THE DREAM, OR THE NIGHTMARE: Stem Cell Crisis Approaching? In the past several days, I have wakened from two very different dreams. In the first, a couple nights ago, I dreamed my paralyzed son Roman stood up. Roman, Gloria and I were in San Francisco, at the bottom of one of those incredible sloping streets, with the pale white buildings, and the Golden Gate Bridge spectacularly beside us, arching across San Francisco Bay. Suddenly Roman got up from his wheelchair. He stretched his arms, tightening his biceps for the sheer joy of living. And took off running. Beautiful bounding golden athletic steps they were, the kind he used to take before the accident. Then he fell, but got up, and ran again, trotting now, but lightly, back to the chair, collapsing onto the cushion exhausted, but beaming, exhilarated. He was rehabbing, getting acquainted with his body again. I slapped my own face, twice. "Go to him," Gloria said, and I ran with my shuffling old man knee-pain steps, and hugged my son and said I had just slapped my face to see if I was dreaming, because it did not seem possible. "I know," said Roman, "I've had this dream so many times before." Then Gloria stirred beside me, and her breathing changed, and I woke up. The second dream was a nightmare. Roman had fallen from his chair, and he was face down on the ground, not moving, and no one could help him. I had to get to him and it took forever, but finally I had my hands on his shoulders and was straining to get him up, to lift him back into his chair. But I was not strong enough. I was straining and struggling, but youth had left me. I was too old and I could not do it, even though Gloria was there, helping, but I don't know what happened. Usually I can't remember my dreams. Why these, why now? Maybe because, in the next few months, everything could come together, or be lost for a generation. Consider: The FDA hearings on embryonic stem cells have been (in my view) deeply politicized, setting the stage to block human trials, an enormous setback; In too many states, "personhood issue" laws are attempting to re-define human life as beginning at conception, which could stop embryonic stem cell research; The Presidential race is dividing Democrats- while Mr. "straight-shooter" John McCain has made promises to both sides on the stem cell research issue: pledging to the Religious Right that he will sign the Brownback bill (criminalizing SCNT) and also that he supports a personhood law-while at the same time claiming to be pro-research; The U.S. Supreme Court just gave a huge gift to the Republicans on the issue of government-backed voter ID cards: potentially denying the vote to literally millions of disabled Americans, who may not have a driver's license; California's magnificent stem cell program continues to be under fire from politicians in Sacramento: Senate Bill 1565 (Kuehl, Runner) is moving forward-which could lead to a restructuring of the entire ICOC; That is not even mentioning other state issues, positive and negative-outstanding stem cell supportive candidates who need and deserve help- enemies needing to be gently retired-- and new science and accompanying mini-issues needing study. Everywhere I look are chores, waiting. The room where I write sums up the situation: a chaotic collection of papers, some stapled, some stacked, some just of kind of there, boxes and books, every shelf overflowing. There is just enough bare floor to walk to the well-worn couch where I do my best thinking, holding up my notes, and closing my eyes to ponder deeply significant matterzzzzzzzzzz. Each passing day makes me realize the work undone.I know I am just one more speck of sand on the beach. But still I want to do as much as I can with that tiny influence, like grit in a monster's eye, distracting it, while other folk can bring it down. Fortunately, whenever I get all frazzled like this, and start groaning and moaning about how everything is too much, Gloria knows what to say: "Do one thing." Oh, okay. One thing. I can do one thing, surely. The most important chore is getting ready for and attending the ICOC meeting. In a couple hours I drive to Los Angeles, to attend the public of the Independent Citizens Oversight Committee. I have my hotel room reserved (not the one where the meeting is being held-that costs $315 a night-but a Motel 6 ten down the road, that only costs $50!) and I have a box of cookies to eat along the way, given to me by Laurel Barches and friends at Cal Berkeley where I just spoke a few hours ago. I hope the ICOC will study and take a position on the April 10th Food and Drug Administration (FDA) hearings on human trials for embryonic stem cell therapies. When I first read the background document* for the hearings, it was disturbing. But as I typed the whole thing, to understand it better, it got worse. The hearing seems to have a political agenda, intending to plant seeds of doubt about the safety of embryonic stem cells, with the ultimate goal of delaying or denying the human trials. An unfair FDA could implant permanent restrictions into public policy. Maybe I am wrong. Hopefully President Bush will not mind there being a success in an area he so vigorously opposed. Certainly the research under consideration did not violate his August 9, 2001 guidelines. But this is the man who twice vetoed the Stem Cell Research Enhancement Act, and who enthusiastically backed Senator Brownback's bill to jail scientists for SCNT research. As if written by a political enemy, the background report appears to offer grounds to change the rules of the long-established human trials process: to block the research. Every scientist knows these rules. Human clinical trials come in different phases: phase one is for safety, to study the risk; phase two is "efficacy"-- to see if it works. But now the FDA committee is raising the bar; instead of the first trials being for safety, the committee suggests it may require guarantees of