Sunday, December 25, 2016

Gene Drive Issues

Gene Drives are an interesting interplay with a set of "tools" available to gene manipulators. The current capabilities of gene manipulation, also we can probably call it gene engineering, is that we have an ever growing collection of "tools". These tools allow bench folks to add this or subtract that from a cell. We can do this with a somatic cell, an existing cell in an existing organ and a germ line cell, a cell from which the organism will eventually be derived. We can add or delete genes and we can in so doing insert a mechanism which will carry on this editing process no matter what the cell becomes as the organism develops. Furthermore if we get this process working in the germ line cell then we can be assured that as the next generation proceeds this inserted tool for manipulating genes within the organism, if not now within the total species, proceeds in a dramatic manner. We lose Mendelian genetics and the tool insertion now produces a single unaltered lineage.

If this gene is of a certain type, say one which produces only a male, then by blocking in all subsequent lines of any females we can effectively wipe out this species when we have just surviving but non-producing males.

This assembly of tools by the genetic engineer has been called "gene drives". In a sense it "drives" certain genes into all members of a species. At least that is the hope. As the Broad Institute states in its licensing statements[1]:

Gene drive. This is a way to rapidly spread a new gene throughout an entire species in nature. This approach might be used to block the transmission of malaria by mosquitoes, but has the potential to disrupt ecosystems… After consulting with external experts and careful internal consideration, the Broad Institute has decided to make available non-exclusive research and commercial licenses for the use of CRISPR technology in agriculture -- but with important restrictions. These include: Gene drive: We prohibit the use of the licensed technology for gene drive.

Now to repeat a simplified version of the Gene Drive we present the steps simplified below. The basic principle is to insert a gene into a species, yes species, which will alter the entire species, such as making them all males and thus no longer able to reproduce.

Start with the above, two sets of chromosomes from a wild type in a species. Classic Mendelian genetics would apply. Now we want to introduce some gene to alter then entire species. Usually was can do that say in an embryo but it would remain on one or even both chromosomes but would filter out. Yet if we could somehow also say introduce a CRISPR/Cas9 combo to rewrite this gene over and over then it would spread across all embryos and thus the species.

Thus the next step is:

Namely figure out the gene, use say a Cas9 or other similar endonuclease, and a target CRISPR to  guide the new gene.
We use some insertion mechanism such as a lentivirus in the embryo with some reverse transcriptase to insert these genes.
Then in the embryo it duplicates and the entire embryo reflects the gene and duplication mechanism.
Then the mating is between this modified and enabled vector with any wild type.

And we introduce the little factory in all off-spring.

Which perform the same tasks and reproduce the gene throughout the targets. Thus we could get all male insects and drive the species to extinction!

As The Scientist notes:

The United Nations (UN) biodiversity meeting, held in Mexico this month, could have ended poorly for scientists working on gene drives, genetic elements that can perpetuate specific mutations and may help cull dangerous mosquito populations. But in spite of environmental activists pushing the UN to ban gene drives, citing the risk of accidental release, the UN’s final agreement—penned December 16—merely urged caution in testing gene drives, Nature reported. Overall, the organization broadly supported further research in synthetic biology. “I’m very relieved,” Andrea Crisanti, a molecular parasitologist at Imperial College London who works with gene drives, told Nature. “It would have been a disaster for developing the technology.”By engineering mutations that render organisms infertile or less infectious, then perpetuating these mutations with gene drives, scientists may be able to reduce the occurrence of certain mosquito-born illnesses and cull invasive species. Gene drives have already been tested in yeast, fruit flies, and mosquitoes, and may soon be enlisted in the fight against malaria. One team hopes to conduct field trials in Africa as soon as 2024.

 In a similar fashion Nature states:

When the CBD last met in South Korea in 2014, gene drives were a largely theoretical idea. They are genetic elements that can quickly spread through sexually reproducing populations. In general, an organism's two copies of a gene — known as alleles — each have a 50% chance of being passed on to its offspring. This limits the pace at which a genetic modification can spread through a population. But gene-drive technology tilts the odds, so that a specific change to one allele is inherited by a higher proportion of progeny. In theory, an entire population could quickly carry the same modification. In the past two years, researchers have lab-tested gene drives in yeast, fruit flies and mosquitoes that are based on a gene-editing technology called CRISPR–Cas9. Crisanti’s team, for instance, is working on gene drives in the malaria-carrying mosquito Anopheles gambiae that perpetuate mutations causing females to become infertile. Spread of this mutation could mean that mosquito populations plummet to levels that do not support the transmission of malaria. The researchers' project, called Target Malaria, has attracted tens of millions of dollars in funding, and the scientists hope to conduct field trials in Africa as early as 2024. Other groups are developing gene drives to quell island rodents and other pests.

This development takes the next step and it presents a rather double edged sword. It is essential to be watched as we move forward.

As I have noted again and again. Silicon Valley apps pale to what bio tech is doing. In bio tech, there is a potentially deadly field at play and any country and enter the game. The cost is low, expertise is required, and somehow we seem to be providing it in our Institutions.