Is gene editing moving too fast? CRISPR scientist raises concerns.

The gene editing technology CRISPR–Cas9 may be Science's 2015 Breakthrough of the Year, but the journey to this point has been fraught with controversy and ethical debates. And it's long from over.

Many scientific breakthroughs are heralded with optimistic applause. However, the advent of CRISPR–Cas9, a gene editing tool that has been employed in a wide array of research ranging from of invasive agricultural pest control to disease resistance in plants and humans, has raised just as many concerns as it has hopes.

On the one hand, medical researchers say, the technology could potentially be a game-changer in stopping hereditary disease. But ethicists worry that such breakthroughs could come with some hefty, unforseen consequences. And others have raised concerns that CRISPR–Cas9 could be used for nefarious purposes such as biological warfare.

For the scientists involved, it may feel like discussion of ethics can't keep up with the fast pace of genome-editing research in recent years.

Jennifer Doudna, a biochemist involved in developing CRISPR–Cas9, certainly felt a disconnect between public knowledge of the issue and the advances happening in labs across the globe.

The lack of discussion even among scientists was concerning, Dr. Doudna writes an a commentary article for Nature News about her experiences since developing CRISPR–Cas9.

"By mid-2014, I was concerned that CRISPR–Cas9 would be used in a way that was either dangerous, or perceived to be dangerous, before scientists had communicated enough about it to the wider world. I wouldn't have blamed my neighbours or friends for saying, 'All this was going on and you didn't tell us about it?'" she writes.

The ethical dilemma centers around how much humans should be able to alter their own traits, the dangers of employing such a technique on human cells and other controversial questions.

Doudna has lost a lot of sleep over the ethical dilemmas. "By the spring of 2014, I was regularly lying awake at night wondering whether I could justifiably stay out of an ethical storm that was brewing around a technology I had helped to create," she writes. 

Even before 2012 was over, when Doudna and colleagues first published the genome-editing technique, at last six scientific papers had been submitted to various journals suggesting various possible uses of the technology, Doudna writes. By the end of 2014, the flood of reports of possible uses for CRISPR–Cas9 had yielded work on crop resistance to pests and mutations associated with disease in mice. One team of researchers even used the technique to alter the genome of cynomolgus monkey embryos, an animal with genetics remarkably similar to humans.

Soon after that February 2014 paper, Doudna found herself wondering, "'How long will it be before someone tries this in humans?'" over breakfast to her husband.

In April 2015, Doudna's pondering became reality. A Chinese research team used CRISPR–Cas9 to snip DNA in defective human embryos in order to correct a genetic defect. 

Although that research suggests potential therapeutic applications for the gene-editing technology, the paper does highlight the risks. Only a few of the embryos actually had the intended alterations to the genome. Others had changes in other places, which could be a dangerous result.

"That type of use of the technology needs to be on hold pending a broader societal discussion of the scientific and ethical issues surrounding such use," Doudna wrote in an e-mail to the Monitor's Pete Spotts at the time.

According to her Nature News account, Doudna had already begin those broader discussions. 

"Towards the end of 2014, my unease outweighed my reluctance to step into a more public discussion. It was clear that governments, regulators and others were unaware of the breakneck pace of genome-editing research. Who besides the scientists using the technique would be able to lead an open conversation about its repercussions?" she writes.

Doudna started with a one-day conference in January 2015, gathering 18 scientists, ethicists and others. That meeting yielded a perspective article in Science advising researchers to slow down, engage in a broader discussion, and set some sort of standards.

"Given these rapid developments, it would be wise to begin a discussion that bridges the research community, relevant industries, medical centers, regulatory bodies, and the public to explore responsible uses of this technology," the authors write. 

They go on to say, "It is critical to implement appropriate and standardized benchmarking methods to determine the frequency of off-target effects and to assess the physiology of cells and tissues that have undergone genome editing. At present, the potential safety and efficacy issues arising from the use of this technology must be thoroughly investigated and understood before any attempts at human engineering are sanctioned, if ever, for clinical testing."

Over the past year, Doudna has given many talks on the topic, engaging people across the country and globe in the discussion. 

"This year has been intense — and intensely fascinating. At times I have wished that I could step off the merry-go-round, just for a few minutes, to process everything," she writes. 

But Doudna and others face an ongoing controversial dialogue as research on CRISPR–Cas9 continues. She writes, "Almost three years after a colleague warned me that a “tidal wave” of research, discussion and debate involving CRISPR–Cas9 was coming, I still don't know when the wave will crest."

See the full article by Jennifer Doudna at: http://www.nature.com/news/genome-editing-revolution-my-whirlwind-year-with-crispr-1.19063.