Joseph Hartman and his wife, Marilyn, smile stiffly as they sit in the Ben Franklin room of the University of Pennsylvania’s student union. He is gaunt and pale, with a long face and cropped, graying hair. She has the delicate frame of a songbird and is prim and neat in glasses and a green and white floral-print dress. They might be posing for a picture--a modern version of American Gothic--except that Joseph Hartman’s body is in constant motion.
Two dozen physicians and biologists politely but intently inspect Hartman as his case is presented by his neurologist. Hartman (not his real name) first sought medical help 13 years ago, complaining of irritability, lack of sleep, the jitters. He soon became unable to work and began to lose his short-term memory.
Only after many years did the chorea begin. The word comes from the Greek for dance, and that is exactly what Hartman is doing now. His hands dart and float in the air as if manipulated by an inebriated puppeteer. His head has a looseness that recalls those toy puppies whose heads once bobbed in the rear windows of American sedans. He watches his own limbs as if from a distance, occasionally reasserting control long enough to force a hand to grasp at the fabric of his pant leg or scratch the nape of his neck. Inevitably, his body rebels and resumes its dance. It is a dance of death.
This is Huntington’s disease: a devastating inherited condition that often waits until midlife to strike. A rare genetic flaw, present in one of every 10,000 people, selectively destroys two small regions of the brain--the putamen and the caudate nucleus--that help control movement. Eventually the muscles cannot be controlled at all; many Huntington’s patients die because they choke on food they can no longer swallow.
The presentation of Hartman’s case is the opening act in a two- day workshop aimed at generating research on how the gene kills brain cells. Hartman and his wife respond to questions. Do you like sweets? asks the woman seated next to Hartman’s wife. The woman could not present a more dramatic contrast to Joseph Hartman. Her blue eyes are clear and probing; she holds her shoulders square and steady. Indeed, Nancy Wexler, a psychologist and president of the Hereditary Disease Foundation, which organized the session, is as elegant and sharp as the tailoring of her cream suit.
After a pause, Hartman replies, I like fruit. He speaks in a shallow voice that seems only marginally under his control. I’ve practically given up candy. My grandchildren say my loss of candy is not a good thing. The joke elicits polite chuckles from the scientists.
Wexler comments to the gathering that Huntington’s victims often crave sweets and rich foods, perhaps to provide the extra energy it takes to keep the body in perpetual motion. Sometimes they’ll get up in the middle of the night and fix themselves enormous dinners, she notes.
Wexler’s familiarity with Huntington’s is not merely academic. Twenty-five years ago, when she was 23, Wexler learned that her mother, Leonore, had Huntington’s disease. That means there is a fifty-fifty chance that she has inherited the genetic mutation and will eventually die just as her mother finally did--just as the man in front of her is slowly dying now.
The specter of the disease has dogged Wexler every day since 1968--Any time I trip on a curb or drop something, I think, ‘Is this it?’ --but she, in turn, has hounded the disease. For more than two decades she has devoted all her energy to finding the destructive genetic misprint and a way to cure it.
In March of this year, a consortium of 58 researchers--including Wexler--announced that they had accomplished the first goal. The gene hunters, as the group was informally called, had discovered Huntington’s lethal mutation: an extended, stuttery repetition of a single DNA instruction. Now many labs are racing to create cell cultures and gene- altered mice that may lead to treatments or, eventually, a way to repair the defect through gene therapy.
Wexler has hardly paused to celebrate. The Philadelphia workshop is the first of a new wave of post gene workshops, one in a series of dozens of similar sessions she has organized over the years. When the presentation of Joseph Hartman’s case draws to a close, Mrs. Hartman grabs some muffins and a glass of orange juice for her husband. Wexler glances at the food and pats Joseph Hartman’s stomach. Keep eating! she says, and hugs him tightly, as if he were a long-lost relative whom she might not see again. In a way, he is.
It is almost impossible to talk about Huntington’s disease without talking about Nancy Wexler. In the fight against the disease, she has functioned not only as scientist but as catalyst, cheerleader, even den mother. Her quest has taken her from lavish fund-raising dinners to congressional hearings, from genetics laboratories across North America and Europe to squalid shantytowns on the shores of a Venezuelan lake. Her personal struggles--with her mother’s illness, with the decision about whether to be tested for the gene--have only added to her credibility. And through it all, she has remained an eloquent advocate for victims of the disease. In September she received the prestigious Albert Lasker Public Service Award in recognition of her work on their behalf.
