Death. And How to Avoid It.

Steve Chapple last wrote for the magazine about Randy Hayes and the Rainforest Action Network.

Dr. Richard Houghten did not choose his parents wisely. His father died at 58, his mother at 51. One grandfather died at 57, another at 47. An uncle, three brothers and his sister all have Type 2 diabetes. He is 59.

The awareness of his own mortality drives Houghten, president and director of the Torrey Pines Institute for Molecular Studies. It drives the rest of us too, of course, but Houghten and the other biotech cowboys on La Jolla’s “Science Mesa” are actually doing something about it.

“It’s all going to happen, Steve!” says Houghten, welcoming me into his office at the institute, a soaring concrete-and-glass structure that reminds me of the corporation in the film “Gattaca.” “But will I be around long enough to see it? No. Your kids? My kids? Guaranteed! You can already grow a human ear in the intestinal tissue of a mouse. Your heart in a beaker--that’s going to happen. The question is whether it’s your heart tissue or whether it can be stem cells. Stem cells are very important. There’s been some cool work with baby teeth recently, so the whole question of abortion may be left by the wayside. There’s pulp in there, in baby teeth, and you can get the cells and multiply ‘em up. It’s a future way beyond what we’re already talking about, and probably way sooner. If someone tomorrow said they had cloned a human, would you be surprised? I’d be surprised if it hasn’t already happened. If you’re rich, think about it, you’ve got a spare $100 million, plenty of technology, a network, and you can fund it. Technically, cloning a human is not nearly so hard as Los Alamos"--says a man whose father helped refine and measure the effects of the first hydrogen bomb.


“You may not like the idea of organ culture--hydroponic cloning--but in a way, what’s wrong with it? You take a few of your cells, your kids’ when they are born, those baby teeth, that umbilical cord blood, and you can eventually replace a rotten kidney, a bad liver, harvest a heart, certain parts of your brain--the whole brain’s a lot harder--if you have Alzheimer’s or whatnot. In the end what’s going to happen is, we are going to live as long as we want to, until we get bored. ‘I’m bored,’ ” Houghten shrugs, pretending to be about 200 years older than he is, “ ‘I’m bored with it all. I want out.’ ” He laughs.

People on the Mesa laugh a lot. Maybe it’s the sequestered beauty of the place, a swimmable surfer’s sea lapping limestone cliffs, palm trees mixed with pines, cool mornings, sunny afternoons, perfect air, a collegial setting, very high and quite justified salaries, and no traffic. Or maybe it’s the astounding beauty on the micro level--imagine using safe viruses as guided-missile vectors to bring new drugs to hidden tumors, or arresting diabetes with protein synthesized from the saliva of the Gila monster, or switching off the “bad genes” for Tay-Sachs, Huntington’s chorea and cystic fibrosis.

Once a sleepy paradise, “Beverly Hills by the Bay,” La Jolla and Torrey Pines Mesa are now at the center of the most concentrated cluster of biomed in the world: more than a dozen major research institutes, among them Salk, Burnham, Scripps and UC San Diego, and 300 companies such as Pfizer, Novartis, Amylin and the aptly named Isis Pharmaceuticals (Isis put the pieces of Osiris back together, long ago, in Egyptian times, when the brain was treated as the most discardable of organs), many within a few square miles of each other, some stretching in a weaving, blinking line, like the twisted strands of the double helix itself, up to Oceanside and down to Mission Bay. In all, 39,000 life-science professionals work in San Diego County, generating near-daily breakthroughs and headlines and bringing in as much money to the new San Diego as either of the old mainstays, defense and tourism.

I’m hoping these people know something--something big--that the rest of us don’t. So I’ve come as a concerned layman to query Houghten on a subject of wide interest: death. Also, how to avoid it.

