John Clark - Mad Scientist
There are things you should know about, just because they're weird. Did you know that people with diabetes exhale rocket fuel? It's true, but it's weird, right? And spontaneous combustion. That's true, too, apparently, albeit in a bigfoot sort of way. People just explode. Mark Roth keeps a file on them, because, well, for one thing, he's interested in the genetics of spontaneous combustion, and, for another, he's interested in what keeps people from exploding, like, all the time. I mean, why shouldn't they? People never ask that. But then, they never ask a lot of things. Human beings are 37 degrees Celsius. That's pretty much the standard. But why? Nobody ever tells you. Y
ou can read a thousand books on bioenergetics and they won't even ask the question. So it's unexplained, and that's when you can learn things. You can learn things when things are unexplained -- when the sword is still in the stone. Take movement, for example. We humans are absolutely programmed to be interested in movement. In fact, if you're a biologist, you're really a movementologist; you study that which moves. You're a slave to the animate. Which, of course, is how Mark Roth got the idea that deanimation really might be the better scene, and found himself in Ripley's Believe It or Not!
Now, Mark Roth is a scientist. He's not a philosopher or a crank. He proves things, experimentally, according to the scientific method. In 2007, he got a MacArthur, so he's a genius, certified. He's got this long, narrow oracular head, shaped like a Corinthian column, expanding as it gets to the gray matter. He's got a flexible nose, 1 or 2 degrees off center. He's got kind, tired eyes -- Vonnegutian eyes -- to which his eyebrows, scroll-shaped, offer fancy punctuation.
He's got a ginger-colored mustache and ginger-colored hair going gray, now that he's pushed into his fifties. He's got long, skinny arms that he waves around, and long, skinny legs covered with ginger-colored freckles that are available to view because he used to be a runner for the University of Oregon and still wears shorts to work, and blue Converse sneakers, and white socks bright with elastic.
He sometimes gives you a goofy double thumbs-up when he thinks he's proved his point, when he's proved that what he's talking about -- be it ball lightning or the philosopher's stone -- is not a crazy idea but rather a gamer. Still, he's got a lot of ideas, for a scientist, and some of them come from unusual sources, like tabloidy news reports and science fiction.
It's a weird thing about scientists -- you would think that they would love science fiction. But they don't. To admit that you get your ideas from science fiction, if you're a scientist, that's, like, career-threatening, man, just like it might be professionally risky to say you work in Mark Roth's lab, no matter how outlandish and game-changing its accomplishments.
And so, yes, Mark Roth is a scientist. But he's a scientist in the way that you used to want to be a scientist when you were a kid, with weird substances -- dangerous substances, toxic substances, indeed the most toxic substances known to man! -- bubbling away in his lab, rather than a scientist in the way that most scientists are scientists, with NIH funding, a stack of grant applications to catch up on, and a commitment to pursue the one or two ideas that got them that precious federal funding to the death.
And so last year, when one of his nephews was in a store in South Carolina and his mother -- Roth's sister -- came by to get him...when the boy wouldn't move because he was so engrossed in the latest edition of Ripley's Believe It or Not! and his mother finally had to yell at him...when the boy trudged dutifully out to the car and, when they were on the road, finally told his mother that she should have let him keep reading that book because Uncle Mark's in it...well, Uncle Mark wasn't exactly displeased when his sister called him later that night to tell him that he'd made Ripley's.
He'd had papers published in Science, he'd had papers published in Nature, he'd had papers published in the most prestigious scientific and medical journals in the world, but Ripley's Believe It or Not!, for his work making suspended animation possible in human beings? He made Ripley's? That was cool, man. That was an honor. That was science.
The funny thing is, suspended animation wasn't even the weirdest idea he had when he made his decision to stop being a reductionist -- which is not only what most scientists are but also what the NIH pays them to be -- and start becoming an expansionist. And it was definitely a decision, a moment of desperate clarity. See, he'd done his share of bricklaying.
He'd done his share of saying, This is the protein, this is the gene -- you know, sitting around the campfire, warming his hands with the other scientists. Indeed, he'd had enough success with RNA splicing at the Carnegie Institution in Baltimore to know two things: First, that some scientists weren't necessarily happy that he'd had success with RNA splicing; and, second, that the same scientists who weren't necessarily happy that he'd had success with RNA splicing wanted him to do RNA splicing for the rest of his natural life. Talk about weird...but that's not what convinced him to leave the campfire. No, what convinced him that he had to start going out into the woods and fetch his ideas from the darkness was...the darkness itself.