Yet when asked, Wexler credits her father with sparking her crusade. There’s something very fundamental about how a family or any human being faces a critical problem, she says. The choices in my family have very much been determined by my father’s reactions to the crisis--how he dealt with it.
Just a few minutes apart, on a hot August day in 1968, Nancy and her sister, Alice, arrived in Los Angeles, answering their father’s invitation to celebrate his sixtieth birthday. Nancy thought something was up; theirs was not a family that was big on birthday parties. Milton Wexler was a tall, urbane man who had succeeded in three careers--as a lawyer, a commander in the Navy, and a psychoanalyst. He has since added another, collaborating with friend Blake Edwards on several successful screenplays. Alice, then 26, was well on her way to a doctorate in history at Indiana University; today she is writing a book about Huntington’s disease. Nancy had recently graduated from Radcliffe and was about to begin graduate studies in psychology at the University of Michigan.
Their father did not tell them anything until he had driven them back to his apartment. There he broke the news that their mother, from whom he had been divorced for several years, was doomed. (In retrospect, he says, many of the behavior patterns that led to the split--depression, irritability, and difficulty relating to others--read like a textbook on the early symptoms of the disease.)
Nancy says she doesn’t really remember much else about that day, except that she knew her mother was dying and that she and her sister decided never to have children. Milton tried to tell them what was known about the disease, but there wasn’t much to tell. Huntington’s afflicts 30,000 people in the United States and places another 150,000 at risk. The gene that causes the disease is dominant, meaning that if a child inherits just one copy of it, he or she will get the disease. As Milton spoke, Nancy’s mind rushed back to the early deaths of Leonore’s three brothers. The brother closest to her, Seymour, was a fantastic clarinetist, she says. When he died, Mother was very upset and went back east. I asked what was going on, and I was told that all of her brothers had died of a hereditary disease, but that we were not at risk.
Once the shock had passed, Nancy, Alice, and Milton rallied around Leonore. But they didn’t stop with that. Milton got in touch with the widow of the disease’s most famous victim, folk singer Woody Guthrie. Marjorie Guthrie was organizing victims’ families into the first organization to call for research, the Committee to Combat Huntington’s Chorea, and Milton decided to form a California chapter of the group. Guthrie’s organization, however, focused on building state chapters and lobbying; Wexler wanted to fund scientific research directly. My father felt very strongly--because it was such a devastating disease--that even though care could certainly be improved, the crucial thing was to find a treatment that took away the symptoms and cured the disease, says Nancy. That no matter how much you padded a bed with lamb’s wool so someone wouldn’t bash their legs and get black and blue on the railings, it was much better to get them out of bed. And that’s been the guiding philosophy.
Eventually the differences forced a split--in 1974 Milton Wexler created the Hereditary Disease Foundation. Even before then, he began pursuing his scientific agenda by setting up a series of freewheeling discussions on Huntington’s; he lured the best and brightest young minds to these workshops by offering free travel and $1,000 honoraria.
He was frustrated by the first meetings, at which young scientists gave old-fashioned presentations bogged down by slides and charts. So he refashioned them. From then on, sessions were held in the round, with no set agenda. What we ask for are people’s imagination, energy, and affection for a weekend, Nancy Wexler explains. If, however, anybody feels inspired to actually tackle some of these problems, we’re quite interested in knowing that.
Allan Tobin, a young neuroscientist from Harvard who knew Wexler from her undergraduate days, says the early workshops were like a game of the blind man and the elephant, where no speculation was too wild. In addition, he fondly recalls how Milton Wexler would sometimes use his contacts in the entertainment community--many of whom also happened to be his patients--to arrange a Hollywood-style party as the centerpiece of meetings held in Los Angeles. There the researchers hobnobbed with the likes of Jennifer Jones, Candice Bergen, and Cary Grant.
Eventually Tobin moved to UCLA and became scientific director of the Hereditary Disease Foundation. He also became the moderator for the Huntington’s workshops, refining a style that one of his colleagues calls a cross between Socrates and Geraldo Rivera. Over the years he and Nancy Wexler have developed the habit of sitting side by side while they watch the assembled scientists play intellectual volleyball. That’s so I can reach out and kick him if he intrudes too much, she jokes. And vice versa.
