gene editing

Designer babies. The term means many things to many people. To some it means kids only dressed in Gucci.

Some say that by doing pre-implantation genetic screening, we are already living in the age of designer babies. Others have been holding out for that time when humans edit their own germline offering the new progeny not only disease repair, but also enhancements. It's also argued there’s a third category in the middle there somewhere, a protection against disease in the future. That’s what He Jiankui attempted.

We don’t know yet if Jiankui was successful. But we know that if he wasn’t, he showed us that the next success is just around the corner. And the next.

“This story is getting more sci-fi every minute. Michael Crichton couldn’t have made this stuff up,” tweeted Eric Topol of the Scripps Institute as the He Jiankui saga unfolded.

“That tweet is in many ways wrong. Science fiction of course can imagine it. Michael Crichton could and did make it up. But other science fiction writers who are more skillful than Michael Crichton have been talking about messing with germline for a long time now."

That’s today’s guest, award winning sci-fi author Kim Stanley Robinson (The Mars Trilogy, Red Moon) at the outset of today’s show. What sets Stan (as he's called) apart from many of those other sci-fi writers, is that he doesn’t think it practical to enhance humans genetically. He’s thought about it his entire career, and like going faster than the speed of light, it’s one of those impractical barriers, he says.

"What would you change? How would you know that was going to make it better without running human experimentation which can't be done. It's not just ethics, it's practicality. We wouldn't know what to do to make ourselves smarter or stronger."

Wait. Did you hear what I heard?! This is a sci-fi writer who specializes in thinking into the future, and he doesn’t think humans can be enhanced!

Well, either he has some mighty big convincing to do, or this was the biggest bomb of an interview ever. I mean, come on, of course humans can be enhanced.

Right?

It’s our first show back after the summer break, and nothing has got us all buzzing about genomics again like a polygenic risk score. It even has Laura Hercher talking about the Human Genome Project doing some delivering, god forbid.

CRISPR has had a rough summer. But still . . . it is CRISPR.

Is Burning Man still cool, we were asked last weekend. Don't know. Don't care. We asked back, is 23andMe still cool?

Then we found sort of an answer in an old rag purchased last week down at the end of the street: "They rode into town on the cool train. They've been shoot'n it up out here in the Wild West makin' trouble for the sheriff. But now they've become one of the big corporations who hire their own guards to watch o'er their stage coach. They're makin' woopy with the big guys."

Surely it's talking about 23andMe.

Laura says 23andMe's heyday is past. Nathan says, no, their best is yet to come. And then he immediately gets excited about Neanderthals and Denisovan's having a love child 50,000 years ago.

Non sequitur?

Some stocks are up on news of big biotech mergers, but others are down on hearing of the latest difficulties of gene therapy. One thing’s for sure—blood diseases are where it’s at.

Speaking of the latest difficulties, we start our January review by going back to that paper out of Stanford about a new obstacle to using CRISPR as a new drug platform. It’s called the human immune system. Major roadblock or small warning light?

“Smart people have been thinking about the wrinkles in CRISPR and Cas9 for a long time. This is one of them, and it’s not going to stop the technology from being used well in people in the long run,” says Nathan.

Neither of our commenters are happy with Luxturna’s pricing of $425,000 per eye. But who is happy with drug pricing these days? How are drug companies supposed to recoup their investment on roughly 2,000 patients?

“We’re gonna have to price these drugs based on the whole platform, but also we’ll have to look at creative things like . . . how successful it is,” says Laura.

Last, but not least, we finish up with the new paper out in Nature showing the sequencing of a reference genome using the MinION handheld nanopore sequencer. Laura says it’s a snooze, but then she comes around.

Sharon Begley joins us for our last show of the year to look back over some of the year’s top stories. She’s the senior science writer at STAT News where she covers genetics, cancer, neuroscience and other fields of biomedical research. Prior to joining STAT, Sharon was the senior health and science correspondent at Reuters, the science columnist at the Wall Street Journal, and the science editor at Newsweek.

If you’re in genomics, you’ve no doubt found yourself reading one of Sharon’s columns. Her range is astonishing, her depth shows years of insider knowledge, and her output prodigious. She managed to write an article on George Church this year that no one had written before. Not easy.

