After playing saxophone in Tel Aviv, Amsterdam, and Boston, Adam Antebi has stepped up to his most challenging gig yet: deciphering the links between endocrinology and longevity in the nematode.
When Adam Antebi (pictured left) graduated from high school in Highland Park, New Jersey, in 1979, his fellow seniors voted him not only Class Brain, but also Most Talented, Best Instrumentalist, Most Artistic, and Best All Around. His classmates' perceptions were prescient. Twenty-four years later, a conversation with the versatile Antebi can drift from the cellular growth patterns of the slithering roundworm, Caenorhabditis elegans, to the legacies of jazz greats John Coltrane and Miles Davis. For Antebi, a molecular biologist who has moonlighted as a professional saxophonist, science and music are as inextricably intertwined as the two strands of DNA's double helix.
Antebi, 42, is currently a research group leader at the Max Planck Institute for Molecular Genetics in Berlin, where he has been unearthing insights into the genetics of development and aging in C. elegans. A brown-headed man with bushy eyebrows and crows' feet around his eyes, he has a thoughtful and deliberative air about him. He is also short and makes no bones about it, figuring that there might be some associated advantages, as recent research on size and longevity hints (see "The Shrimps Shall Inherit the Earth"). One of his grandfathers, who grew up in Russia, was 5' 1", a height that twice spared him from being drafted into the tsar's army; after escaping in a haywagon in the early 1900s, he emigrated to the United States, where he lived to the age of 101. "I, for one, hope that the smaller variants of the human species are longer lived," Antebi says with a grin.
Antebi might look compact, "but he's certainly not a compact person when you get to know him," says friend Per Ljungdahl, a yeast geneticist at the Ludwig Institute for Cancer Research in Stockholm, Sweden. For instance, those who know Antebi call him a geneticist's geneticist who is driven by curiosity and a love of science. "He's more like the old-style C. elegans researcher, in the vein of John Sulston," says David Gems, a geneticist at the University College London, referring to the Nobel laureate who spent years in the lab before publishing his landmark paper documenting the lineage of every cell in the adult worm. "So if there's a [research] problem, however difficult it is, Adam really keeps on with it."
Case in point: Antebi has spent the last decade unraveling the role of a gene called daf-12 in the endocrine pathway that regulates the nematode's growth and life span. It's a "thankless and difficult" challenge, says Gems, because although roundworms produce hormones that control their development, they lack endocrine glands that can be dissected and studied. "Most people just would run a mile screaming from this problem. But to make sense of the organism, somebody's got to do it."
Zigzagging Into Science
The science of how C. elegans matures is a study of genetically orchestrated developmental programs that activate at specified time points in the animal's existence. Similar to the worm's changing stages, Antebi's life has switched between artistic and scientific tracks since he was a child. Raised by parents who were social workers, Antebi grew up in a household infused with art, music, and liberal political views. His mother dabbled in modern dance, and his father, an avid photographer, documented the civil rights movement and Vietnam War protests, exhibiting his work in Manhattan's Soho district. A favorite uncle and aunt were art collectors who later donated a trove of conceptual and minimalist artwork to the National Gallery of Art in Washington, D.C.
Antebi, a nature lover who wanted to be a forest ranger or an ecologist when he grew up, amused himself in his early years by drawing mountain lions, bighorn sheep, bald eagles, and other animals. Then, in elementary school, he discovered music. He and his older brother, Julian, spent hours listening to James Brown, the Temptations, and the Beatles. By fifth grade, Antebi was taking saxophone lessons. In middle school, after hearing Charlie Parker and Cannonball Adderley for the first time, he fell in love with jazz. At the same time, however, he grew increasingly intrigued by what he was learning from his sixth grade science teacher, who made chemistry, physics, and biology "a lot of fun." "I used to enjoy writing the lab reports," he says.
In 1979, Antebi went off to Swarthmore College in Pennsylvania intending to study both music and science. He took a first-year course in molecular biology and got hooked. "I found it incredibly exciting. It was just a whole new world for me," he recalls. He majored in biochemistry, applied to grad school at the Massachusetts Institute of Technology in Cambridge, and got in.