efficacy as well-before it can happen. A scientist may request that phase one and two trials be combined-but to require it from above? That is a new hurdle, and an unfair burden. (Note: some of the following material was included in my previous article, "FDA Stem Cell Hearings Politicized", at Karen Miner's and my website, www.stemcellbattles.com. The committee's paper says, quote: "Given the potential risks of hESC-derived cellular products, data supporting a reasonable possibility of efficacy may need to be particularly strong, and design parameters may need to allow for detection of clinical benefit.Given all these considerations, .phase one trials of hESC-derived cellular products will have to be capable of measuring some indications of efficacy." (emphasis added). The paper also paints the new field in the worst possible terms. It threatens cancer in almost every paragraph. The word "tumorigenic" is repeated perhaps twenty times, like a negative advertising slogan. Anyone reading this unprepared would conclude stem cell research is riddled with the dread disease. Which is not true. Inserting embryonic cells into a body could indeed make a teratoma- a non-cancerous lump of cells-but not if the scientists differentiate the cells into whatever the scientists want them to be. Differentiate means to shape the cells, before you put them in. Consider your own house: the nuts and bolts that hold your dwelling together. All of those little bits of metal start off as white hot molten liquid. So, if you were building your house, would you pour the white-hot liquid metal directly onto the wood? Hopefully not. It is generally advisable to mold the metal into nails or screws or bolts first. Similarly, (as the FDA did acknowledge) once the embryonic stem cells had differentiated, their teratoma days are over. But immediately the committee's document suggests that even a tiny fraction of undifferentiated hESCs (human embryonic stem cells) could cause teratomas. In other words, they claim, if you put in a million stem cells, and 99.9% were differentiated into the just the right kind of cells you want, but even the tiniest few were not differentiated, they might overwhelm the rest and go bad. However, at the hearings, Dr. Jane Lebkowski of Geron presented data, citing a 12 month rodent study, (a very long one for rats which live only about 3 years) during which as much as 5% of the transplanted cells were undifferentiated-but none became teratomas, let alone cancer. The committee discussed a laundry list of new experiments they may consider requiring, in so many different areas, it could delay the field for decades. Example: Dr. Hans Keirstead's experiment with remyelination (Geron) was initially completed in 2002. (This is the one done in the Reeve-Irvine Research Center, partially paid for by the Roman Reed Spinal Cord Injury Research Act.) In the six years since, Dr. Keirstead has been in continual touch with the FDA, answering their requests for replication, etc., amassing a 25,000 page paper trail. (Think what 25,000 pages of paper trail means-if a typical book is 250 pages, he has written or helped write the equivalent of 100 books on the one experiment!) He has met every condition they have offered. And now? A laundry list of new conditions may send him, Geron, Advanced Cell Technology, and Novocell, and the entire embryonic stem cell research field back to the drawing board, conceivably for decades. Both the briefing paper and comments from committee members speak of possibly requiring: · Multiple species of animal studies (long studies, "optimally, for the life span of the animal."-a monkey can live twenty years!) even the possible development of porcine stem cell lines to try on pigs; · New studies not only for already-resolved issues like teratoma formation, but also for the physiological effects of the location in the body where the cells are inserted, and various stem cell interactions with other drugs ("concomitant medications"); · New ways to test for levels of undifferentiated hESCs in the human being him or herself (how do you test that without human trials!) and much more. Caution is one thing; endless study is another. There will never be a time when medical research is risk-free. Any operation can go wrong, even the most normal medical practice can go wrong, which is why you sign release forms at the hospital. If you have knee surgery, it is possible a blood clot may form in your artery and kill you-as happened to one of my relatives. Does this mean knee surgery should be outlawed, because it always contains risk? Is the suppression of science a real worry nowadays? Consider the just-released report by the Union of Concerned Scientists: "Scientific findings are being suppressed and distorted. Eight hundred and eighty-nine scientists personally experienced at least one type of political interference."-Washington Post, Christopher Lee, April 24th, 2008. (emphasis added). I hope the ICOC will authorize a committee to study the FDA's approach to the clinical trials, to make sure everything is on the up, to point out concerns, and areas where the next President and Congress may have to step in. That's why I am making this one particular trip, to make sure the issue gets raised. Well, that plus I am just proud to be a Californian, an American, and a member of this world, in a time when science, hard work, and determination come together- To maybe make our very best dreams come true. *"CTGTAC Meeting #45 Cellular Therapies Derived from Human Embryonic Stem Cells-Considerations for Pre-clinical Safety Testing and Patient Monitoring". To read it, go to http://www.fda.gov/default.htm -- type the word embryonic in the search box, and it will take you to the April 10 hearings, and the background documents. by Don C. Reed Rayilyn Brown Board Member AZNPF Arizona Chapter National Parkinson's Foundation [log in to unmask] ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn