Predator proof fence

EXPERT REACTION: Gene editing for conservation needs in-built protection

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To reach New Zealand's Predator Free 2050 goal, researchers have been considering using gene-editing techniques to rid the country of invasive stoats, rats and possums. New research explores what would happen if these genetically changed pests were accidentally spread outside our borders. The authors say that while there is huge merit in using these technologies for conservation, letting such technologies loose without safeguards could cause international incidents and lead to the loss of public trust in scientists. Any genetic technologies considered for use need to have built-in safety measures to ensure they only affect local populations, they say.

Journal/conference: PLOS Bio

DOI: 10.1371/journal.pbio.2003850

Organisation/s: University of Otago

Funder: The authors received no specific funding for this work.

Media Release

From: University of Otago

Consequences of gene-drive technologies for ecosystems

Scientists working in the vanguard of new genetic technologies have issued a call to ensure that possible applications in conservation will only affect local populations.

Professor Neil Gemmell, the head of the University of Otago’s Department of Anatomy, believes there is still “huge merit” in using genetic technologies for conservation work.

However, he says that standard self-propagating versions “may be uncontrollable” and therefore unsuited to conservation.

In an article published today in PLOS Biology, Professor Gemmell and Assistant Professor Kevin Esvelt of MIT, who first described how gene drive could be accomplished by making CRISPR genome editing heritable, examine the possible consequences of the accidental spread of existing self-propagating gene drive systems.

New Zealand is considering genetic technologies to help eliminate rats, mice, stoats and possums. A gene drive system promotes the inheritance of a particular genetic variant to increase its frequency in a population, which would require fewer invasive organisms to be released in order to spread infertility and ultimately eliminate the population.

In the article, the authors say that Professor Esvelt's original suggestion that  self-propagating gene drive systems might be suitable for conservation “was a mistake”.

“The bottom line is that making a standard, self-propagating CRISPR-based gene-drive system is likely equivalent to creating a new, highly invasive species – both will likely spread to any ecosystem in which they are viable, possibly causing ecological change.”

Introducing such a system “without the permission of every other country harbouring the target species would be highly irresponsible”, they say.

“Even assuming that national sovereignty is morally irrelevant, the social and diplomatic consequences of an unconstrained release should give us pause.

“CRISPR-based gene drive is arguably the technology most likely to help eradicate human scourges such as malaria and schistosomiasis. It would be a profound tragedy if New Zealanders – or anyone else – inadvertently caused an international incident and the consequent loss of public confidence in scientists and governance prevented us from realising other benefits of biotechnology.”

Professor Gemmell says there is strong impetus to use gene drives and other tools to meet the goal set by the government, and supported with $60 million, to eradicate mammalian pests by 2050.

But only localised drive systems, including Professor Gemmell's “Trojan female” technique, Professor Esvelt's recent “daisy drive” technology and “precision drive” approaches that target mutations known to be unique to a particular population, are safe enough to consider.

“The rationale for this goal is simple – mammalian pests remain one of the key threats to the ongoing persistence of New Zealand's native flora and fauna, which has evolved in isolation without such threats for at least 28 million years or more.

“Control of these pest species is a cornerstone of conservation efforts in New Zealand and we see strong dividends in increased reproductive and survival rates of, for example, kiwi when predator control is undertaken. Where predator control is absent, more than 90 per cent of kiwi die before they are a year old.

“New Zealand’s ambitious goal to eradicate these mammalian pests is already generating global interest, in part because there are strong lobbying groups advocating for (e.g. Revive and Restore) and against (e.g. Synbiowatch) the use of gene editing in a conservation framework,” Professor Gemmell says.

“The New Zealand initiative provides an obvious focal point for this emerging debate. But the topic has global relevance and context because gene drives have been proposed for use in other locations where mammalian invaders are a conservation issue, such as the Farallon Islands off San Francisco and the Galapagos Islands.”

The PLOS Biology article calls for an open discussion about technologies considered for the New Zealand context that could readily have global ramifications.

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  • Journal of the Royal Society of New Zealand
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Expert Reaction

These comments have been collated by the Science Media Centre to provide a variety of expert perspectives on this issue. Feel free to use these quotes in your stories. Views expressed are the personal opinions of the experts named. They do not represent the views of the SMC or any other organisation unless specifically stated.

