- American Cancer Society/Getty Images
- Bold headlines linking blockbuster gene-editing tool CRISPR to cancer sent stocks in companies trying to bring the technology to medicine tumbling.
- But scientists who study the technique say the concerns are overblown at best and an incorrect interpretation of the science at worst.
- Ultimately, using CRISPR does not appear to present any challenges that scientists familiar with gene editing have not already faced.
Earlier this week, reports linking the blockbuster gene-editing tool CRISPR to cancer in two studies sent investors scrambling to pull out of companies working on the technology, which is being studied for use in everything from food to medicine. The tool’s precise cut-and-paste approach to gene editing allows for a range of promising medical applications, from curing sickle cell anemia to preventing some forms of blindness.
On Monday afternoon, headlines suggested that cells edited with the tool were more likely to become cancerous. Within hours of the reports being published, shares of Editas Medicine, CRISPR Therapeutics, Intellia Therapeutics, and Sangamo Therapeutics – all of which are trying to bring CRISPR to medicine – took a significant tumble.
But scientists who study CRISPR and other methods of gene editing call the reports “overblown.” They say the link to cancer is tenuous at best and an incorrect interpretation of the results at worst.
“This is absurd,” John Doench, the associate director of the genetic perturbation platform at MIT’s Broad Institute, told Business Insider. “There was a massive overreaction here.”
Like many other researchers involved in the space, Doench read the two studies highlighted in the recent report and published in the journal Nature Medicine. Instead of concluding that the technique causes cancer, Doench read the papers and thought it highlighted facts about how cells behave in response to perceived threats. Most of these are already fairly well-known to people who study gene editing. Tweaking a cell’s DNA is a violent process; when it is done, cells respond by trying to defend or repair themselves. This is one of the biggest hurdles facing most cutting-edge gene editing approaches today. It is not unique to CRISPR.
“I’m honestly trying to figure out why this has generated such a response and I really can’t,” Doench said. “Everything I can see is just related to the stocks and finances and not in anyway related to the science.”
Cells responding normally to a perceived threat
- Samantha Lee/Business Insider
The problem comes down to the basic biology of what happens in cells that encounter DNA damage.
To make changes to DNA, CRISPR breaks key parts of the strands that make up the genetic material in a cell. This cutting and slicing ability is why it’s so powerful; previous tools for gene modification were limited by their inability to precisely target certain parts of a cell’s DNA.
When anything – be it CRISPR or a disease or anything else – slices into genetic material, the “broken” cells try to patch themselves up in a process that’s governed largely by a gene called p53.
If that fix-it gene starts to malfunction, it means cells can’t self-repair. Cancer can occur as a result.
The recent papers did not reveal that editing the DNA of a cell with CRISPR damaged its fix-it genes. Instead, the process appeared to activate them, which is exactly what scientists would expect to happen with many kinds of gene-editing.
In other words, CRISPR turned on the self-repair process, and “the cell is responding as it should,” Doench said.”That doesn’t mean p53 has been inactivated and these cells are now cancerous, it means the cell has done its job.”
A tweet that Nature sent out on Tuesday afternoon with a link to one of the papers appeared to back up this interpretation, saying, “p53 defends against CRISPR-Cas9 genome editing.”
Gaetan Burgio, a professor of genetics who studies CRISPR at the Australian National University, agreed, tweeting, “Beware exaggeration and overstated headlines. The papers say after CRISPR-Cas9 … P53 signaling is activated. They don’t say CRISPR could cause cancer.”
Laboratory cells acquire all kinds of mutations, gene-editing or not
The scientists behind the two recent papers were looking out for another potentially disturbing consequence of using CRISPR on these cells: that their fix-it genes would be shut down after applying the tool – a result that would leave them vulnerable to mutations and cancer.
But that didn’t happen either, according to the two papers. What did happen, however, is that the cells edited with CRISPR were more likely to have mutations on their fix-it genes. But that wasn’t necessarily a result of CRISPR.
In fact, cells in labs have a tendency to acquire all kinds of mutations simply as a result of being in a lab. A 2017 paper published in Nature found, for example, that human embryonic stem cell lines frequently develop mutations without any kind of gene editing being done on them. Many of those mutations also happen to be on the p53, or fix-it, gene.
The last line of one of the most recent papers sums this idea up well, concluding that scientists who are developing techniques using CRISPR should closely monitor the function of the fix-it gene on the cells that they edit using the technique.
This is also something that most biologists – especially those who work in gene editing – already know. Other techniques like zinc finger nucleases, a type of gene editing that can lead to outcomes seen as similar to CRISPR, require keeping a close eye on the fix-it gene, too. That’s a risk scientists are actively monitoring, not a unique issue presented by CRISPR.