Wexler found her true mission, however, not at one of her own workshops but at an outside meeting. It was 1972, and she was attending a symposium marking the 100th anniversary of Long Island physician George Huntington’s landmark paper describing the disease that would come to bear his name. At the meeting Ramón Avila Girón, a Venezuelan psychiatrist, talked about a large population of Huntington’s cases clustered along the shores of Lake Maracaibo, a 130-mile-long brackish lake best known for the vast oil reserves beneath its muddy bottom. Then he turned down the lights and showed a grainy black-and-white film, replete with a tinny sound track of patriotic music.
One after the other, people walking down the streets or sitting in cafés danced to the tune of the Huntington’s gene. Inbreeding, isolation, and a tendency toward large families--one woman had 18 children; one man, 34--had produced an extraordinary, possibly unique, concentration of the mutant gene. It was a total shock, Wexler says. Here were all these Huntington’s cases, practically in every household, not shut away in nursing homes like they are here, not being stared at, but accepted as part of a community.
Though Wexler felt drawn to these people, it would be several more years before she’d have the chance to meet any of them in person. In 1974, after completing her doctoral thesis on the psychology of people at risk for Huntington’s disease, she moved to New York City to teach. Less than two years later she was named executive director of a new congressional Huntington’s Disease Commission to set priorities for federal funding to fight the disease, and she moved to Washington, D.C. At this point Milton Wexler realized that it was time for him to step back a bit from the project he had started: the science was getting more complicated, and Nancy and Allan Tobin had the workshops under control. From there on, says Milton, the story is Nancy’s.
One of the first things she did was as- semble a Venezuela Working Group so that she could follow her instincts and see that the lakefront population was studied. In 1977 her commission gave its recommendations to Congress, and federal funding began to flow to the gene hunt.
Her triumphs were tempered by her mother’s death, on Mother’s Day of 1978. Wexler sadly recalls visiting her mother in nursing homes as the disease took its toll. She was extremely frail. All of us were always afraid when she took a step that she would go careening forward onto the concrete. It wasn’t a soft environment; everything was unfriendly--concrete floors, hard walls, the chairs weren’t soft, the bed wasn’t soft.
Spurred by the loss of her mother, Wexler made preliminary trips to Venezuela in July 1979 and April 1980. In March 1981 she made the first of what would become annual expeditions to collect blood and chart this sprawling Huntington’s family tree. The lineage is now the largest ever documented, numbering more than 13,000 individuals. Day after day, assailed by insects and heat, she and about ten other researchers explored the barrios around Maracaibo and traveled to outlying villages. They worked in local dispensaries or government-built clinics. It was a sauna, Wexler says, describing one of these facilities. We had to scream over people’s heads. The room was packed because this was such a novelty. The Venezuelans were not the only ones to find the experience both odd and compelling. Here was this setting that couldn’t have been more different from anything I’d seen in my life, and yet here was this totally familiar disease, Wexler adds. I was exhilarated and frightened. I felt connected and alienated.
She and her colleagues wanted to take blood samples to use in studies of how Huntington’s does its damage to the body, but because few of the people had ever had blood drawn, they were scared. It was hard to describe why we wanted the blood of healthy as well as sick people, Wexler says. She explained over and over again that the large family tree around Maracaibo could provide special clues to a disease that was hurting people around the world. I told them my mother had this, she says, and that I was at risk. I told them that very far back we were family. They felt that bond. She returned to the United States with blood samples, a crude pedigree, and high hopes.
Those hopes were bolstered by an ongoing revolution in molecular biology. For several years researchers had been refining new tools called restriction enzymes; these enzymes, they believed, which could be used to snip DNA into manageable pieces, would someday let them pick out specific disease-causing genes from the huge, bewildering tangle of DNA that makes up a person’s entire genetic endowment. Each restriction enzyme recognizes its own specific sequence of four to eight nucleotide bases--the building blocks of genes. Wherever it spots that sequence, it makes a cut in the DNA. Over a long stretch of DNA, a restriction enzyme will excise snippets of varying sizes, depending on the number of nucleotides sitting between its cutting sites. Once researchers have the bits of DNA, they can copy them and determine the order of their bases--that is, they can sequence the gene or genes contained in that DNA.
Although more than 99 percent of human DNA is exactly alike from one individual to the next, at certain spots along the chromosomes short stretches of DNA display distinctive variations, called polymorphisms, and these differences are passed within a family from one generation to the next. The variations may mean that a cutting site that exists on one person’s chromosome is missing from the same spot on another person’s chromosome, or that extra nucleotide bases are added between two cutting sites on one person’s chromosome but not on another’s. In either case, when restriction enzymes go to work on the same chromosome from two different people, the resultant fragments may vary in length or weight, and so they can be used to distinguish one person’s DNA from another’s.