Sharon says her audience has a big industry component and certainly includes people with special interest in the life sciences but it’s also for “ordinary human beings . . . people who go to doctors, who’s friends and loved ones get sick.” That Sharon’s articles can be read by anyone, but are of interest to insiders, makes her a great guest here on the program to see how many of our stories make it out to a larger audience. For instance, in this year when 23andMe’s test rivaled the InstantPot for top seller at Amazon, what does the average person think of genomics in 2017?

In answer, Sharon says that the typical American tends to be a genetic determinist, gullible for any genetic association that comes along--this despite being overwhelmingly religious. Does that mean she proactively takes on the role of pushing back with skepticism?

It didn’t take long to come up with our lead story for November’s month in review show. Looking at the pictures of the boy in Germany playing soccer after successful treatment of his rare skin disease is just the kind of images we had in mind when we first heard of stem cell therapies.

The bulk of our discussion moves on to the incredible bullish drive of direct to consumer testing this year, sparked by a decrease in sequencing costs and a favorable political climate. However, this month FDA commissioner, Scott Gottlieb, showed his cards on the topic of DTC testing as well as LDTs in general, surprising many of us.

Laura says the FDA announcement reflects a “sea change” in that the FDA plans to regulate not “test by test, but the testers.”

Nathan cautions that this policy will encourage companies who already have their FDA clearance based on some sound diagnostic tests to then “down the line put out a test that is much more speculative, based on shakier science.” He says this will privilege the bigger companies who are already established in the space over small innovative companies.

It’s November’s genomic headlines with Nathan and Laura.

To honor Laura's pentametric thirst,

We write the summary today in verse.

Was it a quake that had no epicenter,

That silly paper out by J. Craig Venter?

And after years of silencing the market

Has RNAi at last knocked out its target?

Then Nathan gives to yuppies devil's choice.

Which one libs: gluten dough or GMOs?

Back from summer vacation, Nathan and Laura are smoking hot as they look back over some exciting headlines.

The summer boiled over with plenty to talk about, but it was just this week that delivered most of the news for our discussion today. Novartis’ gene therapy based on CAR-T technology was approved Wednesday, making it the first gene therapy to be approved ever in the US. Analysts will be trying to figure out how high high is when it comes to the price tag, but Nathan and Laura explain why this therapy is a big deal for patients.

As for the first gene editing of embryos in the US that happened earlier in August? Nathan says, yes, it’s a first, but the big story is how "strikingly reliable the CRISPR edit is in germline vs the rest of the body."

Finally, we heard a few days ago that genetic testing provider, Invitae (recently featured here on the program) had sent out a large batch of false negative tests. Laura, a genetic counselor, says that in the absence of FDA regulation the system is operating on trust.

“And I want to say,” she adds, “ I trust Invitae. They’re a good lab, and I think they’re handling this well.”

The challenge for the first ever in-human gene editing trial, according to today’s guest, is with the delivery to the body.

“At the moment, the easiest place to deliver your gene or genome editing is to the liver, using AAV which are viruses that seek out and go to the liver cells," says Sandy Macrae, the CEO of Sangamo Therapeutics.

Sangamo is known for two things: They have pioneered the commercialization of an older gene editing technology called Zinc Fingers. And they have done a lot of work in the area of HIV.

Today, Sangamo is enrolling patients in a new trial which they say will be the first "in-vivo" trial using their Zinc Fingers for patients with hemophilia B, Hunter syndrome, and Hurler syndrome. The former gene editing work with the T cells of HIV patients, Sandy says, was done “ex-vivo”, or outside the body.

So why is Sangamo still using Zinc Fingers in the age of CRISPR? Sandy says that the older technology is much better developed for medical applications and is safer. The company has been able to get their off target effects to below the level of detection.

“When I was doing my postdoc, I would have used CRISPR. It’s better if you’re just wanting an easy experiment that isn’t about making a medicine but just getting a quick answer,” he says.

Because Sangamo has been the sole commercial developer of Zinc Fingers with not a lot of intellectual property dispute, the technology didn’t make the big PR splash that CRISPR has—nor, at the same time, did it generate all the fear.

We finish the interview with a question about what was the result of all Sangamo's work in HIV over the years.