Dr Andrea Byrom, director, NZ's Biological Heritage National Science Challenge

Essentially, this paper advocates for taking a precautionary approach to the use of gene drives for conservation, and more specifically, advocates for the 'daisy drive' approach which would massively reduce the risk of an 'invasive' drive crossing international borders and exterminating an invasive species that is native to another country.  Those are very reasonable arguments, but contrary to the implication in the article itself, New Zealand has already taken a cautious and responsible approach to the use of gene editing technologies for mammal pests - the points made by the authors are nothing new.

In the Biological Heritage National Science Challenge we are currently funding the following research with respect to gene editing technology:

  • Computer simulation modelling to explore a suite of different approaches (including but not limited to gene drive) based on known breeding parameters of invasive rodents such as ship rats.
  • Investigation of gene silencing techniques for invasive wasps. This research is not 'gene drive' technology.
  • Connection to international colleagues in the GBIRd (Genetic Biocontrol of Invasive Rodents) team to keep a watching brief on international trends in gene drive technology.
  • Investigation of public attitudes to novel pest control technologies (including gene drive) for wasps and rats.
  • Establishment of a 'bioethics' panel to discuss the ethical considerations of future use of these technologies.

Contrary to the hype, gene drive technology for mammals is still highly theoretical, and I must emphasise that no such research is currently being conducted in New Zealand. We have literally years of technological development ahead of us before we could proceed with deployment in the field, and future use of gene editing technologies, including gene drive, will be in the hands of the public of New Zealand to decide.

Last updated: 17 Nov 2017 8:24am
Dr James Russell, conservation biologist, University of Auckland

Gene drive technology in any implementation is powerful and risky, and thus a precautionary approach to all stages of its development and release is critical. New Zealand already has the most advanced risk management systems in the world for biosecurity and the release of new organisms, including genetically modified ones. We are by our very nature a precautionary society in this regard, which stands us in good stead for responsibly developing and managing the risk of gene drives for pest control, should we have the public mandate.

Gene editing is only an extension of existing genetic modification, which once established in the wild usually becomes irreversible and there is a larger, existing dialogue in both New Zealand and globally about the risks and values of releasing such edited organisms in to the wild, especially ones where we do not want them to self-extinguish within a short time frame.

Esvelt and Gemmell raise a number of pertinent points for once a basic gene drive is established in an ecosystem. However, in discussing the risk associated with hypothetical ecological release of a basic gene drive technology they overlook a number of critical ecological filters. The ecology of the invasive species and its environment are a wrapper for the entire process. Once a basic gene drive is established in a population it could be hard to undo.

However, for a gene drive to establish in the wild might actually be very difficult, let alone more than once. Laboratory animals must actually be bred in sufficient numbers with the gene edit to release in to the environment such that they mate with the resident population and the gene itself establishes. This is what is always overlooked with the application of this technology, and the authors here make the same overestimation – that establishing say rats in to a resident population is trivial. It is not. Indeed all the evidence is to the contrary, that trying to establish rats within a population of already established rats is very difficult.

Although New Zealand is doing no laboratory research in to gene drives, we are investigating through computer models how hard it would be to establish a gene drive in the wild. Even without a gene drive, ‘propagule pressure’ (the number of individuals and their rate of release) is critical in invasions. Previous research has shown that you have to introduce a lot of individuals to establish a population of even an invasive species.

Furthermore, genetic work has shown that rats have a strong incumbent advantage, and even when they do hitchhike on boats, they usually are not successful at establishing in new ports when they arrive. So I think here the authors underestimate the ecological challenges of establishment and overestimate the risk of dispersal and establishment.

Esvelt and Gemmell also make the assumption that a gene drive would be a fertility edit. There are other gene edits one could make, especially those that pair the target species with its recipient ecosystem, e.g. imagine trivially giving all rats in New Zealand a peanut butter allergy and then we feed them all peanut butter. Matching the genetic mode of action to an environmental stimuli might be powerful indeed. When balancing risks we must incorporate uncertainties, such as when ecological consequences may be unknown. However, we will never have complete certainty over how the planet earth and its ecology functions, so the more pertinent question is do we understand enough uncertainty to accept the risk. As for the development of any new scientific technology, no user wants to have 'inadvertently caused an international incident.

