Gene Drive - the new genetic engineering technology promoting the rapid ‎spread of genes into a population. The problem: how to prevent it from ‎spreading out of control?‎

Genetic engineering is currently one of the most discussed subjects. Throughout the world, scientists are focusing their research on altering the genetic code in species of plants and animals to be used in research and in improving our quality of life. In recent years, the field is undergoing a real revolution, thanks to a significant technological breakthrough: an artificial mechanism called “Gene Drive” – allowing genetic changes created by human intervention to compete with natural evolution to spread through entire populations.

In sexual reproduction, all animals produce two copies of the genes; received from their parents, and inherited by their offspring. The probability that each of the two versions of a particular gene are passed on to an offspring is 50 percent, which is the basis for the “Law of Inheritance” defined by Gregor Mendel in the 19th century. In the absence of a competitive advantage for a particular copy of a gene, it will generally mean its distribution in the population will be very mild.

However, there are exceptions in nature in which some DNA molecules, the individual units that carry the genetic material, behave differently, creating a probability of preference for a particular version of a gene over another. In such situations the “preferred” version will spread in a population very quickly, turning into the dominant copy for the entire species.

An example of this is a gene called P element that did not exist until the 1950s, but today can be found in almost every fruit fly in nature, even though it does not give any apparent advantage to the descendants of the fly. Such a process is given the name of gene drive due to the ability of the gene to drive or push itself into a population ahead of other competitors, which contradicts the laws of Mendelian inheritance.

Artificial gene drive

The idea to artificially create the gene drive process was first raised more than 60 years ago, through the theoretical possibility of imposing genetic changes on populations of pest insects. Scientists needed more than fifty years just to develop a basic understanding of how it can be implemented. A leap in this direction has occurred in the last two years following the collaboration between scientists from Harvard University and Massachusetts Institute of Technology (MIT) that yielded the tool CRISPR/Cas9, which revolutionized genetic engineering.

The inspiration for using “CRISPR” was born from watching the sophisticated self-defense system of bacteria against viruses. Bacteria have a mechanism that cuts invading viral DNA and saves it as part of the genetic code of the bacterium itself. The uniqueness of the system is that the same piece of viral DNA is transferred to the descendants of the bacteria, allowing them to identify DNA sequences characteristic of the virus. Since CRISPR can work with many animals, scientists concluded that one can take advantage of the mechanism by artificially changing the “fingerprint”, and creating a new tool that enables precise genetic cutting, pasting, and editing of almost every gene.

The advantage of using CRISPR to create gene drives is to attach it to any gene and cause it to make changes to the second copy of the same gene, which will occur as the genetically engineered individual will mate with a wild type individual. It is also possible to engineer a self-duplicating system and create two copies of the gene in every generation, so the probability of inheriting the desired gene will be 100 percent.

The method is expected to work only in species that reproduce sexually including insects, mammals, reptiles, fish and most plants. The time required for the feature to seep into the majority of the gene pool depends on the length of each generation cycle and the number of individuals used to start the gene drive. For example, if we release ten engineered individuals into the population of one hundred thousand individuals, it would take about 16 generations until the gene we are interested in will be expressed in 99 percent of the population. The method is expected to work much faster in species that reproduce quickly, like insects as opposed to large mammals.

In theory it is possible to assume that the principle for gene drives can work in humans, but even if we decide to make our own genetic changes it would require hundreds of years before the gene seeped into a significant part of the population. By comparison, if we wanted to create a Gene Drive in elephants, whose generations last about the same as humans, in a hundred years we would see merely a fourfold increase in those carrying the engineered gene. And this is true only under the assumption that during all that time no one will change their mind and engineer a gene drive to counter this one.

Even when it comes to agricultural crops the system may encounter difficulties, since a gene drive requires effective mixing within the population, yet presently most produce is grown from seeds in a controlled manner. Similarly, livestock and domestic animal breeding is very controlled, and therefore any genetic modification would be limited only to the local population.

How the system works: illustration of engineered genes spreading through the general population

Prospects and risks

Currently, the gene drive method has not yet emerged from the confines of the laboratory. However, the mere fact that experiments are being performed is enough for the scientific community to raise the issue in public debate in order to consider the full range of risks associated with manipulation of entire populations.

The main concern of a gene drive is the possible appearance of unexpected secondary effects that can change the ecosystem because of an interaction between the target population and its environment. However, the National Academies of Sciences, Engineering and Medicine (the main body that advises the US government on scientific matters) recently published a report confirming the continuation of studies for this technology after reaching the conclusion that the potential benefits outweigh the risks.

Governments, NGOs and research institutes have a great interest in the technology and want to test its ability to contribute to public health, agriculture and environmental protection. However, before the decision is made to release a genetically modified strain into nature, the development of safety mechanisms are required to stop the spread if, heaven forbid, it is revealed that it causes damage.

It seems that at this stage the focus of development for gene drive systems is moving from the field of molecular science to the areas of ecology and the environment. Already researchers have been placing their efforts into a huge experiment, without the use of gene drive technologies, where millions of flies or mosquitoes will be released into nature in order to combat insect populations that are creating nuisances or transmitting diseases. The consequence of such experiments in the coming years will define the approach towards these genetic technologies in both the scientific community and general public.

Intelligent use of genetic engineering for entire populations can be used, among other things, in the current war against malaria and zika that are both transmitted by mosquitoes, as well as in preventing pests from developing resistance to pesticides. In addition, it will be possible to eradicate invading species that endanger entire ecosystems, or even to save animal species that are in danger of extinction. But with all these options it is important to remember the wise words of Spiderman - the comic book hero who knows a thing or two about genetic changes: “With great power comes great responsibility”.