Gene editing for pest control

Some thoughts from Jean Fleming

What is gene editing?

• Gene editing uses bacterial enzymes (the CRISPR-Cas9 system) that are used in nature to chop up the DNA of invading viruses and thus protect the bacterium from infection. As such, the system has been described as a form of bacterial “immune system”. The CRISPR-Cas9 system uses enzymes that can change a single letter of the DNA code in any cell (bacterial or mammalian) very specifically, thus either effectively stopping the gene from working, or fixing a mutation.
• Gene editing changes the DNA sequence. It can therefore be considered to be genetic modification. However no new DNA is added to the gene conveying a new characteristic (eg herbicide resistance).
• These days you can buy an expensive kit, with all the enzymes and solutions required, to get the job done. All you need is a short piece of DNA that will take the enzymes involved directly to the sequence you want to change. See http://www.genecopoeia.com/product/genome-editing-tools/genome-editing/
• Theoretically, for genetic diseases like cystic fibrosis, where a single letter of the code is wrong in sufferers, introducing cells capable of making the missing protein correctly will fix the disease in that individual, possibly for life.
• For more complex diseases, like endometriosis or most cancers, fixing a single gene mutation is unlikely to cure the disease.
• If the DNA in eggs or sperm is edited, the changed DNA will be passed on to the individual’s children, so it will be a permanent change, although it should be possible to reverse edit the gene in exactly the same way.

Inserting a gene for infertility into a rat would normally result in only a 50% chance that the trait would be handed on to the next generation – as the DNA of both parents would be passed on. However, a new technology called the gene drive would enforce the replication of that desired gene (let’s not get into how).

 

• A gene drive is the phenomenon in which the inheritance of a particular gene or set of genes is favoured. Gene drives can arise through a variety of mechanisms and results in the “desired” trait (eg infertility) increasing in a population. Engineered gene drives have been proposed to provide an effective means of genetically modifying populations or even whole species. The result might be the complete eradication of the species, not only in New Zealand, but possibly all round the world.
• Moral and ethical problems arise when one species (humans) want to eradicate  another (mosquitoes, wasps, NZ stoats). “But how do we tackle the tricky ethical questions that the predator-free mission raises? How do we decide what an invasive species is, or whether they pose a threat, and will the new tools we need to do the job be accepted by Kiwis?” http://www.nzherald.co.nz/nz/news/article.cfm?c_id=1&objectid=11923806

And if you think New Zealand is isolated enough to prevent escape of the technology, consider why ship rats are called ship rats. A few escapees carrying the technology might eradicate that species of rat around the world. Remember also, New Zealand has three species of rat alone and our knowledge of the differences and similarities of their genomes is limited.

• The daisy gene drive has been invented to deal with the risk of global spread and eradication of a species. It is a more localized form of CRISPR-based gene drive composed of genetic elements arranged in a daisy-chain such that each element drives the next. Releasing daisy drive organisms constituting a small fraction of the local wild population could drive infertility (for example) into the national population without resulting in global spread. See https://www.responsivescience.org/pub/daisydrives
• Governance of gene drives may be complex. A paper by Austin Wright-Pettibone (“Driving the Future”) proposes four major principles:
  • Principle I: Avoid the use of global drives.
  • Principle II: Localize drives to specific consenting communities.
  • Principle III: Consider gene drive a process for spreading genes, rather than any specific gene-edited product.
  • Principle IV: Expand the Coordinated Framework for Regulation of Biotechnology to include agencies with stakeholder interest in public health and the environment.

Strategies to use gene editing on pests

• The bigger picture: The systems used to edit genes have evolved along with everything else. All over the world people are experimenting to develop medical applications, but also to “fix” malaria, by eradicating or controlling mosquitos. “So what happens is that it spreads and it spreads and it spreads. And this is the fantastic thing,” says Hammond. “Because it allows that gene to be selfish in a population. And in a very short amount of time you can actually transform an entire wild population into a modified population. It’s powerful.” https://www.npr.org/sections/health-shots/2016/12/14/504732533/to-fight-malaria-scientists-try-genetic-engineering-to-wipe-out-mosquitoes
• However, scientists are learning quickly that the system is not quite as simple as they thought.
• Just recently, organisms have been shown to develop resistance to gene editing. “Just as superbugs develop resistance to antibiotics, it’s likely that wild populations will develop resistance to modifications aimed at destroying them. In 2015, researchers demonstrated this, reporting that as an infertility mutation in female mosquitoes was successfully passed on to all their offspring over many generations, resistance also emerged, allowing some mosquitoes to avoid inheriting the mutation.” See https://www.gizmodo.com.au/2017/04/new-zealand-could-use-gene-editing-to-kill-off-its-cutest-predator/ and https://www.engadget.com/2017/02/01/mosquitos-are-beating-gene-editing-with-rapid-evolution/
• A recent paper found hundreds of mutations (in experimental mice) that weren’t supposed to be there, after specific gene-editing. The results contradicted earlier studies that showed CRISPR caused very few of these “off-target” mutations. One of the authors, Stephen Tsang, commented: “We feel it’s critical that the scientific community consider the potential hazards of all off-target mutations caused by CRISPR.”

A simple gene drive is irreversible, but researchers are investigating ways of limiting them so that they spread through most of a population but then cause their own extinction.

• The invasiveness and comprehensiveness of the gene drive has been tempered by a new tool called the daisy drive. This “daisy chain” system reduces the risk that it will drive through a global population.
• The knowledge about gene editing is changing so fast, that opinions held a month ago are sometimes changed the next. The one constant is the need for “public engagement” ie the public needs to make the decision, not the scientists, because the scientists cop the blame when things go wrong. There is also a rise in the number of scientists such as Wayne Linklater and James Steer, who believe we should learn to live with our predators and keep the iconic birds in offshore islands and sanctuaries.
• There have been some really useful New Zealand discussions about gene editing to eradicate pests. Try http://www.radionz.co.nz/national/programmes/ourchangingworld/audio/201840692/we-need-to-talk-about-gene-drives-and-gene-editing and http://www.radionz.co.nz/stories/2018618186/editing-our-genes-pest-control. I attended the latter panel discussion and felt the scientists were all very defensive already and looking to the ethicists and the community for the way forward. There are links in the first web link to other new ideas, such as the use of Trojan females, too.
• And if you are not completely sick of gene editing by now, try http://www.radionz.co.nz/national/programmes/saturday/audio/201859669/kevin-esvelt-sculpting-evolution.