In his youth, Richard K. Wilson, Ph.D., had two heroes: He lived with one, and the other had a Nobel Prize. Wilson’s father was a high-school biology teacher who inspired in his son a passion for science. And James Watson, Ph.D., co-discoverer of the double-helical structure of DNA, inspired in Wilson a decades-long fascination with the genetic code that would shape his career.
Today, as director of the Genome Sequencing Center (GSC), Wilson stands at the forefront of the genetics revolution — one that promises to transform the way medicine is practiced and patients are treated.
The GSC played a leading role in the Human Genome Project, an international effort to assemble in precise order the 3 billion letters that make up the genetic code — an alphabet soup of As, Cs, Gs and Ts. Now Wilson and his colleagues are beginning to see the payoff. They’re getting an intimate view of the complex genetics that underlie diseases such as cancer. And they’re delving deep into the genome to determine how common variations can predispose individuals to diseases.
“Ultimately, we want to know how a person’s genes contribute to the diseases they get,” Wilson says. “The answers will inevitably lead to more accurate, early diagnosis of disease and personalized treatments based on a patient’s genetic makeup.”
Wilson came to Washington University in 1990 after a postdoctoral fellowship at the California Institute of Technology and was named the GSC’s director in 2002. He is highly regarded by his colleagues both for his depth of knowledge and for his vision.
“Rick is a consummate expert in genome mapping, sequencing and technology, and he has shown increasing leadership in the application of these approaches to medical problems,” says Francis Collins, M.D., Ph.D., director of the National Human Genome Research Institute (NHGRI). “Rick is the ultimate team player — he is unflappable, unselfish, disciplined and hard-working. More than any other sequencing center director, Rick is willing to take on important but unromantic tasks for the good of the scientific community.”
With Wilson at the helm, the GSC has been awarded more than one-third of a billion dollars in federal research grants. With that funding, he has led the GSC into a new era in which genome sequencing occurs at a dizzying pace. The $3 billion Human Genome Project took 13 years to complete. Today, GSC scientists can sequence a human genome in as little as four days at a fraction of the cost, vastly increasing the prospect for using genomic information as a basis for making treatment decisions.
Carving out a niche
Wilson’s foray into science began as a young boy. Once a year, he helped his father make batches of homemade agar on the kitchen stove and sterilize glass petri dishes in his mother’s pressure cooker, all so Mr. Wilson’s high-school students could have a hands-on microbiology lesson.
“He showed me how to pour the plates and streak bacteria onto the agar, and we would watch it grow,” Wilson says.
That experience paid off in fifth grade. Wilson used his newly honed microbiology skills to win first place in the school science fair. His project: determining whether two algae-laden lakes in his hometown of Kent, Ohio, were polluted, as many residents believed. He found the lakes, while teeming with microscopic plant life, had normal bacteria levels.
Later, as a college student majoring in microbiology, Wilson took a course in microbial genetics, with the required text being Watson’s “Molecular Biology of The Gene.”
“I was fascinated by this relatively simple molecule that stores and transmits information that is fundamental to life. I knew that’s what I wanted to work on,” Wilson says.
Throughout his career, leaders in the field have sought out Wilson for his expertise. In the early 1980s, his proficiency in microbiology caught the eye of Bruce Roe, Ph.D., one of the first U.S. scientists to sequence DNA. Roe had just learned the technique from Nobelist Fred Sanger, who developed the method at the University of Cambridge. Roe offered Wilson a spot in the doctoral program at the University of Oklahoma and the opportunity to work with DNA firsthand.
“It was really amazing because there were a few other labs that were just picking up the technique, but we were one of the only labs in the country that could do it well,” Wilson says.
Several years later, CalTech molecular immunologist Leroy Hood, Ph.D., met with Wilson and offered him a postdoctoral fellowship if he would lend his expertise in DNA sequencing to help develop a way to automate the process. The current process was laborious and exceedingly slow. Wilson jumped at the chance, and Hood’s team pioneered the DNA sequencer, the machine that later made large-scale sequencing possible.
While Wilson was at CalTech, a group of prominent scientists, including Watson, were making plans to sequence the human genome, a project considered highly controversial for its high cost and questionable merits. Watson, then head of the newly created NHGRI, came to CalTech to discuss the project with Wilson, Hood and others.
“I had the opportunity to sit in a room with Jim and two other guys and talk about what it was going to take to develop the technology and the infrastructure for sequencing the human genome,” Wilson says of his first of many meetings with Watson over the years. “That experience was absolutely amazing.”
Looking to the future
Wilson was lured to Washington University to help sequence the genome of the C. elegans roundworm, a pilot project for the human genome. He also made major contributions to the human genome sequencing effort and readily recalls the jubilation of finishing that project. “You can’t imagine the euphoria,” Wilson says. “It was a huge accomplishment by many, many scientists.”
Since then, the GSC has continued to refine the human sequence and has spearheaded projects to sequence the genomes of the mouse, platypus, chimpanzee, chicken and other organisms. These efforts have allowed scientists to get a clearer picture of the evolutionary tree and begin to find genes that distinguish humans from other animals.
The GSC recently began work on a project to find the myriad genetic alterations in cancer. The research initially focuses on ovarian and lung cancer and glioblastoma, an aggressive brain tumor. The GSC plays a leading role in an international collaboration to sequence the genomes of 1,000 individuals. The project aims to create the most detailed picture to date of human genetic variation and likely will identify many genetic factors underlying common diseases.
Richard K. Wilson
Position: Director of the Genome Sequencing Center and professor of genetics and of molecular microbiology
Education: Bachelor of arts, microbiology, Miami University; doctorate, chemistry, University of Oklahoma
Family: Wife, Allison, a high-school tennis coach; twin sons, Taylor and Evan, 18
Sport: Tae Kwon Do. Wilson holds a fifth-degree black belt.
Hobby: Sports cars. He can be seen driving his convertible 1973 Fiat Spider on warm, sunny days.
Wilson has maintained the GSC’s reputation as a DNA powerhouse by focusing on sequence quality and new technology and by assembling a top-notch staff. The GSC, the Broad Institute in Massachusetts and Baylor University in Texas are the nation’s main academic sequencing centers. While the centers routinely collaborate on projects, the competition among them for funding and recognition is fierce.
“Rick has two special gifts: patience and diplomacy,” says GSC Co-Director Elaine Mardis, Ph.D. “He has a unique ability to bring people together and navigate rocky pathways and clashes of opinion and egos. He also has a great grasp of the big picture and a gift for getting others to recognize what it is and focus on it.”
As the GSC adds next-generation DNA sequencers to its array of technology, the center increases the amount of data it generates by several thousand times each day. A new 16,000-foot data center is being constructed to store all that information and help the GSC meet its massive computing needs.
Faster, more efficient DNA sequencing also is making it possible for the GSC to provide its expertise to University faculty for their own sequencing projects. The GSC recently became the first to sequence the genome of a patient with acute myelogenous leukemia, a project with Tim Ley, M.D., the Alan A. and Edith L. Wolff Professor of Medicine, who studies this type of cancer.
“I think of Rick as a bold adventurer,” Ley says. “To do ‘discovery genomics,’ you cannot be daunted by the scope of the projects or the degree of difficulty or the technology requirements. You just have to decide that something is important and worth doing and then figure out how to do it the right way. Rick has an amazing ability to do this.”