CORRECTION:
In this story (News, Nov. 5,) Dr. Owen Witte was not the person interviewed. The entire article refers to research done by Dr. Jerome Zack, also a professor of Microbiology, Immunology and Molecular Genetics. The California Institute for Regenerative Medicine (created out of Proposition 71) awarded a grant to Dr. Jerome Zack in 2007 for his research on stem cells and to study a way to develop stem cells without using embryos. The $2.25 million grant Witte received from the Prostate Cancer Foundation was not from the state and was to study prostate cancer stem cells and better define the role they play. The article referred to from The New York Times (“Scientists bypass need for embryo to get stem cells”) was published on November 21, 2007, and did not pertain to Dr. Jerome Zack.
The process is fairly simple and has been done many times. But in 2007, the California Institute of Regenerative Medicine gave Dr. Jerome Zack a grant to do it again.
Backwards.
Long maligned by ethical controversy, research on embryonic stem cells has become a political bone of contention. But groundbreaking research at UCLA and Kyoto University suggests the problem can be avoided altogether simply by reversing an existing cell back to a stem cell.
“Everyone was waiting for this day to come,” the Rev. Tadeusz Pacholczyk told the New York Times in 2007. “You should have a solution here that will address the moral objections that have been percolating for years.”
Though the results are not perfect ““ this is where Zack’s work comes in ““ they portend a side step to some major ethical and technical roadblocks that have plagued the field.
“The news spread like wildfire,” said Zack, a professor in Microbiology, Immunology and Molecular Genetics. “It just sent shockwaves through the community.”
The stem cell’s massive appeal revolves around pluripotency, its ability to morph into any cell type. Until recently, this required the manipulation of an egg to produce the cells and destroying the resultant embryo in the harvesting process.
The ethical questions from this sacrifice has hobbled federal funding for further research.
But in 2007, Drs. Kathrin Plath at UCLA and Shinya Yamanaka at Kyoto University announced separately that they were able to reverse the process, turning a mouse’s skin cell back to its pluripotent state.
To do this, Plath and Yamanaka pinpointed four specific genes crucial to stem cell function and implanted them into the mouse cell. The researchers relied on an unlikely messenger: the virus.
With the same lethal efficiency with which they spread AIDS and Ebola, viruses carrying the four genes slip their payload into the cell’s own DNA, causing it to hit rewind.
“What happens is when you put these genes into a mature cell, they make it think it’s a stem cell,” Zack said.
“These genes are master transcription factors that control expression of other genes, so they can change the cell’s expression profile entirely. We end up with something nearly indistinguishable from actual embryonic stem cells by the molecular techniques we’re using.”
If these induced pluripotent stem cells ultimately prove useful in repairing or replacing human organs, their advantages would be enormous.
Because the starting cell would be drawn directly from the patient, this technique requires no sacrifice of embryos. And for the same reason, there would be little risk of rejection by the patient’s immune system.
However, the genes’ powerful effects are a double-edged sword; the insertion process occurs at random points along the DNA and could throw off other parts of the genome.
“Depending where it integrates, the virus can interfere with normal function of the cell,” Plath said. “Imagine if it integrates into an oncogene (a gene prone to cause tumors). They would cause it to express highly and automatically lead to cancer.”
In fact, Yamanaka was able to produce entire mice from these single-cell beginnings, but nearly one-fifth of them eventually developed cancer.
Under Proposition 71, the state of California awarded Zack the grant to tackle precisely this problem.
“There are now new modifications published just in the last couple weeks that don’t necessarily require the genes to integrate into the cells,” he said.
“We’d like to adapt these protocols into the human system and make induced stem cells from different disease states for people with genetic disorders.”
If successful, Zack’s research can make UCLA the hub of future stem cell research.
“We’re excited about the possibilities. It’s kind of risky because we may not be successful, but the reward can be great because there can be procedures available because if there are people who want to use these cells elsewhere, all the procedures are in place.
UCLA’s got several people interested in doing clinical trials eventually. So if we’re successful at this, UCLA is going to be central for several trials taking place in the next few years.”