August 10, 2017

Harder, Better, Faster, CRISPR

The dawn of a new age flashed across the news this summer – dateline Oregon: scientists from the US, China and South Korea together had tweaked the genes of a living human embryo to correct ...

The dawn of a new age flashed across the news this summer – dateline Oregon: scientists from the US, China and South Korea together had tweaked the genes of a living human embryo to correct an inherited flaw that has caused heart failure and sudden death in a lot of young athletes.  And so, finally, suddenly we enter the CRISPR age in bio-technology, when human science takes charge of the human genetic lifeline, to fix it here, tune it there, perhaps re-tailor it in useful ways.  We could be doing it soon with hundred-dollar DIY kits, at home. The Chinese are doing it, too.

As the pioneer in the CRISPR breakthrough Jennifer Doudna says: we have the ability now to edit the DNA of every living person and future generations, too.  “In essence,” Doudna writes, it means the power “to direct the evolution of our own species.”  “Unprecedented in the history of life on earth,” she adds, “beyond our comprehension,” and raising “impossible but essential” questions for which as individuals and as a species, we are “woefully unprepared.”  Jennifer Doudna’s colleague at UC-Berkeley, Michael Eisen starts off our conversation this week. He’s a genetic biologist — who works mainly on fruit flies — and a member of the Berkeley team that epically battled against the MIT-Harvard-Broad Institute faction, over patent claims on CRISPR and its applications.  Online, Michael Eisen has eloquently argued against the whole idea of patenting a public resource.

 

Ben Mezrich who dreamed up “The Social Network” about the making of Facebook and the IT billionaire class. He has a new block-buster in book form, soon to be a movie called “Woolly,” about the mammoth last seen as the Ice Age melted down. The human hero of the story is George Church —  the giant Harvard biologist who means to revive the woolly mammoth with its DNA and his own CRISPR tools. Imagine Indiana Jones in Jurassic Park. 

Antonio Regalado is a key journalist on the CRISPR beat, a minute-to-minute reporter online for the Tech Review, which is owned and managed by MIT.  Among the levels of his CRISPR coverage: the science, the people who do it, the motivations and the money. He tells us:

People are getting rich. In the case of the CRISPR companies, I can see how many shares the scientific founders from around Cambridge have and the amounts are large: eight, nine million, ten million dollars. And yet when I interact with the scientists themselves—George Church, for instance with his sort of lumpy shoes, you know, does money motivate him? He doesn’t act like it. So I think fundamentally I’ve got to believe that people are motivated by the fact that they’re discovering stuff and the glory and that is worth more than the money. But I might be naive.

There are agitated voices inside biology and outside it who want to be heard in the CRISPR conversation, and we invited two of them to speak up. Robert Pogue Harrison is humanities professor, a Dante specialist, at Stanford who podcasts on a great variety of civilized subjects.  Earlier this summer when the Templeton Foundation brought the superstars of CRISPR world to a weekend retreat in California, Robert Harrison was invited to sit in alongside George Church of Harvard and Jennifer Doudna of Berkeley, and speak for the long philosophical and moral view of a scientific revolution. On the phone this week Professor Harrison told us he came away from that meeting more perturbed than he went in. What struck him most was the widespread sanguinity among the scientists.  Under the azure Californian sky, CRISPR-potentiated nightmare scenarios seemed impossible to imagine:

My sense was that most of the people there felt or at least pretended to feel assured that as long as we all remain reasonable as long as we all put our minds together and make informed decisions about CRISPR’s use that everything’s going to be fine. I would have preferred more discussion of the potentially destructive and even catastrophic risks that such a technology introduces into the biosphere.

 

Stephanie Mitchell/Harvard University News Office

Ting Wu leads a genetic biology lab at the Harvard Medical School. And she’s married to her most famous colleague George Church, with whom she has had running debates morning and night for most of 30 years.  In her office this week we asked her to draw some lines she argues over with her husband. She told us: “I am not a line drawer.”  Rather, she’s more of a potentialist — a firm believer that the happiness of future descendents will be largely determined by our willingness to allow for a panoply of personal genetic expressions.

