CRISPR: Five New Debates on Genetic Engineering

This policy brief is written in cooperation with the Norwegian Biotechnology Advisory Board

CRISPR-Cas9 (Clustered regularly interspaced short palindromic repeats) is a recently developed method for making targeted changes in the genetic material DNA. The method is adapted from a naturally occurring process in the immune system of bacteria. It functions as a pair of “genetic scissors”, which can remove, replace or add specific segments of DNA in humans, animals and plants. Science Magazine named CRISPR the breakthrough of the year in 2015.

WHY IS IT GROUNDBREAKING?

Easy, inexpensive and fast: Genetic alterations that previously took months or years to make, can now be done in the course of weeks and at a fraction of the cost. This means that genetic research now can develop much faster.

Precise: Previous methods of genetic engineering have consisted of inserting foreign genes into the DNA of organisms with little precision. The CRISPR method allows for site-specific changes of DNA.

Versatile: CRISPR can be used in all living organisms, which means that many different research disciplines can benefit from improvements of the methodology. The same technology may allow for new applications in a diverse range of fields: salmon farming, cancer treatment, biofuels and much more.

WHAT HAS ALREADY HAPPENED?

The technology was first put to use in 2012, yet researchers have already created virus resistant pigs, cattle without horns and dogs with increased muscle growth.

This year, the US Department of Agriculture approved CRISPR-edited mushroom and maize for sale. Large companies as well as startups are finding new business applications for CRISPR, and millions of dollars have already been invested in the technology. Last year, Chinese scientists used CRISPR in the first attempt ever at modifying human embryos.

This rapid development makes it necessary to bring the debate into the public arena.

FIVE UPCOMING DEBATES

CRISPR alters the premises for several important debates on biotechnology and society.

Should we regulate CRISPR as GMO?

Most genetically modified plants (GMOs) on the market, contain genetic material from foreign organisms, such as insect resistant maize with genes from bacteria. The only GMO-plant that is grown in Europe is this kind of maize. Due to strict regulations as well as reserve among consumers, no GMOs are sold as food in Norway.

Many people do not want to consume these types of products, or fear that growing GMOs will have negative impacts on the environment. GMO plants have also caused controversy, due to monopolies and market power exerted by large multinational companies. Creating such crops has been too expensive and complicated for companies without great resources.

CRISPR drastically lowers the cost and complexity of genetic engineering, which means that the technology potentially also becomes available for small actors. In addition, plants can now be genetically modified without inserting foreign genes. With CRISPR, it is possible to achieve identical results to what one would get with ordinary breeding, only in the course of months rather than years or even decades. A possible use case could be to combine the traits of a fungus resistant type of oats with a type of oats that possesses good nutritional qualities.

The Swedish Board of Agriculture has permitted researchers in Sweden to grow a CRISPR-edited plant without regulating it as a GMO. The decision was based on the fact that the plant does not contain any foreign genes, but was modified by deactivating some of its genes. The European Commission has yet to decide if CRISPR edited plants without foreign genes should undergo the same regulations as other GMOs.

Does it matter if a genetic change was done in the laboratory, if conventional breeding theoretically could have created the same change? Or is the CRISPR-revolution creating a regulative loophole that needs to be shut?

Must we modify animals in order stay competitive?

Previous attempts at creating genetically modified livestock, such as pigs with genes from mice and bacteria, have caused controversy due to unnatural traits or bad animal welfare. CRISPR allows for altering the traits of an animal without introducing foreign DNA.

Norway is well regarded for high quality breeding programs for pigs, salmon and cattle, an industry which is a valuable export asset for the country. International competitors are currently developing CRISPR-modified livestock. In the US, breeders have recently managed to create pigs that are resistant to a common virus, which costs American farmers more than 600 million USD per year. This change was only possible through deactivating a gene using CRISPR.

Scientists at the Norwegian Institute of Marine Research have recently used CRISPR to create sterile salmon. This could alleviate the problem of escaped farm salmon interfering with the wild populations. There is also potential for using the technology in order to improve resistance to salmon lice.

However, the Norwegian salmon and pig breeding industry is reluctant to use CRISPR because the current regulations and conceptions among consumers will place the technology in the same category as GMOs.

If one can use technology to improve the sustainability of livestock and farmed fish, while at the same time maintaining good animal welfare, is there any reason to be afraid? Or is CRISPR-editing a technological quick fix to problems caused by too intensive animal farming?

Shall we alter the human lineage?

All changes made in the DNA of reproductive cells are inheritable. Unlike many other countries, Norway also forbids making these kinds of changes in research on embryos that will not become humans.

For mapping genetic functions, CRISPR is a unique research tool. Should researchers in Norway continue to be limited compared to neighbouring countries?

There is potential to use the CRISPR-technology to prevent inheritable diseases before birth. Such interventions may eliminate great suffering. On the other hand, it also involves a great risk, as mistakes will have consequences for several generations.

CRISPR is the first technology that makes it possible to create genetic changes in human beings before birth. While the ethics of this have been discussed for a long time, it is no longer a thought experiment. Spurred by the recent development, The Danish Council on Ethics issued a statement on the matter. Six members voted for allowing germline editing, while eleven voted against it.

Currently, making clinical interventions in the genetic material before birth is far too risky. Yet, some researchers and laboratories are working towards moving CRISPR from research to reality.

Will making inheritable changes ever become ethically responsible? And will it be ethically irresponsible not to do it, once we have the means?

Treatment versus artificial enhancement

Gene therapy is a way of repairing genetic disorders in living humans without making inheritable changes. This type of treatment has been controversial, as previous attempts have caused serious side effects and casualties. For this reason, the Norwegian regulations are strict, and only severe illness allows for the use of gene therapy.

The increased precision of CRISPR allows for new kinds of gene therapy. For instance, preliminary research have shown promise in treating inheritable blindness and muscle dystrophy.

However, CRISPR may also potentially be used for artificial enhancements such as gene doping, for instance by increasing muscle growth or oxygen uptake, in a way that is undetectable.

The definition of severe illness is very strict in Norway. But if we open up for broader use of gene therapy, where should we draw the line between treatment of diseases, and artificial enhancement of physical and mental capacities?

Do we need more or less control?

CRISPR makes genetic editing available to an increased number of actors. A simple CRISPR editing kit that enables amateurs to genetically alter bacteria and yeast cells at home is being sold for 130 USD online.

Democratization of biotechnology may lead to increased innovation by allowing even small start-ups to participate in genetic engineering. At the same time, this is different from other kinds of innovation: the consequences are far graver when experimenting with living organisms than with computers.

Since the CRISPR method is both inexpensive and relatively easy to use, it is also prone to misuse, such as creating biological weapons. For this reason, American authorities have named CRISPR a potential weapon of mass destruction.

Increased access to genetic engineering can give rise to new opportunities as well as threats. How much control do we need in order to reap the benefits of this technology, while avoiding grave negative consequences?