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Evolution provides us with many genetic power tools – how do we use them wisely?

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By: Daniël P. Melters, Ph.D.

The Red Queen Hypothesis in evolutionary biology: “Now, HERE, you see, it takes all the running YOU can do, to keep in the same place.” (Lewis Carroll, “Through the Looking Glass”)

DNA is a very ubiquitous molecule, sufficient to span the observable universe at least 20 times. Most of this DNA comes from viruses, either in the form of active viruses or in its inactive form incorporated in viral, bacterial, plant, fungal, and animal genomes. To limit the spread of viruses, it is not surprising that evolution has created many ways to contain the spread of these inactivated viruses. We have adopted some of these antiviral mechanisms for our own use.

The discovery of the first bacterial antiviral system, the restriction enzyme, led to the founding of Genentech and thereby the modern biotechnology industry. Despite the ease with which restriction enzymes can be used to cut and paste pieces of DNA together, they are currently limited to use in test tubes (in vitro).

A few years ago, a new genetic tool was discovered that could modify genetic material in living creatures (in vivo). Again, it was a bacterial anti-virus mechanism. This new technology is called CRISPR and its in vivo use brings with it the possibility to edit DNA in order to correct genetic diseases in patients themselves. Just as a slew of restriction enzymes with unique cutting characteristics have been found, a similar scenario seems to be happening with CRISPR with the discovery of more nucleases used to cut specific DNA sequences. The original nuclease used with CRISPR is cas9, but recently another nuclease (cpf1) was discovered. Where cas9 is efficient in deleting genes, cpf1 seems to be good for making small modifications. In the foreseeable future more cas9-like nucleases will be discovered, each with potentially their own unique characteristics, in addition to ongoing efforts to genetically engineer a better cas9 nuclease.

Ethical questions about the use of CRISPR in humans, especially in human sperm and eggs, have arisen. On December 1-3, 2015, the U.S. National Academy of Sciences in collaboration with the Chinese Academy of Sciences and the UK Royal Society, hosted a three-day international summit on the use of CRISPR in human embryos. Although germline editing is strongly discouraged pending continued technological and ethical deliberations over the next few years, it remains a scientific possibility. Based on a single Chinese study, it is still unclear if this route is realistic. After all, cloning mammals has proven much harder than feared in the 1990s, as has creating a petrol-producing algae by genetic editing. Nevertheless, this has not stopped genetic entrepreneurs like Google and Bill Gates from jumping on the CRISPR bandwagon to kick-start the second revolution in biotechnology. One big unknown factor that still remains looming over the development of both the technology and any regulation is the potential misuse of any do-it-yourself CRISPR kits.

In addition to making individual genetic changes at will like those with CRISPR, forces that work on population genetics can be employed. Again they have their roots in evolution. One such potential powerful force is gene drive. Gene drive is caused by a genetic sequence that does not obey the Mendelian inheritance rules (where there is a 50-50 shot for a gene to be passed on from parent to offspring). It is therefore possible to introduce a gene that could, for example, get rid of the malaria parasite by introducing a few GMO mosquitoes into a population of natural mosquitoes. Through gene drive over time the entire population of mosquitoes will carry the malaria-fighting gene. The implication would be that the malaria parasite would not be able to passed on to humans and thus malaria would be eradicated. This sounds like a dream scenario!

However, using gene drive on mosquitoes to eradicate malaria does open a new can of worms. Both for the good – as the need to fumigate would be reduced also reducing the creation of fumigation-resistant insects, including mosquitoes – and for the bad, namely unwanted ecological consequences as a result from for instance horizontal gene transfer. Another unwanted consequence of the gene drive technology would be the near-certainty that it will spread across political borders. To handle such foreseeable international disputes, international regulatory collaboration will be required. One solution to overcome these unwanted consequences of gene drive could be use genetically engineered mosquitoes that would not be able to produce any off spring.

Whatever happens on the side of technology development, genetically modifying organisms remains controversial for the time being. Just think about the hype surrounding the recent FDA approval (after 19 years) of faster-growing “Frankenfish” for human consumption. Part of the problem resides in the highly technical details and extensive use of jargon that permeate the biological sciences. At times, it can be challenging for even scientists to keep up with the fast pace of development in the field of genetics. Once can only imagine what must then be demanded of the public and policy makers. Just look at what CRISPR itself stands for: clustered regularly interspaced short palindromic repeats. From the acronym alone, it is not clear what CRISPR does or means. Only through extensive communication between scientists and the public can a bridge be made that allows for exchange of knowledge about both the technical details and sincere concerns. The absence of many scientists on social media does not help this and actually widens the knowledge gap.

Nevertheless, various scientists have raised their voices about the potential power of gene drive as well as their professional concerns. Sure, gene drive can be used to do many things such as immunize animals that carry human diseases, control insect-borne diseases, spread pest-specific pesticides and herbicides, reduce populations of rodents and other pests, control invasive species, and aid threatened species. Yet, the power of gene drive also brings with it the fear for the unknown. What happens if a gene “goes wild” and crosses the species barriers through horizontal gene transfer? Will we be able to detect this quick enough to control it? What damage will it do if we can’t control it? Will there be any damage? For instance, cross-pollination between GMO crops and natural variants has been observed, albeit their incidences are relatively low and its broader ecological effect mostly unknown. To help curb these concerns, some solutions have been brought forward to help contain gene drive such as by designing it like Lego pieces, where only a complete set would be functional.

These concerns were considered so great that the U.S. National Academy of Sciences felt the need to create a workshop focused specifically on gene drive, in addition to the earlier international summit about the ethics of human genome editing. In short, the meeting showed that while gene drive has potential promises, both scientific and regulatory uncertainties remain, as well as fear about its potential irreversibility if it were to go wild. In other words, more research is needed covering all aspects of gene drive, including educating the public across the globe about the pros and cons.

Just as atomic energy produces both electricity and atomic bombs, thereby bridging the worlds of physics and societal needs, bacterial immune systems and evolutionary forces bridge basic biological research with applied biotechnologies. Society as a whole is moving more and more towards a society where genetics is a driving force for change – in medicine, global health, agriculture, pest-control, the judicial system and in combating terrorism. Understanding the basic principles of biology, genetics, and evolution are a must for policy makers of today and even more so of tomorrow. How else will they be able to support or debate a bill that is guided by or deals with genetic information and manipulation? After all, selective breeding and building a highly interconnected world have resulted in new species (of pets, livestock, and crops) and forced other species to adapt to changes in the environment we made (such as geographical barriers like roads and deforestation, and climate change). Therefore, careful ethical consideration of the wise use of powerful genetic tools and forces is critical, both for use in human, as well as any potential ecological implications. Gene drive as a tool has great potential, since after all, most of the DNA on earth came from the driving forces of selfish genetic elements. Evolution has provided us with many powerful tools and with great power comes great responsibility.

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Written by sciencepolicyforall

December 9, 2015 at 9:00 am

2 Responses

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  1. […] in Brazil appear promising, encouraging trials on a larger scale. A third powerful approach is the use of gene-drives. Gene-drives allow for the propagation of a desired trait, for e.g. sterility, through a wild […]

  2. […] not to say that no oversight is needed. The use of gene editing technology in humans is still controversial, especially in human embryos, as became clear again by a second study published by a Chinese group […]


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