Editor’s note: This is an article from the Spring 1999 issue of UCLA Magazine.
Leena Peltonen remembers the moment she decided to leave her native Finland to come to UCLA. It was a balmy evening two years ago, and she had just been to dinner with some UCLA scientists, who were trying to woo the world-famous geneticist with an attractive job. Peltonen hadn’t yet made up her mind. Now it was after dusk, the Southern California air lovely and mild, and she was walking back alone to the Westwood Marquis. Just as she crossed in front of a little white church near the hotel, something magical happened — something utterly unscientific: The church bells began to ring.
At this point in her story, Peltonen, a vibrant woman with ash-blonde hair and warm brown eyes, smiles a dazzling smile.
“They started to play Finlandia,” she recalls. “I went to my room and called my husband and said, ‘I am so tempted by this possibility that I really would like to go.’ He was in London. He said, ‘OK, let’s do it!’”
Peltonen laughs and leans in closer, as though she is telling you a secret. It’s a striking gesture, warm and unaffected, especially coming from one of the world’s foremost geneticists. With her penchant for bright suits, painted nails and tasteful gold jewelry, the 47-year-old researcher more closely resembles a high-energy CEO than a fusty bench scientist. But then, this is how some of her scientific colleagues describe the head of UCLA’s new Department of Human Genetics: dynamic, charismatic, a people person.
Since arriving in Westwood in July, Peltonen’s presence has triggered excitement throughout UCLA’s scientific community, from microbiology to psychiatry, realizing, as it does, a 20-year dream to found a genetics department in the School of Medicine. Though UCLA has long had a core of remarkable geneticists — Jake Lusis, David Eisenberg and Elizabeth Neufeld, among them — they were dispersed across campus and lacked their own department. This glaring omission was due to the usual variables of faculty moves and budget woes, and was only rectified because of the unprecedented $45-million gift from Leslie and Susan Gonda to build the Gonda (Goldschmied) Center, a state-of-the-art neuroscience and genetics facility.
“Trying to make due by putting together what people in one department were doing with what people in another department were doing didn’t work very well. It was a real minus for UCLA,” says Neufeld, a professor of biological chemistry, who played a key role in recruiting Peltonen. “Now, with Dr. Peltonen’s arrival and the opening of the Gonda Center, we feel very much enriched. To have a department with a chair who’s a scientist of international reputation means we can attract a lot of scientists, we can make advances in the area. It could have an enormous impact in the field.”
It was a difficult decision for Peltonen to leave Finland, where she held one of the country’s most prestigious scientific posts as chair of molecular genetics at the National Public Health Institute. “I was very happy in Finland,” she says. “I didn’t suffer for lack of funds.” But the opportunity to shape the future of genetic research at a university like UCLA is what enticed her.
“It was the challenge of this once-in-a-lifetime opportunity, a brand-new department, a brand-new building and the excellent facilities in the Gonda Center,” she says. “The faculty is very good in showing that they care. There is this genuine sense that one’s work would fly here. I think there are many wonderful people.”
As a condition of her agreement to come to UCLA, Peltonen arranged for a dozen Finnish colleagues — some of whom have worked with her for more than a decade — to join her as part of an exchange program to train the next generation of Finnish scientists. “These geneticists in Finland were really the key technical people,” she says. “I thought if they could bear with me for a couple of years on this side of the ocean, we really could get a quick start.” Peltonen and her husband, Aarno Palotie, a professor of pathology at UCLA, also will return to Finland for two months every summer to keep up their ties to Finnish researchers and clinicians.
In the 20 years that she has been studying genetic defects, Peltonen has identified no fewer than 18 genes related to such common disorders as multiple sclerosis and schizophrenia as well as more obscure diseases like AGT, a rare and horrific brain disorder found only among children in Finland. Energetic and focused, she completed most of that research over the last decade. Last year, Peltonen scored another triumph when she localized the gene for familial combined hyperlipidemia, or FCHL, in a group of Finnish families. The condition leads to the early onset of coronary-artery disease, which remains one of the leading causes of death in the industrialized world.
Amazingly, Peltonen’s findings on FCHL coincided with a study by UCLA geneticist Jake Lusis, who localized the same gene using a mouse model. The two scientists, who only learned of each other’s research when each published a paper in the same issue of Nature Genetics, are now working together in the hope of more quickly identifying the gene. It is just such collaborations that Peltonen intends to foster at UCLA. Around UCLA, there is the palpable, but unexpressed, hope that Peltonen will do for genetics what Nobel Laureate Louis Ignarro and others have done for their fields: put the Westwood campus on the scientific map.
“One of the things that’s so special about Leena is she is absolutely fearless,” says Dr. Edward McCabe, chair of pediatrics. “She’s willing to move into new areas; she is confident that she can do it.”
The timing of Peltonen’s arrival couldn’t be more favorable. Since 1990, an extraordinary federal research effort has been under way to map and characterize each of the 100,000 genes in the human genome — the set of coded instructions contained in our DNA that determines everything about us as individuals. Called the Human Genome Project, this scientific quest is of such far-reaching significance that it has been dubbed “the moon shot of biology.” Scientists have already identified most of the genes through painstaking studies of the 46 pairs of chromosomes nestled in every human cell, but the function of many genes remains elusive.
For these gene hunters, an ultimate goal is to identify the gene or genes linked to certain diseases. Once they’ve done that, they should be able to understand the molecular basis for disease — what happens when the genetic instructions go haywire — and then provide much better diagnosis and treatment. It perhaps goes without saying that whoever unlocks these secrets will make history.
“The genome project has really developed the genetic tools that researchers can now use to tackle these genetic diseases or genetic predisposition to common disease,” says Peltonen. “I don’t think it’s a hyperbolic expression to say that genetics will transform the way medicine is practiced in the future.”
Her influence after just seven months at UCLA is apparent, and not just in the work being done in the porcelain and stainless steel laboratories. One morning in January Peltonen gave a tour of the Gonda Center, skipping down the stairs in her low-heeled pumps, and enthusiastically showing off three oil canvases that had been commissioned from a well-known Finnish painter.
They are hard to miss, positioned in a hallway in the same location on three separate floors. Each is about six feet high and four feet across. Abstract in style, they feel as though they are moving and expanding along the wall, like clouds drifting across the sky. The one on Peltonen’s floor, titled Cloaked in the Cobalt of the Night, has a background of deep-blue circular shapes with gray spirals intended to resemble cells and DNA.
On other aesthetic efforts, she was less successful. On a brisk walk through the bright, airy hallways, Peltonen points out long, comfortable window benches occupying a corner of each floor, designed to provide a communal space for researchers to talk and share ideas. Peltonen wanted all the benches upholstered in a snazzy, zebra-print fabric created by a Finnish architect. She got her wish only on the sixth floor, where her office is located. “So dull!” she pronounces with a playful smile as she passes the muted gray-blue upholstered seating on the fifth floor.
Peltonen’s engaging style and determination to get things done have earned her many admirers. Says McCabe: “She has an innate diplomatic ability. She’s been able to work through very sensitive issues, bringing people together, very effectively. She gets the job done, but she doesn’t tread all over people getting there.”
And there is a strong foundation of humanity, too, in her thinking, says her husband, Aarno Palotie. “She understands astonishingly well how the human being functions as a person. She has the emotional depth that makes her not just a driving woman, a caricature of the movies, but well-rounded.”
Peltonen’s work ethic is clearly evident. Most of her days begin soon after dawn. She usually arrives in her office by 6 a.m., and immediately attacks her e-mail, which she uses to chat with colleagues across the globe. She still is coming to grips with the culture shock of being on a large campus like UCLA.
“I’m a very impatient person,” she says. “Everything here can take so much time. It’s such a huge culture. I came from a very small university, so everything moved very fast.”
Peltonen brings to UCLA a wealth of intellectual resources earned from working in a country that, because of its isolated population and centralized health-care system with detailed records on every citizen, is one of the world’s richest environments for studying human genetics. “She has enormous breadth, a tremendous range of talents and a vision of what needs to be done in genetics,” says Neufeld.
As a geneticist, Peltonen could hardly have chosen a more conducive country in which to be born. Finland is located near the top of the world, a nation of 5 million people spread across a region roughly the size of France. No one knows exactly from where Finns came, but historians believe their ancestors arrived in small groups from Western Europe some 2,000 years ago and there’s been little immigration since. There have been periods in the country’s history during which more than half the population died of hunger, and poverty and isolation conspired to keep the population low. The effect of this extreme isolation was profound: Finns bred with each other over several centuries without knowing it, giving rise to an assortment of strange and terrible diseases not found anywhere else in the world.
