CRISPR-Cas9: understanding gene editing, for the rest of us

Everybody’s talking about this new gene-editing technology borrowed from bacteria—but is there any way to make it understandable to normal folks?

Let’s try.

This is new stuff. It matured to usefulness only in the past three or four years—the original paper was just published in 2012 It lays out the technology folks casually call CRISPR-Cas9.

 

The system lets laboratories essentially cut-and-paste genetic material, with accuracy previously unattainable. Sometimes it just lets you go in and flick a switch, turning something off. It is based on the immune system used by some bacteria, as well as most of the life forms called archaea.

The technique lets researchers select a very specific spot in DNA, and snip it open to remove or insert something. The cell then naturally repairs itself.

The difference from the old genetic engineering techniques, is essentially like the difference between doing archaeology with a backhoe or with tweezers. It's like using a word processor to cut-and-paste instead of paper, glue and scissors.

FOR STARTERS

It’s useful to know a tiny bit about DNA and RNA—the genetic components of anything that is alive. 

DNA is the basic blueprint. In life, it is what dictates whether something will be a temperate fruit tree, or an edible mushroom, or an ocelot or a human.

RNA carries out the instructions of the DNA. 

If it were a football game, DNA would be the rulebook and RNA would be the players.

Is that too strange an analogy? How about this: DNA is the plan; RNA carries out the plan.

BACTERIA DEFEND THEMSELVES

So, researchers in the 1980s noticed that in some bacterial DNA, they were occasionally seeing a repeating pattern. There were sections where a certain bit of DNA would repeat between random other sections, like the apples in this example: Apple, orange, apple, pear, apple, grapefruit, apple, banana …

They called it CRISPR, for Clustered Regularly-Interspaced Short Palindromic Repeats. It was an interesting pattern, but what did it mean?

A couple of researchers figured out that the repeating apples were actually pieces of DNA of a virus that was attacking the bacteria. Those apple pieces would make RNA that would launch and attach itself onto the attacking virus.

Meanwhile, the intervening DNA bits—the orange, pear, grapefruit, banana—would follow up and work with a protein (called Cas9) to go and split apart the virus DNA. 

Thus, the virus was inactivated. And the bacterium was cured from viral disease. Cool stuff.

The immune system of a bacterium acted like a genetic pair of scissors with its own GPS. The GPS gets it to a specific location, and then the scissors snip the DNA open.

Another way to think about it: the bacterium has the ability to recognize a new enemy, and can send out its genetic ninja teams to attack the enemy.

THE LIGHT COMES ON

As they studied it, scientists realized this was a potential tool kit for adjusting genetics--that they could adapt this system to pluck a piece out of DNA changing how the organism works. And they also figured out how to insert a new piece of DNA if necessary, before the cell healed the cut ends.

A genetic Swiss army knife.

A pretty clear explanation of all this is here . 

Here’s a video with some interesting graphics that discusses the system. 

And here is a video of one of the discoverers, Jennifer Doudna, which is a little tougher to understand, but she’s a key player. There are plenty of YouTube videos of her describing the process.

And how important is it? Well, Doudna and Charpentier are getting really famous. They have been named among Time Magazine’s 100 most influential people in the world. They’ve picked up the $500,000 Gruber Genetics Prize and the $3-million Breakthrough Prize in Life Sciences. They just missed this year's Nobel Prize, but they might get it next year.

APPLICATIONS

The world moves forward on the CRISPR front with amazing speed. 

The technology is being used to amend tobacco DNA to produce anti-cancer drugs. There’s work to use CRISPR to turn off genes in cancer cells, effectively killing the cancer. In crops, changes can be so precise that they essentially add nothing to the genome, but still have a favorable effect.

In this paper, from last month, co-author Wendy Harwood of England’s John Innes Centre, said you can make just the tiniest change to turn off a particular feature. 

“Stopping particular genes from working is one way to develop disease resistant crops, for example with resistance to mildew or to produce crops without unwanted compounds including toxins.

“The final plants produced in this way have no additional DNA inserted so they are essentially the same as plants with naturally occurring changes to genes or plants that have been bred using conventional mutation breeding methods,” Harwood said.

WHOA. A NOTE OF CAUTION

Doudna, of the University of California, who worked with Emmanuelle Charpentier of the Max Planck Institute for Infection Biology, in making the discovery, talks here about some of the ethical implications of their finding.

Well, yes. You might be able to cure cancer and cystic fibrosis and sickle-cell anemia and maybe HIV. And you might be able to make new medicines to cure other diseases. And you might be able to engineer crops to fight disease without pesticides. And maybe make mosquitoes that can’t transmit dengue and malaria. 

But you might also bioengineer humans. You want a baby boy who will grow to 6-foot-2, with an IQ of 145, curly black hair and green eyes, and can run a 40-yard dash faster than Usain Bolt? We might be able to engineer that.

Maybe that’s good, but, um, maybe not. Remember the Nazis and eugenics?

Doudna and her team are thrilled about the possibilities of their technology, but wary about some of the implications.

She has called for a “global pause” in redesigning human embryos while we think about those implications.

John Travis, of the journal Science, wrote earlier this month about the National Academy of Science’s International Summit on Human Gene Editing. 

He quotes a mother who lost a child to genetic disease: “"If you have the skills and the knowledge to eliminate these diseases, then freakin' do it.”

But genetic changes are permanent, and “before we make permanent changes to the human gene pool, we should exercise considerable caution,” said another participant at the summit.

Most of the concern expressed to date about CRISPR involves its use in engineering human genetics, not so much other life forms. The Center for Genetics and Society and Friends of the Earth have issued a position statement opposing the use of the technology in humans.

© Jan TenBruggencate 2015