How Jurassic Park Made Woolly Mice Possible (and Vice Versa)

Many years before co-founding Colossal Biosciences, future entrepreneur and champion of genetic research Ben Lamm was just a child growing up in the 1990s. And like any ‘90s era kid, this meant he absolutely loved Steven Spielberg’s Jurassic Park. “I was probably scared at the time, but it was inspiring too,” Lamm says decades later […]

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“I was probably scared at the time, but it was inspiring too,” Lamm says decades later while visiting the Den of Geek Studio ahead of his SXSW keynote talk. “I think all sci-fi has inspired me to be in tech. I’m not a biologist, I’m not from this world. But I just like to build teams of people that are much smarter than me, and I just got really excited about the idea that Jurassic Park-like technology was possible.”

The world has become excited, too, over the last week after Colossal revealed its latest breakthrough ahead of SXSW. In a handful of days, it seems like everyone is suddenly smitten with what Colossal’s dubbed “woolly mice,” genetically-engineered rodents with some of the telltale features of a famed, tusked mammal that died out during the last ice age. And now, more than 11,000 years after the final woolly mammoth breathed its last, the company estimates they’re maybe three years away from bringing the behemoth back.

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“We didn’t mean to, but I think we accidentally broke the internet with the woolly mouse,” Lamm laughs when he first steps into the studio. “We thought they were pretty interesting from a proof-of-concept perspective, and as verification of the edits we’ve been working on the last three years for the woolly mammoth, but then they had this massive adorability factor that we didn’t plan for. Which gives us a lot of hope our first mammoth calves will also be this adorable.”

Indeed, Colossal and Lamm personally have been inundated with emails, phone calls, social media DMs, and pleas from children, parents, and cuddle-enthusiasts around the world about the woolly mouse. Is it a mini-mammoth, some ask, or is this a new species, demand others? Most common, though, is the refrain of can we buy one?

“We’re not letting them breed,” Lamm says with a rueful smile. “We’re not selling them, even though we get so many kids and parents calling us and begging us to sell them.”

What they are doing, however, is seeing if the woolly mouse can become the gateway to bringing back an extinct species—a concept that has fired up the imagination of millions of children, including Lamm once upon a time, ever since Richard Attenborough welcomed Sam Neill to Jurassic Park. Granted, that film was based on a book written by an author intensely skeptical of genetic research—so much so that while the film features sequences of a few tourists getting eaten by dinosaurs, the novel teases a brave new apocalyptic world in which genetic revenants begin devouring babies on the mainland.

When it comes to that element of Jurassic Park, Lamm appears less nostalgic.

“We also know how Dune did and Blade Runner, and a bunch of other fake sci-fi movies that were designed to entertain us [end], right?” Lamm says while considering the age-old question about dabbling in sciences which Crichton equated to Mary Shelley’s Frankenstein. Furthermore, Lamm is quick to point out that the actual scientist who first dreamed of bringing the woolly mammoth back might have inspired Crichton first.

While Lamm is the billionaire investor and booster of Colossal’s work on the bleeding-edge of genetic engineering and CRISPR technology, the company’s other co-founder and lead geneticist, George Church, is the one who first lit onto the idea. He’s also the man who pitched Lamm on the concept in 2021, six years after Church’s genetics research team at Harvard successfully copied woolly mammoth genes onto the genome of an Asian elephant.

“He’d been doing the computational analysis and had the thought that we do have the technologies, and that with enough funding and focus [we could] bring back the mammoths,” Lamm explains. But while those fateful steps might’ve begun in 2015, it’s a dream Church’s research has been circling for far longer—and that Crichton might have borrowed without credit during the writing of his literary screed against the rising tide of genetic research.

“Many people ask if Jurassic Park inspired George around this idea,” Lamm says, “and George will happily say he thinks that he inspired Jurassic Park, jokingly. But there is a page in the first part of the book where there’s a DNA sequence. It’s exactly George’s work with only one letter off. So statistically that’s probably pretty hard, and it’s from published papers that George put out in the ‘70s.”

Still, when it comes to the actual concept of resurrecting dinosaurs from DNA preserved in amber that’s 65 million years old or more, Lamm is graciously dubious about Crichton’s story. While he takes pride in noting the oldest mammoth DNA that Colossal is working with is from 1.2 million years ago, that’s a far cry from dinosaur species which walked the Earth a hundred millions years ago.

“Amber is not the best DNA store, so there is no ancient DNA [of that longevity],” Lamm says. While they can demineralize dinosaur fossils up to a point to extract some genetic material, after a couple of million years it’s a mere shadow of what once was. “You can kind of figure out if this is a Triceratops from a bone if you do demineralize it and run these tests, but we’re talking about fragments of a fragment of fragment. There’s not enough DNA to ever rebuild something.”

With that said, the woolly mice represent a potential proof of concept in Lamm’s mind about the possibility of recreating the mammoth by 2028. After all, the woolly mouse is specifically edited to match the ancient beast in its namesake.

“We actually know what mammoth hair looks like because we pull it from the permafrost,” Lamm notes. They even have a replica of a 12-foot mammoth suspended in ice in their Dallas headquarters (it was a gift from Wētā Workshop, courtesy of Peter Jackson, who is also an investor in Colossal). Yet while most people think of the mammoth’s fur as being gross and matted after millennia in the ice, Lamm explains that “when you actually take Siberian mammoths or Alaskan mammoths out of the permafrost, and if you do have tissue samples or hair, and it gets cleaned off, it is this reddish brown, golden fur. It’s actually quite beautiful.”

