vlhperry
12-16-2006, 09:47 PM
What We Know About
Embryonic Stem Cells
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Maureen L. Condic
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Copyright (c) 2007 First Things 169 (January 2007): 25-29.
Back at the beginning of 2002, there was considerable optimism regarding the promise that embryonic stem cells were said to hold for millions of people suffering from fatal or debilitating medical conditions. Stem cells derived from human embryos, it was claimed, provided the best hope for relief of human suffering. Despite the profound ethical concerns regarding the use of human embryos for medical and scientific research, many Americans embraced this promise and the seemingly miraculous hope it offered.
The challenges facing embryonic stem cells were formidable. First, there was the concern that the cells and their derived tissue would be rejected by the patient’s immune system, requiring the patient to undergo lifelong immune suppression. The three proposed solutions to this incompatibility problem (generating large banks of stem cell lines, cloning human embryos to provide a source of cells that perfectly match the patient, or genetically engineering stem cells to reduce immune rejection) were either socially, scientifically, or morally problematic (or all three). Second, there was the serious problem that embryonic stem cells form tumors when transplanted to adult tissues, and the tumorogenic capability of these cells is difficult, if not impossible, to control. Finally, there was the disturbing fact that science had thus far provided essentially no convincing evidence that embryonic stem cells could be reliably differentiated into normal adult cell types, as well as the disturbing possibility that overcoming this barrier would prove a difficult scientific endeavor.
Despite these concerns, many continued to regard embryonic stem cells with hope, believing that further research would overcome these difficulties and harness the power of embryonic stem cells for the benefit of mankind. Such optimists asserted that it was simply a matter of investing sufficient time, money, and research.
Since 2002, considerable resources have been devoted to just such research. A recent query of the grant database maintained by the National Institutes of Health (NIH) indicates that more than eighty research projects investigating human embryonic stem cells have been funded over the past five years. A research effort of this size represents millions of dollars in public money invested in the medical promise of embryonic stem cells. Indeed, the NIH reported to Congress in September of last year that anticipated spending on human embryonic stem cell research in 2006 was “just $24,300,000.” Since 2002, approximately nine hundred research papers have been published on investigations of human embryonic stem cells, with more than a thousand additional papers investigating the properties of embryonic stem cells derived from animals. Clearly, research on embryonic stem cells has advanced considerably over the past five years, and it is therefore important to revisit the promise in light of current findings.
Stem cell–based therapies propose to treat human medical conditions by replacing cells that have been lost through disease or injury. Unlike an organ transplant, where a damaged or diseased tissue is removed and then replaced with a comparable organ from a donor, stem cell therapies would involve integration of replacement cells into the existing tissues of the patient. The dispersed integration of the transplanted cells throughout the targeted organ (indeed, throughout the entire body of the patient) would make it impossible to remove the stem cell derivatives surgically should any problems arise. Thus, the problem of immune rejection is of particular concern—if transplanted cells are attacked by the immune system, the entire tissue in which the foreign cells reside becomes the target of a potentially disastrous immune attack.
Over the past five years, the scientific community has focused almost exclusively on somatic-cell nuclear transfer, or cloning, as the best resolution to the problem of immune rejection. During somatic-cell nuclear transfer, the genetic information of an unfertilized human egg would be removed and replaced with the unique genetic information of a patient. This would produce a cloned, one-cell embryo that would mature for several days in the laboratory and then be destroyed to obtain stem cells genetically matched to the patient. Based on the success of animal cloning, human cloning was optimistically predicted to be a simple matter. Once we were able to clone human embryos, those embryos would provide patient-specific stem cell repair kits for anyone requiring cell-replacement therapies.
Human cloning has proved to be more challenging than anticipated. Human eggs, as it turns out, are considerably more fragile than eggs of other mammalian species, and they do not survive the procedures that were successfully used to clone animals. Multiple attempts by several research groups worldwide have been unsuccessful in generating human clones. The few reports of the successful cloning of human embryos were either unverifiable press releases or clear chicanery promoted by a quasi-religious group for its own publicity.