History enhanced the field of genetics in Finland in another fascinating way. In 1640, under orders of the Swedish king, the Lutheran Church of Finland began collecting detailed information on its citizens as a way to tax the population. As a result, Finland has fantastic medical records on every individual going back more than three centuries, giving scientists a remarkable tool to trace familial diseases. “Finns are a little like bacteria,” says Peltonen with a smile. “They are very easy targets to study genetically. In complex diseases, like schizophrenia or multiple sclerosis, you can trust that since they had common ancestors all current living individuals share some common genes predisposing them to these complex diseases.”
Peltonen’s desire to pursue medicine was fired as a child growing up in Oulu, a town of just a few thousand people near the Arctic Circle, where her father was an economics professor and her mother a high school teacher. When she was 9, her younger brother developed a severe form of diabetes; he eventually died at age 32. “I think that affected my thinking, that doctors are miracle-makers,” she says.
Peltonen went on to the University of Oulu, earning her undergraduate degree as well as her M.D./Ph.D., but switched her focus to research when she began studying under an inspirational scientist who worked in inherited diseases of collagen. It was a wise choice in other ways, too. Peltonen met her husband, a pathologist and expert in DNA diagnostic techniques, in the laboratory there, and the two have collaborated ever since. In 1978, Peltonen and Palotie moved to the United States, completing postdoctoral work at Rutgers University in New Jersey. It was the beginning of the revolution in molecular biology, and that year, the first two genes were cloned. Peltonen was captivated, and quickly turned her attention to genetic research. “It became very obvious that if you want to understand disease, you must understand genes,” she says.
In 1984, Peltonen and her husband returned to Finland and joined the medical faculty at the University of Helsinki. By now, Peltonen was gaining a reputation in genetics, especially in the area of devastating children’s brain disorders. She painstakingly labored to identify the gene that caused a particularly horrific disease among children who were born healthy and normal but who progressively deteriorated until they were profoundly retarded.
In 1986, when she was 35, Peltonen’s career took a momentous turn when she was recruited to head the newly created molecular genetics unit of the National Public Health Institute of Finland, the country’s most distinguished health and research organization. With the country’s rich population histories and medical database at her fingertips, Peltonen decided to concentrate on diseases that, because of the country’s genetic isolation, were peculiar to the Finnish population and would be easier to trace. And she had another powerful tool at her disposal: a system of free, high-quality health care in which patients trust their doctors and are highly willing to participate in medical research.
One of the diseases unique to Finland is a children’s brain disorder called neuronal ceroid lipofuscinosis, or NCL. To get the disease, a child must inherit a mutated gene from each parent. Though it strikes only about 50 families a year, NCL is especially cruel. Children with the disease appear normal at birth, but by the age of 1 they begin to go blind. Eventually, they lose their brain function and die a slow, brutal death. Because no one knew what caused the disorder, there was no way to prenatally diagnose children with NCL.
In 1988, Peltonen was contacted by a neurologist who had been treating these children. “She came to me and said, ‘Something must be done; this is such a terrible disease. We have to solve the basis of this. We have nothing to offer parents. It’s very frustrating to them.’” Peltonen approached the parents of the affected children, and each agreed to participate in a project to find the genetic cause of the disease. After collecting blood samples from the healthy parents and their sick children, Peltonen set out to scour their DNA for genetic markers — landmarks she could use to narrow the location of the gene. Meanwhile, she also searched their genealogical histories to try to find the origin of the disease.
At the time, the human genome was not well-known, so hunting for genes was an agonizingly slow process. As Palotie explains: “This was very primitive compared to today’s technology. You would run these markers around the genome, then narrow the region where the defective gene was. If some of these markers are always similar in affected individuals, by having 400 markers from all places of your genome, you usually hit with a few of them. Then you try to pull out more of these markers for areas that are similar between these patients. Then you get the statistical confidence that this is the place, but you’re still far away. In the end, you have to combine various mapping techniques.”