I hadn’t seen him since our days in the Bay Area, where he got a PhD in organic chemistry at Berkeley and used to roar to work on a motorcycle, smoking the Bay Bridge at dawn, and where he skydived, free-dived and scuba-dived with great whites off the Sonoma Coast. “A phase,” he says, “that lasted about four years. It was along the lines of ‘Life is short, and I want to do everything.’ I was 25, and it seems like only yesterday.” Now he drives a minivan and holds a joint professorship at Zhejiang University, south of Shanghai, lecturing and sussing out China for manufacturing possibilities. But he says he hasn’t changed. “You’re the same at 15. When you’re very young, you want respect, but now it’s the thrill of doing something that nobody else has done that you know will be successful. It’s better than sex.”

What I like about Houghten as a guide to practical immortality, La Jolla-style, is that I can get him to talk about stuff other scientists will only whisper. Our planned philosophical get-togethers promise to be like Tuesdays with Morrie, if Morrie had chatted a mile a minute, conceptualized at warp speed, banked a few million from his 60 patents and six companies, and thought, just maybe, that he or his kids had a snowball’s chance and so had to excuse himself, right now, to go down the hall and synthesize some peptides, essentially small proteins that can be used both as drug-delivery systems or novel drugs themselves.

“In the lab, we routinely make 6 trillion peptides,” he says, popping his eyebrows. “I can make them all. I have made them all. That’s what I do. We can even test them in the living animal, let its system decide, for pain relief or hyperactivity, say. It’s a phenomenal step beyond the test tube.”

Is Houghten depressed, knowing what he knows, knowing he was born 40 years, shall we say, prematurely?

“No, actually, in a way that’s been a driving force--mortality, time, the ticking clock--for my whole career. We’re going to die, Steve! And what’s going to keep us from maybe not dying? ‘Cause you and me, we’re not going to heaven, way up there in the clouds.” He’s laughing again. “What is the one thing that might not make that happen? Science. I mean, there may be a God, but we are to him as a bacteria is to us.”

Houghten walks me out into the filtered Mesa sunlight, General Dynamics to the left, Novartis to the right. He’s still trying to help me to first base. “Aging isn’t one thing,” he says. “Cancer is hundreds of things; aging probably is too. Why does everything die? That’s the first question to ask. Nothing is immortal. Some cells can be made immortal, but any complex organism has a life span. Why?”

“Can I pose kind of a stupid question?” I ask Sean Oldham, a world expert in signal transduction--intra-cellular communication--in his fly lab on the ground floor of the Del E. Webb Center for Neuroscience and Aging Research at the Burnham Institute, around the corner from Houghten’s complex. Oldham is 37, the father of four daughters, ages 8, 6, 3 and 1. I had already asked him how he slept at night. He said he didn’t.

Now I ask: “Why are fly genes so close to human genes? We don’t look much like flies. I mean, do we?”

The short answer, obvious to scientists who understand evolutionary genetics but strange to anyone else, is that, yes, we do look a lot like flies, at least on the grand micro-scale of things.

“We have arms. They have wings. We are big. They are little. We both have to grow. We both start out as eggs. We both have to differentiate into other functional tissues,” Oldham says. “Drosophila shares some 60% of human genes. A fly functions as an adult with physiological systems that are the same as a human’s. You can take human insulin and it works in the fruit fly. You can take a human gene and a fly that lacks the same gene, put the human gene in--the human gene works just fine, and it can rescue what’s missing in the fly.”

But it doesn’t work the other way around.

“You can’t do that. It’s hard enough to do gene therapy with human genes, let alone putting a fly gene into a human"--and here we get what I first recognize as “the La Jolla laugh,” a sort of Aha, so this is the way the universe really works chuckle. “Theoretically, sure, you could, but you would get in a lot of trouble.”


“No, legally.”

Oldham’s research is showing that aging fruit flies can be made to live longer if certain genes that manipulate and control their insulin-producing pathway are “turned off.” This and similar research conducted in mice and in C. elegans, a translucent little roundworm, are behind the restricted-caloric-intake movement, the idea that eating 30% less will make you live longer.