It was quite possible, the reasoning went, that some of these easy-to-spot polymorphisms sat very close to a disease-causing gene on a chromosome. If so, then the polymorphism and the gene would be likely to stay together, even when the chromosomes get shuffled around, as they do when eggs and sperm are produced. In other words, if you could find a particular polymorphism that consistently traveled with a particular disease, you could use that polymorphism as a marker to tell you that the disease gene was located somewhere nearby. And you’d know that, in any given family, anyone who had the polymorphism would be at risk for the disease.
When Wexler first encountered the idea of using polymorphisms as markers, it was just that--an idea. It was October 1979, and she was hosting yet another workshop. She listened intently as key theorists in the field explained their vision for the future of gene hunting. All the people there were true believers, she says. Once you accepted the premise that you really could find markers, then it was just a matter of time to find the gene. It might take you a million years, but it wasn’t a complete wild-goose chase where if you miss then you end up with nothing. The whole idea looked beautiful.
One of that workshop’s leaders was David Housman from MIT, a friend of Tobin’s. After the meeting, he returned to Cambridge and persuaded one of his graduate students, James Gusella, to focus on finding Huntington’s markers. Gusella, who soon graduated and moved to Massachusetts General Hospital, began identifying and collecting DNA probes--bits of DNA that are made up of the nucleotide bases complementary to those found around a particular polymorphism. A good probe would latch onto only the fragment of DNA containing that polymorphism. Ultimately, of course, the probe Gusella wanted to find was one that latched onto a polymorphism inherited along with a Huntington’s gene.
Collecting the probes was slow work. By 1982--when researchers had discovered only a few dozen polymorphisms--Gusella had his first batch of 13 probes ready for testing, with more waiting in the lab. He was not too hopeful; he noted that it could take 300 probes to more or less cover the entire human genome and find a marker within a reasonable distance of the Huntington’s gene. But when he began to test the probes on DNA from a small Huntington’s lineage in Iowa charted by Michael Conneally, a geneticist at Indiana University, he quickly hit unexpected pay dirt. The third probe in the batch seemed to grab onto a marker that showed up consistently in family members with Huntington’s--but not in those who did not have the disease. Conneally remembers phoning Wexler with the news. She let out a scream, he says.
It seemed inconceivable that Gusella could have gotten so lucky so soon; besides, the Iowa family was far too small to clinch the case. So he turned to Wexler and the Venezuelans. She had been giving him samples of blood since her first collecting trip in 1981--she’d send them along with any researcher heading toward the Boston area--so Gusella had plenty to work with. Conneally ran the statistical checks on his computer. One after the other, the samples confirmed the early finding. Through an extraordinary stroke of luck, they had found a marker for the Huntington’s gene.
As it turned out, the polymorphism used as a marker came from the short arm of chromosome 4, which meant that the Huntington’s gene was there as well. And 96 percent of the time, in each and every lineage, some version of the marker--there are 20 in all--traveled with the Huntington’s gene. That meant that if you could determine which version traveled with the gene in each family, you could tell with 96 percent accuracy whether or not a person would develop the disease.
The finding unleashed an ethical storm. In effect it constituted a predictive test for a disease for which there was still no treatment, much less a cure. And it could be used only on people who had living relatives who were both sick and healthy so that the marker could be traced. Before the marker was discovered, 70 percent of people at risk said they would want to be tested for the disease, if such a test were available. Yet in the decade since the marker test became available, only about 13 percent of the at-risk population has been tested.
Ironically, the Wexlers chose as a family not to use the technology. Both Alice and Nancy said that a positive result for either one would devastate all of them. If you take the test, you have to be prepared to be really depressed, said Nancy. I’ve been depressed. I don’t like it.
With the marker found, Wexler set her sights on the gene itself. She continued to organize workshops and seek out researchers willing to work on the gene hunt. She traveled from coast to coast, from the United States to the United Kingdom--in between forays to Venezuela, of course-- and in early 1984 she and Tobin pulled together the formal Huntington’s Disease Collaborative Research Group. At their suggestion, participants in the group agreed to share information during the search and to share the glory when it came to an end. The collaboration pitted a socialist model- -their group--against several independent laboratories pursuing the gene on their own. They had two main competitors: a lab that had been invited to join but declined, and another that had personality conflicts with people already in the group.
