STOCKHOLM Nobel Laureates in this Swedish capital draw crowds not unlike those you'd find for a popular concert, although perhaps smaller: For the Nobel Lecture in Medicine Friday, the throng arrived early, some with chairs for a more comfortable wait. A few had an impromptu picnic on the floor outside the Jacob Berzelius auditorium at the Karolinska Institute.
This year's Nobel Laureates in Medicine Mario Capecchi of the University of Utah, Sir Martin Evans of Cardiff University in the United Kingdom and Oliver Smithies of the University of North Carolina in Chapel Hill held the audience spellbound for 2 1/2 hours as they explained the fundamentals of gene targeting using embryonic stems cells. It was for their work in that area that the three men share the prestigious award.
The audience, standing-room-only, included a delegation from China, university students, other scientists and pals of the Nobel winners who have flown thousands of miles to attend. All of them grabbed a poster that explained gene targeting and featured photos of the trio; many of them stayed after to have them signed or to pose for photos with a favorite Nobelist.
The crowd would not have surprised the woman a reporter chanced to meet on the bus en route to the lecture. She said she has set aside Monday afternoon and evening to watch the Nobel Award Ceremony and banquet on TV. In the '50s, she said, anyone could get in, as she once did. Now, "most of us, at least those of us 50 and older, watch spellbound," she said. "Here in Sweden, it is a very important thing."
Several of those waiting in line for the lecture said they try to go every year.
As for the lectures, they were decidedly scientific, all designed to explain the principles of inserting a selected genetic change, whether the addition, deletion or modification of a gene, into mice.
Mouse blastocysts are cultured to yield embryonic stem cells, then DNA that will change the gene is inserted into a "target vector," and that's put into the embryonic stem cells. In a process called homologous (meaning similar) recombination, the targeting vector locates and combines with the intended gene. The cells that then contain the alteration are injected into mouse blastocysts that are inserted into a surrogate mouse mom, to develop chimeric mice. When that mouse breeds with a normal mouse, about half of the offspring will have the desired alteration, and researchers can then learn what they want about it.
It boils down to, "If we give you a modified copy of a gene, can we fool you into thinking it's a genuine copy," Capecchi said.
Capecchi told of early research that began with wondering if viruses replicate well because they have DNA and moved on to how to use DNA for gene targeting. He and Smithies discovered a process independently, while Evans' work made it possible to use the knowledge in live mice. Then Capecchi offered a peek at ongoing and future research.
For example, his lab continues to seek answers to synovial sarcoma, an aggressive cancer that attacks membranes that line the joints, usually in children and young adults. It is often very rapidly fatal.
The cancer starts with a translocation. One gene on a chromosome becomes damaged and breaks, then part of it incorrectly fuses with another broken gene. The two normally have opposite functions, one activating other genes and another inactivating them. The mutant gene may take several forms, including one that's particularly deadly.
They use gene targeting to activate the fusion gene in various cell muscles or their precursors to study when the result is cancer and when it isn't. From that, they hope to eventually see a treatment for the disease.Following the lecture, the Nobel Laureates were honored at a reception. Over the weekend, they'll attend the Nobel Concert and rehearse for Monday's big event.