In 1995, Roth's wife, Laurie, gave birth to his second daughter, Hannah. She was born with Down syndrome and a heart with one ventricle. Mark Roth was thirty-eight years old. He was, by this time, a researcher at Fred Hutchinson Cancer Research Center in Seattle, and if his daughter survived, he was looking at having a dependent for as long as he was alive.
He met with Laurie and told her, Hey, whatever happens, life as we know it is over. This being an academic, this bricklaying, this grant-seeking, this paper-publishing, this encoding of proteins, this scientific nut-gathering, this career of increments, this life of the most punishing and irrevocable patience -- well, it's not going to cut it.
The obligation of Hannah had liberated him to seek the scientist in himself, and the scientist in himself wanted nothing less than to change the world -- to pursue science for the sake of human benefit, not in the long term, but right here, right now, while Mark Roth was still in his breathing period, whether he knew the molecular basis of the benefit or not.
And then Hannah died. She died after heart surgery. She was just over a year old.
And then Mark Roth began to fail. Like, unequivocally. He was still doing experiments, he was still doing science, but it was as if he were experimenting with failure itself. He was committed to it. He didn't think there was enough of it. He was going to see where failure took him.
Gorking 101: Roth's serum will render an animal -- a mouse, say -- dead to all appearances. And hours, or a day, later, he can bring it back.
The first failure? Immortality. He'd gotten interested in the possibility of immortality. You know, it's not like we don't know the secret of immortality. We do. We know where it is, anyway. It's in the gonads. I mean, you have a child, you become immortal -- humans know that, in the same way that fruit flies know that. It's intrinsic knowledge, evolutionary knowledge. But what most people don't know is that we can sort of see immortality, under an electron microscope. The immortal cells that are found in the gonads are called germ cells, and what makes them different from all the other cells in the body is that they're lumpy. They've got these lumps inside them called P-granules, so that's where the secret of immortality has to be -- in the lumps.
So Mark Roth got very interested in the lumps. But he wasn't the only one. He was racing to identify one of the lump proteins. And he lost. He lost to Susan Strome, a scientist now at UC Santa Cruz. And there was no second prize. Science is like Glengarry Glen Ross that way. First prize is the Cadillac, second prize is you don't get funding. Second prize is you have to figure out what to do next.
What Roth figured out to do next was to fail again -- to fail again while making good on his promise to create something of immediate benefit to human beings. See, it's notoriously hard to diagnose the autoimmune disease lupus. But back when he was doing RNA splicing, Roth had figured out a way to do it, and now he set about trying not only to develop the test but to take it to market -- himself. And he did it. For three years, that's all he did, nonstop: He developed the test, got the patent, and then went out and got FDA approval for what he had created. He was, as far as he knows, the first scientist ever to get FDA approval for a diagnostic test all by himself, without the help of a corporation, in an academic setting. Now he had just what he wanted -- something that solved a problem, something that actually helped people.
You know how many people it helped? Roth makes a steering wheel with his arms to show how many people it helped. It helped nobody. It was a big zero. Not because it didn't work; rather, because there was no market for it. Or because there was a market for it, but it wasn't big enough to convince any pharmaceutical company to manufacture and distribute it. A test that helped solve the age-old problem of diagnosing lupus? Roth couldn't give it away. He still gets e-mails from people who think that they might have lupus, or that their kids might have lupus, and who want his test. And he has to answer that his test does not exist.
So there he was, Mark Roth, at the turn of the century, not just an unfunded scientist at Fred Hutchinson Cancer Research Center but a legendarily unfunded one -- the king of interim funding, who told colleagues that he wanted to be the guy who changed medical science forever, and then, in the next breath, told them all about spontaneous combustion. Or suspended animation. Brilliant guy, Mark -- but people actually laughed at him, with his weird ideas. And yet he learned something from his failures, and what he learned was not that he was too weird; it was that he wasn't weird enough. His thinking was too small. If you want to change the world, you've got to change your thinking first. And the only way to do that is to take refuge in the unexplained, in the places where the sword is still in the stone. He had a notebook to that effect.
Filled with unexplained phenomena and sci-fi gleanings, and he would page through it to figure out the weird idea he could turn into the big idea. He was a little like Goldilocks at this point: This one's too far out there, this one's not far out enough. He was looking for the one that was just right when he started going through the file he'd kept of people who have survived hypothermia. Skiers in Switzerland, lost in avalanches; drunks in Chicago who fell asleep in the dead of winter -- for all intents and purposes, they were dead, except that they weren't, except that they could be revived, hardly the worse for wear. Weird, right? Suspended animation. And that's the gamer.
