Medical research: Cell division
In 1962, Leonard Hayflick created a cell strain from an aborted fetus. More than 50 years later, WI-38 remains a crucial, but controversial, source of cells.
The woman was four months pregnant, but she didn’t want another child. In 1962, at a hospital in Sweden, she had a legal abortion.
The fetus — female, 20 centimetres long and wrapped in a sterile green cloth — was delivered to the Karolinska Institute in northwest Stockholm. There, the lungs were dissected, packed on ice and dispatched to the airport, where they were loaded onto a transatlantic flight. A few days later, Leonard Hayflick, an ambitious young microbiologist at the Wistar Institute for Anatomy and Biology in Philadelphia, Pennsylvania, unpacked that box.
Working with a pair of surgical scalpels, Hayflick minced the lungs — each about the size of an adult fingertip — then placed them in a flask with a mix of enzymes that fragmented them into individual cells. These he transferred into several flat-sided glass bottles, to which he added a nutrient broth. He laid the bottles on their sides in a 37 °C incubation room. The cells began to divide.
So began WI-38, a strain of cells that has arguably helped to save more lives than any other created by researchers. Many of the experimental cell lines available at that time, such as the famous HeLa line, had been grown from cancers or were otherwise genetically abnormal. WI-38 cells became the first ‘normal’ human cells available in virtually unlimited quantities to scientists and to industry and, as a result, have become the most extensively described and studied normal human cells available to this day.
Vaccines made using WI-38 cells have immunized hundreds of millions of people against rubella, rabies, adenovirus, polio, measles, chickenpox and shingles. In the 1960s and 1970s, the cells helped epidemiologists to identify viral culprits in disease outbreaks. Their normality has made them valuable control cells for comparison with diseased ones. And at the Wistar Institute, as in labs and universities around the world, they remain a leading tool for probing the secrets of cellular ageing and cancer.
“Here’s a clump of cells that has had an enormous impact on human health,” says Paul Offit, chief of the division of infectious diseases at the Children’s Hospital of Philadelphia. “These cells from one fetus have no doubt saved the lives of millions of people.”
Few people, however, know the troubled history of the cells — one that may offer lessons for modern researchers seeking to work with human tissues. Six years after deriving his famous strain, Hayflick made off with stocks of the cells and later started to charge for shipping them, prompting an epic legal battle with the US National Institutes of Health (NIH) in Bethesda, Maryland, about who owned the cells. That struggle nearly destroyed Hayflick’s career and raised questions about whether and how scientists should profit from their inventions.
What’s more, the WI-38 strain has helped to generate billions of dollars for companies that produce vaccines based on the cells, yet it seems that the parents of the fetus have earned nothing. That recalls the earlier development of the HeLa cell line, named after the woman whose tumour gave rise to the cells and chronicled in Rebecca Skloot’s book The Immortal Life of Henrietta Lacks (Crown, 2010). As with HeLa, the WI-38 case highlights questions about if, and how, tissue donors should be compensated that are still urgently debated today. Last month, for example, some scientists in the United States found themselves barred from using new stem-cell lines derived from human embryos because women had been paid for the eggs used to make them (see Nature http://doi.org/mv2; 2013).
The story of WI-38, unlike that of HeLa, also has its own controversial twist because it was derived from an aborted fetus. For 40 years, anti-abortion activists have protested against the use of WI-38 and vaccines developed from it. “It’s still a live issue,” says Alta Charo, a professor of law and bioethics at the University of Wisconsin Law School in Madison. “We still have people who refuse to take these vaccines because of their origins in fetal tissue.”
When Hayflick opened up that icy package from Sweden in 1962, he was working at the vanguard of virus research in the United States. At the time, the Wistar Institute was led by Hilary Koprowski, a polio-vaccine pioneer who hired Hayflick to run the centre’s cell-culture laboratory and supply cells to researchers. But Hayflick also began investigating whether some human cancers might be caused by viruses. To do so, he needed a resource that did not yet exist: verifiably normal human cells that could be reliably grown in the lab. Fetal cells, he thought, were an ideal candidate, because they were less likely to have been exposed to viruses than adult cells.
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