1A showdown is coming in the civil war that embroils America over the fate of embryos, the beginnings of all human life. In this instance, the battle involves human embryonic stem cell research. Two recent developments this year have the potential of fundamentally changing the outcome of this struggle that divides our nation.
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- On July 30 Geron Corporation, Menlo Park, Calif., announced that the U.S. Food and Drug Administration (FDA) had notified the company that the hold placed on its spinal cord therapy involving modified human embryonic stem cells had been lifted, allowing clinical trials to proceed for persons with recent spinal cord injuries. The pre-clinical trials were based on a study with rats, whose spines had been injured experimentally, paralyzing them, then injected with modified human embryonic stem cells, enabling them to increase their ability to achieve locomotion. The study was funded by Geron and led by Hans S. Keirstead, Reeve-Irvine Research Center, University of California at Irvine.
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- On August 23, a federal judge, U.S. District Court Judge Royce Lamberth, granted an injunction blocking the federal funding of embryonic stem cell research, ruling that such research violated federal law, specifically, the Dickey-Wicker Amendment. The court ruled in favor of a suit filed in June by researchers who said human embryonic stem cell research involved the destruction of human embryos.
These developments are the fallout of a conflict that involves the status of a class of human beings called variously the unborn or embryos. On one side of this class warfare is a segment of the American population that supports embryonic stem cell (hESC) research, claiming that cures stemming from dissected and modified embryos are on the horizon for numerous diseases, as well as providing an option for organ replacement. They think that the use of human embryo parts for scientific purposes is valid. Material for such studies are obtain by using a pipette to suck out the life juice of an embryo from the egg's shell and incubating the resultant stem cells in Petri dishes, subjecting the culture to a variety of manipulations, such as chemicals and genetic alterations.
2 On the other side are those who argue that embryonic stem cell research is unethical in that it involves subjugating one class–the unborn–for the benefit of another class–the born–and ends in the taking of human life.
As in any war, there are two enemies. The name "enemy" merely depends on what side you stand. To effectively determine what side you choose to support and how to fight this war, one must have an understanding of the language and values of each side. Parts I, II and III will help you choose sides. This series will help one explore the terrain of embryonic stem cell research, the jargon it employs and its goals, as well as its feasibility to succeed in its claims. A war fought in the dark is hard to win, especially when the enemy can see you, but you can't see them. Your being in the dark, your ignorance, is what the enemy often relies on to win.
Following is a three part series on human embryonic stem cell research that will hopefully shed a little light.
While scientists engaged in such research claim that cures are on the horizon, and that blocking such funding is, as some have said, "criminal," what is rarely addressed is the fact that therapies involving human embryonic stem cells to date have never worked. In fact, some of the leading initial supporters of embryonic stem cell research are now jumping ship, saying that it is a futile path and that research would be better spent on adult stem cell research, which does not involve embryonic destruction (See remarks in this series by Douglas Melton, Harvard University cell biologist, Part III, p. 25).
The position supported by this investigation is this: not only is embryonic stem cell research immoral because it destroys nascent human life, but to date no credible research has demonstrated that such cures by means of hES cells are feasible, that is, embryonic stem cell research lacks proof that the concept of such cures is valid. Most pre-clinical trials have been limited to mice or rat models, which leading researchers have claimed are unreliable. Until researchers can demonstrate that there is a likelihood that such cures are possible via hES cells, a moratorium should be declared on all such research. This series explores why.
- Part I investigates why research involving human embryonic stem cell and human cloning is immoral.
- Part II explores the ethics of embryonic stem cells reseach by asking two central questions: what does it mean to be human and how important is the individual?
- Part III provides evidence in support of a moratorium on embryonic stem cell research and human cloning, reasoning that the field lacks credible proof that the concept will work for humans.
3For the layman, embryos and embryonic stem cells are an unexplored world. However, they represent the very beginnings of all of our citizens. We all started this way and all such embryos constitute human life–even embryonic stem cell scientists grant that.
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What many investigators argue, however, is that such research is permissible because of the "greater good" it may accomplish and other like concepts. That is, even though it destroys human life, it should be allowed because it can save human life.
They view the new ruling by Lamberth as obstructive and standing in the way of medical progress. Pat Oliphant at GoComics satirized the decision, drawing Lamberth as a monkey judge wielding an ax and a hammer, storming into a stem cell laboratory, with white-coated researchers saying "How nice. Another learned district judge come to help us with our work (Sunday funnies 8-29-10, 2010)."
Writing in The Huffington Post, Don C. Reed, sponsor of California's Roman Reed Spinal Cord Injury Research Act of 1999, said in "Overturn Dickey-Wicker Abomination, or Forget Stem Cell Cures for a Generation:"
The Dickey-Wicker Amendment will eventually be seen as the anti-cures abomination it is. Future generations will look back upon us, and wonder how we could have been so stupid–to have the tools of cure in our hands, and put them aside.
He advocates repealing the Dickey-Wicker Amendment altogether, which is not too surprising, since the Roman Reed Spinal Cord Injury Research Act of 1999 in California provided the initial funding to Geron's work with embryonic stem cells (Chakrabarti, 2010).
