WORK ON EDITING HUMAN GENES MAKING STRIDES
Technology could reverse incurable inherited diseases, but critics fear designer baby abuses
Everyone has genetic traits they wish they hadn’t inherited. Some, such as diseases and disabilities, are serious. Others are matters of preference, like hair colour or height. But at some point, we’ve all looked in a mirror and wished we could shut off a gene or two. In a lab in a Toronto hospital, scientists are working on doing just that.
Researchers at the Hospital for Sick Children used a new gene editing tool called CRISPR-Cas9 to edit the embryonic cells of mice and give them the same mutation as Gavriel Rosenfeld, a teenager from the U.K. with a rare form of muscular dystrophy. Soon the researchers plan to inject the mice with a virus that contains the CRISPR-Cas9 guide, which will find and remove the duplicated portion of the gene.
If everything goes according to plan, lead investigator Ronald Cohn hopes to test the treatment on Rosenfeld in two to four years. And if that works, everything changes. On the plus side, incurable diseases could be better treated and maybe even reversed. But critics say the technology could also lead to designer babies and other abuses.
For Cohn, he imagines a future where health-care professionals could use CRISPR (which stands for clustered regularly interspaced short palindromic repeats) to cure inherited diseases with custom treatments.
The technology is only a few years old, but advances are happening fast and investors and major corporations are paying attention. CRISPR startups and research projects have already attracted more than US$1 billion in investment from venture capitalists, major pharmaceutical companies and even agricultural giant E. I. du Pont de Nemours and Co. (DuPont).
Often compared to the find-and-replace function in a word processor, CRISPR makes gene editing cheap and precise. The technology has the potential to solve a wide range of humanity’s toughest problems, from cancer to peanut allergies — and make billions of dollars for those who got in early.
A report from research firm MarketsandMarkets predicts the gene editing market will be worth US$3.5 billion by 2019. Intellia Therapeutics Inc. and Editas Medicine Inc., two companies focused on CRISPR technology that went public in 2016, already have a combined market cap of about US$1.5 billion.
But CRISPR also has the potential to cause great harm. Most countries, including Canada, have banned gene editing research involving human embryos or changes to genetic material that would be passed down to future generations, which could result in irreversible unintended consequences since there is certainly a lot of money to be made in the CRISPR gold rush.
Like the guy with an X-ray and an industrial drill who is going to find gold a lot faster than the one standing in a stream with a sieve, CRISPR isn’t the first gene editing tool. But it’s the cheapest, most precise and most promising.
Scientists in 2012 discovered that a system bacteria used to fend off viruses can also be used to make a cut-and-paste tool to change DNA sequences. Other scientists started using the tool, leading to a flood of breakthroughs over the past four years.
The technology is challenging conventional standards about how to perform biotech research. Developing a new drug normally involves clinical trials on hundreds of people, but what if the drug is designed to edit a genetic duplication that’s only present in one person in the world? That’s the challenge Cohn faces at SickKids. As regulations and standards are created, he believes it’s important to be both flexible and cautious.
“This is going to require an open mind and a willingness to engage in conversation,” Cohn said. “But when it comes to safety, we have to be ultra-conservative.”
Researchers have yet to test CRISPR on a human subject, with a cancer-related clinical trial funded by tech billionaire Sean Parker expected to be the first.
Of course, scientists might find it doesn’t work as well on humans as it did in a petri dish. The technique might cause new mutations in the process of correcting the one it’s trying to fix. It could also miss the intended target and edit the wrong part of a gene, or be rejected by the patient’s immune system.
Yet the excitement over CRISPR has been compared to the hype over stem cell therapies, which have been similarly touted as the solution to a wide variety of ailments.
In the U.S., unscrupulous entrepreneurs have taken advantage of people’s unwillingness to wait for science to catch up to expectations by opening clinics offering expensive, dubious treatments.
But Michael Schmidt, an analyst at Leerink Partners LLC who covers the CRISPR genome editing company Intellia Therapeutics Inc., said he doesn’t think hype alone can explain the rush of interest.
Big names such as AstraZeneca PLC, Novartis AG, Google Ventures and Bill Gates wouldn’t be pouring money into CRISPR research and startups if it didn’t hold serious promise, he said.
“The commercial potential for gene editing is huge,” he said. “It’s an incredibly exciting technology.”
The excitement has already led to some contentiousness, such as a patent dispute between scientists at the University of California at Berkeley and the Broad Institute of MIT and Harvard who each claim to have invented the technology. Companies licensing technology from the party that ends up losing could be wasting their money.
Schmidt said he thinks a settlement or cross-licensing agreement is more likely than a decision that divides the CRISPR industry into winners and losers.
“It’s not one company, one winner takes all. I think there is definitely space for multiple winners.”
Agricultural giant DuPont wants to be one of those winners. In October, the company announced a partnership with Caribou Biosciences Inc., a startup that’s affiliated with one of the parties staking a patent claim on CRISPR.
DuPont hopes to make — and profit from — the first ever CRISPR-engineered crop. It’s developing a hybrid variety of corn, aiming to have it ready for farmers to plant by 2021.
The CRISPR-engineered corn promises bigger yields and a higher starch content, but there’s another reason the technology has piqued DuPont’s interest. The U.S. Department of Agriculture has taken
The commercial potential for gene editing is huge. It’s an incredibly exciting technology. It’s not one company, one winner takes all. I think there is definitely space for multiple winners.
the position that CRISPR editing falls outside scope of its genetically modified food regulations, since it doesn’t involve introducing genes from another plant or animal.
There has been far more backlash against genetically modified food than the possibility of genetically modified humans, said Udo Schuklenk, Ontario research chair in bioethics at Queen’s University in Kingston, Ont.
If CRISPR is used irresponsibly, it’s possible to imagine all sorts of extreme scenarios: parents creating designer babies; Hitler-like figures wiping out entire races; the entire Jurassic Park franchise coming to life.
But Schuklenk said there’s more reason to be excited than fearful, noting the ban on editing embryos and genetic material passed down to future generations takes care of the truly nightmarish possibilities. “These things are not as dangerous as people think they are,” he said.
A much more pressing ethical dilemma is how to price the type of individualized treatments being researched at SickKids, Schuklenk said. If a company works with Cohn to develop custom injections that cure rare inherited diseases, should that company be allowed to charge whatever people will pay to save their own lives?