by Ben Mezrich
“Dr. Church, I need to do this. I’ve dreamed of doing this. It will validate my existence.”
Maybe it had been over-the-top, but Church had been impressed enough to put him in touch with Brand and Phelan, and their phone discussion blossomed into an invitation to join the Revivalists.
“Once we’ve got the genome of a mammoth,” Luhan continued, “we need to find the genes that code for the traits we’ve chosen. Hair, ears, subcutaneous fat, and hemoglobin.”
As complicated as that sounded, it was one of their simpler tasks. The key to identifying the four traits actually lay in the Human Genome Project. Since the HGP had been completed back in 2003, scientists had moved on to identifying the roughly twenty thousand specific sequences of genes amid the over three billion base pairs of DNA that coded for traits in humans, from eye color to various inherited diseases and conditions.
So, if the team wanted to figure out a specific gene in the Woolly Mammoth sequence—say, red hair—they would choose a similar trait in the human genome that was already sequenced, and then use a computer matching program to isolate the similar sequence within the Woolly Mammoth genome. It was as easy as plugging parameters into a search engine: Google DNA.
Hair, ears, subcutaneous fat, hemoglobin—they were all searchable genes, as soon as they had their Woolly Mammoth genome. Tusks, among the other traits they hoped to work on later in the project, would be more difficult. Humans don’t have tusks, so locating DNA coding for tusks in a Mammoth would take guesswork and trial and error.
“Once we’ve figured out the genes we need,” Luhan continued, “we begin the process of synthesizing them.”
They all understood that they weren’t going to clone a Woolly Mammoth. They were going to make one. They weren’t going to transfer genetic material from a frozen carcass, they were going to create the material in a dish and implant it within a living elephant cell.
It was synthetic biology, which Quinn did every day at Warp Drive. Unfortunately, that real-world experience hadn’t been enough to get him into graduate school; without the right college pedigree and the right recommendations, he had been rejected wherever he’d applied. The lab did have non-Ph.D.s, but Quinn wasn’t a Harvard employee, so, technically, he wasn’t allowed to work in the Church Lab, and he had to be brought in for the Revivalist meetings as a guest of one of the postdocs. But his hands-on experience made him an important, capable part of the team.
“And then we place the genes into the elephant cell,” Quinn said, typing the fourth and final stage of their work into the laptop.
That was the magic act, the transformation in genetics that George Church was leading—no longer reading, but writing DNA.
Quinn could feel Luhan looking him over, and he knew what she was thinking. This fourth stage of their project would be cutting-edge science, with the emphasis on cutting. Because the process by which they would place those genes into the elephant’s living cell represented one of the most important developments in modern science.
CRISPR—“clustered regularly interspaced short palindromic repeats”—was a scientific breakthrough that revolutionized genetic biology. A new method of editing large numbers of genes simultaneously, it had jumped onto the scene just six months earlier, through a pair of papers published in Science magazine, one of which had come from George Church and the Church Lab itself (including Luhan), plus three other papers in the same month. Multiple labs claimed credit for having invented CRISPR.
Luhan, Bobby, and Margo had come of age as scientists using CRISPR, and they understood it as well as anyone. Quinn worked with CRISPR every day, and in fact often volunteered to speak at local high schools, because he knew, as complex as the science behind CRISPR might be, it was such an important tool that everyone should have at least a basic understanding of how it worked.
Over the past few months, he had tried to come up with simple ways to explain what was essentially now the primary tool in genetic engineering.
With high school students, he started with the basics. Every cell in every living creature contained a copy of the creature’s genome—the double strands of DNA, made up of billions of base pairs of molecules, that coded for every trait or characteristic that made the creature what it was. Those double strands, known as the double helix, the discovery made by James Watson, Francis Crick, and Rosalind Franklin in the fifties, were connected in pairs of chemical bases: the chemical adenine paired with thymine (A-T) and the chemical cytosine paired with guanine (C-G).
