CRISPR-Cas9 setback proves cancer is still a puzzle. But it’s not doomsday yet.
Few recent biotech developments have created greater buzz than the CRISPR-Cas9 gene-editing technology. Among other things, it was projected as the great hope against cancer — until recent research appeared to suggest it could actually increase cancer risk. Is the dream souring, or are we seeing irrational panic?
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Vikas Dandekar
14 Jun 2018
ALAIN PITTON/NURPHOTO VIA GETTY IMAGES
"The art of medicine is long, Hippocrates tells us, and life is short; opportunity fleeting; the experiment perilous; judgment flawed." — Siddhartha Mukherjee, The Emperor of All Maladies: a Biography of Cancer
The emperor is throwing tantrums again.
Scientists from Cambridge University and Sweden’s Karolinska Institutet recently announced something that cancer researchers were least expecting: Editing cell genomes using CRISPR-Cas9 (molecular scissors) may inadvertently increase cancer risk.
The news sent shock waves through the stocks of gene-based therapy companies in the US. Nasdaq-listed CRISPR Therapeutics, the company that pioneered CRSIPR-Cas9 and is still heavily researching it with the goal of eliminating defective cancer-causing genes, tumbled 12% in a day. Another firm Intellia Therapeutics lost 9% of its stock value.
A separate study by Swiss drug giant Novartis delivered similar results, nearly dashing hopes of new ways to fight cancer.
Stat News, a leading US news site on medical, pharmaceuticals, and health-related issues explains the twin setbacks thus:
"The Karolinska and Novartis groups tested CRISPR on different kinds of human cells — retinal cells and pluripotent stem cells, respectively. But they found essentially the same phenomenon. Standard CRISPR-Cas9 works by cutting both strands of the DNA double helix. That injury causes a cell to activate a biochemical first-aid kit orchestrated by a gene called p53, which either mends the DNA break or makes the cell self-destruct."
The p53 gene is known to be one of the causes of ovarian cancer, colorectal cancer, and lung cancer among others. CRISPR-Cas9 has been hailed as one of the most promising weapons to cut out or replace part of a gene that may trigger proliferation of cancerous cells. Little wonder that the new question marks around the technology have made scientists and investors nervous.
CRISPR has been studied in animal models and cancer cell lines. The goal is to see how it can be used to repair cancer-causing genes.
China is a leader in testing CRISPR technology. In 2017, CRSIPR was used in 20 trials, mostly in China.
A New Scientist report says doctors removed immune cells from the blood of a person with lung cancer, used CRISPR to disable a gene calledPD-1, and then returned the cells to the body.
In 2016, an advisory committee of the US National Institutes of Health approved a proposal to use CRISPR-Cas9 to help augment cancer therapies that rely on enlisting a patient’s T cells, a type of immune cells.
In 2016-17, a CRISPR/Cas-based approach to genetically engineer adult rodent brains in vivo was successfully demonstrated.
Earlier, the US Food and Drug Administration had reportedly put on hold an application for clinical trials of a new genome editing-based treatment for sickle cell disease, co-developed by CRISPR Therapeutics and Vertex Pharmaceuticals.
Not quite doomsday
In the melee of adverse research findings, it is easy to lose sight of the fundamentals of medical research: Uncertainty — miraculous success or unexpected failure — is an inherent part of any research.
The first study published in the journal Nature Medicine found unexpected consequences of CRISPR-Cas9 use. “We managed to edit cancer cells easily, but when we tried to edit normal, healthy cells, very little happened,” says Emma Haapaniemi from Karolinska Institutet.
"When we looked at this further, we found that cutting the genome with CRISPR-Cas9 induced the activation of a protein known as p53, which acts like a cell’s alarm system, signalling that DNA is damaged, and opens the cellular ‘first-aid kit’ that repairs damage to the DNA. The triggering of this system makes editing much more difficult."
We have seen no evidence of any of these effects in our studies and do not believe the theoretical risks described in these papers apply to CRISPR Therapeutics’ programmes.CRISPR Therapeutics spokesperson
Jussi Taipale from Cambridge University words his observations carefully. "We don’t want to sound alarmist, and are not saying that CRISPR-Cas9 is bad or dangerous. This is clearly going to be a major tool for use in medicine, so it’s important to pay attention to potential safety concerns," he says in a press note.
Echoing similar views, most experts say this is not the end of the road for CRISPR-Cas9. Scientists quoted by leading news outlets in the US downplayed the findings but clearly underlined the need to have a functional p53 gene before and after the genome engineering.
ET Prime got in touch with Cambridge-based CRISPR Therapeutics, led by CEO Samarth Kulkarni, an IIT Kharagpur graduate with a PhD in bioengineering and nanotechnology from Washington University. “We have seen no evidence of any of these effects in our studies and do not believe the theoretical risks described in these papers apply to CRISPR Therapeutics’ programmes,” a company spokesperson tells ET Prime.
"We apply CRISPR for gene disruption or high-efficiency gene correction, neither of which are the focus of these reports. In all cases though, we seek to evaluate potential risks carefully and assess thoroughly as we advance our programs to the clinic," the spokesperson adds.
While the clinical phase to test the technology will be eagerly watched, John Carroll, editor of Endpts, a widely followed website specialising in the pharmaceutical and biotech industry, suggests the need for cautious optimism. Caroll says CRISPR-Cas9 is a brand-new field in drug development, with lots of unanswered questions.
“This new study will certainly focus plenty of attention on the risk of cancer and will require a special focus as researchers launch human studies. I'd like to see plenty of discussion, but I seriously doubt that the entire gene-editing field will be scuttled because of it. It's alarming, but no reason to panic,” he says.
