by David Prentice
August 2, 2008
A team of scientists from Harvard University and Columbia University has reprogrammed skin cells from two elderly patients with ALS (Lou Gehrig’s disease), producing iPS cells, an embryonic-type stem cell. Then from the iPS cells, they produced cells resembling motor neurons, the type of neurons that are attacked in the disease. This is the first time any embryonic-type stem cell has been created directly from a patient. The iPS cell technology, developed by Dr. Shinya Yamanaka of Japan, directly reprograms normal cells such as skin cells into an embryonic stem cell type, using the addition of 3-4 genes. No embryos, eggs, or cloning are used in the process. Yamanaka first developed the technique in mice, then transferred the same process to use with human cells. The first human iPS cells were announced in November 2007 by Yamanaka and by Dr. James Thomson. In the few months since then over 100 human iPS cell lines have been created by various labs, but this is the first published instance where iPS cells were created from a patient with a specific disease. Further work will be needed to show whether the immature neurons that were produced can mature to functional motor neurons in the lab dish, whether they are similar to the motor neurons in ALS patients, and if they can provide any clues to the development of the disease. The team hopes that they can use the iPS-derived neurons to study the disease in the lab.
The Harvard team, led by Kevin Eggan, had been attempting to create patient-specific stem cells for over two years, by trying to produce embryonic stem cells from human embryos by cloning (somatic cell nuclear transfer, SCNT) but had failed, in part because of the scarcity of human eggs (see Pining for Clones, Whining for Eggs) as well as the tremendous inefficiency of the cloning process. One of Eggan’s co-authors, Christopher Henderson, noted that if the iPS technique holds its promise in producing neurons and other cells for research, it will probably replace the cloning approach. Dr. Rudolph Jaenisch of MIT, another cloning scientist, noted that the iPS cell technology “is so much easier, [with] so many fewer restrictions and problems - ethical as well as others.” Jaenisch’s lab had also tried the cloning concept in mice and failed, but succeeded with the iPS cells. These same reasons led Prof. Ian Wilmut, cloner of Dolly the sheep, to give up on cloning in favor of Yamanaka’s technique.
The results of this study should put another nail in cloning’s coffin. Eggan still insists that he will continue with cloning research, but all the results are flowing from iPS cells. The New York Stem Cell Foundation, previously a die-hard supporter of cloning and very critical of iPS cells, wasted no time in trumpeting their “critical funding role” in the new study. One of Eggan’s major funders, the Stowers Institute, has relentlessly pushed cloning. Stowers poured $30 million into Missouri in 2006 to pass Amendment 2, a state constitutional amendment to secure the right to create cloned human embryos. Stowers CEO, William Neaves, has said that “the ultimate goal is not to create therapies with somatic cell nuclear transfer” but also that “The ultimate goal of all lines of this research is to be able, eventually, to reprogram ordinary body cells so that they could be used for therapy to replace cells that have been destroyed by injury or disease.” Sounds like iPS cells are achieving that goal. One company that rejected the iPS technique is Advanced Cell Technology (ACT). William Caldwell, CEO, had said in January 2008 that iPS “is not a substitute for what we’re doing now.” ACT was recently reported on the verge of bankruptcy. Similarly, Thomas Okarma, CEO of Geron, ignoring the facts and statements of the scientists, said that the iPS technique was “too complicated and too expensive.” (Maybe he should look at what happened to ACT.) Cloning continues to fail, iPS cells keep delivering results.
Back to some inaccuracies in most of the news reports on this latest study. What they did was show for the first time that iPS cells, an embryonic stem cell, could be made directly from patients with a disease (without harming the cell donor, and without using eggs, embryos, or cloning), and also that they could produce in the lab a specialized cell type similar to that affected in the disease. But is this the first instance of a disease-specific human cell line? No, there are lots of those, going all the way back to 1952 and the very first cultured human cell line, the HeLa cell line (the disease in that instance was cancer.)
But isn’t this the first instance of a patient-specific stem cell line? No. That honor belongs to the Australian group led by Professor Alan Mackay-Sim of Griffith University, that already made patient-specific and disease-specific stem cell lines. They isolated adult stem cells from the nasal tissue of patients, including Parkinson’s patients. AND they turned those stem cell lines into the type of tissue affected in the patient,. AND they have already gone beyond the iPS result; they used their adult stem cell lines in an animal model of Parkinson’s disease. AND the adult stem cells successfully treated the disease in the animals. Without tumor formation.
So the current iPS cell result is a nice advance, but it’s not the first evidence of patient-specific or disease-specific stem cells, and certainly not the best.