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If you have been following CRISPR technology, ethic issues have been frequently adressed by scientists and even a pannel of experts from the pioneers of CRISPR technology. Human embryos have been used for CRISPR experiments to cure certain types of diseases. Hopefully, this technology is not used for 'cosmetic' procedures....

For your question "How should researchers approach public interactions on CRISPR/Cas9?"

I think first the public should know that this technology has a great potential to cure some human diseases. And in fact, some diseases such as 'hearing loss', 'blindness', 'muscle disease" have been treated using this technology in mice and obtained exciting results. The data looks pretty promissing.

Thank you for your stimulating question.

Advantages and Concerns of CRISPR: Genetic/ genome engineering had been there for a long time. CRISPR/Cas9 tool makes it easier to target any location on the genome, hence increased precision. The major concerns are wiping out a whole species through gene drive, ability to create designer babies, pathogens, unintentionally creating invasive plant and animal species that could compete and replace natural species due to their newly attained property, etc., Hence, it is important to take cautions while creating and releasing genetically-modified organisms (GMOs) in the environment and human consumption.

CRISPR, Public Access and Need for New Regulations: CRISPR/Cas9 is an easy to use tool. The simplicity of the procedure is due to the requirement of two components, a single protein (Cas9) and a single guide RNA (sgRNA).

A "do-it-yourself" (DIY) company called Odin, with the aim of democratizing CRISPR-technology, sells DIY-CRISPR-kit for 200 USD to genetically engineer bacteria and yeast (links below). They also sell human myostatin targeted CRISPR plasmid for 20 USD (they claim this plasmid cannot be directly used for human or animal experiments as they supply. But, sooner or later there might be DNA-delivery tools available from other DIY-groups. And there might be services for custom-made CRISPR tools for targeting any gene of any organism. Or it can be used for aesthetic purposes, like luminescent tattoos. The possibilities are end-less).

http://www.the-odin.com/diy-crispr-kit/

http://www.the-odin.com/human-myostatin-knock-out-targeting-crispr-cas9-plasmid/

(DIY Biohackers Are Editing Genes in Garages and Kitchens) https://youtu.be/s5s1uqI5HmY

As the interest in genome engineering increases and the tools become easily available to general public, there will be a boom in the growth of amateur enthusiast/ citizen scientist/ kitchen scientist/ biohackers. They would be producing bio-engineered plants and animals. The same is true with the plant/animal-biotechnology based food/seed/pet companies. Hence, it is important to properly define GMOs and make sensible guidelines for their usage.

GMOs need new definition and better regulation: The current definition of GMO is narrow, outdated, misleading, confusing and not complete. This makes it hard to categorize mutated plants/ animals and hence its regulation. It is time to re-define and re-categorize all the plants/ animals that are used by humans either as food, ornamental plants or pets.

For example, according to today's standards,

- we do not consider a plant/ animal a GMO if we modify its genome by exposing it to DNA-damaging radiation/ chemical mutagens.

- If you delete/ mess-up with an existing gene in a plant, it is not considered as GMOs.

Only if the plant gets a new gene inserted from a different species it is considered as GMO (e.g., BT-crops have a new insect-specific toxin gene from a bacteria, Bacillus thuringiensis).

(Hank Greely: Ethical & Societal Issues) https://youtu.be/HIefDm26F2g

(To be or not be a GMO, that is the question. | Stefan Jansson | TEDxUmeå) https://youtu.be/kyrsNa1jLpo

---> All products of genetic-engineering (including radiation induced random mutagenesis; agrobacterium, viral, physical and synthetic vector mediated gene-transformation/ CRISPR-Cas9 modification, etc.,) must be considered as GMOs/mutant. They are artificially created mutants and kept away from natural varieties to avoid genome-instabilities that may arise.

---> Traditional plant breeding (based on assisted pollination, crossing, hybrids, selectively propagating natural variants) must not be confused with genetic-engineering or genetically-modified organisms (GMOs).

Our Story: Let's imagine you want to become a vegetarian. You become fond of a Veg-burger sold by a company. Years later, you find out that the Veg-burger you eat is actually made from meat. The company named it as "Veg-burger" because the company might have less customers if it was labelled as "Meat-burger".

Information and Informed Decision Making: The companies should label the GMO or GMO-containing food appropriately and explicitly as GMOs or more specifically (e.g., radiation mutants, transgenics, CRISPR'ed, etc.,) not with misleadingly fancy names (e.g., Innate Potato, Arctic Apple, Golden rice). Due to business and marketing reasons, the companies will not address the drawbacks of GMOs, if any.

We (as the public) have the right to make informed-decisions, on either to use GMOs or natural products. The researchers have the responsibility to inform the public with unbiased information, to discuss both pros and cons equally of GMOs, including those created by CRISPR.

Natural Evolution Vs Traditional Plant Breeding Vs Genetic-Engineering: The companies and plant-biotechnology-promoters argue that there is no difference between natural evolution, traditional plant breeding and genetic-engineering. It is not true at many levels and the consequences are not the same. Human desire-driven design is not the same as the environmental pressure driven evolution.

When new changes are made in a plant (e.g. gene insertion/ deletion/ mutation/ rearrangement), it might cause

+ Genomic Instability (Long-term effect ?): the long-term consequences on the genome stability or the changes in the natural pathways are not entirely known (e.g., during different seasons, conditions, etc.,). When there is not enough information, we dismiss their importance.

- - The major disadvantage of gene-therapy (genetic-engineering in humans) is that the modification/ integration of a gene at off-target sites can lead to genomic instability and development of cancer.

- - If, such genomic instabilities may take many generations to show up in plants, do we have a back-up plan to restore healthy, natural plant species?

- - The plants produced by genetic-engineering have less variations, hence susceptible to new pathogens/ diseases and go extinct easily.

+ Perturbations in the Natural Biological Pathway of Plants (?): All the genetic engineering process have off-target effects, including CRISPR/Cas9. The plants are selected based on the changes in the gene-of-interest and the resulting phenotype. It is difficult to know the long-term effects of all off-target effects. Biology is complex and the mechanisms are inter-dependent. When we make changes to reduce oxidation of an apple or potato, what are its consequences on other biological functions of the plant?

+ Ecological Degradation (?): - The evolution process is slow; the animals and plants that depend on those plants have time to co-evolve with the new changes. Hence, it might destabilize the natural biosphere.

Natural Selection Vs Human Selection: The previously available genetic-engineering tools were slower to produce results. But, it has produced many GMOs, which has penetrated all places in the globe. The food/agricultural products that are native or natural varieties are diminishing.

CRISPR/Cas9 is a powerful and essential tool for uncovering the biological process. It is a better tool than what we had before. But, we should use it responsibly.

CRISPR-technology will create more varieties of genetically modified crops with human-desired properties, faster than ever before. If the researchers continue to promote genetically-modified-organisms are the same as the natural variants, the natural plants will go extinct without we noticing it.

The conclusion is not to stop producing crops with improved qualities using CRISPR, but to identify them as GMOs (mutants) and clearly label them. To educate the public with unbiased information on the pros and cons of GMOs.

Conservation and cultivation of natural food crops must be actively promoted. Once the gene/ pathway for a given trait is identified by CRISPR or any other genetic engineering technique, efforts must be taken to identify natural variants or to produce those traits with sustainable traditional breeding techniques. Or to develop technologies to rebuild natural habitat for plants. Meanwhile, the GMOs can be used temporarily. For producing biological products other than food, GMOs can be grown under controlled conditions.

If no awareness or actions are taken, all the remaining natural species will be wiped-off. GMOs will be the new natural.