See a full transcript of this show on Medium.

Podcast • August 11, 2016

Apocalypse Now?, Part 2: A Remade Man

Our apocalypse series began one week ago with one grim vision of the future. What if our machines managed to take control of their own code? If they began to self-regulate, even self-replicate? It’s an imaginable scenario—but ...

Our apocalypse series began one week ago with one grim vision of the future. What if our machines managed to take control of their own code? If they began to self-regulate, even self-replicate? It’s an imaginable scenario—but one that’s still far off in the future.

But it sounds familiar in the biotech capital of Boston/Cambridge. Messing with our own code: that’s exactly what we human machines are up to, right now and more and more, in labs across this city and around the world. Thanks to a number of scientific breakthroughs—in particular, the editing technique known as CRISPR/Cas9—have made possible the manipulation of multiple genetic “sites,” in the service of eliminating genes that harm or hinder—or even to introduce genes that remake, strengthen, and speed up the species, or big parts of it.

The science-minded animators at Kurzgesagt have taken on CRISPR, and why it is being treated as a kind of genetic Holy Grail—or point of no return:

This show is prompted by the incredible pace of progress, and also by some fretting about what the unlocking of the genome might do. We’re inspired to live alongside George Church, the super-confident Harvard scientist behind some of CRISPR’s wildest possibilities: including reprogramming or ridding the world of malarial mosquitoes, reversing aging, and rescuing the woolly mammoth from extinction.

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Church—bearded, striking—knows he’s presiding over a revolution, and speaks, to be fair, in terms of numerous safeguards against the apocalyptic possibilities.

But our guests, writer/physician Siddhartha Mukherjee and the philosopher Michael Sandel, remind us that tomorrow’s biotechnology will have an almost unimaginable capacity to surprise, that there may be Robert Oppenheimers among the genetic Edisons.

Mukherjee refers us to the 1905 prophesy of the Mendelian biologist William Bateson, who said:

“The science of heredity will soon provide power on a stupendous scale; and in some country… that power will be applied to control the composition of a nation.”

That may mean the revival of eugenics on a 21st-century, pay-to-play model. Does that make it OK?

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We close with Pardis Sabeti, the biologist at the center of the Ebola fight of 2014. That wasn’t an apocalypse, but it was a serious cataclysm: a horrifying, hemorrhagic virus attacking a third-world healthcare system and against, for too long, global sluggishness and indifference. Sabeti says she works by day and worries at night on the prospect of a manmade superbug—Ebola set loose in the air.

Sabeti’s lab at the Broad Institute, like George Church’s, is full of brilliant postdocs pipetting solvents, running centrifuges, all in the service of reading and writing genomes. But in some ways, she’s playing a prudent, even heroic kind of defense to the bioengineers’ offense: trying to make the virus extinct, but without any concept of transhumanism.

Sabeti paid tribute to Dr. Sheikh Humarr Khan, who finally died of Ebola after months of tireless work with more than 80 infected patients at Kenema Government Hospital. If there’s to be hope of global readiness for a biopocalypse—a dreadful attack on human bodies, exploiting weaknesses in our genes or in our governments—it’s going to hang on ordinary human hands and hearts, like Dr. Khan’s.

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Watch our guest Siddhartha Mukherjeeauthor of The Gene, discuss the genetic theater of the Rio Olympics:

Podcast • August 25, 2012

Bernd Heinrich and our Journey — from Life to Life

I went out to the wild woods of western Maine in the late summer to inhale the biologist Bernd Heinrich‘s experience of Life Everlasting — and just to behold a modern man in a cabin ...