The world would seem to agree as the woolly mouse has already become a pop culture icon, appearing everywhere from Saturday Night Live to dubiously on a new meme coin. As per the Colossal CEO, the features which make them freakishly cute are also reflective of what we expect a revived woolly mammoth to be.

“We had three big targets, and we made eight edits across seven genes using precision gene-editing,” Lamm says. Those targets included hair color, the wavy nature of the fur, and the genetic fat metabolisms of mammoths. “So of all the mice that were born, all 38 of them were healthy. They all had the edits, and we had 100 percent editing efficiency with zero off-target effects, and we delivered it all in one delivery, which is called multiplex-editing.”

The result is a creature the co-founder estimates is one of the most genetically-modified organisms on the planet, and one which Colossal hopes to prove could survive in the frigid conditions of the Siberian tundra, just like an actual woolly mammoth.

“We probably need about six to 12 months to verify cold-tolerance,” Lamm admits when asked if the mice could survive in the frost. “They’re still within the statistical range of what mice typically are. Obviously their fur is much thicker, so they look bigger, but size-wise they’re about the same.” Hence why Colossal is working with an ethics board to experiment humanely and safely with the mice and test how cold-tolerant they might be. The findings will be amended into an updated version of the scientific paper Colossal has already published.

The goal, of course, is to do the same on a much larger scale with the genetic code of an Asian elephant, the closest living relative of the extinct woolly mammoth. Ideally, Lamm hopes to reintroduce what he calls mammoths to the Arctic ecosystem in the years and decades to come.

This again might get the blood up of some skeptics, including possibly Crichton if he were still alive. Consider that Crichton very shrewdly included a passage in his Jurassic Park novel where the chief geneticist on the island, Henry Wu, thinks to himself that because they have used frog and other amphibian DNA to complete the code of dinosaurs, what they created at Jurassic Park are not actually dinosaurs at all, but genetic freaks. (It’s a detail Spielberg conspicuously omitted in his film adaptation.)

However, the possibility of bringing back the woolly mammoth is literally a whole different kind of animal. For starters, Colossal is not splicing in miscellaneous DNA strands into their woolly mice or eventual mammoths, but rather targeting similar genes and editing them to match. Furthermore, Lamm is also quick to discount the question of whether what he and Colossal are hoping to make is an actual replica of the species of mammoth that went extinct some 11,000 years ago.

“We’ve been very clear about this, that we’re trying to do what’s called functionally de-extinction, right?” says Lamm. “We want to put animals back into their natural habitat and help the ecosystem, and we want to de-extinct core biodiversity that’s been lost in traits. So it’s functionally de-extinction. It is not possible to clone an extinct species. You need a living cell and there’s just no living cells from that long ago. So I think it’s important that people understand the difference between what’s possible and what’s not.”

The CEO likens it to anyone going on 23andMe and discovering what percentage of Neanderthal they might actually be in their own personal genetics. “Would you say that you’re a hybrid or do you say you’re a Neanderthal hybrid with Homo sapien, or do you say that you’re an evolved Neanderthal, because they did come first, or do you say that you’re a Homo sapien?”

Humans like compartmentalizing data and placing everything in neat boxes, Lamm contends, but “speciation is more like a river. All of these species evolve from each other, and we’re all hybrids of a hybrid of a hybrid.” Therefore Lamm wouldn’t qualify a potential new woolly mammoth as a hybrid or subject it to any other qualifier.

“It isn’t a cold-adapted mammoth or allele-adapted Asian elephant, which is what some people love to say about our work,” Lamm says. “We think that if it solves the functional aspects of a mammoth, if it has ancient DNA from a mammoth, and if it has the lost genes to a mammoth, we just call that a mammoth. If people want to call it ‘mammoth 2.0,’ they can. Or if people want to say 40 words to describe it, they can too.”

Plus, unlike Attenborough’s John Hammond in Jurassic Park, Colossal didn’t get into this business to build a tourist destination. They seek to use the mammoth to restore an ecosystem and aid conservation—and even the fight against climate change.

“There’s been these peer-reviewed papers that show that the reintroduction of cold-tolerant megafauna and more biodiversity back in the tundra actually creates this proliferation of all these additional species of both flora and fauna because of this cascading effect of seed dispersal, defecation, herding, and trampling the permafrost snow in the winters,” says Lamm. “It can actually even keep the ground temperatures colder in the summer months. So there’s this weird halo effect that we’ve seen in these isolated populations when we’ve reintroduced cold-tolerant species that are much smaller than mammoths back into the Arctic already.”

That’s not a bad trade on an ever-warming planet. Nonetheless, the Ian Malcolm in the back of all our heads has to ponder how you can predict the side effects of reintroducing an extinct species (or at least a variation of it) into a modern ecosystem tens of millennia after the fact. Wouldn’t such a return unto itself constitute an invasive species?

“It’s all about measuring intended versus unintended consequences, and the rewilding process is one that’s really measured,” Lamm considers. “So like when they put wolves back in Yellowstone or bears back in different parts of Europe, or different marsupials in Australia, it’s a very thoughtful, measured process with indigenous people groups, colleges, and private landowners. We’ve actually started putting out papers around this, and we even studied things like migratory patterns for caribou.”

He continues, “We don’t want to put mammoths in an area where indigenous people don’t want them, where they would disrupt migratory patterns of other species. We are really looking to identify these areas that could have the best impact on the ecology, the best for the mammoths, without causing unintended consequences.”

One might even say they are looking to prove that life finds a way.

The post How Jurassic Park Made Woolly Mice Possible (and Vice Versa) appeared first on Den of Geek.