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4On the other hand, some believe that the argument of the "greater good" is reminiscent of cultures devoted to human sacrifice, where children were burned in fire or adults had their hearts cut out to propitiate the gods, that is, their life was taken to achieve a perceived advantage for the greater good of the population, such as fertility, rain or abundant crops. Regenerative scientists, they reason, are asking us to sacrifice human embryonic life to help the remaining population gain greater health, such as replacements for bodily parts that have become diseased or injured.
Concerning embryonic stem cell research, syndicated columnist Cal Thomas commented that "pro-choicers view the destruction of human life the way ancient societies viewed child sacrifice. For them, it is as close as they can get to a religious rite (Thomas, 2010)." Embryonic stem cell scientists and abortionists are viewed by some as the high-priests of this rite, with the altar being the laboratory or the operating table.
This series argues that because hESC research destroys human life and because to date no credible animal experiments have shown that hESC research has the potential to save human life or to cure, hESC research should be impermissible for ethical reasons.
Experiments at the rodent level have demonstrated that embryonic stem cells when modified and injected into mice or rats can repair hearts and spinal cords. However, mice and rat models are significantly different than humans. Researchers have stated that therapies based on such result are not necessarily predictive of success in humans.
Nevertheless, the FDA has approved a clinical trial involving acute spinal cord injuries in human subjects based on success with experimental rodents. The trial has the potential of either substantiating the claim that human embryonic stem cells can contribute to human cures–or discrediting it.
Monkeys or mice?
One of the major questions the FDA must decide is whether cell therapies need to be tested in nonhuman primates before they enter humans, according to Gretchen Vogel noted, writing for Science June 10, 2005, in "Ready or not? Human ES cells head toward the clinic."
As noted, what one demonstrates in mice may not work in humans. A research study by the Whitehead Institute for Biomedical Research observed in a news release that "mouse and human ES cells differ in a number of significant ways, raising the very real possibility that breakthroughs in mouse stem cell science simply won't be reproducible with human stem cells." (Scientists create more pluripotent human embryonic stem cell, 2010)
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5But, according to Malcolm Moos of the FDA's division of cellular and gene therapies, "Non-human primates are not the default choice and in fact are seldom the best choice (Vogel, 2005)."
However, James Fawcett of the Cambridge University Centre for Brain Repair in a review article on "Repair of spinal cord injuries: where are we going?" says that primates would be the best option, but pose difficult challenges. He notes that:
Primates would be the most convincing large animal model for verification of treatments. However, the practical difficulties are formidable. Primates tolerate complete spinal injuries poorly and are difficult to care for, although partial spinal injury is better tolerated in some species. Animal care considerations mean that it is not acceptable to injure large numbers of primates for open ended experiments, and the cost and logistics are prohibitive (Fawcett, 2002).
"Proof on concept" pre-clinical trials have been conducted in a variety of primates. For instance, a rhesus monkey was the first primate to have adult cells cloned into embryonic stem cells, as reported by J.R. Minkel in Scientific American November 15, 2007, in "Primate stem cell barrier broken–embryonic stem cells derived from adult primate cells suggest humans may get their turn yet."
"This unequivocally shows you can generate stem cells from primates, and we're primates," says stem cell biologist Robert Lanza, chief scientific officer of the Worcester, Mass., company Advanced Cell Technology, who was not involved in the research.
"It's a giant step toward showing that human therapeutic cloning is possible," he added, referring to the concept of creating stem cells matched to an individual's immune system to repair tissue damaged in spinal cord injuries and by diseases such as diabetes, Parkinson's and Alzheimer's (Minkel, 2007). Therapeutic cloning involves extracting stem cells from cloned human embryos.
However, while monkeys match humans much better genetically than mice, even this proof of concept trial was not fully predictive. To date, no one has been able to clone a live monkey or a human (See Part III, page 20 of this series).
When it comes to spinal cord injuries and their repair, researcher Keirstead is not convinced that transplanting cells into primates is a prerequisit trial. "The question is, are we going to learn any more from putting human cells into monkeys than putting human cells into rats? I'm not sure we know."
For now, Moos says the FDA will evaluate this issue, and others, on a case-by-case basis (Vogel, 2005).
6And in the case of injecting human embryonic cells into humans to cure spinal cord injuries, rats or mice suffice for the FDA as pre-clinical trial models. The agency has placed its bet in favor of thinking that if it works in rodents it will work in humans.
And, as mentioned, we now have another trial–a legal one. A federal court is weighing in on the federal funding of embryonic stem cell research, ruling against it.
Embryonic stem cell research on trial
The time is ripe for an inquiry. Embryonic stem cell research is now on trial, both clinically and legally. Both trials will probe the issues raised in Parts I, II, and III of this series.
In this introduction:
Section 1. will delineate the clinical trial by Geron, explaining both the hopes and the apprehension accompanying the trail.
Section 2. will cover the recent series of lighting fast judicial moves effecting this research, namely, the banning of its federal funding by a judge via a court injunction, then later upheld by that same judge, then reversed when federally funded hESC research was temporarily allowed with the preliminary injunction being stayed by the U.S. Court of Appeals until the outcome of a trial.