“To anyone who would actually use gene editing, this was already baked into the cake,” Doench said.
- Markets Insider
- Two independent studies by Novartis and Karolinska Institute showed that CRISPR-Cas9 may increase the risk for cancer by disrupting function of the essential p53 DNA repair protein.
- CRISPR Therapeutics‘ stock was down 15.3% Monday morning, while Editas and Intellia, two other companies developing CRISPR-related therapies dropped 7% and 8% respectively.
- This finding only affects some of CRISPR’s therapies.
There could be a big issue with a revolutionary gene-editing tool.
CRISPR-Cas9 is a gene-editing tool made up of a group of molecules that can find a specific gene in a cell and alter it. In theory, it’s supposed to be able to tackle genetic-based diseases like cystic fibrosis and cancer.
However, two independent articles published by Novartis and Karolinksa Institute in the journal Nature now report the application of the CRISPR-Cas9 may inadvertently increase the risk of cancer by hijacking proper functioning of the p53 protein. Mutation of the DNA-repairing p53 accounts for a large proportion of cancers.
The CEO of CRISPR Therapeutics said in a comment to STAT News that while the results are plausible, it may apply to the DNA replacement function of CRISPR more than the DNA excising function of the gene-editing tool. However, he said there will be increased scrutiny as CRISPR develops and is tested to make sure it doesn’t turn cells cancerous.
In response to the new data, CRISPR Therapeutics’s stock was down 15.3% Monday afternoon, while Editas and Intellia, two other companies developing CRISPR-related therapies dropped 7% and 8% respectively.
“We’ve observed no signs of this type of toxicity or cells transforming into cancer or tumors in Intellia’s in vivo and ex vivo programs,” Intellia said in an email statement to Business Insider.
This isn’t the first time speculation has surrounded the gene-editing therapy. In January, concerns over immune response to infection caused the stocks to take a dip. In May, the FDA put a hold on the first clinical trial of CRISPR before it was underway.
Although this finding presents a problem for stem cells and other therapies which trigger the p53, it does not seem to affect therapies that edit T-cells to treat cancer, for example.
- Jim Young/Reuters
- The German drugmaker and chemical company Bayer has finalized a $66 billion blockbuster deal to gobble up the agricultural behemoth Monsanto.
- On Monday, Bayer said it would drop Monsanto’s 117-year-old title.
- The name drop appears to be part of a strategic move geared at distancing the colossal new company from negative publicity surrounding Monsanto and genetically modified organisms.
The German drugmaker and chemical company Bayer has finalized a $66 billion blockbuster deal to gobble up the agricultural giant Monsanto.
In a statement on Monday, Bayer said it planned to drop Monsanto’s 117-year-old title and would henceforth be known only as Bayer.
“Bayer will remain the company name. Monsanto will no longer be a company name,” the company said. “The acquired products will retain their brand names and become part of the Bayer portfolio.”
The name drop appears to be part of a strategic move geared at distancing the new behemoth from negative publicity surrounding Monsanto and genetically modified organisms.
First announced in September 2016 as part of a move designed to boost agricultural research and innovation, the merger is the largest acquisition in Bayer’s history and doubles the size of its farm business.
Distancing itself from the Monsanto label
- Thomson Reuters
You can’t utter the name Monsanto in public and not be met with at least one stink eye.
For decades, the company has been met with public outrage and disgust linked to its history of controversial dealings with farmers and its standout role in popularizing GMOs. This spring, Monsanto landed a spot on a well-known list of the 20 most hated companies in America.
The decision to drop the Monsanto moniker, then, is no huge surprise.
On a call with reporters on Monday, Liam Condon, the head of Bayer’s crop-science division, said Monsanto had “actually itself considered changing its name” at one time, but elected “not to do that, apparently for cost reasons.”
Still, Condon said, “it was an issue for some time for Monsanto management … to try to improve the Monsanto brand.”
“We’re extremely proud of all we’ve accomplished as Monsanto and are eager to continue to accelerate innovation in agriculture as we look forward to a future under Bayer,” Christi Dixon, Monsanto’s public-relations lead, said in a statement to Business Insider. She added that in the interim, while Monsanto operates independently of Bayer, “it will be business as usual for us, including our company name.”
Monsanto is also moving to invest more deeply in advanced tools for gene editing, a process that can be capitalized on for agricultural purposes to make cheaper but higher-quality produce. Many companies are moving away from tweaking crops’ DNA with GMOs and other crude methods of genetic modification in favor of more precise techniques like Crispr.
