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
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