Simple bacteria had developed a natural system to protect their own genomes—their double strands of DNA—from attacks by viruses. To defend themselves, they employed a protein called Cas 9 that could act like a molecular pair of scissors. When a virus attacked, spreading its genetic material into the bacteria, the Cas 9 protein, guided by a string of messenger RNA—a single strand of nucleotides that carries information from DNA and uses that information to assemble proteins—that would match up with the invading DNA, would slice the virus’s genetic material at precise points in its connected pairs. The RNA essentially became a targeting system, allowing the Cas 9 to slice and destroy invading viruses.
Six months ago, a few teams of scientists across the globe—including Jennifer Doudna, Martin Jinek, Feng Zhang, Le Cong, and Prashant Mali, as well as Luhan in Church’s lab—realized that the Cas 9 protein could also be used to cut strands of DNA from other organisms besides viruses. They could use synthetically created guide RNA to aim Cas 9 at any chosen sequence of genes, slice them out, and then replace them with a different sequence, created in a lab. In his paper in Science, Church had demonstrated for the first time that the CRISPR technique could be successfully used in human cells.
In short, placing Woolly Mammoth genes into elephant cells was as simple as designing a guiding segment of RNA to match the base pairs at the ends of the sequence that coded for whatever trait you were hoping to replace—and the Cas 9 would do the rest. The RNA would line up the synthetic gene with the similar elephant gene, slice the DNA with the Cas 9 molecular scissors, and the genome itself would reattach the new, Woolly Mammoth gene in its place, through a natural healing process.
The elephant cell would no longer contain an elephant gene. Instead, it would contain a synthetic Woolly Mammoth gene, coding for the desired Mammoth trait.
“And when that succeeds—when we’ve proven our ability to insert a Woolly Mammoth gene into an elephant cell—we shift our work to the stem cells.”
Stem cells are the undifferentiated cells within every living thing that can give rise to the diversity of other cells that make up the living whole. Most cells are specialized and don’t change that specialty—the cells making up an ear or a hair remain that of an ear or hair. But stem cells can differentiate to become anything: ears, hair, heart, lungs, hemoglobin, tusks. A genetically changed stem cell could give rise to all the different traits of a Woolly Mammoth. And those traits would then be inheritable and inherited. The new creature wouldn’t just look like a Woolly Mammoth and behave like one. It would be a Woolly Mammoth.
At that point in the meeting, Luhan took total control, splitting up the team in order to take on the various tasks. Bobby and Margo would contact the zoos in search of elephant samples. Luhan would do her best to obtain a complete Woolly Mammoth genome, and then go through the genetic sequence searching for the specific traits they wanted to replicate. And Quinn would begin to design and prepare the CRISPR components they would need to implant the synthesized Woolly Mammoth mutations into the elephant genome.
By the time they were ready to leave the café, their excitement was as keen as a pair of molecular scissors.
“Just remember,” Bobby said, smiling, as he gathered up the laptops, “it’s only science fiction until we remove the fiction. Then it becomes real.”
CHAPTER EIGHTEEN
Early 2013
Two days later, Bobby wasn’t smiling after cold-calling zoos and conservation parks, trying to get access to elephant tiss
ue. He held a desktop phone against his ear and listened to the braying of the zoo manager on the other end of the line. Bobby was hoping to get a word in before the manager worked himself past all reasoning, but the guy wasn’t even pausing to breathe, his words were just running into one another like a train jumped free from its tracks.
“No,” he said, finally breaking into the frenzied zoo manager’s monologue. “We aren’t going to clone your elephants. We just need a little sample for our experiments . . .
“No, we aren’t going to kill any elephants. Why would we want to kill elephants . . . ?
“Yes, I have seen that movie. Yes, the dinosaurs were very frightening . . .
“Yes, I’ve seen that movie, too. No, we aren’t trying to make scary mutant animals . . .”
He considered hanging up, but he’d already introduced himself as a member of the Church Lab and didn’t want to appear rude. He felt a certain level of responsibility—especially since he was sitting in Church’s office, in Church’s chair.