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Never Let Me Go
If the Geron trial using embryonic stem cells is successful in restoring function in human patients and if the federal trial ends in restoring federal funding for embryonic stem cell research, we may be inching closer toward the dystopian world envisioned in the newly released film "Never Let Me Go" by Kazuo Ishiguro. The movie is set in Britain where children are educated in a boarding school called Hailsham. However, these children are not your typical children. They are clones bred for a sole purpose–organ donation–and their goal in life is to achieve "completion," a euphemism for dying, by giving up their bodily parts for transplants.
Speaking to a classroom of these children, a guardian explained their fate one day:
None of you will go to America, none of you will be film stars. And none of you will be working in supermarkets as I heard some of you planning the other day. Your lives are set out for you. You'll become adults, then before you're old, before you're even middle-aged, you'll start to donate your vital organs. That's what each of you was created to do.
What is most maddening about the movie is that the clones never speak up about their fate, they never try to escape, but simply accept their role in life, namely, to be organ donors–that dying to make others more healthy is their destiny. They have apparently been brain washed and do not protest. The only difference between embryos used for cloning and the clones of "Never Let Me Go" is that while the clones of that movie had a psychological reason for not speaking up, embryos have a physical reason–they are too small to do so (Never Let Me Go by Kazuo Ishiguro, 2010).
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Geron clinical trial
7 Let us begin with an overview of the newly FDA-approved Geron trial. As mentioned, the trial is based on a study funded by Geron and led by Keirstead, involving the departments of Anatomy and Neurobiology, Neurobiology and Behavior, and Neurosurgery, Reeve-Irvine Research Center, College of Medicine, University of California at Irvine. The study was reported in the Journal of Neuroscience, May 11, 2005, titled: "Human Embryonic Stem Cell-Derived Oligodendrocyte Progenitor Cell Transplants Remyelinate and Restore Locomotion after Spinal Cord Injury."
That title, translated into laymen's terms, essentially means that cells derived from human embryonic stem cells have been transplanted by injection into the experimenally induced injured spines of rats, growing a new sheath around the injured spinal cord, restoring its function and thereby the rats' ability to move better.
The stakes are high because of the players involved in this trial and the monitary investment.
- Geron funded the research by Dr. James Thomson of the University of Wisconsin-Madison in which Thomson first derived human embryonic stem cells. It has exclusive and non-exclusive rights for the commercial application of this research. As the Geron Corporation stated:
Geron has a license from the Wisconsin Alumni Research Foundation (WARF) which grants Geron exclusive commercialization rights to three cell types (cardiomyocytes, neural cells and pancreatic islet cells) and non-exclusive rights to three other cell types (hematopoietic cells, osteoblasts and chondrocytes) for therapeutic and diagnostic products; and non-exclusive rights to commercialize research products based on six cell types. Pursuant to Geron's agreement with WARF, Geron may transfer the undifferentiated cell lines only to Geron collaborators for work on projects described and directed by Geron (Stem cell lines, 2010).
Geron has invested $170 million developing its treatment for spinal cord injury (Cusworth, 2010).
- Research leading to the clinical trial was carried out by Keirstead. Video footage of Keirstead's paralyzed rats walking after being injected with the stem cell treatment got widespread attention during California's Proposition 71 campaign, and helped persuade voters that cures were right around the corner (Vesely, 2010). The initiative authorized $3 billion in funding for stem cell research and research facilities, creating the California Institute for Regenerative Medicine (CIRM), which currently provides approximately $250-300 million per year for stem cell research in California (Robert Klein, 2010, and Injunction against Federal Funding for Stem Cell Research, 2010).
- Keirstead's laboratory is located at the Reeve-Irvine Research Center, a leading center for spinal cord injury research. It was named for the late Christopher Reeve, noted for the motion picture portrayal of the fictional superhero Superman, and was launched by a $1 million grant from philanthropist Joan Irvine Smith. It is funded by CIRM and private donations (The mission of the Reeve-Irvine Research Center, 2010).
- The NIH has invested more than $500 million in human embryonic stem cell research, spending an estimated $88 million in 2008 (The promise of human embryonic stem cell research, 2020 and Stem cell research, 2010), and has campaigned for the continuation of embryonic stem cell research.
"Proof of concept" in rats
8As the spinal cord study led by Keirstead noted:
Here, we undertook a proof of concept experiment to determine the feasibility and efficacy of using human stem cell derivatives to promote remyelination and functional recovery in the injured adult rat spinal cord. In the present study, human embryonic stem cells (hESCs) were induced to differentiate into high-purity oligodendrocyte progenitor cells (OPCs) before transplantation (Keirstead, 2005).
The research team reported on the development of a protocol that encouraged hES cells to differentiate into OPCs. Oligodendrocytes, a type of cell in the central nervous system, surround and insulate the long fibers through which the nerves send their electrical messages. Progenitor cells are precursors that can differentiate into other cell types, in this case the myelin sheath, the technical name for the coating that surrounds the spinal cord like insulation on electrical wiring. This sheath is often lost during spinal cord injuries.