The elusive prize to generate the first human clone appeared to be won in March 2004, when a South Korean group led by Hwang Woo-Suk reported in the prestigious professional journal Science that they had generated a human stem cell line from a cloned human embryo. A year later, in June 2005, this same group sensationally reported that they had successfully generated eleven patient-specific stem cell lines from cloned human embryos and had dramatically improved their success rate to better than one in twenty attempts, bringing cloning into the realm of the possible for routine treatment of human medical conditions. Hwang was hailed as a hero and a pioneer, and his reported success evoked an almost immediate clamor to remove the funding restrictions imposed by the Bush administration on human embryonic stem cell research, lest America fall hopelessly behind South Korea in developing therapies.
By fall 2005, however, the cloning miracle had begun to unravel. Colleagues of Hwang raised serious concerns about his published studies, launching an investigation into possible scientific fraud. By December, it was conclusively shown that all the claimed cloned stem cell lines were fakes. To date, no one has successfully demonstrated that it is indeed possible to clone human embryos, and, based on the failed attempts of Hwang and others, human cloning is not likely to be a simple task, should it prove possible at all.
The scandal surrounding Hwang’s audacious fraud raised multiple concerns about the ethics of embryonic stem cell research. Investigations revealed that Hwang had used thousands of human oocytes for his unsuccessful attempts, not the hundreds as he had originally claimed. The medical risks associated with egg donation (the potential complications include both sterility and death) raise serious questions about the morality of conducting basic research on human cloning. Given that Hwang pressured junior female colleagues into donating eggs for his research, how can the interests of female scientists be protected from such professional exploitation? Given that thousands of human eggs from more than a hundred women were used by Hwang and not even a single viable cloned human embryo resulted from this research, how can the medical risks to women entailed by this research possibly be justified?
The technical challenges encountered by Hwang are not particularly surprising. Experience from multiple laboratories over the past decade confirms that it is extremely difficult to clone any animal. Cloned embryos are generally quite abnormal, with those that are sufficiently normal to survive to live birth typically representing between 0.1 and 2 percent. The problems do not end with the technical difficulty of somatic-cell nuclear transfer itself. Extensive evidence indicates that even the cloned animals that make it to birth are not untarnished success stories. Following Ian Wilmut’s production of Dolly the sheep, the world’s first cloned mammal, it was almost immediately evident that Dolly was not normal; she experienced a number of medical problems that resulted in her being euthanized, due to poor health, at the age of six years, about half the lifespan of a healthy sheep. Dolly was the only clone to survive to live birth out of the 277 cloned embryos Wilmut’s group generated, yet this success did not prove that cloning can produce a normal sheep. Dolly was merely normal enough to survive to birth.
In the past five years, a number of studies have carefully examined patterns of gene expression in mice and other cloned animals that survived to birth. Not one of these animals is genetically normal, and multiple genes are aberrantly expressed in multiple tissues. Both the severity and the extent of these genetic abnormalities came as a surprise to the cloning field, and yet, in retrospect, they are not surprising at all. The fact that most cloned embryos die at early stages of development is entirely consistent with the conclusion that somatic-cell nuclear transfer does not generate normal embryos, even in the rare cases where clones survive to birth. Thus, the optimistic contention that “therapeutic cloning” would fix the immune problem facing potential embryonic stem cell–based therapies for humans seems thus far entirely unsupported by the scientific evidence.
Embryonic Stem Cells
--------------------------------------------------------------------------------
Maureen L. Condic
--------------------------------------------------------------------------------
Copyright (c) 2007 First Things 169 (January 2007): 25-29.
Back at the beginning of 2002, there was considerable optimism regarding the promise that embryonic stem cells were said to hold for millions of people suffering from fatal or debilitating medical conditions. Stem cells derived from human embryos, it was claimed, provided the best hope for relief of human suffering. Despite the profound ethical concerns regarding the use of human embryos for medical and scientific research, many Americans embraced this promise and the seemingly miraculous hope it offered.