(Image in banner: watchara/Shutterstock)
Few recent biotech developments have created greater buzz than the CRISPR-Cas9 gene-editing technology. Among other things, it was projected as the great hope against cancer — until recent research appeared to suggest it could actually increase cancer risk. Is the dream souring, or are we seeing irrational panic?
Share Gift this article
Vikas Dandekar
14 Jun 2018
ALAIN PITTON/NURPHOTO VIA GETTY IMAGES
"The art of medicine is long, Hippocrates tells us, and life is short; opportunity fleeting; the experiment perilous; judgment flawed." — Siddhartha Mukherjee, The Emperor of All Maladies: a Biography of Cancer
The emperor is throwing tantrums again.
Scientists from Cambridge University and Sweden’s Karolinska Institutet recently announced something that cancer researchers were least expecting: Editing cell genomes using CRISPR-Cas9 (molecular scissors) may inadvertently increase cancer risk.
The news sent shock waves through the stocks of gene-based therapy companies in the US. Nasdaq-listed CRISPR Therapeutics, the company that pioneered CRSIPR-Cas9 and is still heavily researching it with the goal of eliminating defective cancer-causing genes, tumbled 12% in a day. Another firm Intellia Therapeutics lost 9% of its stock value.
A separate study by Swiss drug giant Novartis delivered similar results, nearly dashing hopes of new ways to fight cancer.
Stat News, a leading US news site on medical, pharmaceuticals, and health-related issues explains the twin setbacks thus:
"The Karolinska and Novartis groups tested CRISPR on different kinds of human cells — retinal cells and pluripotent stem cells, respectively. But they found essentially the same phenomenon. Standard CRISPR-Cas9 works by cutting both strands of the DNA double helix. That injury causes a cell to activate a biochemical first-aid kit orchestrated by a gene called p53, which either mends the DNA break or makes the cell self-destruct."
The p53 gene is known to be one of the causes of ovarian cancer, colorectal cancer, and lung cancer among others. CRISPR-Cas9 has been hailed as one of the most promising weapons to cut out or replace part of a gene that may trigger proliferation of cancerous cells. Little wonder that the new question marks around the technology have made scientists and investors nervous.
CRISPR has been studied in animal models and cancer cell lines. The goal is to see how it can be used to repair cancer-causing genes.
China is a leader in testing CRISPR technology. In 2017, CRSIPR was used in 20 trials, mostly in China.
A New Scientist report says doctors removed immune cells from the blood of a person with lung cancer, used CRISPR to disable a gene calledPD-1, and then returned the cells to the body.
In 2016, an advisory committee of the US National Institutes of Health approved a proposal to use CRISPR-Cas9 to help augment cancer therapies that rely on enlisting a patient’s T cells, a type of immune cells.
In 2016-17, a CRISPR/Cas-based approach to genetically engineer adult rodent brains in vivo was successfully demonstrated.
Earlier, the US Food and Drug Administration had reportedly put on hold an application for clinical trials of a new genome editing-based treatment for sickle cell disease, co-developed by CRISPR Therapeutics and Vertex Pharmaceuticals.
Not quite doomsday
In the melee of adverse research findings, it is easy to lose sight of the fundamentals of medical research: Uncertainty — miraculous success or unexpected failure — is an inherent part of any research.
The first study published in the journal Nature Medicine found unexpected consequences of CRISPR-Cas9 use. “We managed to edit cancer cells easily, but when we tried to edit normal, healthy cells, very little happened,” says Emma Haapaniemi from Karolinska Institutet.
"When we looked at this further, we found that cutting the genome with CRISPR-Cas9 induced the activation of a protein known as p53, which acts like a cell’s alarm system, signalling that DNA is damaged, and opens the cellular ‘first-aid kit’ that repairs damage to the DNA. The triggering of this system makes editing much more difficult."
We have seen no evidence of any of these effects in our studies and do not believe the theoretical risks described in these papers apply to CRISPR Therapeutics’ programmes.CRISPR Therapeutics spokesperson
Jussi Taipale from Cambridge University words his observations carefully. "We don’t want to sound alarmist, and are not saying that CRISPR-Cas9 is bad or dangerous. This is clearly going to be a major tool for use in medicine, so it’s important to pay attention to potential safety concerns," he says in a press note.
Echoing similar views, most experts say this is not the end of the road for CRISPR-Cas9. Scientists quoted by leading news outlets in the US downplayed the findings but clearly underlined the need to have a functional p53 gene before and after the genome engineering.
ET Prime got in touch with Cambridge-based CRISPR Therapeutics, led by CEO Samarth Kulkarni, an IIT Kharagpur graduate with a PhD in bioengineering and nanotechnology from Washington University. “We have seen no evidence of any of these effects in our studies and do not believe the theoretical risks described in these papers apply to CRISPR Therapeutics’ programmes,” a company spokesperson tells ET Prime.
"We apply CRISPR for gene disruption or high-efficiency gene correction, neither of which are the focus of these reports. In all cases though, we seek to evaluate potential risks carefully and assess thoroughly as we advance our programs to the clinic," the spokesperson adds.
While the clinical phase to test the technology will be eagerly watched, John Carroll, editor of Endpts, a widely followed website specialising in the pharmaceutical and biotech industry, suggests the need for cautious optimism. Caroll says CRISPR-Cas9 is a brand-new field in drug development, with lots of unanswered questions.
“This new study will certainly focus plenty of attention on the risk of cancer and will require a special focus as researchers launch human studies. I'd like to see plenty of discussion, but I seriously doubt that the entire gene-editing field will be scuttled because of it. It's alarming, but no reason to panic,” he says.
(Image in banner: watchara/Shutterstock)
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