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| Injured spinal cord. Goal is to re-grow damaged zone in humans. |
The procedure worked for newly injured rats, but not for ones with older injuries. For animals that received oligodendrocytes precursors seven days after their injury, the cells survived and apparently helped repair the spinal cord's myelin. Within two weeks, treated rats scored significantly better on standardized movement tests than control animals, which had received human fibroblasts or a cell-free injection.
But, when researchers injected cells 10 months after the injury, they saw no effect. The cells survived but were apparently unable to repair the long-term damage. For that reason, Keirstead said, Geron's clinical trial will only target newly injured patients (Vogel, 2005).
What the researchers were attempting to do was mimic the process that normally transpires within an embryo–that is, differentiation of the stem cells into various bodily parts, such as precursor cells to the myelin sheathing–from extracted embryonic stem cells that had been cultured in a laboratory.
Keirstead was interviewed at UC Irvine in Orange County, California, by Roger Cooper for Life and Times on KCET, a PBS member-television station in Los Angeles. An animation showed a rat dragging itself across a floor with paralyzed legs, then, following an injection of the modified stem cells, walking again.
9Here is a partial transcript of that interview (Interview transcript with Hans Keirstead, 2007):Roger Cooper: In this animation, it's easy to see. There is something wrong with this rat. Because of spinal cord injury, the rat is partially paralyzed, dragging its rear legs. But after treatment with stem cells, remarkable change. The simulation shows results achieved in real lab rats, a breakthrough first accomplished at UC Irvine. The question now is, if rats can be made to walk again, can humans?
Dr. Hans Keirstead: It works in rats. Let's hope it works in humans.
Roger Cooper: Causing rats to walk again is just one aspect of the research into human embryonic stem cells. UCI is now a major center for investigation in stem cells, cells that have the ability to grow into any kind of tissue in the body.
Dr. Hans Keirstead: In my laboratory, I've got thirty-two researchers.
Roger Cooper: Hans Keirstead is the neurobiologist who injected stem cells into rats.
Dr. Hans Keirstead: I started my career here at UCI trying to find new ways, new angles, to approach spinal cord injury.
Roger Cooper: Spinal injury blocks signals from the rat's brain to its feet. In essence, Keirstead grew stem cells that could reconnect the broken wiring or axons.
Dr. Hans Keirstead: I found that, after spinal cord injury, the encasement that allows axons or wires of the spinal cord to conduct electricity is removed, so I designed a therapy that involved replacing the cell type that put the wrapping on the wires of the spinal cord. In effect, what we have done is restore the ability of the injured spinal cord to conduct electricity above and below the injury site.
Roger Cooper: His findings are dramatic, but could the stem cell therapy work on people who were paralyzed? Keirstead would like to find out through human trials...
10And it is those human trials that have just been approved by the FDA. Jodi Xu, writing in the Wall Street Journal, October 11, 2010, in "Geron enrolls first patient in stem-cell treatment study," noted that two months following FDA approval, Geron enrolled the first patient for its early-stage human-embryonic stem-cell treatment for spinal-cord injuries at Shepherd Center, a spinal-cord rehabilitation hospital in Atlanta. (Xu, 2010). Details of the landmark clinical trial are being kept confidential, Geron said. (Fox, 2010).
Patients getting shots of GRNOPC1
What is being injected into the injured spines is a population of living cells containing precursors to oligodendrocytes that Geron calls GRNOPC1 (Oligodendrocyte progenitor cells–GRNOPC1, 2010). It is short for Geron Oligodendrocyte Progenitor Cells.
Here is a brief overview of the procedure used to culture these OPCs as developed by Keirstead's team. It is a direct quote from the published study and while a layman is not expected to understand the scientific language being employed, the quote is provided to demonstrate the complexity of trying to mimic outside an embryonic environment what nature automatically does within an embryo. Instead of skipping over this technical section, the reader is encouraged to read it to get a feeling for the intricacy of the process. Here is the relevant section describing a portion of the process of encouraging the embryonic stem cells to differentiate into oligodendrocyte progenitor cells:
Cell culture. The H7 and H7-enhanced green fluorescent protein (eGFP) hESC lines at passage 32 and the human fibroblast (hFb) line at passage 48 were obtained from Geron (Menlo Park, CA). Cells were expanded in hESC growth media (Carpenter et al., 2001) and differentiated (Nistor et al., 2005) according to published protocols. Dissociated cells were placed for 2 d in 50% hESC growth media and 50% glial restriction media (GRM). GRM consisted of DMEM:F-12, B27 supplement (Invitrogen, Carlsbad, CA), 25 µg/ml insulin, 6.3 ng/ml progesterone, 10 µg/ml putrescin, 50 ng/ml sodium selenite, 50 µg/ml holotransferin, 40 ng/ml tri-iodo-thyroidin, 4 ng/ml basic FGF (bFGF), and 10 ng/ml epidermal growth factor (EGF) (Sigma-Aldrich, St. Louis, MO). Cells were then exposed to transition media supplemented with 2 ng/ml bFGF, 20 ng/ml EGF (Sigma-Aldrich), and 10 µM/ml all-trans-retinoic acid (RA) (Sigma-Aldrich) in DMSO (Sigma-Aldrich) for 1 d.