But after finishing at Swarthmore, he flipped back to music once again, spending a year in Israel working professionally with a motley international group of musicians who played contemporary jazz--everything from blues to swing--in Tel Aviv. The band's leader was an American with leftist political ideas, who saw jazz as a meld of artistic freedom and form that could express every element of the human experience from the sacred to the profane; viewed through such a lens, music had the power to make the world a better place. It was a formative experience, Antebi says: "It really had a big impact on my thinking about not just music but life--looking at [the questions], How is the world the way it is, and what can we do to bring it to a better level?"
When his year abroad was up, Antebi had to decide on his career track. "I never felt comfortable with a decision to play music professionally," he says. "I didn't feel complete, it's as simple as that; I wanted to do something in science." So in 1985 he headed to MIT--arriving a semester late--and to introductory courses taught by Leonard Guarante, David Botstein, and Gerald Fink that opened his eyes to "the beauty of genetics and gene regulatory networks," he recalls.
Beer and Bebop
Inspired, Antebi joined Fink's genetics lab at MIT's Whitehead Institute. Working with postdoc Hans Rudolph, he identified the gene for an enzyme that helps control protein secretion in yeast. To figure out where in the cell the enzyme functioned (in the Golgi apparatus, it turned out), Antebi devised an elegant fractionation technique--a realm of cell biology he initially knew nothing about.
The Fink crew didn't only study yeast cells. It also used them to make beer. Antebi and Ljungdahl, then a Fink postdoc, were the lab's brewmeisters, concocting lagers, pilsners, and ales from scratch three or four times a year. They bought huge sacks of barley and hops and made malt mash extracts in the lab. "We used to let it ferment under our desks. You'd hear these bubbles coming up," recalls Antebi, chuckling. "The beer was really good, if I don't say so myself."
Despite his immersion in science, the music never stopped; whenever he could find the time, Antebi pulled out his sax. "I was the 'artist-in-residence' at the Whitehead Institute. I had my saxophone at work, and late at night, between 9 and 11, I would just go to the top floor ... and practice." Now and then, after 12 hours at the lab bench, he'd join jam sessions at the renowned Boston musical hot spots Ryles Jazz Club and Wally's Café. He sat in several times with famed jazz pianist Jackie Byard, whom he'd met in Israel; he also occasionally played backup for the popular ska band Bim Skala Bim and recorded with the group on its CD, How's It Goin'? Ljungdahl remembers seeing Antebi perform at a party celebrating the album's launch. "You see this guy on stage, and you don't understand why he's doing science, because you know he could be out there having another life," says Ljungdahl. "Not that science is bad--in fact, I love it--but ... you can just tell that he has that much talent." The bebop bug struck again after Antebi finished his Ph.D. in 1991. "I [had been] working so hard, I didn't really have time for music. And I just wanted to let that part of myself bloom again." He packed up his sax and took off to Amsterdam, where he joined a group of musicians called Men Without Heads. "That was a wild and crazy time," he says, recalling how they all lived together in a dilapidated, mouse-infested studio. "We played in some of the wackiest places." Once, they did a gig at a casino: "It was like a Fellini movie--there were dwarves and clowns and strange-looking people," he says. Another time, Xaviera Hollander, the Dutch madam who documented her sexual exploits in her notorious book, The Happy Hooker, heard the group playing on the street and invited them to perform at her birthday party. "She had an old Jewish grandmother, so [the party] was pretty tame," Antebi recalls.
Timing Is Everything
Six months later, Antebi returned to the States, recharged. "I was raring to do both science and music." Wanting to take his genetics into a multicellular organism, he'd already arranged a postdoc with developmental neurobiologist Edward Hedgecock, who studies C. elegans at Johns Hopkins University in Baltimore. "I basically sat down at the microscope and learned the worm inside and out. ... I really like microscope work to this very day. Studying worms is ... similar to practicing music: You can sit down, look at things, go over, and learn new things."
At Hedgecock's suggestion, in 1992, Antebi began investigating worm mutants called mig-7 and mig-8, which showed delays not only in the normal migration of particular gonadal cells, but also in other growth processes in the skin and intestine. Over the 5 years of his postdoc, Antebi demonstrated that mig-7 belongs to a class of genes that determine when other genes that spur developmental events switch on and off; mutations in mig-7, he found, alter the worm's progression through the third stage of larval growth.
