Gene editing offers promising results on many fronts, if fears are surmounted
National Cancer Institute
It’s easy to talk about gene editing and genetic modification in terms that sound like science fiction. But as much as that may drive clicks for media sensationalists, it does more harm than good for those who really want to understand where the science came from and where it’s going. Not only does it blur the very clear line between genetic modification (“transgenic” or GMO; splicing together DNA from different genomes) and gene editing (manipulating the traits expressed by a single genome), but it overlooks the fact that humans have been deliberately altering genetic traits in plants and animals for thousands of years, as many 13,000 years by some estimates.
Long before we really understood what genes were, we worked out by trial and error, harvest after harvest, spring after spring, which characteristics to breed into or out of our crops and livestock. Today we have the understanding and the gene sequencing and gene editing technologies to make those changes without having to endure lifetimes of random mutations and imprecise improvements before reaching a desired outcome. And the result is genetically identical to what our ancestors would have arrived at eventually: a natural expression of the potential of the genome.
To get a better understanding of the state of the gene-editing industry and its potential in the near future, we need to look past the sensationalist headlines and see what types of problems gene editing is solving in plant science, animal husbandry and human health.
Plant Science: Editing for the Consumer
In the field of plant science, we’re beginning to see the first applications of CRISPR and similar gene-editing technologies come to market. For many companies, the promise of these technologies has inspired a marked shift away from transgenic plant candidates targeting growers (e.g., GMO corn that sustains higher-yields) to gene-edited products targeting consumers.
After a big Series C fundraising round led by Google Ventures, Benson Hill (full disclosure: TechAccel is an investor) has turned its attention to using gene-editing capabilities to improve the nutritional profile, taste and other consumer-facing qualities of soy, peas, and other fruits and vegetables. To that end, in December 2019, the company launched Benson Hill Seeds, which will be explicitly focused on delivering its eMerge portfolio of non-GMO soybeans along with new offerings targeting the evolving health concerns of consumers.
Other companies in plant science have expressed similar interests. Calyxt (NASDAQ: CLXT) has developed a gene-editing technology that uses TALENs (transcription activator-like effector nucleases), a promising alternative to CRISPR. Calyxt is focused on genetic improvements that can, for instance, give cheaper soybean oil the taste and quality of olive oil. The company is also looking to increase the amount of insoluble fiber in wheat, creating a gut-healthy and additive-free alternative to Metamucil® for people who need more fiber in their diets.
The biggest obstacle to the growth of these products, however, is uncertainty about worldwide regulatory practices for gene-edited crops. A few years ago, the USDA decided not to regulate gene-edited crops in the same way it regulates GMOs. The agency took the evidence-based view that gene editing is just another breeding tool, producing organisms that could just as easily have come about by random genetic mutation.
However, in the EU, regulators are approaching gene-edited crops more like GMOs. So companies have to be careful where their crops get exported. If they stay in the US, they’ll have little issue. But if companies produce something like corn or soy, which have significant export markets, they’ll have to be very careful not to run afoul of regulatory approval processes.
Animal Husbandry: Editing Out Suffering
Compared to plant science, the prospects for gene editing in animals are much more complex, both in terms of the science involved and the regulatory landscape. But while the role of gene-editing in the industry hasn’t changed as drastically, there are some important milestones to note.
With the outbreak of coronavirus taking its toll on the world, more thought and awareness is focused on the tools we can develop to protect animals and humans from diseases that are communicable and zoonotic (an infection or disease that is transmissible from animals to humans). While there is no gene-editing approach to mitigate the effects of COVID-19 (coronaviruses are zoonotic) at the moment, researchers at the University of Missouri have already shown that gene editing can make a litter of pigs resistant to porcine respiratory and reproductive syndrome (PRRSV), a virus for which there is no other known cure.
Most of the advances in gene editing are for animal health target issues, like disease, that primarily affect producers. But as more consumers demand transparency into how the animals they eat are treated in life (animal welfare), the line between consumer and producer concerns is getting blurrier.
Consider the results of a study from the University of California at Davis, in which gene-edited cattle successfully passed on a polled (hornless) trait to their offspring. Hornless cattle are desirable to producers, who want to prevent their livestock from injuring workers and each other. Currently, the dehorning process is painful and potentially damaging for calves: essentially the horn “buds” are cauterized with a hot iron or a caustic substance. Once you know that, it’s not hard to imagine consumers paying a premium for beef that hasn’t been hurt in this way.
Across the industry, as consumer preferences continue to skew negative against GMOs, there is a growing opportunity to achieve similar results with gene editing. By example, in 1989, before gene editing was a viable option, AquaBounty developed a fast-growing GMO salmon.
To date, the salmon is still not available for sale in the US or abroad (in great part the result of regulatory hurdles placed on the product by the FDA – a human pharmaceutical drug regulatory agency). In the meantime, the company has used gene editing to achieve similar growth results in tilapia without introducing any foreign DNA.
Human Health: Overcoming Fear to Save Lives
Ultimately, the success of any of these endeavors depends not on regulatory decisions made by governments, but on public understanding and acceptance of gene editing as a process distinct from transgenic modification. There is an understandable fear that the commercial promise of these tools is blinding some researchers to their potential ethical and physical consequences.
In 2018, when Chinese scientist He Jiankui announced the birth of twin girls whose DNA he had modified by gene editing before birth, the scientific community and the broader public quickly condemned the work as a monstrous breach of ethics. He has since been sentenced to three years in prison, but the cloud of suspicion raised by the incident continues to obscure other much more promising advances in human health made possible by gene editing. One of the major ethical lines he crossed was using gene editing to alter the germ line of an embryo, giving it traits that would be passed on to progeny. But there are many promising applications of gene editing that get results without altering patient’s germ lines.
Researchers recently used CRISPR to edit a patient’s bone marrow cells to produce a protein that alleviates the painful, life-threatening effects of sickle-cell anemia. Another study is showing that gene editing could be used to treat LCA10, an inherited form of blindness caused by a genetic mutation. Perhaps most exciting of all, TALEN and CRISPR technologies are being used to engineer CAR-T cells, which have shown enormous potential in treating the most aggressive cancers.
The promise of a cancer solution that is tailored to an individual’s immune system and avoids the damage caused by chemo and radiation therapies is drawing big commitments from across the industry. Intrexon, for instance, recently divested a number of its non-human gene therapy businesses (including gene editing in plants and animals) and rebranded as Precigen (NASDAQ: PGEN) pushing forward an immuno-oncology solution based on gene-edited CAR-T cells, among others.
The Future of Gene Editing
At its foundation, the future of gene editing depends on how we balance our fears against our needs and wants. Our global food crop needs to be able to feed 9 billion people by 2050 without producing so much waste. Those billions of people want access to healthier, better-tasting food. As the global middle class expands, we need to be able to accommodate their increasing desire not just for meat, but for transparency into how their meat is raised and produced. And as our planet gets more crowded, we need to radically rethink how we approach disease prevention in humans and animals.
Gene editing holds tremendous promise as a tool we can use to adapt to these challenges and deliver on consumers’ needs and wants simultaneously. But to unlock the full potential of gene editing, we need to overcome the fears surrounding it. I believe these fears have little basis in scientific evidence. But more importantly, I believe that the deep history of deliberate trait selection in plant and animal breeding shows us that the benefits of gene editing really aren’t anything new. We’ve been using genetics to feed and care for ourselves for millennia. If we take full advantage of everything we’ve learned about genetics in that time, we will benefit by feeding and caring for ourselves for millennia to come.