This media was then replaced with 100% GRM supplemented with 20 ng/ml EGF (Sigma-Aldrich) and 10 µM/ml all-trans-RA in DMSO for an additional 7 d. RA was then omitted from media for the duration of the differentiation protocol. Cells were exposed to GRM supplemented with 20 ng/ml EGF for 25 d. At day 28, cultures of floating yellow spheres were plated in T75 flasks coated with 1:30 Matrigel for 1 week. Cultures were then exposed to trypsin-EDTA (Invitrogen) for 2-5 min, plated on 1:30 Matrigel substrate, and cultured for 1 week in GRM supplemented with 20 ng/ml EGF. Thus, the differentiation protocol took 42 d.
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11Basically this is a recipe for taking blank embryonic stem cells, putting them in a broth, called a "growth media," and coaxing them into growing into precursor cells for the myelin sheath, hoping that upon injection they will grow into that sheath in the patient. Added to the broth are such ingredients as progesterone (a female hormone), growth factors and acid. The culturing takes 42 days. All these steps have to go just right. The trial has two goals: 1. to see if the procedure is safe and 2. to determine if it can restore function.
As mentioned, the hope behind this protocol is that the researchers can duplicate in a test tube what is going on naturally in an embryo regarding differentiation, that is, that they can direct the cells to make specialized bodily parts in the laboratory, in this case OPCs that will help regrow the myelin.
"We're very optimistic," Thomas B. Okarma, president and chief executive of Geron Corp., said after receiving the green light in July from the FDA following years of delay to study patients partially paralyzed by spinal cord injuries. "If we're right, we'll revolutionize the treatment of many chronic diseases (Stein, 2010)."
But to many scientists, it is a long shot.
Most stem cell researchers view Geron's plans with hefty skepticism and caution that a premature rush to treat patients using ES cells could seriously damage the already controversial field.
"The most sobering thing about [hES] cells is their power," says neuroscientist Clive Svendsen of the University of Wisconsin, Madison, who works with both fetal and embryonic stem cells. As noted by Vogel in "Ready of not? Human ES cells head toward the clinic:"
The extreme flexibility and capacity for growth characteristic of ES cells makes them ideal for producing large quantifies of therapeutic cells to treat, say, diabetes or spinal cord injuries. But these same traits also increase the risk that renegade cells could, as they have in animal studies, cause unwanted side effect, ending up in the wrong place or even sparking cancerous growth."The ES cell is basically a tumor-forming cell," says neuroscientist Anders Bhjorklund of Lund University in Sweden.
Even a benign tumor in the central nervous system would be serious, says Svendsen. "Any sort of growth in the spinal cord is not good news (Vogel, 2005)."
But troubling growths in the Geron's preclinical studies have haunted the firm's research involving GRNOPC1. As Geron noted:
In one of the preclinical expansion studies, a higher frequency of animals developed cysts in the injury site than had been seen in numerous foregoing preclinical studies with clinical grade GRNOPC1, including the IND [Investigational New Drug]-enabling studies. We notified the FDA of the findings from this animal study and the trial was put on clinical hold in August 2009. As part of ongoing work to optimize GRNOPC1 manufacturing and product release, we developed new candidate markers and assays as additional release specifications for GRNOPC1. We completed an additional confirmatory preclinical animal study to test the new markers and assays, and subsequently submitted a request to the FDA for the clinical hold to be lifted .
12In July 2010, the FDA notified us that the clinical hold placed on our IND application has been lifted and Geron's Phase I clinical trial of GRNOPC1 in patients with acute spinal cord injury may proceed (hESC-Derived Oligodendrocytes–GRNOPC1, 2010).
But as Bob Stein in the Washington Post noted August 30, 2010 following Geron's announcement in "Human tests set for stem cells," the tests are worrying many proponents: Some argue that the experiments are premature, others question whether they are ethical, and many fear that the trials risk disaster for the field if anything goes awry.
"We desperately need to know how these cells are going to perform in the human setting," said John Gearhart, a stem cell pioneer at the University of Pennsylvania. "But are we transplanting cells that are going to cause tumors? Will they will stay where you put them and do what you want them to do?"
His concern is echoed by other stem cell researchers.
"There's a lot of angst around these trials," said Evan Y. Snyder, director of the stem cell program at the Sanford-Burnham Medical Research Institute in San Diego. "There's going to be this perception that if the cells do not perform well, the entire field will be illegitimate."
The trial is designed primarily to ensure the cells are safe. But researchers also will look for signs that the therapy restores sensation or enables patients to regain movement.
"If we were able to do that, it would be a phenomenally positive result," Okarma said (Stein, 2010).
The high-profile political debates may have already set expectations for the field too high, especially among patients who face devastgating diseases, noted Bernat Soria of Miguel Hernandez University in Alicante, Spain. Honesty, not hype, is key, she said.