Even within the group, collaboration on this large a scale often created tensions and resentment. Sometimes someone would charge that one group was withholding a particularly useful marker, or that another was not sharing data as quickly, says Tobin. Whenever there was a question about whether someone was sharing, I would call the person and say, ‘Gee, it would be awfully nice if you brought that material to the meeting.’ So it was typical for people to come with little tubes of recombinant DNA that contained a new marker, a new piece of DNA from the suspect region of the chromosome where we thought the Huntington’s gene was located. They would distribute it at the beginning of the meeting, and of course then everybody felt better.
Wexler traveled from lab to lab through the 1980s, soothing bruised egos, seeking new talent, and cheering on anyone who was losing momentum. Conneally remembers when he was having trouble finding a place to store cell cultures from the Iowa family on whom the first marker tests had been performed. The only available mutant cell bank, in Camden, New Jersey, took a maximum of three samples from any family. They were persuaded and cajoled by Nancy to take more, he recalls. She got it up to 15 individuals. We collected blood from 30 and sent it to them. They couldn’t simply throw it away, so they stored it.
Through it all, Wexler returned to Venezuela each year, collecting blood and data until the pedigree spread like polka-dot wallpaper along the corridors outside her office at Columbia University Medical Center in New York, where she had begun lecturing and doing research in 1985. She began to pick up some peculiar patterns, patterns similar to ones Conneally had told her he’d seen in the Iowa family and others. For instance, in some families the gene did not wait until middle age to strike but hit children as young as two. In these juvenile-onset cases, it struck with particular intensity, causing stiffness in addition to the chorea, and death within a decade. And in most of the juvenile cases, the affected parent was the father: indeed, as a Huntington’s father continued having children, often successive children would develop the disease earlier and earlier in life.
Wexler particularly remembers one woman in Venezuela who had been sick from the time she was 14. Now she was 21 and she lay dying in a clinic. Her body had wasted away and stiffened to immobility. When Wexler, sitting at her bedside, enfolded the woman in one of her trademark hugs, the woman smiled up at her. It took a while to develop, but it was a radiant smile, Wexler says. Yet I knew that chances were, the next time we returned she would be dead. She remembers the frustration. I felt like I was staring at the answer, she says with quiet intensity. I knew that locked in that woman’s body was the answer to how Huntington’s disease works.
Nothing could slow her down in the pursuit of that answer. When she wasn’t in Venezuela, or touring labs, or hunting for talent, Wexler joined her father to raise money for the foundation. One of her more successful forays came when she spoke at a dinner hosted by Dennis Shea, a prominent Wall Street financier whose former wife has Huntington’s and whose children are thus at risk. In that one night $1 million was raised for the Huntington’s fight.
It would take more than money to win this battle, however, and the gene hunters were working with several handicaps. Although Huntington’s was the first gene mapped to a specific chromosome through markers, the markers didn’t lead directly to the gene, as the researchers had hoped. Indeed, researchers looking for other genes--those searching for the cystic fibrosis gene, for example--were able to use the marker techniques to capture their quarry much more quickly. The Huntington’s hunters, though, had trouble finding markers on both sides of the gene, which would help them narrow their search. Furthermore, they had no biochemical clues as to what the gene might actually be doing, so they couldn’t search for it in any logical, function-based way. Then, in 1990, they realized they had been looking in the wrong place altogether.
Their efforts had been aimed at a portion of chromosome 4 near the very tip, a confusing region of about 150,000 base pairs that Wexler calls the Twilight Zone of genetics. As they continued to rule out chunks of DNA, the gene, like a tantalizing mirage, always seemed to lie just out of reach. Finally Gillian Bates of the Imperial Cancer Research Fund in London managed to clone the entire tip of the chromosome--a step that would ensure rapid isolation of the gene. But any optimism generated by that development was quickly squelched when the gene hunters realized the gene wasn’t there. Instead, Marcy MacDonald, a senior researcher working with Gusella at Mass General, found evidence that the gene lay 2 million nucleotide links down the DNA chain in the opposite direction. The group had already suspected that this region might hold the gene but had avoided it because it contained about 2.2 million nucleotide pairs and might require a decade or more to sequence. The frustration was enormous, yet they had no choice but to take a breath, switch their focus, and press on.