“It’s a social experiment in humans,” says Oldham, as futile as it is fashionable, “since eating too little has no benefit. There are also side effects. In flies, the mutants are dwarfs. They are sterile. You don’t want to live longer if you are sterile and a dwarf, as a fruit fly or a person.” He laughs. “It’s a complex system, and we are tweaking it by taking one gene off here, another there. The Holy Grail is to do it in such a way that you get longevity without the associated side effects, which can include a loss of muscle mass. You don’t want life extension with 200 years of hip replacements. Some researchers don’t necessarily care whether you extend life span. They want to restore the decline in organ function, in the heart, the immune system, so that you will live happier and more productively. That’s the balance we’re tackling now.”

On the way out of Burnham, I stop for ice cream. In a lower courtyard at 3 in the afternoon, Bill Stallcup, a professor of developmental neurobiology, is churning vanilla with mixed berries for his post-docs and fellows. He tells me a story about a group of La Jolla scientists who attended a meeting in Boston. The plane was late. They didn’t have time to change and arrived at dinner the way they went to work on the Mesa--polo shirts, chinos, cargo shorts. “Here come the Californians,” gibed one Harvard professor.

“So was he jealous or annoyed?” I ask.

“Oh, he came out to La Jolla two years later,” Stallcup says, “so I guess jealous.”

“My view is that life extension is not necessarily the object,” says Fred Gage, trim, 55, an expert on neurogenesis and stem cells and chair of the faculty at the Salk Institute, a 15-minute walk from Burnham. “The object is to have quality of life for as long as you live. What you would like is that the period of time from deterioration to extinction be made as short as possible, out to the biological maximum. Whether you want to extend life is a separate discussion. If you don’t improve quality of life and you get life extension, well--" He laughs, softly.

The groundbreaking experiments that Gage and his lab have conducted have improved the quality of life for a great many people, changing the way we live in the process. Headlines on his lab’s research projects tell the story: “Exercise Makes Mice Smarter,” “Human Brains Do Sprout New Cells,” “An Enriched Environment Stimulates An Increase in the Number of Nerve Cells in Brains of Older Mice.”

“Cognitive decline can be reversed,” Gage explains, because there is a small population of immature nerve cells in the mature brain, and these can be switched on by focused learning in a challenging environment or simply by regular exercise. “From the time a cell is born in your brain till it matures into a functioning neuron with electrical-physical activity takes about a month. It doesn’t just turn on like that--" Gage snaps his fingers. Your brain also turns cells on according to what you do, whether you’re a veteran London cabby, musician or scientist. On the other hand, acute stress causes the baby brain cells in the mature brain to lie fallow and undifferentiated.

“You can boost neurogenesis, nearly double the number of neurons being formed, even in an aging adult. The first results [in 1997] were so striking,” Gage says, “that the few couch potatoes in my lab decided to start running at lunch. We’re still struggling with the conceptual framework: Why is it that the adult brain has retained this capacity for generating new neurons, so reliably, across so many species?” He cites the theory of an evolutionary value in grandparents’ helping to care for those still of reproductive age.

I find the concrete buildings at Salk boxy and stark, but Paul Heyer, in “American Architecture: Ideas and Ideologies in the Late Twentieth Century,” writes: “Louis Kahn’s Salk Institute for Biological Studies ... aspires within its own spirit to an order achieved through clarity, definition, and consistency of application. It stands as a testament to Kahn’s word, ‘Order is.’ ”

“Order is,” indeed. Salk and Kahn’s working temple is as cluttered and creative as a kindergarten on the inside, with beakers and bulletin boards and pictures of babies and James Watson, anoles and Rio de Janeiro. Only on the outside does it flip to mid-'60s functionalism.

“Here the emphasis is on ideas,” Gage says. “People come from the East Coast and they can be frustrated. They ask who’s in charge. But nobody’s in charge. Everybody just wants to get their work done. If getting together helps me get my work done, then OK. It’s a Darwinian selfishness--if this community is strong, then I will be strong. Originally, senior scientists like Salk set a standard that was very, very high. Young scientists coming in knew what it meant to be the best from these people, who weren’t hung up on accolades but were more excited by ideas, by productivity, than by being Herr Professor--a community of scholars, a generosity of spirit. Biotech is a real boon to this community. Used to be, you’re into the money, you must be a bad guy. There was a 10-year period of changing what it meant to be a scientist.”

