetically engineered mosquitoes that transmit a lethal gene to their progeny, which die before reaching adulthood. These engineered mosquitoes have been successfully used to lower mosquito populations by more than 80 percent in certain parts of Brazil. Oxitec says this is an ecologically friendly approach because only one species is targeted, as opposed to chemical spraying that affects many organisms. But the release of genetically modified organisms into the environment has met with opposition. Another approach is to infect the mosquitoes with the bacterium Wolbachia, which makes it harder for the mosquitoes to transmit viruses. The bacteria can be passed through eggs, making this a self-sustaining method. Initial results in Brazil appear promising, encouraging trials on a larger scale. A third powerful approach is the use of gene-drives. Gene-drives allow for the propagation of a desired trait, for e.g. sterility, through a wild population. Though gene-drives have been tested in laboratory scales, it might be not so easy to deploy it in public yet, mainly because of concerns that it would be very difficult to reverse things if something undesirable happens.

Remarking on the three approaches, Dr. Peterson, Centers for Disease Control and Prevention, said, “We don’t know about the efficacy of any of them on a wide enough scale… For now, we’ve got to deal with what we have.” Experts say that the traditional methods of mosquito control need to be intensified, till we have proven the large-scale efficacies of the new approaches and/or developed an effective vaccine. (Andrew Pollack, The New York Times)

Scientific Integrity

How cases like Flint destroy public trust in science

While the Flint water crisis is being investigated, disturbing reports emerge about how studies that showed a problem in Flint’s drinking water were dismissed. In Fall 2015, a team of researchers in Virginia Tech, led by Dr. March Edwards, examined the lead content of drinking water in Flint homes. The study revealed that the 90th percentile reading was 27 parts per billion. The Environmental Protection Agency considers 5 parts per billion a cause for concern, and 15 parts per billion as the limit above which the problem should be fixed. However, tests conducted by the city showed lead levels within safe limits. The Michigan Department of Environmental Quality responded saying that the state was perplexed by the study results, but not surprised, given that Dr. Edwards’ “group specializes in looking for high lead problems.” According to reports, the city’s water testing results had been “revised by the Michigan Department of Environmental Quality to wrongly indicate the water was safe to drink.” The state officials attempted “to use power instead of logic and scientific reasoning to defend and hide their actions,” says Dr. Edwards. Similarly, studies done by Dr. Mona Hanna-Attisha, pediatrics program director at Michigan’s Hurley Medical Center, were also initially criticized. Her study showed that the percent of children with elevated blood lead levels doubled, or tripled in some areas, after the change in water source. When the state later analyzed its data using the same approach as Dr. Hanna-Attisha, the results matched.

Dr. Naomi Oreskes, science historian at Harvard University, says that though these events may not classify as “science denials,” they constitute a less-defined category of “no one likes bad news.” “Why didn’t government officials take it seriously when scientists tried to raise an alarm?” she asks. When government officials responsible for people’s safety commit acts like these, it crushes the public’s faith in science, and exacerbates problems such as denial of climate change or the safety of vaccination. How do we prevent problems like Flint from reoccurring? The answer is not clear yet, but some suggestions include conducting better checks and balances by independent researchers not affiliated with the government, and not overlooking the role of universities in protecting public welfare. According to Dr. Aron Sousa, the work by Edwards and Hanna-Attisha should reinforce the public’s faith in good science. (Chelsea Harvey, The Washington Post)

Have an interesting science policy link?  Share it in the comments!

Written by sciencepolicyforall

February 2, 2016 at 9:00 am

GMO mosquitos to combat dengue and chikungunya: Regulatory agencies stretched by rapid advances in recombinant DNA technology

with 4 comments

By: Daniël P. Melters, PhD

Female Aedes aegypti via James Gathany/CDC

Juan was admitted to a hospital in Turbaco, just outside Cartagena, Colombia yesterday. He is the third member of his family to be admitted in the last two weeks. His wife and cousin were both diagnosed with chikungunya, which is currently epidemic in most Caribbean nations, including Colombia. Although his symptoms were similar to theirs, they are less severe. After medical testing, it is confirmed he contracted the endemic dengue virus. This is not surprising, as the same mosquito, Aedes aegypti or yellow fever mosquito, transmits both viruses.

On the other side of the Caribbean hope may soon be released. In the Florida Keys, an experimental trial with a new method to combat mosquito-borne diseases is being considered by the U.S. Food and Drug Administration (FDA). The biotech company Oxitec, a spin-off from Oxford University, has developed a genetically modified mosquito that can reduce the number of mosquitos carrying dengue viruses with surgical precision. If the FDA approves the experimental release of hundreds of thousands of GMO mosquitos, it could bring down the number of dengue-carrying mosquitos in the Florida Keys by 80-90%. This anti-mosquito technology is particularly promising for developing nations buckling under the financial and social burden of endemic dengue as it more cost-effective than traditional fumigation.

Mosquitos are responsible for transmitting various human pathogens such as dengue, chikungunya, river valley fever, yellow fever, and malaria – to name a few. Each year, millions of people die as a direct result of such mosquito-borne diseases, mostly in developing nations, including Colombia. About 390 million people are infected with the dengue virus each year and the number is on the rise. This rise can be attributed to both the aggressive nature of its host (A. aegypti) and the increase in the host’s habitat as a consequence of global warming. Although originally from Africa, the principle vector for dengue viruses, A. eagypti, is now endemic throughout the tropical and subtropical Americas.