See, it wasn't like Roth ever let go of the dream of immortality. He was still obsessed with the lumps. He just began thinking about them in a different way. Okay, the lumps are immortal -- so what do they do; how do they achieve that end? And here's the answer: They do nothing. They're quiescent. They're couch potatoes! They're immortal, because for all intents and purposes -- in terms of movement -- they're already dead! And maybe that's what immortality is. People always think of it in terms of living forever. But maybe it just means not dying -- not dying when you're supposed to die, surviving the mortal moments. We don't know what life is, anyway. Not really. We just know what life does -- it burns oxygen. It's a process of combustion.
We're all just slow-burning candles, making our way through our allotment of precious O2 until it becomes our toxin, until we burn out, until we get old and die. But we live on 21 percent oxygen, just as we live at 37 degrees. They're related. Decrease the oxygen to 5 percent, we die. But, look, the concentration of oxygen in the blood that runs through our capillaries is only 2 or 3 percent. We're almost dead already! So what if we turn down the candle's need for oxygen? What if we dim the candle so much that we don't even have the energy to die?
And so began Mark Roth's career as a deanimator. As a gorker. Gorking is...well, gorking. You take away some creature's supply of oxygen, you're gorking it, man. The trick, of course, is bringing it back. In the beginning, that wasn't so easy, because in the beginning Roth was just free-associating. He was using heavy water, rat poison, and he was a deanimator without being a reanimator. Other scientists were laughing at him: Hey, Roth, did you suspend anything today? But then he did. He gorked some nematodes -- roundworms -- with nitrogen. An inert gas, sure, but it crowded out the oxygen available to them; it diminished the atmosphere.
Roth took them to the Death Hole, which was an atmosphere of less than 1 percent oxygen. They died. But then he took them beyond the Death Hole, and they came back when oxygen was reintroduced. There was life beyond the Death Hole! So he tried carbon monoxide. Talk about gorking: Colorless, odorless, the agent of choice for many of the world's yearly cull of suicides, CO is Thanatos in a bottle -- but it didn't kill the worms. It just dimmed the candle, not by taking away the supply of oxygen but rather by preventing the worms from using it. And that was the leap that Roth made -- employing toxins for benefit. Using one of the most toxic substances known to man to interfere with the toxic effects of oxygen.
See, when creatures die of hypoxia, they don't die because they don't have enough oxygen; they die because they're still burning the oxygen they don't have enough of. What Roth did was find a way to turn off -- or turn down -- the fire. What he did was find a way to separate the living cell not from oxygen itself but from the capacity to use it.
Still, that was worms, and he was looking for human benefit. It wasn't as if he was ever going to convince any sane human being of the benefit of carbon monoxide. So one night in 2002, he was watching TV, thinking of what he usually thought of -- what kind of toxins he might be able to use to stop mammals from burning oxygen. He was watching Nova. It had a feature on these caves in Mexico that exhaled great lungfuls of hydrogen sulfide, an egg-smelling gas more toxic than carbon monoxide by a factor of ten. Nothing should live in those caves; instead, the caves were full of all sorts of fascinating creatures that tempted spelunkers to go down to see them. And the spelunkers had to be really, really, really careful or else they'd get gorked.
They had to wear all sorts of special gear or else they'd get gorked with one breath of hydrogen sulfide. Deanimated with a single breath! Roth didn't sleep for three days. He ran around telling anyone who would listen about hydrogen sulfide, and plenty of people -- his neighbors, mostly -- who wouldn't.
And by the time he stopped burning, he had figured out not only the utility of hydrogen sulfide as a beneficial toxin but also as a kind of metaphysics, based on the duality of oxygen and sulfur. Did you know that the existence of DNA -- life -- predated the existence of oxygen? Did you know that the earliest life existed not by breathing oxygen but rather by eating rocks? Did you know that the rocks were sulfur? Did you know that we're descended from those rock-eating microbes? Did you know that our bodies make hydrogen sulfide? Did you know that our bodies probably use hydrogen sulfide to keep from burning up on oxygen? Did you know that sulfur was also called brimstone? That before Jesus was raised from the dead, he went into a cave?
Of course, Roth was still unfunded. He was still a failed and unfunded researcher who was now seeking to buy large quantities of poison gas in the year following 9/11. He didn't go to the NIH for it, that's for sure. He went to Mark Groudine, the head of his department at Fred Hutchinson. He asked Mark G. for the $20,000 that would enable him to buy a few tanks of hydrogen sulfide and the equipment that would allow him to measure the responses of the mice he intended to gork. Mark G. worked right next to Mark R. and had been listening to two or three ideas a day from Mark R. for years. He gave him the money. Roth gorked the mice.
