The End Specialist. Drew Magary
that it feels like Eugene is located right across the Hudson. A reporter named Mike Dermott wrote a huge piece about Oregon last week. I never bothered to read it before. But I’ve now read it a dozen times in the past couple hours. I can nearly recite it from memory. Copied from Slate:
THE MAN WHO CONQUERED DEATH
By Mike Dermott
Graham Otto never set out to conquer death. Actually, he was just hoping to help out the redheads of the world.
“I’m a redhead,” he noted in his private journal, which I was granted exclusive access to by the Otto family. “I’ve yet to meet a redheaded guy who enjoys being a redhead.” The name of the gene is MCR1. It’s located on chromosome 16. And according to the complete map of the human genome, it’s the gene that causes red hair (along with a rare condition called brittle cornea syndrome). Working with a team of fellow geneticists, Otto targeted this gene in hopes of finding a way to color hair through gene therapy. “It wasn’t the most noble of genetic experiments,” he wrote. “It was the sort of thing a wealthy university like U. Oregon does from time to time, when it feels like playing around.”
“He was excited about the potential business aspect of it. We all were,” recalls his wife, Sarah. “Frankly, I was just thrilled at the prospect of never having to pay three hundred dollars for highlights ever again.”
He didn’t fit the traditional scientist mold. Otto had attended Oregon on a partial scholarship for track and placed as high as eighth in the two-mile event at the 2000 Prefontaine Classic. He was an outgoing man, who always preferred company while working in the lab and who was always able to talk about his work in ways that laymen found not only accessible but downright fascinating.
“I think that’s what made him such a great teacher,” says UO President Raymond Lack. “He was passionate about his work, but not to the point where he became insular. You never felt like he was talking over your head about any of this stuff. He made it sound interesting, even entertaining. And trust me, that’s rare among his peers. I’ve always considered his communication skills a rare gift for anyone, in any profession.”
In terms of changing hair color through gene therapy, Otto was a miserable failure. The problem wasn’t extracting the redhead protein from gene. That proved easy for Otto and his self-described team of “Hair Bears.” The problem was replacing the color. “If you take away a person’s genetically predisposed color, you essentially give them colorless hair—albino hair,” he wrote. “You have to eliminate that protein in the gene and you have to find a way to add the color of your preference, and that’s where the engineering becomes close to a technical impossibility.” Otto experimented with altering proteins found elsewhere in the DNA helix of fruit flies (who can have red eyes that are triggered by the same gene), trying to activate a different color. “We tried blue. We tried brown. We tried green. Nothing worked.”
Exasperated one night in the lab, Otto became careless. In the midst of deadening the red protein in that day’s current batch of flies, he removed an extra protein from the gene as well. “I knew exactly what I had done,” he wrote. “But it was late, and I didn’t feel like starting over. Every good scientist knows that if you contaminate the original sample, you toss it. But I didn’t. I figured it wouldn’t make a difference in the end, so I went ahead and injected the vector. It was pure sloppiness.” When Otto returned the following morning, nothing unusual had occurred. He tried to introduce a new color protein into the flies’ DNA, but it again failed. He placed the batch of flies aside and began taking on a new group of test subjects.
But then something odd happened to that tainted sample of flies. “They wouldn’t die. A fruit fly usually lives for less than two months. And even then, within twenty-four hours or so, you usually begin seeing a handful of them drop. But none of the flies I injected with the vector dropped. Ever. They just kept flying around.”
Up until Otto’s serendipitous mistake, it was assumed that biological aging was controlled by hundreds, if not thousands, of separate genetic proteins found in the body—proteins that worked in concert to determine the rate of aging across various parts of an individual. “We always assumed that a thousand different internal mechanisms and external factors worked together to trigger the aging process,” says Dr. Phillip Frank, head of genetics at the National Institutes of Health. “When you think about it, you begin aging from the second you’re born. Our studies showed that specific proteins in your body activated all the different physiological processes and free radicals that go into both growing up and growing old. There was no master switch.”
Until Graham Otto came around.
The tainted fruit flies carried on living for weeks and weeks, with an apparently limitless supply of energy. The only dead fruit flies Otto found in their container were their offspring (the altered genes, Otto discovered, weren’t passed on), the offspring of their offspring, and the offspring of their offspring’s offspring. The original flies remained alive and fluttering about indefinitely. Otto acted quickly, retracing his footsteps from that late night in the lab, finding the supposedly unimportant protein he had mistakenly altered, and replicating the experiment again, without altering the original protein in the gene. Again, the altered flies had a seemingly indefinite lifespan.
The supposedly innocuous portion of the gene Otto had messed with turned out to be much more important than he had ever envisioned. He rushed to form his own independent biotech firm and called a lawyer to draft a patent for the protein. “Normally, this is something you do over the course of years,” he told Lack in an e-mail. “But we’re doing it in a week, because if we can replicate it across species, maybe there’s something there.” And replicate it he did, across mice, rats, guinea pigs, and others, including his own aging golden retriever, Buggle. In all instances, the altered animals appeared ageless when compared to their respective control groups, never growing old past the day the vector was introduced into their system. And all of them remain alive and well today, in tourist displays set up by the university—except for Buggle, who remains comfortably in the Otto household.
Despite his extroverted nature, Otto wasn’t known as a cocky, presumptuous man. The only careless thing he did in his life was to mistakenly alter the wrong gene in those fruit flies. So when he published his findings, he insisted only on reporting what he had found, and didn’t speculate on the potential enormous worldwide impact of his research. Nevertheless, many in his field declared it junk science. “It was just too easy of an answer,” says Dr. Frank. Still, while many questioned Otto’s findings, they didn’t hesitate to recreate his experiments. And they soon found that his discovery was everything he said it was. Far more than that, actually. “He understated the results, because he didn’t want to sound like some kook. He refused to call it a cure for aging,” says Sarah Otto. “But that’s what it was, and the follow-up research proved it.”
To see if the gene therapy worked in humans, Otto solicited an unlikely test group: patients with early onset Alzheimer’s Disease. “A disease like Alzheimer’s is triggered specifically by the advance of age,” Otto wrote in a subsequent email to Lack. “So if we administer the cure to people who are just developing the disease, we can do two things. One, we can potentially prevent further damage to their brains. Two, we can see within a shorter period of time if the cure takes hold. Normally, when you do a CAT scan of Alzheimer’s patient, you see changes—sometimes rather drastic changes—to the brain over a short time span. You can see the dark spots, the ‘cobwebs,’ as it were.”
The ten initial test subjects received monthly CAT scans after being administered the cure. “In every case, the cobwebs stopped growing,” noted Otto in his second published report. “The dark spots on their brains remained dark but never expanded, which is unheard of in Alzheimer’s patients. We studied them for over a year and not one of them saw the disease advance past the early stages. Their brains remained perfectly, blessedly intact.” Two of the patients have since died from unrelated causes; the remaining eight are alive and well.
By the time Otto had published these subsequent findings, the biotech community was busy stress-testing the cure in every conceivable way. Not once were they able to poke a hole in what Otto had discovered. So miraculous were the cure’s effects that many