Esvelt and Gemmell suggest gene drives 'should only be built to combat true plagues such as malaria', after arguing that gene drives shouldn’t be released in to the wild, but this seems to unfairly bias human interests such as personal health over biodiversity. Even mosquitos are also native somewhere and from a New Zealand bird’s perspective (and many humans) rats are also a plague of animal predation and human disease that would not be missed. I think therefore that rats can be considered a plague on the same level as mosquitos.

Esvelt and Gemmell ask if 'we want a world in which countries and organizations routinely and unilaterally alter shared ecosystems regardless of the consequences to others?', but I think there is already ample evidence that this is exactly what is already happening today, e.g. the United States in the Paris climate accord, and so this form of governance is a much larger issue than for gene drives alone.

Last updated: 17 Nov 2017 8:24am
Dr Emily Parke, philosopher of science, University of Auckland

This article gives an important cautionary perspective on the release of gene drives in New Zealand (or anywhere). A central aspect of the discussion from an ethical perspective is the fact that not all gene drive technologies are equal: local drive systems would present fewer risks and ethical concerns—at least in principle—than releasing gene drives which we know have the potential to spread globally.

Alongside the community dialogue the authors call for surrounding development of gene drive technology, scientists and regulators should endeavour to increase public understanding of the technology itself, with an eye to this point that not all gene drive technologies are equal. It is easy to get carried away imagining the possibilities (this article follows closely on the heels of the recent announcement of 'do it yourself' mail-order CRISPR kits!), so transparency about the scope and limitations of the actual technology being developed will be a crucial aspect of this public dialogue.

It would also be good to see further discussion following from this, with an eye to more concrete milestones or checkpoints in gene drive development, at which attention should be given to specific ethical, social, or regulatory issues.

Last updated: 16 Nov 2017 2:46pm
Professor Barry Scott, Institute of Fundamental Genetics, Massey University

This is a timely article on the need for caution in developing standard gene drive systems for conservation. Given the scale of the pest issue in New Zealand and the urgency with which we need to find better solutions to prevent further extinctions there is a great temptation to look for ‘silver bullets’. Gene drive has been actively promoted as a new genetic technology with huge potential to help us achieve a ‘predator-free’ status in New Zealand, although some have questioned the feasibility of this approach.

The perspective in PLOS Biology by Esvelt and Gemmell is a particular perspective of the authors urging greater caution in the development and use of these technologies and for more open community discussion. They do highlight there are already some promising new genetic technologies being developed such as the ‘daisy drive’ system which has a self-limiting break built into the system that may improve safety. Undoubtedly even more sophisticated gene drive systems will be developed as the science advances.

The paper does not cover the scientific challenges still to be overcome to develop such systems for most of our pests. There is an underlying assumption in the article that gene drive systems could be developed for most pests and that they will work. We already know from recent experiments that evolution of resistant alleles that cannot be cut and copied will inevitably evolve in the population, which they reference, but there are still major challenges, some probably still unforeseen, associated with the reproductive biology and population genetics that may well limit the feasibility of the system actually working in the field.

The authors also make a plea for community involvement at the outset in the development of these technologies, which I totally support. Trust building is crucial. Science can answer the ‘can’ but not the ‘should’ question.

While these are my own views, I am also the co-chair of an expert advice panel set up by Royal Society Te Apārangi in 2016 to prepare a series of work pieces on these topics. These will help inform the New Zealand public of the science and societal issues that arise from gene editing technologies. The first two of these papers, one on the use of gene editing in healthcare and the other on pest control, will soon be released.

The work piece on pest control highlights how little we know about the reproductive biology of our major mammalian pests including possums, stoats and rats and the low likelihood of a gene drive system being developed in the near future. Insect pests such as wasps will be more amenable to such solutions but again much research is required.

Novel solutions for control of pests in our threatened ecological systems are urgently needed in our race against time to prevent further extinctions but there will be no quick fix. Genetic solutions are a promising new tool but we do need to proceed with caution and a sound understanding of the biology underpinning the control measures. It is crucial that we continue to invest in research in these areas, especially those directly relevant to New Zealand. There is also a need to put in place a framework for community trust building so that societal values and ethics are taken into account as the science develops.