Even the skeptics say Geron chose a plausible target for the first trial, as spinal cord injuries may be significantly easier to tackle than diseases such as diabetes or Parkinson's.
Still, many scientists worry that Geron is moving too fast. They point to gene-therapy trials in which one young patient died of an unexpected immune reaction and others developed deadly leukemia (Vogel, 2005).
13The world awaits the outcome of the Geron trials.
"If human embryonic stem cells are going to be useful in treating humans, someone has to be the first one to try it," said Hank Greely, a Stanford lawyer and bioethicist. "They need to have their fingers crossed and hold their lucky rabbit's foot and be really careful in their preparations, because before you try something in humans you never know what's going to happen (Stein, 2010)."2.
Injunction banning federal funding
While a trial is going on at the scientific level, another trial looms–this one of a legal nature. U.S. District Court Judge Lamberth August 23 issued a preliminary injunction that prohibits the National Institute of Health from funding embryonic stem cell research under the new guidelines issued by the Obama Administration, arguing that the research violated a ban on the use of federal money to destroy embryos.
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In his 15-page ruling, Lamberth said the Obama administration's policy violated a 1996 provision of law known as the Dickey-Wicker Amendment. Lamberth wrote, "As demonstrated by the plain language of the [amendment], the unambiguous intent of Congress is to prohibit the expenditure of federal funds on 'research in which a human embryo or embryos are destroyed'...This prohibition encompasses all research in which an embryo is destroyed, not just the 'piece of research' in which the embryo is destroyed."
What the defendants argued was that the "piece of research" on stem cells did not violate the amendment because the stem cells which were involved in the research had been harvested from embryos which had been destroyed previously.
14The Dickey-Wicker Amendment is the name of an appropriation bill rider attached to a bill passed by the United States Congress in 1995, and signed by former President Bill Clinton, which prohibits the Department of Health and Human Services (HHS), including the NIH, from using federally appropriated funds for the creation of human embryos for research purposes or for research in which human embryos are destroyed. It states:
The Human Subject Protection regulation 45 CFR 46.208(a)(2) states that:SEC. 509. (a) None of the funds made available in this Act may be used for–
(1) the creation of a human embryo or embryos for research purposes; or
(2) research in which a human embryo or embryos are destroyed, discarded, or knowingly subjected to risk of injury or death greater than that allowed for research on fetuses in utero under 45 CFR 46.208(a)(2) and Section 498(b) of the Public Health Service Act (42 U.S.C. 289g(b)) (Title 42, Section 289g(b), United States Code).
(b) For purposes of this section, the term "human embryo or embryos" includes any organism, not protected as a human subject under 45 CFR 46 (the Human Subject Protection regulations) . . . that is derived by fertilization, parthenogenesis, cloning, or any other means from one or more human gametes (sperm or egg) or human diploid cells (cells that have two sets of chromosomes, such as somatic cells).
The risk to the fetus must be minimal and the purpose of the research must be development of important biomedical knowledge which cannot be acquired by other means. Minimal risk is defined as that the probability and magnitude of harm or discomfort expected in the study are not greater than those ordinarily faced in daily life or the performance of routine physical or psychological tests (Stith-Coleman, 1998).
Lamberth's ruling was in response to a lawsuit filed by two researchers from Boston and Seattle engaged in adult stem cell research, who agrued that in addition to violating the Dickey-Wicker Amendment, the 2009 guidelines would "result in increased competition for limited federal funding" and claimed that the policy harmed their own chances of getting funding for similar research not involving embryos.
Lamberth initially threw out the case, but the U.S. Court of Appeals in D.C. on June 25 ruled that the plaintiffs had legal standing to file the suit. Several of the original plaintiffs–including the Christian Medical Association and Nightlight Christian Adoptions–dropped out of the suit. Lamberth ruled that the researchers' claim is strong enough to stop federal authorities from "taking any action whatsoever" to implement funding guidelines pending trial (Federal judge blocks Obama administration embryonic stem cell policy, 2010).
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15The two researcher are Dr. James Sherley, a biological engineer at Boston Biomedical Research Institute, and Theresa Deisher of Washington-based AVM Biotechnology.
In his opinion, Lamberth noted that the Dickey-Wicker Amendment provides that no federal funds shall be used for "research in which a human embryo or embryos are destroyed, discarded, or knowingly subjected to risk of injury or death..."
He noted that that contrary to the defendants' argument, the term "research" as used in the Dickey-Wicker Amendment has only one meaning, i.e., "a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge."
Lamberth stated that the language of the statute does not support the defendants' alternative definition of research as "a piece of research," pointing out that had Congress intended to limit the Dickey-Wicker Amendment to only those discrete acts that result in the destruction of an embryo, like the derivation of ESCs, or to research on the embryo itself, Congress could have written the statute that way. See full text of the Lamberth decision.
Louis Guenin, a lecturer on ethics in science at Harvard Medical School, saw a challenge coming to such research. He warned shortly after Obama was elected president that Congress needed to act on the issue. Guenin, who supports federal funding for hESCs, worried that an Executive Order, like the one Obama issued on March 9, 2009, would be vulnerable to legal challenges.
