“2019 is the year when the training wheels come off and the world gets to see what CRISPR can really do for the world in the most positive sense,” said Berkely-based gene-editing scientist Fyodor Urnov. Turns out, he wasn’t wrong.
The groundbreaking CRISPR technique, that has allowed gigantic strides in the realm of gene-editing since making a splash in 2012, is ready to enter clinical trials, with the technology already in use to treat strains of cancer in humans in the US.
A spokesperson at University of Pennsylvania, Philadelphia, confirmed to NPR Tuesday that the study that had been approved for cancer has finally started. Two cancer patients, one with myeloma and the other with sarcoma, received CRISPR treatment after standard ones failed and caused malignant cells to reappear.
This news came a day before a Chinese scientist who had shocked the world last year by using CRISPR to create genetically modified babies was put in TIME Magazine’s list of 100 most influential people of 2019.
What exactly is CRISPR?
Our genes are coded with instructions for making proteins. The “letters” in our DNA are four chemical building blocks—adenosine, cytosine, guanine, and thymine, known simply as A, C, G, and T, arranged in a double helix structure of 6 billion building blocks, in a very specific order.
But a single error in that sequence can be deadly; the reason for over 10,000 inherited diseases is a single defective gene; may of these diseases are incurable, such as cystic fibrosis, haemophilia, muscular dystrophy, and Tay-Sachs.
In sickle cell disease, for example, one building block—an A—is mistakenly converted to T in a gene that makes haemoglobin.
“It’s like having one typo in a book containing 6 billion letters,” says Matthew Porteus, MD, PhD, an associate professor of paediatrics at Stanford, and a scientific co-founder and advisory board member of CRISPR Therapeutics, a company that uses CRISPR technology.
“We spent six years trying to repair that one mutation using older gene-editing technologies, but with CRISPR, we finally had a tool that was much easier to use and far more efficient.”
Cut and paste
Scientists’ confidence in CRISPR, a technology that allows scientists to make very precise modifications to DNA, burns bright.
CRISPR “gives us a way to ultimately control the evolution of any organism—including ourselves. It is a profound thing. Human beings have now learned enough about our own genetic code that we can change it at will,”
Jennifer Doudna, one of the inventors of CRISPR genome-editing technology, told Quanta magazine. “It’s kind of crazy to think about.”
CRISPR is essentially a method by which problem-causing genes are targeted, deleted, repaired and reinserted, in hopes that it will destroy the cancerous cells.
Unlike traditional gene therapy, where viruses are used to insert new genes into infected cells, CRISPR treatments directly make changes in the DNA, using targeted molecular tools.
Some have billed the gene-editing technique as revolutionary as it has the potential to cure (perhaps even prevent) many diseases, including ones that require regular transfusion, by simply fixing the mutation. CRISPR could also enable scientists to repair genetic defects or use genetically modified human cells as therapies.
Ethical concerns cast a cloud
With scientists finally taking tangible first steps to make that dream a reality, it is equally important to draw the line when confronted with the unlimited possibilities CRISPR presents us with.
First, let’s talk about what Chinese scientist He Jiankui did and how his actions have led to calls for a moratorium on gene-editing of heritable traits.
He, who teaches at the Southern University of Science and Technology in Shenzhen, China, had used CRISPR to edit genes in human embryos, altering the DNA of twin baby girls, reportedly to make them immune to HIV.
That means the changes he made would be passed down for generations to come. He crossed a line that genetic engineers had respected for decades and reaffirmed in February 2019. He also did it before most scientists thought it was safe to try CRISPR-Cas9 technology in the womb.
Although the experimental embryos were not viable, some worried that fertility clinics would start using CRISPR to genetically engineer children with traits parents might want, like making them stronger, taller or smarter.
Doudna, who had been one of the first to criticise the move as premature and unnecessary, was also the one to nominate He for the TIME citation. She did it to draw the international scientific community’s attention to develop better guidelines for permissible genome-editing in humans. According to her, He’s fateful decision is one of the most shocking misapplications of any scientific tool in our history.
The year ahead in CRISPR research
Nonetheless, she is optimistic that the gene-editing tool she co-developed will continue to empower basic biological understanding; Doudna, however, does not want to perpetuate obliviousness while experimenting with the technology.
Instead, she wants the scientific community to focus on how to safely apply genome-editing to cure genetic diseases, fight cancer, accelerate drug development, create transplant organs, and develop more nutritious crops.
Several other human trials of CRISPR are starting or are set to start in the US, Canada, and Europe to test CRISPR’s efficacy in treating various diseases. Even in these carefully monitored medical trials, the fear of unintended consequences lingers.
At UPenn, treatment would involve removing immune system cells from 18 patients, genetically modifying them in the lab and infusing the modified cells back into the body. These modified cells are hoped to target and destroy cancer cells. “Findings from this research study will be shared at an appropriate time via medical meeting presentation or peer-reviewed publication,” a university spokesperson wrote in an email to NPR.
Other trials sponsored by CRISPR Therapeutics of Cambridge and Vertex Pharmaceuticals of Boston are designed to treat sickle cell disease around the country, and beta thalassemia (BT). The first BT patient was recently treated with CRISPR’d blood cells in Germany, Toronto, and London.
Another noteworthy study is trying to treat an inherited form of blindness known as Leber congenital amaurosis; for this, scientists will, in a first, use CRISPR to edit genes while they are inside the human body.
What can go wrong with CRISPR?
In utero editing, for example, in the process of curing a child, CRISPR could potentially expose a healthy mother to risks, including dangerous immune reactions. As it takes place in her fallopian tubes, it can also make changes to other unfertilised eggs.
The process has been found to be the most effective in case of disorders like sickle cell disease while promising breakthrough treatments for certain kinds of cancer. Other inherited diseases, such as cystic fibrosis and muscular dystrophy, may be more difficult to treat because they affect different cell types in different organs, claims this study. Moreover, as Stanford bioethicist Dr Mildred Cho worries, even if CRISPR proves successful, the financial cost will be prohibitive for many patients.
Her colleague Hank Greely, a professor of law, says, “People are most worried about enhancement, using CRISPR to give babies superpowers,” making it a tool to perpetuate further ableism. He also argues against gene-editing in the womb. “Rather than changing genes in an embryo, you just select an embryo that doesn’t have the dangerous genes, using preimplantation genetic diagnosis.”
He also airs fears that CRISPR may be weaponised by turning ordinary cowpox virus into smallpox, so there may be some merit in the fact that the Obama administration listed gene-editing as one of the four biggest threats to the US and humankind in general. What’s needed, Greely says, are well-thought-out, well-enforced federal regulations that make it difficult for CRISPR to be misused accidentally or intentionally.
Thus, it is not enough to ensure that gene-editing doesn’t raise dystopian fears about re-engineering the human race or is exploited to create designer babies. It is also essential to refrain from regarding CRISPR as the panacea for every genetic disorder out there.
Prarthana Mitra is a Staff Writer at Qrius.
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