Further work revealed that mig-7 and mig-8 were daf-12 and daf-9, respectively. These genes, which lie downstream of the C. elegans insulin-like signaling pathway, were already known to influence the worm's ability to shift into a hibernation phase called the dauer state; moreover, mutations in various genes affecting dauer formation could lengthen a worm's life (see "Growing Old Together"). Antebi's work was the first to establish that daf-12 connects the pathway that controls developmental timing to the dauer and longevity circuits in C. elegans.
Meanwhile, true to his goal of pursuing both passions, Antebi practiced the sax in the morning before going to lab. Now and then, he played evenings at African-American clubs around town, including the Sportsmen's Lounge, located in an edgy part of town. "The way they advertised it is, 'Armed security guards--we escort you to and from your car.' It was a little bit dangerous," Antebi recalls.But Baltimore jazz legends frequently showed up at the club to jam. "It was a pretty amazing scene for a lot of young players."
The highlights of his jazz experience came during this time. In 1995, Antebi played with the Whit Williams Big Band at Artscape, Baltimore's annual summer arts festival, in a concert backing up Aretha Franklin. He then got a gig with a group of well-known musicians performing at the 70th birthday party of famed saxophonist Jimmy Heath. "I played a couple of solos ... and I had a sax battle with Jimmy Heath on the blues. It was just awesome." He also recorded with drummer William Goffigan along with stars Cyrus Chestnut, Marshall Allen, and Victor Gaskins.
Tracking the Worm Trail Overseas
In 1997, Antebi embarked on a new adventure. With his wife, Helen, a classically trained pianist who ran her own business producing concerts in the Baltimore-D.C. area that featured European musicians, he moved to the Max Planck in Berlin for a 5-year research stint. The government-funded institute was forging a unique conglomeration of human genetics, genomics, and various model organisms under one roof, and it offered substantial funding to support Antebi's research. "It's been liberating for me," he says. "They give me the freedom to pursue my own ideas and to still do some bench work myself."
Compared with American scientific culture, the barriers to communication between research groups at the Max Planck are harder to overcome because departments are big and often self-contained, says Antebi. Still, that hasn't stopped collaborative efforts, he says, and on the whole, working and living in Berlin has been a life-enriching experience. "In general, I consider myself a bridger," he says. "I like to bring ideas together, I like to bring cultures together. I like to connect things and see big pictures."
Antebi encourages young American scientists who are interested in venturing abroad to take the leap. "There are plenty of really fantastic labs all over Europe, and you learn so much when you're in a different culture." Berlin has been a fantastic place to raise a family, he says, because the German social system puts a strong emphasis on good health care and education. And the arts are far more accessible to the populace than in the United States. Whereas a ticket to the opera can cost well over $100 in the U.S., "here, you can get a seat for $35," he says.
Following the trails of daf-12 and daf-9, Antebi has continued to break new ground in elucidating where these genes function in the dauer pathway. In parallel with molecular biologist Don Riddle of the University of Missouri, Columbia, he and his colleagues reported that C. elegans enters the dauer state when it runs low on a hormone produced by daf-9 that normally binds to the daf-12 receptor (see "Hard Times Teach Life-Extending Lessons"). The results place daf-9 upstream in the pathway from daf-12. "At the moment Adam, more than anybody else, is working out where exactly the different genes involved in endocrine signaling in the worm are actually functioning," says Gems. Moreover, the results indicate that this hormone is a steroid. Given that mutations in daf-9 as well as daf-12 alter longevity, the findings provide some of the first evidence that a steroid molecule influences life span--raising the prospect that similar steroid hormones might play an analogous role in humans.
Between running a lab and raising two young boys, Antebi has had to give music a rest--but probably not for long. Antebi's 3-year-old, Soren, is already learning to play the violin. "He's awesome. He's just starting, and he has incredible form," says Antebi. Odds are that the entire clan will soon be giving concerts in the living room. Antebi plans to bring his brood back to the U.S. next year so that the family can be closer to relatives; he's been interviewing at various universities in search of a new academic home. Wherever he lands, Antebi is sure to show up with both his microscope and his sax.
* Ingfei Chen, a contributing editor for SAGE KE in Santa Cruz, California, didn't make the cut as a clarinet player in high school band.