In 1999, NIH officials made a distinction between derivation of hESCs and research on derived cells. They argued that use of cell lines did not violate the specific language of the Dickey-Wicker Amendment. In his decision, Judge Lamberth said that NIH's distinction was invalid. Although Guenin says he's frustrated by the situation, he believes the judge is correct in ruling that funding for hESC work is incompatible with current law. The same would be true for research that involved killing bald eagles, he says. "It's illegal to kill the birds. Even if someone else shoots the birds for you, you're still going to go to jail because you're complicit in an arrangement in which the birds are killed," he says.
To be on safe legal ground, Guenin and others say, Congress needs to remove the prohibition against embryo research or pass a law explicitly allowing federal funding of research on hESCs (Vogel and Kaiser, 2010).
"The Obama administration has attempted to skirt the law by arguing that they are only funding research after the embryos are destroyed," said Charmaine Yoest, chief executive of Americans United for Life. "That Administration policy is in violation of the law (Yoest on stem cell ruling, 2010)."16Scientists working with embryonic stem cells said patients will suffer by having to wait longer for science to develop new treatments and cures. Plus, the injunction is apparently worrying investors. In a stock market commentary by Andrew Klips for StraightStocks.com in "The Dickey-Wicker Amendment Scaring Investors?" he noted that "The news of Judge Lamberth's decision sent stem cell related companies on a slide (Klips, 2010)."
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Advanced Cell Technology Inc. is using the cells to grow retinal pigment epithelium cells that restored vision in rats and mice with a rare childhood disease called Stargardt's macular dystrophy. The Santa Monica-based company has asked the Food and Drug Administration for permission to use the cells in a clinical trial. But without any prospect of federal funding, the research would be in doubt, said Lanza, the company's chief scientific officer.
"This is criminal," Lanza said. "We are talking about people going blind, people who are dying from a terrifying array of diseases (Kaplan and Levey, 2010)."
Dr. Francis S. Collins, director of the NIH, issued in response to the injunction the following statement:
Human embryonic stem cell research holds great promise for the development of treatments for people threatened by potentially curable diseases. The recent court ruling that halted the federal funding of human embryonic stem cell research could cause irreparable damage and delay potential breakthroughs to improve care for people living with serious diseases and conditions such as spinal cord injury, diabetes, or Parkinson's disease. The injunction threatens to stop progress in one of the most encouraging areas of biomedical research, just as scientists are gaining momentum-and squander the investment we have already made. The possibility of using these cells to replace those that have been damaged by disease or injury is one of the most breathtaking advances we can envision. Human embryonic stem cells also represent a powerful new approach to the early stages of screening for new drugs, and may hold the secrets to creating entirely new, targeted clinical therapies. We must move forward-without delay-to sustain this field of research that provides so much hope for thousands of patients and their families (NIH Director's Response to Stem Cell Injunction, 2010).
Francis S. Collins
But are such statements being issued by the stem cell community the truth or hype?
Is the injunction stopping the federal funding of human embryos actually criminal, like Lanza claims? Even taking the term "criminal" to mean outrageous, is it "criminal" for a judge to make a ruling to protect human life and uphold a statute? Is this injunction prohibiting their destruction "criminal" for the embryos? Or is this statement hyperbole? In fact, is the name-calling a mask for an unethical science?
Further, does human embryonic stem cell research hold "great promise" for the development of treatments for people threatened by potentially curable diseases and is it "one of the most encouraging areas of biomedical research"?
Will the recent court ruling that halted the federal funding of human embryonic stem cell research "cause irreparable damage and delay potential breakthroughs" to improve care for people living with diseases and conditions such as spinal cord injury, diabetes, or Parkinson's disease?
Or should the injunction serve as the first step in declaring a moritorium on embryonic stem cell research?
17Is the possibility of using these cells to replace those that have been damaged by disease or injury "one of the most breathtaking advances we can envision?"
And must we "move forward–without delay–to sustain this field of research that provides so much hope for thousands of patients and their families"?
Lanza says that such an injunction is criminal because "We are talking about people going blind, people who are dying from a terrifying array of diseases." Could it be that by diverting funds from more realistic fields of medical research that embryonic stem cell research is, in fact, functioning as a roadblock to the development of treatments for disease and injury?
This three-part series is an attempt to answer these questions.
Such questions will also be addressed by the two trials, the scientific one ongoing now via the Geron Corporation, and the legal trial that will determine if the federal funding of human stem cell research is legally permissible. Plus, the Dickey-Wicker Amendment, which is the basis of the recent legal ruling by Judge Lamberth, may be subject to repeal.
Both trials will help determine the future of human embryonic stem cell research, as well as whether human embryos deserve protection from exploitation and destruction.