Roth's lab started gorking everything in sight: yeast, nematodes, mice, rats, dogs, pigs...but it was the paper Roth published the previous year on zebra-fish embryos that would finally get him federal money. Not from NIH, though. The zebra-fish paper was about stopping the heart of zebra-fish embryos. It was about switching their hearts on and off. The paper reported that the Roth lab was able to switch off the zebra-fish hearts for, like, nine hours before switching them back on again. I mean, those fish were dead....And so one day in 2001 Roth got a call in his lab. It was from DARPA. That's the Defense Advanced Research Projects Agency.
That's the Pentagon's arm for applied scientific research and "high risk, high payoff" freethinking. It's a strange, oxymoronic place that, aside from the creative lethality of its intentions, might be Mark Roth's institutional counterpart. "Did you really do what you say you did?" the DARPA program manager asked Roth. When Roth assured him that yes, he did, and that what he was doing was trying to get people not to die when they have heart attacks, the DARPA guy said, Well, we're trying to get people not to die when they bleed out, and he started working on getting Roth paid.
Roth never did get NIH money, though. Well, he had some, for some bricklaying work he was doing on chromosomal separation. But when he published his first paper on suspended animation and thanked the NIH for its support, the NIH freaked. What's suspended animation, after all, when you could be putting federal money into advancing our knowledge of chromosomal separation? But he never really was an NIH guy anyway, because he was never really interested in the mechanism of suspended animation -- he was interested in the effect. He was interested in the benefit.
There are people in his lab who are, at this moment, trying to account for the genetics of suspended animation and the role of hydrogen sulfide in the maintenance of metabolic flexibility, but Roth is a pragmatist. It sounds funny, calling a guy who says that he's interested in exploring the genetics of spontaneous combustion a pragmatist, but Roth grew up poor outside Philadelphia.
After their father died, he and his brothers grew up in a boys' school that doubled as an orphanage, and though you lose some things when you get sent away from home at age seven -- you lose love -- you do become pragmatic and self-sufficient. Which is why once Roth deduced that there was the possibility that his use of hydrogen sulfide to dim the candle could change the standard of critical care not just in warfare but in hospitals around the world, he founded a biotech company in 2005 to market it.
It's called Ikaria, after the island with regenerative sulfur springs mentioned by Herodotus. We're not talking about a company that might market, say, a diagnostic test for lupus here; we're talking about a company whose scientific mission is ruthlessly subordinated to the values of human benefit and scalability; we're talking about a biotechnology firm that, although started with venture capital, wound up purchasing a company that deals in pharmaceutical gases, such as the nitric oxide used to save the lives of blue babies; we're talking about a company with revenues of $200 million a year, a company that, until the collapse of the financial markets, was expected to go public with one of the biggest biotech IPOs ever.
Mark Roth is a major stockholder. He has always considered himself more of a throwback -- a throwback to the days before basic science meant the ferreting out of molecular mechanisms. Now he wants to be a throwback to the days when scientists were rich men who could fund themselves. He wants to be a success so he can go back to pursuing failure. He wants to go away from the campfire, into the woods, and have the option of not coming back.
You know what his problem is now? He was, and is, right. That's not necessarily a good thing. He knows a lot of guys who are right. And it's all over for them. The greatest freedom in the world -- and the only real freedom for a scientist -- is the freedom to be wrong. And that's the freedom Mark Roth is underwriting, with a company committed to saving the lives of bleeding and burning men.
Mark Roth keeps a little bottle on his desk, a pharmaceutical-sized vial full of clear liquid. It's got an orange plastic cap and a gold ribbon wrapped around the neck. It's a hydrogen-sulfide derivative, and Ikaria's first suspended-animation product. It's completed Phase 1 trials in Australia and Canada. It's being tested on humans, to make sure it's safe. He's gorking people now!
He's dimming human candles! It's also being tested on pigs in Texas. The military is doing those tests. They're doing surgery on anesthetized pigs, and then gorking them, to see if they survive the bleedout. If it works, it's going to be considered for emergency use in Iraq. Would it have saved the life of his daughter? It might have. She died a month after the surgery, but basically she bled out. She bled out.
You know, a few years ago, Roth went to Alaska on a trip. He went to Fairbanks, and it was freaking cold, man. It was 30 degrees below zero, and he saw something that he never forgot. He saw crows flying. These were creatures made of feathers and hollow bones. They had no right even to be alive at 30 below, but there they were, and they were flying. The image has haunted him to this day, because he can't explain it. And that's what science is.
You do the same thing day after day, you see the same thing day after day, and then suddenly you see something unaccountable, impossible -- believe it or not -- and it stays with you. All creatures die. But the things that haunt you, they get to live forever.
Date: 9 Dec 2008 | Author: mesmerX | Category: News
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