“CRISPR” is a powerful gene-editing technology that is revolutionizing biomedical research. It allows researchers to quickly, and cheaply, target and edit genes at precise locations along the lengthy DNA chains of organisms. The big hope is that CRISPR (pronounced “crisper”) could help researchers correct mutations in the human genome, effectively treating genetic diseases. But some fear CRISPR might lead to the creation of designer babies, or unleash consequences we cannot predict.
“Think of it like editing text,” says Dr. Janet Rossant, a researcher who uses CRISPR in her lab at Toronto’s Hospital for Sick Children. “You can cursor in and you delete a few words, paste in a little sentence. And that is what people can now do in the genome. You can do it in bacteria, you can do it plants, you can do it in animals, you can do it in human cells.”
The hopes and fears surrounding CRISPR are explored in the Nature of Things documentary The Genetic Revolution.
Editing human genes is restricted in Canada
One of the biggest controversies of CRISPR is the possibility that it might be used to make permanent alterations in human genes that are capable of being passed on to children. For example, genetically altered babies could be produced that grow up to be faster, more powerful athletes. But not in Canada. Under the Assisted Human Reproduction Act of 2004, editing the human genome is punishable by up to ten years in prison.
The law makes it illegal for researchers to alter the human genome, in any way that could be inherited. For example, there is nothing stopping an adult from taking skin or muscle cells from their body, altering them through gene editing (perhaps to fix a protein deficiency), and replacing them. Where the law takes issue however, are any changes to “germ line” cells — those that could pass on edits to a future human. Namely, eggs or sperm.
Recently, Canadian researchers, working through an organization called the Stem Cell Network, have been calling for the federal government to change the law — not because they want to make designer babies, but because they want to learn more about human reproduction, embryo development and gene function.
“What [researchers] want to do with human embryos at this point is modify them and see what happens in the very early stages, when you can still grow the embryo in a petri dish — but you can’t do that in Canada,” says Rossant. “The Act basically says even if you are not going to put that back into a mother, into the uterus, you cannot even try it because it might have the potential to modify the [inheritable] germ line. That is the interpretation.”
In Rossant’s lab, research is focused on the genetic control of normal and abnormal development in the early mouse embryos — which is also perfectly legal. One of her team’s major goals is to aid human reproduction through discoveries made in mouse embryos, such as improving the chances of fertilized eggs implanting in a mother’s uterus.
Using CRISPR and other gene editing techniques, Rossant’s team have made several breakthroughs. “We learn a lot from the mouse,” says Rossant, “but what we find is that not everything is the same in humans. If we could modify and explore the genetic functions in the human embryo, we would have more information about how to improve in vitro fertilization, how to understand why humans have a lot of early pregnancy loss, and just understand fundamentals of how we develop.”
Rossant says investigating the differences between similar gene systems in mouse and human embryos is important because the same processes may take place at different times of development in the two species.
“It is a real potential difference” between mouse and human embryos, says Rossant. This difference could be investigated by CRISPR-enabled editing of the corresponding genes in a human embryo, but because of the Canadian law, she thinks it will have to happen in labs in other countries where researchers work under the approval of regulatory bodies rather than under an inflexible law that is “carved in stone.”
Ethicist: Canada's law blocks people's right to benefit from scientific discoveries
“The criminal law is just like a hammer,” says Stem Cell Network member Dr. Bartha Knoppers, “It is not the way science should be governed.” Knoppers is director of the Centre of Genomics and Policy at McGill University. A lawyer and bioethicist, she helped draft UNESCO’s Universal Declaration on the Human Genome and Human Rights. She argues that Canada’s law violates the UN’s Universal Declaration of Human Rights because it blocks people’s right to benefit from scientific discoveries.
In other countries, the law does not have such a tight grip on using gene editing. For example, fertility specialist John Zhang travelled to Mexico to successfully implant a human embryo with the combined DNA of three parents — something that remains illegal in many countries, including the U.S., where Zhang is based.
“We would favour a more regulatory approach,’ says Knoppers. In France or the United Kingdom, government agencies examine emerging technologies for their quality, safety and impact on human rights before restrictions are put in place. Knoppers believes “a more responsive system that reflects not only changes in technology but also reflects changes in society” could be used to determine the use of specific research methods, such as CRISPR with human germ lines.
Despite the law, Rossant says she hasn’t heard of any Canadian researchers leaving the country to pursue this research, or simply defying the law. “Certainly, there are no rogues in Canada because of the criminal law,” says Rossant. “I don’t think anybody would be so foolish.”
Rossant and other Canadian scientists continue to push for the ability to use CRISPR in human embryos, as a way to understand and prevent genetic diseases like cystic fibrosis or Huntington’s disease. However, there are still many safety efficiency considerations that need to be ironed out before we start seeing this technology in Canadian labs and clinics. “CRISPR gene editing is never one hundred percent efficient. It always has the risk of other un-targeted mutations and you certainly would not want to pass on unwanted effects into the next generation.”
Watch The Genetic Revolution on The Nature of Things.