Drivers of Change 2022 – Biotechnology

The latest instalment in our series on Drivers of Change is biotechnology. Although there are some overlaps with the 4^th Industrial Revolution Driver we considered last time – notably the use of AI – we think that trends in biotechnology are significant enough to be looked at separately.

The gene editing tool CRISPR/Cas-9, which won its inventors the Nobel prize in 2020, is an extremely powerful tool which has myriad applications in food and agriculture, and in medicine. Techniques such as prime editing are taking CRISPR’s capabilities further – this technique “snips” just one strand of DNA rather than both as CRISPR does, which can be lethal to cells, and produce unintended edits.

Other advances are producing smaller versions of Cas-9 that can be transported by popular genome therapy vectors, such as the Adenovirus-Associated Viruses (AAV) and address an even wider range of diseases.

Epigenome editing could be even more versatile. These molecular tools target the epigenome, the chemical tags adorning DNA and its surrounding proteins that govern a gene’s expression and how it ultimately behaves. Unlike DNA editing, where the changes are permanent and can include unintended results, epigenomic edits might be less likely to cause harmful off-target effects and can be reversed. They can also be more subtle, dialling a gene’s impact up or down, rather than just switching it on or off.

Agricultural applications can confer resistance to devastating plant diseases, pests and parasitic weeds; enhancing nutritional content; delaying ripening to reduce post-harvest losses; building resilience to climate impacts and unpredictable weather patterns, such as floods, drought and high temperatures; and improving grain quality and yield. These advances could be key to sustainable agriculture in Africa.

Kenya received applications for gene editing of banana and yam to resist two destructive plant viruses. Other gene editing research efforts are focused on making pigs resistant to Africa swine fever and sorghum that is resistant to the plant pest striga. The country sees this as a way of supporting its drive to become a middle-income country.

Pesticide-free plants: gene edited plants can manufacture RNA interference (RNAi) that kills off specific pests.

Drought-tolerant cattle: introducing the SLICK gene into cattle enables them to cope with temperatures increases and they are better suited to areas where temperatures are predicted to increase due to climate change

Altering a mosquito’s gut genes to make them spread antimalarial genes to the next generation of their species shows promise as an approach to curb malaria, suggests a preliminary study

In medicine, CRISPR-Cas tools have the potential for therapeutic usage in different diseases, including genetic diseases, infectious diseases, cancers, and immunological diseases (autoimmunity and immunodeficiency). A wide range of diseases are being explored, including inherited blood disorders (such as sickle cell disease and hemophili), Duchenne muscular dystrophy,  congenital genetic lung disease like cystic fibrosis, neurological disorders (Parkinson’s disease, Alzheimer’s disease, and Huntington’s disease), and genetic deafness.

Away from gene editing, other advances in biotechnology are creating interest. The carbon reduction opportunities of laboratory grown meat is one appealing area. Lab-grown chicken is selling already well in Singapore.

Ethical issues around gene editing and genomics are beginning to emerge.

• Affordability: a common pill used to treat cholesterol might cost $5 per day, approximately $1,825 per annum, compared with a biotech drug that comes with a $20,000 per year price tag or more.
• Intellectual property – there were concerns with genetically modified seeds that farmers were being exploited; they were required to sign an agreement promising not to save the seed produced after each harvest for re-planting, or to sell the seed to other farmers, so must buy new seed every year. Fortunately two-thirds of CRISPR patents are owned by universities, so there is the potential that similar issues can be avoided.
• Privacy: it will be possible to know that a 6-year-old may develop serious heart complications later in life. The question now is whether a prospective employer has the right to know about this. How will this knowledge impact the person’s ability to get a job, mortgage, or insurance?
• Precision medicine, that takes into account individual variability in genes, environment, and lifestyle for each person predict more accurately which treatment and prevention strategies for a particular disease for each individual, in contrast to a one-size-fits-all approach. Naturally individually tailored treatments will be more expensive than generic ones leading to the prospect of increasing medical inequlity
• Germ-line editing: bioethicists generally believe that human genome editing for reproductive purposes should not be attempted at this time. Issues include safety, informed consent of future generations, “designer babies”.
• Stem cell research on embryos: of particular concern to religious group.

Biotechnology advances also raise the prospect of bio-terrorism and the need to build defences to it CRISPR-Cas9 could theoretically also be used to alter pathogens to make them more transmissible or fatal. Alternatively, it could turn a non-pathogen, such as a harmless microbe, into an aggressive virus. The technique may even be able to alter a virus to make it dangerous for a larger range of species than it currently infects, or make it resistant to antibiotics or antivirals.

Countries are taking different views on how to legislate gene-edited (GE) products, whether they should be differentiated the older Genetically Modified Organism (GMO) technology, and its negative connotations to some consumers, commentators, farmers, retailers, politicians and lawmakers. The European Court of Justice (ECJ) ruled that all organisms produced by biotechnology were to be considered GMOs and to be regulated as such, while the US has called for more permissive policies on allowing new crop technologies. The UK approved draft regulations to simplify the approval process for research trials on plants aligning gene-editing with plants produced through traditional breeding rather than the previous alignment with GMO technology. It is possible that the drought in Europe may cause the EU to change its position.

The Food Standards Agency published consumer research that suggested that the more informed consumers were, or became, the more accepting they were of precision bred or genome edited (GE) food.  Research also suggests that consumers tended to find GE food more acceptable than GM food.  Most consumers felt it would be appropriate to regulate GE foods separately from GM foods – having recognised them as two separate techniques that should be treated as such. It is possible though that a “Frankenfoods”-style campaign by sections of the media could turn public opinion in a different direction.

Investment in biotech companies is growing rapidly, with some concerns it may be becoming excessive. President Biden recently announced funding of $2 billion for the National Biotechnology and Biomanufacturing Initiative, a “whole-of-government” effort to further biotechnology and biomanufacturing innovations in health, climate change, energy, food security, agriculture, supply chain resilience, and national and economic security.  Over $1bn was raised in venture capital funding for gene editing in 2021.

As always, SAMI likes to think through the second-order effects of change. With biotechnology, most of its effects seem to be beneficial, but regulators do need to be aware of the ethical concerns and the possibilities for abuse.