Medicine's Holy Grail
Page 3: The Breakthrough
Saturday, August 18, 2001
Ever since the study of embryo development early in the 20th century, scientists suspected a powerful precursor cell must be present to give rise to all the varieties of tissues that constitute a human.
But not until the late 1950s did a pair of Canadian researchers prove that these elusive stem cells actually exist. Earlier that decade, researchers had begun to investigate whether stem cells - also called seed cells at the time - could be found in the adult body, particularly in bone marrow.
Since blood is frequently regenerated, scientists thought that it was an obvious place to look for precursor cells. They assumed that there were at least three types of seed cells, since marrow produces three different kinds of cells to create the blood supply: red blood cells, white blood cells and platelets.
Toronto researchers Ernest McCulloch and Jim Till, working at the Ontario Cancer Institute on Sherbourne Street, transplanted bone marrow from one group of mice to another. Less than two weeks later, they spotted lumps in the marrow and spleen of the recipient rodents. Guessing that these lumps were blood-cell colonies that had grown from a single cell, the scientists expected to find only one type of blood cell within the colony. Instead, they discovered that all three types had sprung from a single precursor cell, a stem cell.
"This showed that a single cell gave rise to all three different types. It proved for the first time that there was such a thing as a stem cell," said McCulloch, a University of Toronto professor and senior scientist emeritus at the cancer institute.
The discovery, reported in 1961, opened the field of stem-cell research and led to a revolutionary treatment for people with diseases such as leukemia and anemia and immunodeficiencies. In 1968, doctors at the University of Minnesota performed the first bone-marrow transplant, using stem cells to replenish a patient's blood supply.
The idea that an adult body might still possess multipotent stem cells came with the study of a bizarre form of cancer called teratocarcinoma, for the mythological monster "terrato." These tumours grow spontaneously out of the eggs in a woman's ovaries or the sperm in a man's testes.
The tumours can balloon to the size of big grapefruits, with stem cells forming random tissues throughout. The frightening masses might be covered in hair, be complete with blood vessels, have bone or teeth sprouting within, and be rich in nerve cells. Scientists who poked them discovered that the tumours could recoil in a nervous reaction.
Researchers in the 1970s learned to grow these teratocarcinoma tumours in mice and then extract from them the stem cells that clearly had the potential to become various cell types. Growing these cells in the lab, researchers found that they could indeed grow into cells of the heart, kidney, liver and even the brain.
Janet Rossant, who worked on mouse teratocarcinomas 30 years ago, said of the stem cells found in them: "They behaved very well in terms of their growth, but they also grew tumours."
In 1980, researchers in California and Cambridge reported that they had for the first time extracted stem cells from a mouse embryo. "This was a really important breakthrough," said Rossant, a senior scientist at Toronto's Mount Sinai Hospital. With mouse embryonic stem cells, scientists could manipulate genes and grow mutant mice for medical research.
The notion that stem cells could also be extracted from a human embryo always hovered as a possibility, but the idea was so fraught with ethical dilemmas that few scientists rushed to explore the area.
But the value of such experiments proved too exciting to resist after 1996. That year, researchers at Indiana University demonstrated that they could extract mouse embryonic stem cells and then chemically induce them to become heart cells, which could then be implanted into a mouse heart and integrate smoothly into the organ.
The accomplishment raised the prospect of scientists being able to manipulate stem cells into growing whatever tissue they desired. But first, they would need a supply of human stem cells if they hoped to grow tissues for human use.
In 1998, James Thompson at the University of Wisconsin reported that he done just that.
In a landmark experiment, the biologist worked with human embryos that were considered surplus and due to be discarded after being created in a fertility clinic.
Interrupting the molecular choreography of early life, Thompson managed to squeak in and extract the embryonic stem cells while they were still dividing - at their prolific, blank-slate stage before they could differentiate to form the various cell types in the human body. He then grew these precious human embryonic stem cells in a lab dish.
Days later, John Gearhart at Johns Hopkins University reported that his research team had discovered and isolated embryonic stem cells that had migrated into the reproductive organs of an aborted fetus - calling them embryonic germ cells.
Together, the two reports offered scientists the opportunity to become mechanics of the human body - repairing and replacing tissues and organs not with scalpels, drugs or artificial substitutes, but with brand new human parts.
Next page: The Potential