Leaving the institute, I stop in a parking lot fronting the Torrey Pines Gliderport to watch what I imagine are intrepid post-docs as they defy death--thrillingly, slowly, hang gliding on puffs of air above Black’s Beach, a mecca for surfers and the unclothed far below. I’ve heard there’s a fatality nearly every year. Gage says he prefers playing squash for longevity.

“If you could live forever,” Houghten had asked, “would you spend the rest of eternity doing everything? Hang gliding? Mountain climbing without a rope? Or cloistered in a room with books, afraid to take any risks?” Mortality in the future could be like hemophilia today. Which makes you feel more alive?

“As a commercial endeavor,” writes Cynthia Robbins-Roth in “From Alchemy to IPO: The Business of Biotechnology,” “combinatorial chemistry didn’t exist until 1990, when Dr. Richard Houghten at the Torrey Pines Institute for Molecular Studies in La Jolla, California, founded a company around a revolutionary new technology. Although chemists traditionally took many steps to synthesize a single compound, Houghten developed a way to synthesize many compounds in relatively few steps. Building on earlier work that used a solid substrate to synthesize peptides, Houghten accelerated the process through the use of ‘tea bags'--porous membranes containing solid beads that could be exposed to a variety of chemical groups, thus adding them onto a core structure, or ‘scaffold.’ ”

Combinatorial chemistry--"combichem” in biowonkese--allows huge libraries of drugs to be created and quickly tested for medical use, a valuable development in curing disease and, on the Mesa, in creating wealth. Houghten’s share of Multiple Peptide Systems, a privately held garage start-up he funded with his own “pocket money” in 1986, came to be worth about $12 million by the 1990s. In 1996, he took his Trega Biosciences public, riding it up and down the Nasdaq, selling it at one point and then buying it back.

The first big San Diego biotech company was Hybritech, which used monoclonal (from one cultured cell) antibodies to diagnose disease. It was started in 1979 by UCSD medical professor Ivor Royston, biochemist Howard Birndorf and executive Howard Greene with $300,000 in venture capital. (Genentech was the big dog of the time, formed in the Bay Area in 1976.) La Jolla, long home to the Salk Institute, ramped up in 1986, when Eli Lilly bought Hybritech, which had grown to 800 employees, for about $500 million. The legendary Royston went on to co-found Forward Ventures, San Diego’s major biotech funding group.

Houghten, himself once a researcher at Scripps, recalls that in the ‘80s, forming your own company was seen as “economic prostitution” by many scientists in academia. Now it’s almost the expectation of ambitious professors. “You can’t just have a therapeutically cool idea,” he says. “You have to have an idea with commercial potential, paired with people with the right financial and business acumen to match the discovery. It’s an exciting time on the Mesa, but the last two to four years have seen a shaking of the tree. Now the fruit is ripe. In the next five to 10 years, people will be knocked back on their heels by what we come up with. The public wants stuff to fall out of the sky, but often it’s the quiet advancements that sneak up on you, the progress in antivirals and stem cells.

“In the beginning, I saw that I could lose every penny. If you’re a scientist or an entrepreneur, know that it can all disappear, and embrace that loss. And if you can’t, don’t do it. You might not want to if you’re 80, but when you’re 40--" He laughs.

Eventually I ramble off the mesa.

At the Living Room, a coffeehouse as bohemian as La Jolla gets, Isabelle Rooney, an MD/PhD associate director at SGX Pharmaceuticals, a drug-discovery company specializing in cancer therapies, points to her 4-year-old daughter Genevieve’s perfect skin. “Skin is hard. I have little doubt we will come close to curing cancer in 20 years, at least controlling it, as we do AIDS, but skin is tricky.” I gather she means regenerating it, keeping it smooth as a baby’s bottom, as we non-scientists like to say, but--cancer cured, and in 20 years? “I should hope so,” says Rooney. Genevieve hands her 2-year-old brother Lincoln a messy hunk of blackout cake. “I had Lincoln’s cord blood frozen. It costs $100 a year to keep it, a place in Texas. For the stem cells. May come in quite handy for Lincoln in 50 years. I froze Genevieve’s too. Lincoln, please use this napkin.”

At Scripps Institution of Oceanography, I gaze under a microscope at a bryozoan, a moss-like intertidal creature--this species more like a dirty Brillo pad--as it filters seawater. Dr. Margo Haygood and her PhD students are cloning some genes of a bacterium that lives symbiotically with the bryozoans. The bacterium produces a chemical called bryostatin that the Brillo pad uses to make its larvae taste bad to hungry fish. The chemical, coincidentally and wonderfully so, also renders human cancer cells less dangerous. It will be a neat trick to clone the genes, pop them into another bacterium and tease this milk-cow into manufacturing the rare compound, but the real problem, explains Haygood, is one of intellectual property rights, patent laws and the usual non-science headaches on the way to FDA acceptance.

Sunset, La Jolla Shores Playground. I lift my 5-year-old daughter onto the parallels. She rattles down them like a howler monkey with a leopard behind, then runs to join her kindergarten pal Camilla Zanetti, whose dad, Maurizio, a professor of medicine at UCSD, is developing a universal vaccine against cancer. Cool. The process, which targets an enzyme called telomerase--important in aging but out of control in the ageless cancer cell--was FDA-approved for Phase I clinical trials last year and is headed for Phase II, perhaps in volunteers with prostate cancer, a leading killer of “dinosaur dads” like Maurizio and me. Zanetti, who worked with Jonas Salk, has set up a company around the technology, known as transgenic lymphocyte immunization.

“It would be nice see your daughter become a grandmother,” he says in his soft Venetian accent.

A few weeks later, Rooney calls. She is very excited. She’s solved something big. Two years of work, a large team of scientists under her direction. “It’s just so wonderful to figure out what nobody else has!” What is it? I ask. What’s the implication? Pause. “Well, I guess that’s proprietary.” For cures? For drugs? SGX Pharmaceuticals targets a range of cancers, and maybe much more I don’t know about. “Yes! All that!” she says.

“Do we have to talk about immortality? Why can’t we talk about immorality?” Houghten jokes on my next visit. “What would you do to live longer? Would you give up fatty foods, lose 30% of your body weight, give up sex?”

Pretty much all the way to the sex part. I believe orgasm clears the arteries, at least in the middle-aged male.

Houghten laughs. “But you’re probably going to run out of orgasms around age 99, 100.”

I was hoping he had made some progress.

“Mortality is the basic fear, immortality the need and the desire and the wish,” Houghten begins, rapid-fire, “because death’s nasty, and you’re rotten and moldy and bugs are eating you and everybody that’s ever been alive is dead, except the ones alive now. There’s this huge fraud on the part of the biomedical community, Steve. Every single person dies. Nobody comes out of here alive. We pass a baton of new information from generation to scientific generation in a grand relay, but--

“Lots of theories come and go. Free radicals, vitamin E--whoops, too much screws up your liver. It’s like the Woody Allen movie ‘Sleeper.’ He wakes up 200 years later to find that tobacco makes you live longer and carrots make you die young. A lot of science du jour. If an expert makes the news, people think they’d better start eating blueberries or taking that supplement, antioxidants, drinking red wine--oops, my liver is gone. I’m more amazed as I get older that we exist at all, physiologically and spiritually, not religiously. It puts me in a state of awe, the biochemical mechanisms, the subatomic particles, it’s so beyond any nice little fairy tale they told you as a kid. It’s so much more symmetrical, more beautiful, more organized. It just works.”

But expanding life span?