How do Oxitec’s genetically modified mosquitos reduce the general mosquito population? Their strategy is to only release genetically modified male A. aegypti. These males will mate with females in the wild and pass on a modified gene to their offspring. Mosquitos with this gene require the presence of tetracycline, a broad-spectrum antibiotic, during their development to survive and therefore, they will die before they mature. Furthermore, only female mosquitos bite humans, as they need the amino acid isoleucine from human blood to make their eggs. The risk of any human being bitten by a genetically modified mosquito is negligible.

The major advantage of genetically modified mosquitos over conventional mosquito control measures is the species-specific approach. A. aegypti males will only mate with A. aegypti females. All other insects, including mosquitos that don’t bite humans, will remain unharmed. In contrast, the most commonly used mosquito control method involves large-scale fumigation with insecticides, which kills insects indiscriminately.

The FDA’s decision to consider allowing the Oxitec researchers to release hundreds of thousands of genetically modified male mosquitos has sparked skepticism about the safety and ecological consequences of the proposed release – skepticism that is shared by about 10-20% of the residents of the Florida Keys, according to a recent survey.

One fear is that removal of A. aegypti would be disastrous for the ecosystem, since the ecosystem would lose a pollinator and a food source for many animals. Although this fear might ring true for other species, experts agree that it is unlikely that even losing all of the over 3000 different mosquito species will permanently harm the ecosystem as their niche will most likely be replaced by other insects. Therefore, the potential loss of one mosquito species would have a minimal effect.

Another fear is that removal of A. aegypti will allow more space in the ecosystem for the invasive Asian tiger mosquito (Aedes albopictus) to invade. The Asian tiger mosquito is also capable of transmitting yellow fever, dengue, and chikungunya and has already conquered large parts of Central America and the southern states of the US. To counteract this latter fear, Oxitec is currently developing a genetically modified Asian tiger mosquito by adapting the same principles as the genetically modified A. aegypti.

Thus far, Oxitec has completed three major ecological studies in Brazil, Malaysia, and the Cayman Islands, where they claim an 80-to-90 percent decline in A. aegypti populations over three months. To conduct these studies, Oxitec teamed up with local officials. In April 2014, Brazil’s National Technical Commission for Biosecurity approved the commercial release of genetically modified mosquitos. For the past 5 years, Florida’s Mosquito Control District, which is in charge of mosquito control in the Keys, have been working with Oxitec to get approval from the FDA for similar experimental trials.

Though the fear of genetically modified organisms is not backed by science, the fear itself is still real. After all, an entire food industry has grown around the promotion of not using genetically modified foods. In 1975, the potential for public distrust of recombinant DNA technology (or genetically modifying organisms) was foreseen by scientists. This led Maxine Singer and Paul Berg to organize the Asilomar Conference on Recombinant DNA. At the conference, a group of biologists, lawyers, and physicians discussed the potential biohazards and regulations of biotechnology. They drafted voluntary rules, which still impact regulatory guidelines for biotechnology today.

Regulating the safety of genetically modified crops and pharmaceutical biotechnology products is the domain of the FDA, EPA, and USDA. The EPA and USDA also regulate pesticides and insecticides (under the Federal Insecticide, Fungicide, and Rodenticide Act or FIFRA and through the Animal and Plant Health Inspection Service (APHIS)). Typically, the FDA does not deem it necessary for GMO crops to be approved pre-market, unless the expression of a foreign protein differs significantly in structure, function, or quality from natural plant proteins and is potentially harmful to human health. The FDA has established a voluntary consultation process with GMO crop developers to review the determination of substantial equivalence before the crop is marketed.

The FDA has seemingly created greater hurdles for the approval of genetically modified animals. The review by its Center for Veterinary Medicine of a genetically engineered protein to increase the milk output of dairy cows took some nine years. In the 1990’s the FDA began a review of a genetically engineered Atlantic salmon. In 2012, the agency published a draft Environmental Assessment for the genetically modified salmon with a preliminary finding of no significant impact. As of December 2014, the FDA has not made a formal decision.

In both of these cases, the genetically modified cow and salmon are meant for human consumption. In this regard, the genetically modified mosquito differs greatly. It is intended to reduce the mosquito population and thus prevent mosquitos from biting humans and subsequently transmitting pathogens. Whether this will affect the speed at which the FDA could approve the proposed experimental release in the Florida Keys remains to be seen. A positive development here is the approval by the FDA for the start of clinical trials for genetically modified T lymphocytes to control the number of HIV particles in patients and thus stem the HIV infection.

Mosquito-borne diseases are a great health burden, especially in developing nations, as Juan and his family are experiencing. A cost-effective and precise application to limit the harm caused by mosquitos could potentially benefit billions of people. Yet, the safety of the public and the environment need to be respected and addressed. It is clear that a new era of using genetically modified organisms is here even before society has fully embraced GMO crops. Regulatory agencies now have to catch up to facilitate their safe and effective development. To advance this process, it is imperative that the FDA, Oxitec, and the Mosquito Control District (in this case) clearly and factually communicate with the public about what their course of action is, what the results are, and most importantly what the risks are and how these risks are being mitigated. If the public does not accept GMO mosquitos to combat mosquito-borne disease, the technological advancements for all GMO products will be hampered.

Written by sciencepolicyforall

March 18, 2015 at 11:32 am