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Immortalizing a Piece of Yourself

Stem cells derived from volunteers for the Personal Genome Project will be disseminated globally.
October 31, 2008

Scientists around the globe may soon be studying tiny bits of George Church. The Harvard Medical School professor of genetics will be one of the first people to have stem-cell lines created from his skin cells propagated and distributed worldwide–along with a record of the cells’ donor’s identity and genetic and medical quirks.

Skin biopsy: George Church, a participant in and leader of the Personal Genome Project at Harvard Medical School, undergoes a skin biopsy. Scientists will develop cell lines from Church’s skin cells, which will be distributed to scientists around the world for research.

Church and his collaborators hope that the cells will add a new dimension to genetic studies of human disease. Most studies compare genomes of a group of people with a particular phenotype–say, diabetes or heart disease–with healthy volunteers. But adding stem-cell lines, which can be differentiated into the myriad tissue types affected by disease, should allow scientists to search for molecular changes that are the intermediary between genes and the manifestation of a disease. “For nearly every genetic trait variation, there is a change at the cellular level,” says Church.

This new addition to genomics studies comes thanks to induced pluripotent cell reprogramming, a recent breakthrough in stem-cell research that allows scientists to create immortal cell lines from healthy human donors that, like embryonic stem cells, can both replicate themselves and differentiate into many types of tissue. While cultured cells are a ubiquitous part of biomedical research, used to test drugs, study disease, and engineer tissue, most cells cannot form different tissue types, and they come from anonymous donors–meaning that medical and other characteristics of the donor are unknown. In addition, many “immortal” cell lines, which can divide indefinitely, are derived from tumor cells and thus have abnormal chromosomes.

Church won’t be alone in distributing his cells. The scientist aims to create hundreds or thousands of cell lines over the next few years as part of the Personal Genome Project, an effort that he launched two years ago to capitalize on advances in gene-sequencing technologies. So far, the project has enrolled 10 volunteers–and garnered headlines, mainly for its genomic-era exhibitionism. Volunteers, including Harvard psychologist Steven Pinker and entrepreneur Ester Dyson, released their medical records and preliminary genetic analyses on the Web earlier this month. But media attention has mostly ignored that fact that they’ve also given something that may be even more personal. Each has undergone a skin biopsy, which will be used to generate stem-cell lines.

The lines will allow scientists to study cells with a known genetic and clinical profile. Those working with cells derived from Steven Pinker, for example, would know that he suffers from basal cell carcinoma, lichen planus (an inflammatory skin condition), and Reynaud’s syndrome (a hypersensitivity of the fingers and toes to extreme temperatures).

“This is the first real step in quantifying how different genomes function to produce us,” says James Sherley, a stem-cell biologist at the Boston Biomedical Research Institute and one of the project’s first 10 volunteers. “The answers to why genome expression is not deterministic, to how environment influences genotypic expression, to how the same genome can produce an eye, a heart, and a brain–all of these mysteries and more [lie] in this rich experimental milieu.”

Church aims to enroll 100,000 volunteers in the next phase of the project, creating a correlated database of genetic, medical, and trait information that can be complemented with cells from the subjects of interest. Scientists around the world could then design their own experiments around the data, using the cells.

The ambitious project is still in its very early stages. So far, Jay Lee, a scientist in Church’s lab, and In Hyun Park, also at Harvard, have derived stem cell lines from two of the volunteers: Church and Rosalynn Gill, a founder and chief science officer at Sciona, a personal-genomics startup in Aurora, CO. Initial studies of the cells have focused on genes involved in inflammation, an immune reaction that plays a role in most human ailments, including stroke, diabetes, autoimmune disease, and aging.

Lee says that the experience of studying his boss’s cells has been unique. “Deriving tissues, such as hair, from someone you know is strange,” says Lee. “It’s a phenomenon never seen before in modern medicine.” He adds that sharing his findings with Church, even though they are preliminary and difficult to interpret, has given him pause.

In addition, because the cells carry the genetic blueprint of their donors, they could be used to determine, and perhaps publish, genetic characteristics that donors and their families may not want to know. Pinker, for example, says that he’s unsure if he wants to know whether he carries a genetic variation that dramatically raises his risk for Alzheimer’s disease.

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