It took Peltonen and another scientist seven years to find the gene. In January 1995, they traced the mutation to a site on Chromosome 1. When Peltonen learned what the gene actually did, she was amazed: Its function is to make a protein that removes fatty acids, or lipids, from the cells. If this process is disrupted — as it is in babies with NCL — the brain cells die. This finding, it turns out, was significant not just for NCL, but for understanding the molecular process behind other brain disorders. “This is so fascinating,” says Peltonen, “because we’d have never thought that something involved in the lipid metabolism would be so dramatic for brain cells. This has now become obvious in many other diseases. So in many ways it opened a new concept of how crucial this lipid modification of the protein is for brain cells.
“I think this is a beautiful story,” she adds, “how a globally uninteresting disease in a small corner of the world opened a new field of research. I think it’s an educational story. You can’t always bet which project produces the most valuable biological information.”
Peltonen’s discovery of the gene led to the development of a prenatal screening test for NCL, and parents who may be at high risk can now receive genetic counseling. To Peltonen, this ability to provide families with knowledge of predisposition to a specific disease is at the heart of her approach to human genetics.
“I think human beings are built so they want to know why their child is sick,” says Peltonen, the mother of two. “If there is not a proper reason, they feel alarmed. Why did this happen? Was it one beer too much during pregnancy? Or did I do something wrong? Mothers have a tendency to think, ‘It was me, it was my fault.’ They’re used to carrying the blame. That’s a concept that has been missed when this genetic information has been criticized.”
Even if her discoveries do not ultimately lead to a cure, Peltonen views her research in a broader context. The knowledge of how a single gene malfunctions in a bizarre disease like NCL, for example, can spark tremendous insights into what happens in more common diseases like Alzheimer’s. That is the hope and promise of genetics.
“We still don’t know why the brain cells specifically die,” says Peltonen, speaking of NCL. “Why don’t all the other cells die, too? The molecular defects are still under investigation, and we need multiple experimental systems. The possibility of being so close to the Brain Mapping Institute and other groups who are studying neurobiology was one of the temptations that enticed me to UCLA. This is how we are going to find our answers.”
On a cold Friday in late January, Peltonen is breezing through back-to-back meetings in her office. One is with a development officer to plan a March luncheon for the high-powered group Women and Philanthropy, featuring a topic loosely called “Genetics and the Human Spirit.” Peltonen has agreed to be the keynote speaker, but in typical fashion she hasn’t stopped there. She has offered to corral other UCLA researchers to speak, made suggestions about the guest list and even raised the possibility of starting a fund-raising group called “Friends of Genetics.” About the only duty she hasn’t volunteered for is arranging the flowers for the centerpieces.
At the moment, Peltonen is preoccupied with one of her doctoral students, Niklas Jarvinen, who arrived from Finland just three days before. Jarvinen — very Finnish with his blue eyes, blond hair and pale skin — has dropped by to discuss his progress in locating a certain gene. The gene is implicated in another dreadful children’s disease, one going back 40 generations in Finland, that affects the motor neurons responsible for movement. The disease typically becomes apparent during the second trimester of pregnancy, when women realize the fetus isn’t moving. Using the DNA of five Finnish families and their fetuses, Jarvinen has thus far mapped the gene to a region of Chromosome 9. But the student still has a long ways to go to determine its precise spot.
“Again, this disease is not a public-health problem,” Peltonen says. “But if you consider the more general concept, that we are looking for a molecule that is essential for normal development of our motor neurons, it is a very basic, very crucial finding, which is needed to understand how we develop as human beings.”
Among the challenges Peltonen now faces working at UCLA is dealing with a non-homogeneous population that is far more genetically diverse and far more wary of medical research than in Finland. But after discussing the issue with many of her colleagues, she is not discouraged.
“In Finland, you can approach families by simply sending them letters. Here, with the diversity of the population, you have to apply a much wider spectrum of strategies. But I don’t see this as being much of a problem.”
In fact, the change in clinical approach may actually be stimulating for Peltonen. Perhaps it’s not so surprising, but the Finnish geneticist seems to view her new surroundings with a sense of awe. “I’m still so fascinated by the wonderful campus of UCLA,” she says, looking out her office window onto a gorgeous, sunny day. “If I walk around the campus in Helsinki, everybody looks the same. If I walk around the campus at UCLA, there is such tremendous diversity. You see all the different haircuts, all these different faces. If I’m really depressed or it’s a blue day, I go to the campus.”
