In the wake of the Nobel Prize for chemistry being given to two scientists who developed the gene-editing tool CRISPR, below is an excellent article on what CRISPR has done for us, and what it's likely to do in the future.
We'd offer just one qualification to the article, which is titled, "CRISPR GMOs ― They’re cheap and fast, but are they good?" The article quotes the media as hailing CRISPR as "a tool that can simply and cheaply edit the genomes of everything from wheat to mosquitoes to humans".
But when it comes to commercialising a CRISPR product, it actually isn't cheap at all.
There can be three different types of licence for technologies like CRISPR: evaluation, research, and commercial licences. Researchers have to take out different licences at different stages of product development.
Evaluation and research licences to use CRISPR are often granted cheaply by the technology owners, as the mostly large companies that own the technology want it to be used in the development of a product that can in due course be commercialised. But at the commercialisation stage things can quickly get very expensive, with large companies demanding high payments, in the form of commercial licence fees and royalty payments on product sales, for the use of their technology.
So CRISPR products won't be cheap and will always be controlled by the large companies that can afford to take them to market.
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CRISPR GMOs ― They’re cheap and fast, but are they good?
by Pat Thomas and Patrick Kerrigan
Organic Consumers Association, Nov 4 2020
https://www.organicconsumers.org/blog/crispr-gmos-theyre-cheap-and-fast-but-are-they-good
[links to sources at this URL]
This year’s Nobel Prize for chemistry was awarded to two scientists ― Emmanuelle Charpentier and Jennifer A. Doudna ― “who transformed an obscure bacterial immune mechanism, commonly called CRISPR, into a tool that can simply and cheaply edit the genomes of everything from wheat to mosquitoes to humans.”
According to the Nobel Prize committee the “genetic scissors” of CRISPR “have taken the life sciences into a new epoch and, in many ways, are bringing the greatest benefit to humankind.”
But have they? Really?
There’s a concept that even most business school dropouts will understand: "Good, fast, cheap. Choose two."
In other words, if you want to produce something good and fast, it won’t come cheap; if you want it cheap and good, it won’t be fast; and if you want it cheap and fast, then it won’t be good.
Surely a panel of eminent scientists can get its head around this expression of compromise?
Fast and cheap editing of the human genome?
The choice compromise, to prioritize cheap and fast over good is, in many ways, the real story of CRISPR GMOs.
CRISPR is one of a suite of technologies used to perform a new kind of genetic engineering called gene-editing. CRISPR doesn’t actually create anything itself. Its main function is to make a cut in a strand of DNA, which is why it is referred to as “genetic scissors”. After the cut, the organism will either be left to repair itself/mutate or be given “instructions” via the insertion of other genetic material, on how to repair itself in a way that creates a unique new organism.
CRISPR has been in the background of genetic engineering since the early 2000s, but has really only come to prominence since 2012 when Charpentier and Doudna published a paper showing that more precise cuts in DNA could be made by combining a protein, Cas9, with CRISPR. Today when people refer to CRISPR it is usually shorthand for this CRISPR/Cas9 system.
A timeline of CRISPR achievements shows it’s been used experimentally to delete, insert and modify DNA in human cells and other animal cells in the lab. It’s been used to create experimental transgenic animals such as mice, rats, zebrafish, pigs and primates―again, in the lab.
Between 2014 and 2015 scientists reported that CRISPR could regenerate muscle tissue in experimental mice with Duchenne muscular dystrophy and cure a rare liver disease, also in experimental mice.
It has also been investigated as a way of growing human compatible organs in genetically modified host animals, e.g. pigs. Biotech companies are also experimenting with CRISPR insects as a way of controlling insect-borne diseases such as malaria, transmitted by mosquitoes, and Lyme disease, transmitted by ticks.
Most of these are still aspirations rather than realities and, in the interim, multiple problems with the technology have also surfaced.
A 2017 study caused a furore when it claimed that CRISPR caused huge numbers of off-target effects in gene-edited animals. That study was eventually retracted and a second report, which showed that the human immune system resisted changes induced by CRISPR/Cas9, was shrugged off by biotech scientists as a solvable problem.
But, in June 2018, two studies (here and here) published in “Nature Medicine” demonstrated that cells altered with CRISPR may be missing key anti-cancer mechanisms, increasing the risk that those cells will initiate tumors. This finding was harder to dismiss and what’s more it wasn’t new.
