SEATTLE — Molecular biologist Anthony James is at the forefront of Culicidae and genome editing research. There are currently 3,500 known species of mosquitoes and James specializes in the world’s deadliest kinds, including the Anopheles and Aedes mosquitoes.
The Anopheles mosquito, carrier of the malaria parasite, is responsible for more than 400,000 deaths every year. The Aedes mosquito, the common host of yellow fever, is responsible for 60,000 deaths each year. The Aedes mosquito is also a carrier of Zika, chikungunya and dengue (a virus that now threatens 50 percent of the world’s population in more than 100 countries).
For years, James’ goal was to find a way to manipulate mosquito genes so that they could no longer spread the aforementioned diseases. Until recently, James’ research was fundamentally theoretical, but by combining an innovative new technology, CRISPR-Cas9, with an inheritance technique referred to as a gene drive, biotechnology has brought about extraordinary possibilities for the elimination of mosquito maladies.
With CRISPR technology scientists are now able to modify, erase and rearrange the DNA of mosquitoes. CRISPR-Cas9 works in two fundamental ways. The enzyme Cas9 cuts through DNA, essentially acting as a cellular surgical tool. Within CRISPR (clustered regularly interspaced short palindromic repeats) lies an RNA guide (a DNA messenger) that leads Cas9 to the precise nucleotides it needs to cut.
This genome editing technology is groundbreaking in its precision and accuracy because it allows scientists to dispatch an artificial aspect to any location of a mosquito’s genetic material. Once it arrives at its destination, Cas9 cuts out the undesirable DNA sequence.
Combining the editing potential of CRISPR with a gene drive that promotes specific elements of inheritance, scientists are staring down a solution that could potentially save millions of lives. Gene drives have the potential to override regular rules of inheritance because some genes are “selfish” and are more likely to be inherited. Synthetic gene drive systems and site-specific genome technology allow scientists to spread traits into a population.
Therefore, scientists can alter the genetic code of a mosquito species such as Anopheles by attaching the desired DNA sequence onto a “selfish” gene before releasing them to mate. Given a purposeful genetic trait alteration, this could make Anopheles mosquitoes incapable of transmitting the deadly parasite and spreading malaria to millions of people.
Combating the Aedes mosquito poses more difficulty because it carries a number of different pathogens. This species of mosquito would require a gene drive that would sterilize the insect so it would be unable to transmit Zika, yellow fever, dengue and chikungunya.
By targeting female reproduction in the Aedes species, scientists would replace the natural gene with one that would guarantee sterility. If enough of these engineered loci were released, an entire species would carry these alterations in fewer than three weeks.
What’s the catch?
While these genome editing discoveries hold incredible potential, they raise distressing ethical concerns. Correcting genetic flaws or enhancing genetic traits that would pass to the following generation is a slippery slope.
Releasing a genetic mutation into a rapidly producing population may have unpredictable and irreversible consequences. In addition, transfer of DNA between species may shift viruses and other pathogens causing unexpected maladies to which there could be no natural cure.
However, in recent years, guidelines and protections in genetic engineering have proved effective and improved the lives of millions. Furthermore, CRISPR-Cas9 technology alters, deletes and redesigns DNA as opposed to introducing DNA from other species.
Faced with the ethical challenges of rapid scientific and technological development, it would appear easier to choose inaction. Yet there are millions of lives at stake and inaction seems equally if not more troubling.
CRISPR has already transformed cancer research through the engineering of tumor cells and stem cell research for hemophilic patients. It has also been used to correct genetic flaws responsible for muscular dystrophy and cystic fibrosis. Genome editing technology is also revealing which DNA sequences are responsible for diseases such as AIDS.
Without action, the U.S. Centers for Disease Control and Prevention estimates at least 3.5 million people in Puerto Rico may contract Zika. Puerto Rico warrants urgent and comprehensive aid as positive tests for people with suspected Zika virus infection increased from 14 to 64 percent in less than six months in 2016.
Scientists expect up to 600 million more people to be exposed to Zika carrying Aedes mosquitoes as the planet warms, as the mosquitoes thrive in tropical climates. For the sake of those dependent on the potential of this technology, there is an ethical responsibility and an urgency to use genome editing wisely and effectively.
– Emma Royce