The end came in far less than a decade. In 1992 several laboratories--including the two not in the collaboration--began focusing on a fairly small portion of the target area and isolating a number of genes, though they had no way of knowing which was the Huntington’s culprit. In January of this year MacDonald began sequencing one very large gene that had caught her attention. Close to the spot at which its protein-building instructions begin, MacDonald found a trinucleotide repeat, a kind of broken-record repetition of the three nucleotide bases--cytosine, adenine, guanine--that make up the genetic instruction for the amino acid glutamine. When she and Gusella compared genes from normal and Huntington’s chromosomes, it seemed that the number of repeats was always higher in the Huntington’s genes. We said, ‘This can’t be true. It can’t be this easy,’ MacDonald recalls gleefully.
Drawing on a vast pool of DNA samples from 75 different Huntington’s families--including some from the United States, Canada, Mexico, China, Japan, Africa, Germany, Italy, France, and, of course, Venezuela--MacDonald and two co-workers went into a frenzied two-week period of lab work. Over and over, they spread fragments of DNA onto treated plates, then ran an electric charge through them. The fragments, showing up as black bands on a white plate, separated by weight as they moved across the plate in response to the charge. The heaviest fragments, which contained the most repeats, traveled the shortest distance; the lightest fragments, containing the fewest repeats, traveled farthest. The researchers were able to tell the number of repeats in each fragment by determining precisely how far it had moved.
In every instance the genes fell into line. In normal individuals there were between 11 and 34 repeats of the glutamine code; Huntington’s patients had 37 to 86 repeats. There was no ambiguity, no overlap. In addition, some of Wexler’s most perplexing puzzles began to come clear. The researchers found that the youngest victims carried the most repeats, and that the number of repeats tended to expand as the gene was passed from generation to generation. They also found that sperm cells from a man with Huntington’s could range wildly in the number of repeats they carried, though the rest of the man’s tissues had but one consistent number. Researchers are now looking into whether, as these men age, they have a higher proportion of sperm with lots of repeats.
After the final experiment, on February 26, the triumphal report was sent to the journal Cell. As promised, it was signed simply the Huntington’s Disease Collaborative Research Group. And when the participants’ names were listed at the bottom, Nancy Wexler’s was among them.
The press conferences and parties followed quickly. A month after the paper was published, everyone flew to Dennis Shea’s estate in the Florida Keys for a communal sigh of relief. They had been going there once a year since 1987, spending their days working on the beach, and their nights at a bar called Woody’s, listening to the hard-driving rock and roll of the house band, Big Dick and the Extenders. This time was no exception. When Big Dick saw the scientists at the bar, he stopped in midsong. The 6- foot-6 singer called to David Housman, who was wearing a T-shirt printed with the likeness of a tuxedo, Hey, Doc, why don’t you come up here and tell the folks what you did! Self-consciously but with pride, Housman jumped onto the stage and said, We’re molecular biologists, and we’ve just found the gene for Huntington’s disease. Nancy Wexler sat in the back and grinned.
Within days, Wexler was bouncing from Los Angeles to New York to Texas, planning more workshops--first the Philadelphia conference, then a conference on the riddle of the trinucleotide repeats. It is the repeating sequence that now consumes her. How does the stuttery repeat change the normal gene into a killer? After the gene was pinned down, the researchers quickly found that it was expressed in every tissue--yet it seems to devastate only a few cells found deep in the brain. Why? There are some signs that mitochondria, the energy factories in cells, might be harmed by the altered gene product, but how?
The answers to these questions may come from yet another collaborative group Wexler began to put together a few years ago. This one will share the precious supply of several hundred brains and other pathological specimens from Huntington’s victims around the world-- including the 21-year-old woman from Venezuela, who died just months after Wexler last saw her. The hope is that this tissue might hold new clues to the workings of the disease, and that it might divulge its secrets to researchers willing to work together.
Wexler returned to Venezuela late last winter, just before the Cell paper was published. She went mainly to gather new data--the work is never truly done--but also to spread the good news. She walked through a maze of alleys in a shantytown near Maracaibo and saw old friends from her years of research, many of whom were showing signs of chorea. As she waved at them and smiled, she says, she couldn’t help but visualize on their faces the broken-record repeat from the plates back in the laboratories, like the shadows cast by a venetian blind. Everywhere she looked, the trinucleotide stutter looked back, dizzying in its persistent mystery.
I had spent so many years being so curious about what it was, studying all these people whose bodies contained the mystery, Wexler says. And suddenly it was superimposed on them, almost like a silk screen. It was an image without words, saying, ‘Here’s the answer. And here’s another question.’