Speaking in an interview in "Scientific American”, Emma Haapaniemi, the lead author of one of the studies noted that this cancer-seeding effect can be missed in the (usually cheap and fast) small-scale studies where scientists only focus on editing one gene in one cell type. Crucially, she said that “other teams have noticed the effect” but had chosen not to talk about it.
By December 2018, a Chinese scientist He Jiankui had announced, on YouTube, that he had made the first CRISPR-edited babies―twin girls named Lulu and Nana. The purpose of his experiment was to see if he could stop the twins contracting HIV.
The announcement brought into laser focus both scientific and ethical problems that surround the dash towards gene editing human beings. CRISPR co-inventor Jennifer Doudna admitted to being “horrified.” Francis Collins, director of the National Institutes of Health, called the experiment “profoundly disturbing.”
Others criticized the laboratory process used by He as rushed and sloppy. There were concerns that ethical consent had not been sought, that the write up of the experiment was not peer reviewed and had been conducted in secrecy and in contravention of 2017 guidance issued by an international panel of scientists led by the U.S. National Academies of Sciences, Engineering and Medicine.
By January 2020, a Chinese court had sentenced He to three years in prison for “illegal medical practice.” Shorter sentences were handed down to two of his assistants.
More recently an editorial in “Nature” took the gloves off, publishing a study which showed that CRISPR editing of human embroys “wreaks chromosomal mayhem”.
Problems in animals too
As we reported earlier this year, similar problems have been seen in CRISPR-edited farm animals.
Much of the current research and development is focused on health problems in livestock raised in intensive, industrial systems. Thus, genome editing has been proposed as a way to protect farm animals from disease by raising their immune response to diseases like Porcine Reproductive and Respiratory Syndrome (PRRS) and African Swine Fever (ASFv) in pigs and Infectious Salmon Anemia (ISA, or “salmon flu”) in farmed salmon.
Researchers are also looking to create animals with desirable commercial attributes, such as the ability to produce more muscle mass (meat) while consuming less feed.
They are also trying to engineer animals to withstand environmental stressors, such as cattle with “slick” coats that protect them from extreme heat.
The health and welfare issues being addressed with CRISPR experiments are real; but most of them are also manmade—a consequence of the crowded factory farm conditions in which the animals are raised and the spread of industrial livestock operations into geographical areas (e.g. tropical climates) not well suited to this kind of farming.
Results thus far have not been encouraging. A “Wall Street Journal” investigation reported multiple unintended effects including enlarged tongues in rabbits and extra vertebrae in pigs bred to be extra meaty.
Ever optimistic, proponents claimed that CRISPR will eventually produce animals that have smaller environmental footprints and encourage better welfare. Soon, they said, farmers will no longer have to dehorn cattle or cull male chickens.
CRISPR has yet to achieve this but another type of “genetic scissor”, TALENS was used to produce the first hornless cows. Biotech company Recombinetics proclaimed its 2018 experiment with gene edited hornless cattle in Brazil a roaring success, crowing that their GMO dairy cows were 100% bovine.
That claim was fairly swiftly upended when researchers at the U.S. Food and Drug Administration (FDA) studied the gene-edited cows more thoroughly only to find that the genome of one of the experimental animals contained a sequence of bacterial DNA
Genetically, the gene-edited cow was part cow/part bacteria. The import of this is not clear but, in theory, this gene―which also carried an antibiotic resistance trait―could be taken up by any of the billions of bacteria in a cow’s gut or body and spread from there to beyond the farm.
Criticism from the scientific community suggested the whole process had been rushed and sloppy.
On publication of the FDA data in the journal “Nature,” Brazil abandoned its plans to grow its herd of hornless GMO dairy cattle.
Heather Lombardi, division director of animal bioengineering and cellular therapies at the FDA’s Center for Veterinary Medicine suggested that the Agency remained cautious:
“There’s a lot out there that I think is still unknown in terms of unintended consequences associated with using genome-editing technology. We’re just trying to get an understanding of what the potential impact is, if any, on safety.”
This kind of genetic mix-up proved to be all too common. Researchers working with experimental gene-edited mice have found bovine, goat and bacterial DNA in the genomes of the mice―contamination sneaks into the genome from the standard culture medium for mouse cells.
An agricultural revolution?
A 2020 review in “Nature” proclaimed a brave new world in crop biotechnology:
“CRISPR technology, which is widely used for plant genome editing, will accelerate the breeding of food crops beyond what was imaginable before its development.”
