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Monster Tumor and a Little (Cloned) Lamb:
A Brief History of Cell Engineering

1963: Ernest McCulloch and James Till, Canadian researchers, discover the presence of self-renewing cells in mouse bone marrow.

1973: Gail Martin, a researcher at the University of California, San Francisco, and Martin Evans at University College London begin studying cancerous tumors in mice, called teratocarcinomas — from teratos, the Greek word for monster. The tumors contain several types of tissue, including bits of bone, hair, and teeth. Also inside the tumors are primitive stem cells that can develop into any type of cell in the body. The researchers hypothesize that several types of those cells must be present to grow the parts of a developing human.

1981: Evans and a colleague publish a paper in the journal Nature that demonstrates that a single cell from an embryo could "differentiate" into a wide variety of cell types. Jamie Thomson, a young investigator at the University of Wisconsin, isolates stem cells in mice. Martin, whose experimental results echo those of Evans, grabs naming rights for their research subjects. She calls them "embryonic stem cells."

1982: Research by Curt Civin, an oncologist at Johns Hopkins, leads to the discovery of a method for isolating stem cells from blood cells. Scientists use Civin's research to create new tests for diagnosing leukemia.

1988: Thomson successfully moves his stem cell research from mice to monkeys.

1996: Using a test tube and a technique called somatic nuclear cell transfer, Scottish researchers create Dolly, the cloned lamb. Stem cell researchers draw inspiration from the less-than-blessed event. They credit the Scottish researchers with demonstrating that cells can be "reborn" and put to other purposes. Thomson opines that the making of Dolly showed that the arrow of time is not irreversible.

1998: Working at Johns Hopkins, John Gearhart, a professor of medicine, and Michael Shamblott, a postdoctoral researcher, publish a paper showing that human primordial germ stem cells, ones that normally become sperm or egg cells in the body, could be made using human fetal tissue. Almost simultaneously, a team led by Thomson succeeds in culturing human stem cells from embryos. The germ cells prove difficult to work with because they resist being picked apart in a lab dish. Eventually, embryonic stem cells become the desired research tool for a vast majority of cell researchers.

2001: In August, President George W. Bush puts restrictions in place that limit federal funding of stem cell research to experiments done using more than 60 previously existing lines developed from embryos, effectively placing a chilling effect on broad-based research in the United States; Thomson appears on the cover of Time.

2002: The International Society of Stem Cell Researchers forms, signing on 150 charter members. Since then, the group has grown to include more than 2,600 researchers from nearly 50 countries.

2004: The scientific community sharply criticizes Hwang Woo-Suk, a South Korean researcher, after he claims to have cloned humans using embryos donated by two junior scientists in his lab — an ethical breach on many levels. Two years later, not long after being named South Korea's "Supreme Scientist," Hwang is fired after his publications are exposed as a fraud.

2006: Shinya Yamanaka, a Japanese surgeon-turned-researcher, discovers that four of 250 genes that are activated in embryonic stem cells can be used to "turn back the clock" on regular human blood cells. The genes, including one that causes cancer, are now known as the "Yamanaka factors." He also develops a method for returning the adult cells of a mouse to their embryonic state.

2007: Thomson and Yamanaka announce separately that their labs have used the Yamanaka factors to reprogram human adult skin cells to behave much like embryonic ones. The result — induced pluripotent stem cells, or iPS cells — can be used to make many types of tissues in the body. Ethicists and theologists who oppose the use of embryonic stem cells applaud the findings, seeing iPS cells as an alternative to destroying embryos. However, the virus used to carry genes in those cells has the potential to cause cancer in patients.

2008: In August, biologists at Harvard convert common pancreatic cells into insulin-producing ones in diabetic mice — a new way to reprogram cells without taking them all the way back to their embryonic stem cell-like state. They hope to begin human trials using this type of "genetic surgery" by 2013. In November, Yamanaka announces a method for reprogramming normal tissue cells into iPS cells without using a virus, eliminating one major barrier to investigating how a disease afflicts a specific patient.

2009: In January, President Barack Obama is inaugurated and hints strongly that he will overturn the Bush restrictions on embryonic stem cell research. One week later, the federal government approves the first human clinical trial in U.S. history using embryonic stem cells, which will be used to treat people who suffer paralysis from spinal cord injuries. The trials could begin as early as this year. In March, Obama reverses the Bush restrictions.
— MA

Go to "Tiny Cells, Huge Possibilities"
Go to "A Cluster of Ethical Questions"
Return to April 2009 Table of Contents

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