In March, Monsanto put $125 million behind the gene-editing startup Pairwise, a company whose founder, Haven Baker, told Business Insider he aimed to bring the first fruit tweaked with Crispr to grocery-store shelves – a development he expects in five to 10 years. Tom Adams, who was Monsanto’s vice president of global biotechnology, left to become the CEO of Pairwise this spring.
- Researchers using the genetic-editing technology CRISPR have successfully modified the DNA in cells from Huntington’s disease patients.
- The feat shows it might be possible to to use CRISPR to treat Huntington’s, which is currently incurable and fatal.
- CRISPR is a way to edit DNA cheaply and efficiently; researchers think it could transform the ways we treat any sort of genetic condition.
- But before CRISPR can be used to edit the DNA of living humans, scientists say it needs to be made safer and more efficient.
In people with Huntington’s disease, the nerve cells of the brain start to break down over time.
The disease is fatal, often within 10 to 30 years, and as of now, there is no cure.
But Huntington’s disease is caused by a single genetic mutation– it’s triggered by an inherited gene, making it something researchers call a Mendelian disorder. Because of that, it’s a prime target for scientists working with technologies that edit specific parts of genetic code.
In a recent study, scientists took a step toward using what’s often referred to as the most revolutionary genetic technology in existence, CRISPR, to tweak the genes that cause Huntington’s.
In people with the disease, due to a certain repeated section of genetic code, a toxic protein gets produced that accumulates and causes neurodegeneration. Usually symptoms begin to appear when patients are in their 30s or 40s. People start having trouble controlling movements and balancing, which is followed by difficulties with speech and swallowing as well as cognitive problems.
But a group of researchers from Poland were successfully able to edit cells from Huntington’s patients. The team took cells from those patients, and used CRISPR to slice and inactivate disease-causing sections of DNA. That drastically reduced the amount of neurodegenerative proteins produced – by approximately 70%.
“Our strategy is safe and efficient, and no sequence-specific side effects were observed,” Dr. Marta Olejniczak, an associate professor at the Institute of Bioorganic Chemistry in Poland who led the study, said in a news release.
Getting to the point when we can safely and accurately edit genes to treat Huntington’s disease with CRISPR would be a huge deal. Not only could this enable researchers to treat what has long been considered an incurable disease, it may also indicate that other Mendelian disorders like sickle-cell anemia, Tay-Sachs disease, and cystic fibrosis could be effectively treated with similar CRISPR techniques.
Demonstrating effective use without side effects is a big step in getting there. But showing that a method works safely in cells is many steps away from using a treatment in humans.
The promise of CRISPR
CRISPR is essentially a cheap and easy way to edit DNA.
The tool involves a small group of molecules that uses RNA to find a specific section of DNA that it can tweak. It can cut a section out, add in new genetic material, or even replace an undesired section with new genetic code – a biological “find-and-replace” operation for genetic code.
Jennifer Doudna, a biologist at the University of California at Berkeley, is credited as one of the first researchers to discover CRISPR.
“We’re basically able to have a molecular scalpel for genomes,” she previously told Business Insider. “All the technologies in the past were sort of like sledgehammers.”
If the tool proves successful in people, it might be possible to do far more than address genetic disorders. Scientists could change genes to reduce risk factors for other diseases and potentially even improve human health in other ways.
- Samantha Lee/Business Insider
Treating Huntington’s – and then more diseases
As the researchers wrote in the new study, prior studies have used other genetic editing tools to prove it was possible to remove the segment of genetic code that’s responsible for Huntington’s. Unfortunately, doing so created new complications, especially when genetic editing tools sliced both of the connected strands of DNA.
Editing genetic code with CRISPR can lead to unintended consequences, too. Researchers have been able to successfully make desired edits by delivering a package of CRISPR molecules to cells, but sometimes these packages have only made some of those edits, not all. Other times, the tool has made too many undesired off-target tweaks, which could be dangerous.
In this particular study, the research team overcame these obstacles by using a specific CRISPR package designed to avoid off-target effects. (There are many different collections of molecules that can form different CRISPR tools.)
The Polish team used what’s known as a CRISPR Cas9 nickase. Instead of slicing both strands of the DNA double helix (something that can result in new undesired mutations), the nickase just slices one of the strands, which the study authors wrote can make for a much more precise edit.
At least in the cells they tested, that approach worked.
However, researchers say they’ll still need to make this method more precise and better understand it before it could be tried in people. For now at least, there’s still a lot we don’t know about how modifying the genetic code affects patients.
But making modifications without causing off-target effects is an exciting, important step toward eventually using CRISPR to help people. Researchers think it could even be possible to edit human embryos and remove the sections of genetic code that cause these diseases before people are born.