About a year ago (Signs of Spring 13, May 13, 2017) I wrote about the proposed use of the CRISPR gene editing system and a “gene drive” replication amplification system to help control Lyme disease (by eliminating the critical intermediate host in the Lyme disease cycle, the white-footed mouse) and malaria (by altering the genes of the Anopheles mosquito vector that transmits the Plasmodium parasite to make the physiology of the mosquito inhospitable or even toxic for the Plasmodium organism).
CRISPR, you may remember, is a technology that employs specifically engineered RNA sequences and a protein that cuts (and pastes) DNA in order to line up a sequence of DNA at a specific gene locus and then insert it into the DNA strand. A “gene drive” utilizes a recognized interaction between an organism’s homologous chromosomes in which one of the homologous chromosomes contains a specific DNA sequence that makes an enzyme that spontaneously cuts the DNA sequence of the other chromosome. This is very similar to CRISPR except that in this system the “cutting” gene sticks a copy of itself into the severed DNA sequence. The “gene drive,” then, results in the amplification of a gene passing through generations in a population.
These CRISPR/gene drive systems have been evaluated carefully since for many of these applications their theoretical outcome is the extinction of their target species. Nature, however, seems to have some other ideas in this matter.
For example, a paper in Science Advances (May 19, 2017) found that genetic variations at the CRISPR insertion site, even quite rare variations, can interfere with the success of the gene insertion. Researchers found that even a 1% gene variation at a CRISPR site was enough to negate any attempted CRISPR/gene drive control in as few as six generations. The use of these CRISPR systems, then, can only be successfully applied to a very select number of extremely non-variable genes.
Also, a paper published in PLOS GENETICS (October 4, 2017) showed that mutations in a population of Anopheles mosquitoes into which a reproduction disrupting gene drive had been inserted quickly restored fertility in the mosquitoes and broke down the operation of the gene drive.
As Dr, Ian Malcolm (played by Jeff Goldblum) said so memorably in Jurassic Park, “life, uh, finds a way!”
Another, slightly less elegant way to control insect populations is to infect them with bacteria that disrupt their reproduction or life cycle. Male mosquitoes infected with the bacterium Wolbachia pipientis, for example, produce fertilized eggs that do not survive. Release of large numbers of Wolbachia infected male mosquitoes, then, should result in declines in the mosquito population.
The Asian tiger mosquito (Aedes albopictus) is an exotic species that is steadily spreading across the eastern, midwestern and southwestern United States. Periodically, Asian tiger mosquitoes are even collected here in Western Pennsylvania in the summer, and there is evidence that the species may be evolving a tolerance to our long, cold winters. These tiger mosquitoes can carry a wide variety of pathogens including the viruses that cause yellow fever, Denge fever, Chickungunia and Zika. (see Signs of Spring 13, May 19, 2016 for more discussion of Asian tiger mosquitoes).
Control of Asian tiger mosquitoes is difficult because of the species’ great flexibility in reproduction (even very small water pools are sufficient for their egg laying and larval development) and the mosquito itself can tolerate very wide ranges of environmental conditions. The use of Wolbachia infected males to try to control tiger mosquitoes was approved by the EPA last year. This summer Wolbachia infected male Asian tiger mosquitoes will be released in twenty states under the direction of the biotech company MosquitoMate.
Controlling pest organisms via inducing changes in their genes or infecting them with bacteria, then, are two approaches for biocontrol. Another approach involves changing the plants on which the pest (typically a crop destroying pest) feeds. One of the most common ways that a crop can be modified for biocontrol is to insert a gene into the plant that codes for the synthesis of a chemical that acts as an internal pesticide. For the past twenty years a very common insecticidal insertion into plants has been the toxin producing gene from the bacterium Bacillus thuringiensis (Bt). These Bt-modified plants have included corn, cotton and soybeans. According to statista.com some 80% of all corn and cotton grown in the United States is now Bt-modified.
In a paper published in Nature Biotechnology (October 11, 2017) researchers at the University of Arizona document the growing resistance of a variety of potential crops pests to the insecticidal toxins produced in the Bt-modified plants. The precipitous decline in the effectiveness of Bt-modification was startling. It was noted, however, that the use of cropland “refuges” (fields in which non-Bt-modified crops were planted adjacent to the fields with the Bt-modified plants) slowed down the development of Bt resistance. These refuges, apparently, increased the chances that a Bt-resistant pest individual would mate with a non-Bt-resistant pest individual, thus slowing down the spread the Bt-resistance gene in the pest population.
So there are lessons here: a year ago it seemed like CRISPR and gene drives would allow us to so precisely tinker with human pathogens and crop pests life cycles that we could easily eliminate both vector transmitted diseases and a long list of serious crop pests within a few generations of their life cycles. Many scientists began to envision a world free of disease and in which food crops could be grown with maximum efficiency. We now know that we didn’t really understand the system with which we were working. We now know that the forces of evolution will resist our clumsy attempts to take control of Nature. We need to know so much more!