“Well, it’s a pretty simple thing to expand the average person’s life span 20 to 30 years. You just say, if you have this gene, this gene, this gene, don’t drink. Or, you have a predisposition to diabetes or pancreatic cancer. Very soon, we’ll be able to test your DNA and cull out the life-threatening genes. They can do it in animals. Then, instead of getting cancer in your 50s, you might make it to your 90s.” He laughs. “The diagnostic component of longevity is coming to the forefront. If you could be painted in a body wash that would make every speck of skin cancer glow, you could zap it all. Diagnostics is flowing into therapeutics, and therapeutics will be individualized. Vioxx is a great drug, but if you are that tiny outrider who can’t handle it, you’re dead--yet your brother can take it. When stem cells and organ culture really come online, we will be able to grow the part of your body that we know from DNA testing, perhaps at birth, is going to blow up in 50 years. It’s your liver, your cells, no rejection, boom, and you’re OK. Or, who knows, maybe you’ll be dysfunctional, like an old car with a new water pump. We’ll see.”

Houghten mentions a friend who has developed an inexpensive mobile test for free-fatty acids: a prick of your thumb and the tech will know whether you’ve had a heart attack or bad Chinese food, no need to be brought to the ER in an ambulance or even to see a full MD. As the arteries constrict, unbound free-fatty acids are released, almost before you clutch your chest. After genomics and proteomics--the analysis of protein diversity, structure and function--will come metabolomics, the ability to measure all the metabolites the body uses and generates, in real time. During a down-tick in biotech in 2002, few believed in Houghten’s inventor friend, but the test was eventually licensed to big pharma.

“You seem bothered today, Steve. This death thing getting to you?”

I hate it when these hard-science guys stray into social science territory. “I’ve taken a childish way out,” I admit, “and immersed myself in the concept of immortality, intellectualization as a defense against death. So what?”

Foggy dawn. I pedal my bike up the Mesa, past the Scripps Birch Aquarium, where male sea horses incubate their young in body pouches, to the UCSD Biological Sciences 2005 Dean’s Symposium, “RNA: Beyond the Central Dogma.”

This year’s symposium honors Sydney Brenner, who, his bio states, “established the existence of messenger RNA and demonstrated how the order of amino acids in proteins is determined. He also conducted pioneering work with the roundworm, a model organism now widely used to study genetics. His research with Caenorhabditis elegans garnered insights into aging, nerve cell function and controlled cell death, or apoptosis. He was awarded the Nobel Prize in 2002.” The South African enfant terrible, born to impoverished parents, had learned to read at age 4 from the newspapers used to cover the breakfast table. Not too long after, he fell in with the American James Watson and the Brit Francis Crick, who even more famously plotted out the shape of the double helix in the early 1950s.

Sometimes it’s best not to know whom you’re dealing with. The talks at the symposium are, at times, as far above my head as Houghten’s heaven, yet I find myself seated at lunch beside Brenner and Sidney Altman, a Nobel winner from Yale, who all too easily surmises that I had been an English major.

“The way to live longer is not to eat so much,” says the nearly octogenarian Brenner, starting on a turkey sandwich, “because all the proteins and genes involved in aging are the same ones involved in the regulation of sugar metabolism. I know someone who has actually done this on himself, a professor at Caltech,” he says to Altman. “He’s lost about 60 pounds by restricting his sugar.” Brenner chews, shrugs. “Unfortunately, I think the machinery just goes to pot. It’s like a television or a motorcar, lots of parts to age, and there are no keys.”

Brenner is a crusty delight, that rare gene sequencer with a flair for amusing insights: “DNA makes RNA and RNA makes protein and protein makes--money.” In the 1970s, he was the scientific advisor to Victor Rothschild and David Leathers, among the original bankrollers of biotech, helping to form companies such as Genzyme, which bridged the gap between plasma and medical devices and gene therapy, and also Amgen, both multibillion-dollar corporations today in terms of market capitalization.

Will the next 40 years of science bring extreme life extension?

“Probably not,” replies Brenner. “We’ve extended it pretty well, but then people will find other things to die of. I think you could extend it today simply by getting people to look after their bodies.... They think the drug industry will come along and save them with a pill at the end. There seems to be a complete fascination in this country with immortality, and I think the epicenter is California. But it’s going to be hard to fix the problem. It may just be really impossible. One thing you learn from science is that some things just can’t be done"--he pronounces it cawn’t, in his lilting South African accent--"and you just have to accept that. Part of the culture of America in general is the frontier, and we will cross the frontier, but we may have come to an end to it.”

