At a conference in Washington in 2015, French microbiologist Emmanuelle Charpentier discussed the ethical impacts of Crispr-Cas9, a new form of tiny molecular scissors that she and UC Berkeley biologist, Jennifer Doudna, discovered could be used to alter genetic code and create genetically modified organisms (GMOs). Charpentier had detected an interaction causing a key molecule to clasp to a second molecule called Crispr, which then guided a protein called Cas9 to modify genetic code. While scientists disagree over who owns the rights to the technology that was later developed based on these discoveries, consumers remain uncertain as to its impacts. Many consumers are adamantly opposed to modifications in heritable human code or in agriculture. In fact, Charpentier received a threatening letter from anti-GMO activists about the perceived safety and environmental concerns surrounding gene modification.
The trial over the rights to commercialize Crispr-Cas9 began in late 2016 and is expected to come to a resolution this month. The Broad Institute won key patents and spent tens of millions on lawyers to defend it against an interference proceeding initiated by UC Berkeley and Charpentier. Importantly, a number of proteins related to Cas9 were recently discovered, including CasX and CasY reported by Doudna, and Cpf1 reported by Broad scientist Feng Zhang and colleagues, which promise more sophisticated genome editing and ease the singular focus on the Cas9 lawsuit.
Amid the ongoing patent battle, Crispr-Cas9 and associated genome modification tools are enabling next generation, precision GMO crops, which may circumvent regulatory hurdles and even qualify as organic. Such technological innovations in the GMO space open up new opportunities to improve the nutrition and growth yield of crops. Precision GMO crops are a top-down solution to meeting global nutritional demands and may simultaneously undermine the enterprise of local farmers and fishermen.
With the aim of improving the growth yield and sustainability of crops, Caribou Biosciences, one of Doudna’s companies, is collaborating with DuPont to grow wheat strains edited for drought resistance and a waxy corn that can be eaten or used to produce stronger adhesives. Companies testing and producing “Crispr crops” escape onerous regulations. UC Berkeley researcher Maywa Montenegro observed that “to U.S. regulators, most organisms currently under development may not be considered genetic modification. This is because U.S. policy is product-based, and with many types of Crispr edits, the product will not include foreign genetic material. In cases where editing introduces sequences from close crop wild relatives, the product might even be genetically indistinguishable from the results of conventional crossbreeding–and, say researchers, could even qualify as organic.”
Last month, the White House suggested updates to biotech regulations in a plan called the Coordinated Framework for Regulation of Biotechnology. A draft guidance suggested giving the FDA purview to regulate a raft of technologies relating to genetically modified (GM) animals. It suggested that any intentional change to an animal’s genes meets the definition of a “new animal drug” as it is intended to “affect the structure or function of the body of the animal.” A second proposed rule suggests employing existing techniques to alter plant genes, which could be grandfathered without further onerous regulations. However, new gene modification approaches such as Crispr-Cas9 may be subject to regulation. The guidelines remain up-in-the-air under a new presidential administration that has pledged to cut corporate regulations by up to 75 percent.
In 1987, Monsanto Corp conducted its first field trials of GM crops. In 2000, British biochemist Peter Bramley reported on the creation of “golden rice” after discovering that a single bacterial gene could convert the phytoene compound into vitamin A. This cassette of genes has significant health benefits and could be added to rice to boost its vitamin A content. Since then, Monsanto has modified crops to improve global nutrition and economic development. In September 2016, Monsanto Corp licensed a Crispr-Cas9 patent from the Broad. A spokesperson for Monsanto noted the company had a longstanding commitment not to sell or to propagate “sterile seed technology” (known as “terminator seeds” in the anti-GMO community). Monsanto intends to use Crispr-Cas9 to benefit farmers by improving yield, reducing drought, and promoting disease resistance in cash crops. On June 30, 2016, largely speaking to the safety and nutritional value of golden rice, 107 Nobel laureates signed a letter in support of “precision agriculture GMOs,” including organisms now modified with Crispr-Cas9.