It hadn’t been his choice to make the calls from there; he’d have been perfectly happy using his cell phone in the café. But Luhan had convinced him he’d sound more official if there wasn’t a din of background chatter behind him. And besides, Church wouldn’t be returning to the office anytime soon.
At the moment, Church was off putting out a huge public relations fire, tangentially related to the Woolly Mammoth Revival project and his work on de-extinction. As Bobby understood it, the problem arose from an interview Church had given to the German magazine Der Spiegel back in January. The interviewer had taken note of a passage in Church’s most recent book, Regenesis: How Synthetic Biology Will Reinvent Nature and Ourselves, which had laid out the idea of de-extinction and the science that would allow them to revive the Woolly Mammoth, as well as other extinct species. One of those species Church had mused about in the book was the Neanderthal. After explaining the steps of genetic engineering necessary to revive the Woolly Mammoth, the passage read:
The same technique would work for the Neanderthal, except that you’d start with a stem cell genome from a human adult and gradually reverse engineer it into the Neanderthal genome or a reasonably close equivalent. . . . If society becomes comfortable with cloning and sees value in true human diversity, then the whole Neanderthal creature itself could be cloned by a surrogate mother chimp—or by an extremely adventurous female human.
After the interview was published, it was distorted, in Church’s view, by the MIT Technology Review to make it seem as if Church had already moved well beyond theory in his work—and the Review essentially placed a “Want Ad” for women who would carry to term a Neanderthal baby. Church was at a Martin Luther King’s Day barbecue when his cell phone rang. He picked up to hear the dean of Harvard Medical School on the other end.
“Did you put out a call asking for women to volunteer to carry a Neanderthal baby?” the dean asked.
The situation would have been humorous, if it hadn’t caused such an uproar. Church had been forced to contact numerous newspapers and magazines, including the Boston Herald, to explain that he was not, in fact, in the process of bringing back the Neanderthal species. Even more bizarre, the Church Lab had received hundreds of letters from women volunteering to carry the first Neanderthal baby, proving two things. There were plenty of “extremely adventurous female humans” out there in the Greater Boston area. And genetics was a powerful tool, but also an ethical minefield. It was incredibly easy for a scientist to be misunderstood when speaking to the general public. No matter how well-meaning a scientist is, there were always going to be people imagining the worst.
Bobby was learning that lesson again, firsthand.
Every call had been the same. At first, the zoo managers were respectful, impressed by the Harvard name. But as soon as Bobby mentioned genetic engineering, their attitudes changed to suspicion, fear, even anger. Everyone he talked to jumped to the conclusion that he was trying either to clone their elephants or turn them into some sort of genetic monster. No matter what Bobby told them, they kept turning him down.
“We just need a little sample,” he said, trying again. “The elephant won’t even notice.” Bobby may have been minimizing the process a bit; the elephant would certainly notice when they harvested a small amount of tissue, but it wouldn’t cause the animal any pain, or have any lasting effect.
The zookeeper did not want to listen. Bobby sighed, thanked him for his time, and hung up. He crossed out another name on the list. He was getting dangerously near the bottom of the page and considered giving up; perhaps they could find some frozen elephant material at another lab, or at some culture bank at a university. But Luhan would say that it was better to have a live, fresh cell. To someone as determined as Luhan, it wouldn’t matter how many people had said no. It only mattered that one said yes.
Bobby shifted to the next entry on the list, a private zoo in a suburban area about forty miles west of Boston. According to Bobby’s notes, they had a four-year-old pair of healthy young African elephants.
He didn’t expect much as he dialed the number, but when a kindly-sounding older gentleman answered the phone, he put on his most official-sounding voice and started into his appeal, honed by forty hours of straight rejection. He explained the Woolly Mammoth Revival project, then asked for the tiniest of cell samples.
To his surprise, he didn’t get an immediate no. Instead, the man told him he was welcome to visit the zoo and take a look at the animals for himself. Then the man added: “Considering what you’re trying to do, I don’t think you’ve really thought this through. But I’m happy to help if I can.”