I can’t tell if Altman is rolling his eyes or wants to talk.

“What do you think?” I ask him. “Are Americans inclined to think anything can be beaten, even death?”

“No,” he says.

There’s some dead air here. Brenner and I wait for him to elaborate. But Altman is as terse as his lecture, the title of which was “RNase P.” Period.

“There is an old joke,” Altman says. “You can live a longer life, but it sure as hell is going to be boring.”

“I mean,” says Brenner, “stay with the life span you’ve got. That’s what I think!” And he launches into a discussion of “social therapeutics,” how to extend human life by conquering influenza, tuberculosis, “the man-created disease, addiction,” AIDS, cholera, dysentery. “The biggest change in life span was one great act of public health,” he says, “when we learned to separate the water we drank from the water we excreted in.”

“I don’t want to achieve immortality through my work. I want to achieve it through not dying,” Woody Allen once said. It’s a lot for this senescent English major to wrap his fears around. I walk to Jose’s Courtroom, probably the last establishment in La Jolla that doesn’t offer chocolate martinis, and enlist the help of two Dutch beers. The waitress (age 31) is trying to induce Chano, the swamper (age 56), to dance to “One Fine Day,” blasting over the speakers.

“What’s the matter, Chano, doesn’t your wife like to dance?”

“You don’t know the half of it,” Chano sighs. “She used to love to dance, and now she says el tiempo pasa y se lleva todo con el y nunca regresa.

I ask what that means.

“Time goes by and it takes everything with it, and it never returns,” he translates.

“I tell my kids,” says Houghten, who has two grown children and three younger ones, “ ‘Put me in the ground and plant a seed on top of my grave.’ ” Once his body is reduced to a pencil point of neutrons, protons and electrons--"all there is,” he says--then, well, matter is neither created nor destroyed, we are but the dust of stars, and all that jazz. Why do we die? We don’t. We age unto death.

Houghten invites me to a ballgame, Padres vs. Marlins, with his wife, Pam, who works with kindergarten children. Torrey Pines Institute for Molecular Studies has a block of seats in the Toyota Terrace overlooking first base. On the drive down La Jolla Scenic, Houghten wants to know who’s the most impressive person I’ve talked to. I hedge, assuming this is a mirror-mirror-on-the-wall question. But what Houghten wants to know, I realize, is something deeper, sadder, more than career. Is somebody working on something he doesn’t know about, has someone found some answers through good science or blind luck, a clue that will take us beyond the personal “extermination” point, as Fred Gage so nicely put it? If we could hold out for 30 more years, who knows what others might discover to take us beyond--to escape velocity, they call it in rocket science. Houghten, just a fan on his way to a ballgame, wants to know because, well, death may or may not be a joke, but his clock is ticking.

It’s “Trevor Time.” We arrive late to the game. Soon it’s the 7th inning, and 43,000 fans jump to their feet, filling Qualcomm Stadium with a mass of waving white flags--or, rather, twirling Trevor Time T-shirts. The first Padres pitcher is tiring. Trevor Hoffman, appropriately known as “The Closer,” takes the mound.

I ask Houghten what an amyloid is. “They did an autopsy on a 113-year-old woman in Los Angeles, oldest autopsy ever done, nothing wrong with her, ‘Cause of death: Old age.’ Her brain was full of amyloids.”

“It’s a protein--" Houghten is twirling his Trevor Time T-shirt as goofily as everybody else. “Get too much of it--"

“But it’s not a problem when we’re young?”

“No. It just mucks things up over time, one sequence of molecules bonds to another, and another, until it clogs the cell, can’t get rid of it, makes old people tired.”

Hoffman fires one-two-three pitches. Three strikes, the batter is out. Next batter gets four, he’s out. Third batter, two strikes, then a pop-up. Trevor Time! A surgical strike. It’s all over for the Marlins.