Proceedings B recently published a Special Feature entitled ‘Natural and synthetic gene drives’, which looks at the current state of affairs of both natural and synthetic gene drive systems, with the aim to identifying knowledge gaps and possibly predicting the outcomes of synthetic drive release. Guest editors Nina Wedell, Anna Lindholm and Tom Price tell us more about this exciting special feature.
There is a lot of buzz about gene drives, which are remarkable naturally occurring phenomena in which genetic elements selfishly manipulate reproduction to transmit themselves at a high rate to the next generation, allowing them to spread rapidly through populations. New synthetic versions of these elements can be engineered in the lab. Synthetic drivers can be designed in ways that could reduce the prevalence of pests, for example by converting an entire population to one sex. Alternatively, they could be used to reduce the harm a vector does, such as making mosquitoes less able to transmit malaria. They could also be used to make beneficial species more robust to human-induced disturbance. These developments raise many scientific and ethical questions, such as how can we predict what happens if a synthetic gene drive system is released into the wild? And what process should we follow to reach a decision on whether to release gene drives in the first place? Our view, as researchers on the evolutionary biology of natural gene drive systems, is that there is extensive work on natural systems that can help us to better understand the predicted dynamics of synthetic drive systems in the wild, and perhaps inspire new developments in synthetic drive. In turn, developments in synthetic drive can synergistically inform work on natural drive, showing us what is possible, even if it has never evolved. To improve dialogue between researchers in these areas and researchers involved in ethical aspects of applications of gene drive, we have put together this Special Feature.
This Special Feature includes empirical, theoretical and review papers from 15 research teams covering diverse aspects of natural and synthetic gene drivers, in a range of animal and plant species. The contributions are broadly focussed on (i) synthetic drive systems, (ii) natural drive systems, and (iii) practical implementation and wider ethical considerations of gene drives. This collection of papers highlights predicted dynamics of synthetic drive systems under various potential scenarios in the wild. The costs of drive, the evolutionary dynamics of the suppression of drive, and the mechanisms of how drive is achieved, are examined and evaluated in natural drive systems. Collectively, the contributions demonstrate the tremendous potential of gene drive systems, but also highlight several outstanding knowledge gaps. In particular, the wider ethical and societal implications of harnessing and unleashing the power of selfish genes in natural populations are still only in the early stages of being addressed. Several general conclusions also emerge from the individual contributions in this Special Feature. Understanding fitness costs of drive systems is very important for predicting the dynamics of gene drives and the evolution of drive suppressors. Differential costs may also hold the key to explaining the likelihood and how quickly suppression evolves and for predicting the long-term stability of gene drive.
We believe that the best route to understanding how synthetic drivers will spread over ecological time, and be altered over evolutionary time, is to examine how naturally occurring drive systems behave in nature, and thereby mitigate the risk of unintended consequences and side effects. We whole-heartedly agree with the views of Lunshof & Birnbaum (2017) that understanding the long term consequences of gene drives, both beneficial and harmful, is essential for ethically assessing their use in nature. Input from researchers working in different fields, including evolutionary biology, is critical, and we must talk to each other. Gene drive needs more integration to consider biosafety and ecological impact to ensure its safe and effective use. We firmly believe that these aims are impossible without input from ecologists, evolutionary biologists, gene drive builders, modellers, regulators, and people who understand the cultural context, as well as ensuring sufficient political and public support. There is clearly much work to be done.
We also encourage researchers to be alert to gene drives that have not yet been discovered or designed. Natural gene drives have overwhelmingly been found in model organisms, almost certainly because drives are hard to detect, so they are only discovered in well studied systems. There are likely to be enormous numbers of gene drives in nature with bizarre and fascinating mechanisms undreamt of by current gene drive research. We strongly encourage ecologists and evolutionary biologists to look for signs of drive in the organisms they study. But natural drives will be limited to those that can evolve by plausible evolutionary pathways. In contrast, synthetic drives can potentially be designed that could never evolve in nature. Our increasing understanding of the fundamental molecular mechanisms of gametogenesis, symbiosis, kin recognition, cooperation, and survival, increase the options for manipulating these mechanisms to create novel drivers. The genomic and biotechnology revolutions are sure to produce fascinating examples of natural and synthetic drive in the near future, and the future looks incredibly bright for research into gene drive. But the benefits promised by synthetic drives can only be delivered if we can successfully navigate the ethical quandaries created by this radical expansion in our ability to manipulate natural populations.
Special Features in Proceedings B aim to highlight a topic of importance or interest to biologists and include both review and research articles covering different aspects of it.
References: Lunshof, J. E., & Birnbaum, A. (2017). Adaptive Risk Management of Gene Drive Experiments: Biosafety, Biosecurity, and Ethics. Applied Biosafety, 22(3), 97–103.
Image credit: Kent Smith, www.smittytown.com