Bobby was too excited to try to figure out what the man’s cryptic warning meant.
Step one of the Woolly Mammoth Revival, completed: They’d found their elephant cells.
* * *
Two days later, Bobby joined Luhan, Quinn, and Margo at their regular window table at Elements Café, and the four of them gathered around one of the laptop computers. The screen was open to a video shot from Bobby’s cell phone, taken not fourteen hours earlier. His phone had been held close enough to the chain-link fence surrounding the elephant habitat at the private zoo that most of the enclosure was visible. A grassy pasture led up to a kidney-shaped, man-made lake, which was surrounded by a few bushes and the kind of low trees found on a savannah. For a few seconds, they saw nothing else, and then, down the center of the screen, a middle-aged man came running as fast as he could toward the fence. One hand held on to his hat, the other clutched a large hypodermic needle. His face was contorted in fear. Dirt kicked up from the heels of his boots as he plunged down the center of the pasture, heading for a pair of barricades on a steel secondary enclosure that ran just inside the chain-link fence.
He’d almost made it to the barricades when the elephant pursuing him came into view. Onscreen, it looked twice as large as Bobby had remembered, and it was moving fast, almost as fast as the zoo manager. Its huge, floppy ears were pinned back against the sides of its head, its tusks were raised, and its trunk was curled up into the air, a jagged semaphore. The look in its eyes was pure anger, and the entire zoo—and the camera—seemed to shake as it charged forward.
A few seconds later, the zoo manager made it through the barricade and the chain-link fence, gasping as he locked everything shut behind him. The elephant skidded to a stop a few feet from the barricade, then pawed at the ground with an enormous padded foot. Finally, it gave a shake of its massive head, turned, and started back in the direction it had come.
As the computer screen went black, Luhan was the first to speak.
“African elephants seem to be a bit aggressive.”
Quinn coughed. “You think? He didn’t even come close to getting a sample in that needle.”
“We really don’t want to turn one of them into a Woolly Mammoth,” Bobby said, his voice dejected.
None of them needed to complete his thought. They had all seen Jurassic Park. Rampaging Woolly Mam
moths tearing up the Siberian countryside were not going to win any of them a Nobel Prize.
“So what do we do?” Margo asked.
There was a brief pause, and then Luhan shrugged.
“We pivot.”
From a genetic standpoint, African elephants had never been their first choice. As a species, Asian elephants were much less aggressive and temperamental, and so were also a much better fit for their project. Genetically, they had more in common with the Woolly Mammoth than the African species and thus were a closer relation to the Mammoth, which would make the actual sequence engineering a little easier. This made sense, since the Asian elephant came from the same continent where the Woolly Mammoth had lived in its largest populations.
Luhan had made progress obtaining the sequencing. The Reich lab at Harvard had kept its word, and the Revivalists had gained access to the beginnings of an okay sequence of the Mammoth genome. Luhan had already begun running the necessary search programs to find matches for the traits they were looking for: hair, ears, subcutaneous fat, and hemoglobin.
Soon, they were going to need their elephant samples, and Asian elephants were more difficult to find. An endangered species, Asian elephants’ wild population was fewer than fifty thousand animals. Their population had declined by at least 50 percent over the past three generations, approximately sixty to seventy-five years.
“They’re not in many zoos,” Quinn said, picking up on the rest of the team’s thoughts. “If zookeepers gave Bobby a hard time about giving us access to African elephants, they’re going to be even tougher letting us get close to an endangered species.”
They were all quiet for a minute as they thought, the ambient sounds of the café behind them reverberating. Finally, Luhan broke the silence.
“Well, we don’t need the whole elephant,” she said.
“What do you mean?” Margo asked.
“Our eventual goal is stem cells, right?”
In order to implant a genetic change—Mammoth DNA—into the elephant species DNA, they needed a stem cell. Originally, that was going to be something they would seek after they’d experimented on living elephant cells.