Last updated: 15 Nov 2017 2:55pm
Melanie Mark-Shadbolt, Kaiwhakahaere, Te Tira Whakamātaki, the Māori Biosecurity Network; Māori Research Development Manager – Kaiarahi Māori, Bio-Protection Research Centre, Lincoln University; Māori Manager, New Zealand’s Biological Heritage National Science Challenge

On the one hand, Esvelt and Gemmell’s paper in PLOS Biology expresses the same concerns Esvelt articulated in his visit to Aotearoa New Zealand earlier this year. That is that New Zealanders, particularly tangata whenua, need the opportunity to determine if gene drive technologies, and the potential consequences of its use, are something we wish to pursue. The thoughts articulated in the paper are not new or unique to Esvelt and Gemmell, and in fact, the authors incorrectly imply that work is going on in Aotearoa New Zealand that simply is not, and will not for a very long time. 
 
On the other hand, the paper is self-indulgent in that it unashamedly pushes for the use and consideration of their research, including Professor Gemmell’s ‘Trojan female’ technique, and Professor Esvelt’s ‘daisy-drive’ technology. 
 
From an indigenous researchers perspective what this paper does do is clearly highlight two growing concerns in the research space. 
 
The first being an increasing lack of cultural accountability in academic journals who seem happy to publish anything without thought, consideration, or commentary from the communities those papers have extracted from, taken swipe at, or made promises to. While we expect individual researchers to be responsible & accountable for their work (and in fact Prof Esvelt calls for this) academic journals seem to be immune to such requirements.

A good example that Prof Gemmell is well aware of, is the continued publication of articles that sequence genes of taonga (sacred) species without the permission of the kaitiaki (caretakers), tangata whenua or indigenous communities who relate to those species. PLOS Biology perpetuates, to a lesser degree, that same behaviour by not checking the situation in Aotearoa New Zealand before approving the article for publication. 
 
The second issue is what I deem bad research-dating behaviour, or rather how to build respectful relationships with indigenous peoples/communities. Increasingly researchers are seeking opportunities to work with and engage with indigenous communities i.e. Māori. Relatively few, however, are actually committed to investing their time into building long-term relationships, despite being continually told that that is what is required.

Relationships are built on partnership. Partnerships, as my husband likes to remind me, require both sides to commit equally and to communicate honestly. However, some researchers by-and-large continue to push an extractive model whereby they attempt to take intellectual property from communities in return for 'the greater research good’. This model is naïve to the political situations that indigenous communities are operating in, and often places those communities in culturally unsafe positions.

Esvelt made a commendable and bold statement when he was in Aotearoa New Zealand promoting daisy-drive. He stated his technology would and could only be used in Aotearoa New Zealand under a co-governance model with Māori. However, his naivety of the political situation Māori are in, and the publication of this paper without talking to the other partner (Māori) more than likely will have consequences for that partner (Māori) that the author (Esvelt) did not consider.

Pessimistically, it is now possible that Māori may never get co-governance in the discussion and/or development of gene-drive technologies in Aotearoa. Optimistically, however, this paper could be the wake-up call the science sector in Aotearoa New Zealand needs to work in partnership with Māori and preserve New Zealand’s leadership on the world stage.
 
We must all commit to being useful academics and good research partners, and I ask the authors; is this paper useful and does it represent good partnership with your communities (funders, colleagues, Treaty partners)?

Last updated: 15 Nov 2017 2:53pm
Professor Peter Dearden, Department of Biochemistry, University of Otago

Esvelt and Gemmell’s paper expresses some key concerns about the use of gene drives in New Zealand for conservation-related purposes. While it is good to see some debate on this issue, I think the manuscript under-represents the work going on in scoping these novel technologies in the Biological Heritage National Science Challenge and Predator Free 2050.

No-one is currently advocating for the use of the experimental and untested technology of gene drives as they are conceived in their most basic way. What is being discussed is exploring the gene drive concept, including those modifications mentioned in the Esvelt and Gemmell paper.

Gene drives are a technology with risks and benefits. Without good solid research on the technologies, in containment and through computer modelling, we are unable to determine these risks and benefits effectively. Esvelt and Gemmell’s paper rather jumps the gun in signalling the scale of these risks in the absence of data. I really hope that this will not preclude us doing the necessary research to test this technology to determine if it is fit for purpose.

Esvelt and Gemmell’s paper also under-reports the world-leading research the Biological Heritage National Science Challenge is undertaking in understanding social attitudes to new technologies in pest control. This research is just coming to fruition, and I am looking forward to having real data in this area, rather than the assumptions that we have now.

Last updated: 15 Nov 2017 7:30am

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