I went out to the wild woods of western Maine in the late summer to inhale the biologist Bernd Heinrich‘s experience of Life Everlasting — and just to behold a modern man in a cabin he built himself, almost as simple as Thoreau’s. Of course I am wondering: how many of us could learn to live as Bernd Heinrich does for months at a stretch? Could he teach me to see what he’s been watching in this wilderness for 60 years?

Bernd Heinrich made his professional reputation getting to know ravens and bees the way his friend Edward O. Wilson got to know ants. They are among the great naturalists surviving in the DNA era when, as Wilson has remarked, big-time science has little time for anything larger than a cell. Heinrich is an all-round woods watcher of birds and plants. He can place us on the calender, within a day or two (as Emerson observed of Thoreau) just by looking — in this case, at the goldenrod coming into bloom. “The nights are getting colder. The fireweed is fading out. Spirea is coming in. You can see the color fading in the birches…”

Bernd Heinrich hooked me five years ago with his autobiography, about himself as a 10 year old German immgrant boy running wild in these same Maine woods. And he’s hooked me again with his reflection on The Animal Way of Death in the subtitle of Life Everlasting. The short form is the notion that it’s not from dust we come, to dust we shall return. It’s life all the way, unless we bury ourselves in metal caskets. The trick in grasping the point is to watch animal recycling in nature.

So we spend the afternoon looking at what vultures have done to a fallen porcupine in the woods, and what maggots are doing to a road-kill squirrel that Bernd has brought back to his cabin. “Icky stuff,” as Bernd says. The trick is to rethink the “Nevermore!” from Poe’s Raven. He might have said: “Ever after!” If a raven’s beak gets our remains, we’ll be on the wing, literally, almost immediately.

I’m reminded specially of Jesus’ words in the Gospel of John 12:24, which Dostoevsky fixed as an epigraph at the start of The Brothers Karamazov: “Verily, verily, I say unto you, Except a corn of wheat fall into the ground and die, it abideth alone: but if it die, it bringeth forth much fruit.”

So we are watching something very grand going on and reflecting on big ideas of life through death — of resurrection, perhaps, and the reincarnation of bodies and ideas. “Without recycling,” Bernd Heinrich remarks, “all life would grind to a halt.” And I’m observing that death and recycling, as in the kernel that falls to the ground, may be the only route to immortality.

A week later I’m loving Bernd Heinrich’s train of thought. His implication, for starters, of a natural religion based our physical links to an unimaginably vast network — and of a moral obligation to all living things. “Not just to your neighbor,” he is saying, “but to the whole ecosystem.”

We’re the only animal with the knowledge that we’re part of something else… this knowledge of a physical connection with the rest of life; and it’s not a belief, it’s a knowledge…

We’re speaking of physical immortality. In the book I was also thinking of reincarnations, not only from physical to physical, but also in the case of humans especially, we are each seeded by ideas. We talked about Ed Wilson. He said: Bernd, you could run a marathon in two and a half hours. And that planted a seed in my mind, and I got out and started training, and I became an ultramarathoner and I ran also a marathon in two hours and twenty-two minutes. And in 24 hours I ran 156 miles, and it was a national record. So our immortality is not just physical. We are one of the few species who have immortality that is transmitted mentally, through ideas…

As Ed said, you know, the interest is more and more in the cell rather than in the organism.
Fewer and fewer people are actually in contact with the nature around us that really affects us. In other words, you can’t really know, for example, the plight of the ravens or the vultures unless you are out in nature… We don’t have enough naturalists… I am afraid of our power to cause damage. I see us as a plague who overruns our whole planet and upends the balance and creates an ecosystem that’s very, very simple where we don’t have this recycling, for one thing. And just the buildup of toxic effects, ad infinitum. It just seems like: when I was a kid nobody ever really thought about it. The idea that you could destroy the wilderness was just unthinkable. But now we’re thinking about it… because it’s actually happening.

Bernd Heinrich at his wilderness camp in Western Maine with Chris Lydon, August 2012