However, Greenpeace continues to voice opposition to “precision agriculture,” arguing that if the goal is to improve the health and welfare of developing countries, money could be better spent on promoting diverse diets through “ecologically farmed home and community gardens.” Greenpeace published a position paper arguing that GM crops fail to deliver on crop yields and global nutrition—a claim reiterated last fall in a controversial New York Times article. In response, Monsanto executive Robert Fraley noted that “nearly 20 million farmers around the world choose to invest in genetically modified seeds for two decades” and that “in the United States alone… soybean yields have increased by a remarkable 28 percent and corn yields by nearly 32 percent” since the introduction of GM crops 1996.
In 2010, six million Indian farmers planted Monsanto’s pest-resistant “Bollgard,” or Bt cotton seeds, on 250,000 acres in India, tripling cotton production over a decade. Discussing the viability of Bt cotton, Monsanto spokesperson Camille Scott said that “with the combination of higher yields and reduced pesticide costs, India’s cotton farmers have increased their incomes… Therefore, villages where farmers are planting Bt cotton have seen improvements in access to services, such as telephone systems, electricity, drinking water, better internet connectivity, banking services, and better access to markets.” But, local farmers and the Indian government remain unsatisfied with the arrangement. Last March, the Financial Times revealed the emerging rift between Monsanto and the Indian government after the latter slashed royalties paid to Monsanto’s local joint venture.
Scientists are now studying how to leverage high-powered photosynthesis machinery to transplant a cassette of genes into rice and wheat. This could increase growth yields by 50 percent, thereby boosting farmers’ overall agricultural production. A second approach to improving crop growth is to disrupt a natural sunshield to promote constant photosynthesis. By slipping extra copies of three genes from a mustard plant known to weaken the shield, scientists increased the size of a tobacco plant by 20 percent. Similar dynamics are being tried with a promise of a “Blue Revolution.” In 2006, the world consumed 110.4 million metric tons of fish—half of which was produced by aquaculture. The United Nations Food Agriculture Organization estimates an additional 28.8 metric tons of fish will be needed by 2030.
In 2015, the Food and Drug Administration (FDA) approved the first genetically engineered animal for consumption: the “AquAdvantage” salmon. AquaBounty generated a construct that includes a “gene cassette” from the Pacific Chinook salmon that can be spliced into the Atlantic salmon, allowing it to grow up to 13 times the size of natural Atlantic salmon. Local fishermen argue that fish stocks would do better if consumers ate less popular, amply available fish, such as monkfish, wreckfish, or Chilean seabass. Ecologists suggest a potential danger in releasing a fast-growing fish with an advantage into the ocean: it could out-compete other fish and dominate a niche in the ocean, reducing genetic diversity, and thereby leading the fish population to be at risk for a crash if it is exposed to a pathogen.
Indeed, researchers are also testing gene modification to promote disease resistance. In the fall of 2016, work was underway in the Pacific to sequence the genomes and create gene modifications to scallop, abalone, and shrimp, not only to alter genetic code to increase the size or market value of meat, but also to improve disease resistance against viruses and syndromes. Scientists have also engineered mice and mosquitos to produce antibodies resistant to Lyme disease and Zika virus, respectively.
However, as journalist Claire Ainsworth notes, “an edit succeeds in making an insect immune to infection, it also creates a strong selective pressure for the pathogen to evolve a means of getting around the modification.” Therefore, if the insect is altered so that it does not spread a disease, pathogen, or virus, evolution is still at work, and may “escalate the arms race” and cause insect infections to evolve into more dangerous pathogens. Montenegro wrote: “In what scholar Donna Haraway calls the ‘god-trick,’ we thought of genetics as the key to scientific mastery of nature, as if there was no context, no agency in the object, no imperfection in human knowledge. Molecular science somehow licensed us to treat genes as separate from ecology and bodies. We now are fathoming intricate interactions between genes and environments, and ecosystems whose changes aren’t smooth or predictable, but that bristle with threshold effects and emergent properties. We’ve come to appreciate the inseparability of nature and culture in complex systems.”