But it’s worth emphasizing that CRISPR is not “widely used” in agriculture, that development of CRISPR and other gene-edited crops has been slow and fraught with problems. Except in very limited circumstances, we are not eating these new GMOs―although U.S. Government regulators have done their level best to remove any barriers to market, including largely deregulating products of CRISPR.
In 2016, for example, a CRISPR gene-edited non-browning mushroom got the green light from the United States Department of Agriculture Animal and Plant Health Inspection Service (USDA-APHIS). The mushroom, however, has still not been put on the market.
Nor have the CRISPR-edited corn, soybeans, tomatoes, pennycress and camelina that USDA-APHIS have granted regulatory waivers to.
Although the endless PR noise around CRISPR says that it brings consumer benefits, we should also be clear that consumers don’t benefit from non-browning food. Browning is a sign that fresh food has begun to spoil. By covering up the browning process retailers and restaurants can sell food that is past its best and consumers will never know.
The same question of benefit hangs over the head of the Calyno, a soya oil which, in 2019, became the first gene-edited oil to make it onto the market in the U.S.
Like those hornless cattle, Calyno is gene-edited using TALENS, not CRISPR, to produce a “heart-healthy” oil with no trans fats and less saturated fat.
Calyno oil isn’t for sale in supermarkets yet, though Minneapolis-based manufacturer Calytx has recently began direct-to-consumer sales via its website. Instead, it has made its way to fast food restaurants, mostly in the Midwest.
Calyxt says the oil can be used for salad dressings and sauces, but its most likely destination is the fryer. The manufacturer boasts that its oil has a 3-fold greater fry life compared to conventional soybean oil. In other words, you can keep frying food in the same quantity of Calnyo for even longer than other oils.
In what way is this better for humankind?
Deficits and dark sides
Here’s the problem: although gene-editing with CRISPR has long promised limitless benefits for humankind, we’re not eating it, we’re not growing it and we’re not taking medicines made from it or undergoing medical procedures that involve its use.
The public is not clamoring for gene edited crops or foods, whatever their promised benefits. In fact public views on GMOs food continue to span from skeptical to outright hostile. A recent global survey by Lloyd’s Register Foundation, which sought the views of 150,000 people in 142 countries, found that 48% of people believed GM foods were more likely to bring harm rather than benefit over the next 20 years.
Interestingly this report frames GMOs as a controversial technology in the same vein as nuclear power and artificial intelligence and suggests GM concerns can’t be resolved until wider food system concerns such as rising levels of contaminated food―once again a problem of the industrial system―are resolved.
CRISPR has undoubtedly benefited the scientific community, making research and experiments in manipulating life faster and cheaper to perform. It’s so fast and so cheap, in fact, that do-it-yourself CRISPR kits, which can be used at home, can now be purchased on the internet.
As a result, biohacking has now become a real concern; so much so that in 2019 California introduced a law―the first in the U.S.―to try and curb it.
A significant proportion of gene editing research focuses on eliminating genetic diseases and this is a worthy goal. But with tools like CRISPR, it’s also possible to create weapons of mass destruction. As a result, in 2016, James Clapper, then (now former) U.S. Director of National Intelligence, identified CRISPR as a threat to national security.
Calling CRISPR out as a potential WMD may have surprised some. But, in addition to assisting in the creation of funky pink pineapples, it can also help make killer mosquitos or plant pathogens that wipe out staple crops across wide swathes of land or airborne organisms capable of altering human DNA in vivo.
It can be used to alter a pathogen’s DNA to make it more virulent and more contagious (essentially the same gain-of-function research implicated in making the coronavirus more virulent).
Commenting on the report, Daniel Gerstein, a senior policy researcher at the RAND Corporation and a former undersecretary at the Department of Homeland Defense, noted:
“Biotechnology, more than any other domain, has great potential for human good, but also has the possibility to be misused. We are worried about people developing some sort of pathogen with robust capabilities, but we are also concerned about the chance of misutilization. We could have an accident occur with gene editing that is catastrophic, since the genome is the very essence of life.”
So the question for the eminent scientists on the Nobel Prize panel remains―on what basis was this award made? And in what concrete way has CRISPR really benefited the whole of humankind?
CRISPR may be cheap. It may be fast. But, as yet, there’s nothing unequivocal to suggest it’s good.
Pat Thomas is a journalist, author and campaigner specializing in food, environment and health. See more on her website.
Patrick Kerrigan is OCA’s Retail and Organic Standards Coordinator
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