18Chakrabarti, Spandan (2010, October 14) World's first human clinical trial starts with human stem cells. The People's View. Retrieved from http://www.thepeoplesview.net/2010/10/worlds-first-human-trial-starts-with.htm
Fawcett, James (2002, December) Review: Repair of spinal cord injuries: where are we, where are we going? Spinal Cord. Retrieved from http://www.nature.com/sc/journal/v40/n12/full/3101328a.html
Federal judge blocks Obama administration embryonic stem cell policy (2010, August 25) Medical News Today. Retrieved from http://www.medicalnewstoday.com/articles/198856.php
Fox, Maggie (2010, October 11) First patient treated in geron stem cell trial. reuters. Retrived from http://www.reuters.com/article/idustre69a32i20101011
hESC-Derived Oligodendrocytes–GRNOPC1 (2010, October 25) Geron Corporation. Retrieved from http://www.geron.com/products/productinformation/spinalcordinjury.aspx
Injunction against Federal Funding for Stem Cell Research (2010, October 18) Reeve-Irvine Research Center. Retrieved from http://www.reeve.uci.edu/news-injunction-federal-funding-stem-cell-research.html
Intervew transcript with Hans Kierstad (2007, July 17) Carecure Community, from KCET Life and Times interview. Retrieved from http://sci.rutgers.edu/forum/showthread.php?t=85396
Kaplan, Karen and Levey, Noam N. (2010, August 24) Ruling a blow to stem cell research: A federal judge blocks U.S. funding for all projects involving the use of material from human embryos. Los Angeles Times. Retrieved from http://articles.latimes.com/2010/aug/24/nation/la-na-stemcells-20100824/2
Keirstead, Hans S et al (2005, May 11) Human Embryonic Stem Cell-Derived Oligodendrocyte Progenitor Cell Transplants Remyelinate and Restore Locomotion after Spinal Cord Injury. Journal of Neuroscience. Retrieved from http://neuro.cjb.net/cgi/content/full/25/19/4694
Minkel, J.R. (2007, November 15, 2007) Primate stem cell barrier broken–embryonic stem cells derived from adult primate cells suggest humans may get their turn yet. Scientific American. Retrieved from http://www.scientificamerican.com/article.cfm?id=primate-stem-cell-barrier-broken
Never Let Me Go by Kazuo Ishiguro (2010, November 14) The complete review. Retrieved from http://www.complete-review.com/reviews/ishigk/neverlmg.htm
NIH Director's Response to Stem Cell Injunction (2010, August 26) National Institute of Health. Retrieved from http://www.nih.gov/about/director/08262010statement_stemcellinjunction.htm
19Oligodendrocyte progenitor cells (GRNOPC1) (2010, October 23) Geron Corporation. Retrieved from http://www.geron.com/grnopc1trial/grnopc1-sec2.html
Patrick Cusworth, Patrick (2010, October 14) Landmark stem cell trial begins. MercatorNet.com. Retrieved from http://www.mercatornet.com/articles/view/landmark_stem_cell_trial_begins/
Robert Klein (2010, October 18) California Institute for Regenerative Medicine. Retrieved from http://www.cirm.ca.gov/Board_Robert_Klein
Stein, Rob (2010, August 30) Human tests set for stem cells. The Wasthington Post. Retrieved from http://www.washingtonpost.com/wp-dyn/content/article/2010/08/29/AR2010082903888.html
Stem Cell Lines (2010, October 16) Geron. Retrieved from: http://www.geron.com/technology/stemcell/stemcelllines.aspx
Stem cell research (2010, November 5) Congressman Bart Stupak. Retrieved from http://www.house.gov/stupak/issues_stemcell.shtml
Stith-Coleman, Irene (1998, January 29) Human Embryo Research. CRS Report for Congress. Retrieved from http://www.law.umaryland.edu/marshall/crsreports/crsdocuments/95-910_STM.pdf
Sunday funnies 8-29-10 (2010, August 29) Jill Stanak. Retrieved from http://www.jillstanek.com/2010/08/sunday-funnies-40/
The mission of the Reeve-Irvine Research Center (2010, November 6)Reeve-Irvine Research Center, University of California, Irvine Retrieved from http://www.reeve.uci.edu/about.html
The promise of human embryonic stem cell research (2010, November 5) National Institute of Health. Retrieved from http://www.nih.gov/about/director/stemcell/testimony_09162010.pdf
Thomas, Cal (2010, October 6) Cal Thomas commentary October 6, 2010. Retrieved from http://www.calthomas.com/index.php?news=3050
Vesely, Rebecca (2010, October 16) Immortal Cell. Retrieved from http://immortalcell.com/DonReed.html
Vogel, Gretchen (2005, June 10) Ready or not? Human ES Cells head toward the clinic. Science, New York. Pages 1534-1538.
20Vogel, Gregtchen and Kaiser, Jocelyn (2010, August 25), What's next with the stem cell injunction? Retrieved from http://news.sciencemag.org/scienceinsider/2010/08/whats-next-with-the-stem-cell-in.html
Xu, Jodi (2010, October 11) Geron enrolls first patient in stem-cell treatment study. Wall Street Journal. Retrieved from http://online.wsj.com/article/sb10001424052748703794104575546371842991324.html
Yoest on Stem Cell Ruling (2010, August 23) Court strikes down Obama administration stem cell policy. Americans United for Life. Retrieved from http://www.aul.org/2010/08/yoest-on-stem-cell-ruling/