The challenges facing embryonic stem cells were formidable. First, there was the concern that the cells and their derived tissue would be rejected by the patient’s immune system, requiring the patient to undergo lifelong immune suppression. The three proposed solutions to this incompatibility problem (generating large banks of stem cell lines, cloning human embryos to provide a source of cells that perfectly match the patient, or genetically engineering stem cells to reduce immune rejection) were either socially, scientifically, or morally problematic (or all three). Second, there was the serious problem that embryonic stem cells form tumors when transplanted to adult tissues, and the tumorogenic capability of these cells is difficult, if not impossible, to control. Finally, there was the disturbing fact that science had thus far provided essentially no convincing evidence that embryonic stem cells could be reliably differentiated into normal adult cell types, as well as the disturbing possibility that overcoming this barrier would prove a difficult scientific endeavor.
Despite these concerns, many continued to regard embryonic stem cells with hope, believing that further research would overcome these difficulties and harness the power of embryonic stem cells for the benefit of mankind. Such optimists asserted that it was simply a matter of investing sufficient time, money, and research.
Since 2002, considerable resources have been devoted to just such research. A recent query of the grant database maintained by the National Institutes of Health (NIH) indicates that more than eighty research projects investigating human embryonic stem cells have been funded over the past five years. A research effort of this size represents millions of dollars in public money invested in the medical promise of embryonic stem cells. Indeed, the NIH reported to Congress in September of last year that anticipated spending on human embryonic stem cell research in 2006 was “just $24,300,000.” Since 2002, approximately nine hundred research papers have been published on investigations of human embryonic stem cells, with more than a thousand additional papers investigating the properties of embryonic stem cells derived from animals. Clearly, research on embryonic stem cells has advanced considerably over the past five years, and it is therefore important to revisit the promise in light of current findings.
Stem cell–based therapies propose to treat human medical conditions by replacing cells that have been lost through disease or injury. Unlike an organ transplant, where a damaged or diseased tissue is removed and then replaced with a comparable organ from a donor, stem cell therapies would involve integration of replacement cells into the existing tissues of the patient. The dispersed integration of the transplanted cells throughout the targeted organ (indeed, throughout the entire body of the patient) would make it impossible to remove the stem cell derivatives surgically should any problems arise. Thus, the problem of immune rejection is of particular concern—if transplanted cells are attacked by the immune system, the entire tissue in which the foreign cells reside becomes the target of a potentially disastrous immune attack.
Over the past five years, the scientific community has focused almost exclusively on somatic-cell nuclear transfer, or cloning, as the best resolution to the problem of immune rejection. During somatic-cell nuclear transfer, the genetic information of an unfertilized human egg would be removed and replaced with the unique genetic information of a patient. This would produce a cloned, one-cell embryo that would mature for several days in the laboratory and then be destroyed to obtain stem cells genetically matched to the patient. Based on the success of animal cloning, human cloning was optimistically predicted to be a simple matter. Once we were able to clone human embryos, those embryos would provide patient-specific stem cell repair kits for anyone requiring cell-replacement therapies.
Human cloning has proved to be more challenging than anticipated. Human eggs, as it turns out, are considerably more fragile than eggs of other mammalian species, and they do not survive the procedures that were successfully used to clone animals. Multiple attempts by several research groups worldwide have been unsuccessful in generating human clones. The few reports of the successful cloning of human embryos were either unverifiable press releases or clear chicanery promoted by a quasi-religious group for its own publicity.
The elusive prize to generate the first human clone appeared to be won in March 2004, when a South Korean group led by Hwang Woo-Suk reported in the prestigious professional journal Science that they had generated a human stem cell line from a cloned human embryo. A year later, in June 2005, this same group sensationally reported that they had successfully generated eleven patient-specific stem cell lines from cloned human embryos and had dramatically improved their success rate to better than one in twenty attempts, bringing cloning into the realm of the possible for routine treatment of human medical conditions. Hwang was hailed as a hero and a pioneer, and his reported success evoked an almost immediate clamor to remove the funding restrictions imposed by the Bush administration on human embryonic stem cell research, lest America fall hopelessly behind South Korea in developing therapies.
By fall 2005, however, the cloning miracle had begun to unravel. Colleagues of Hwang raised serious concerns about his published studies, launching an investigation into possible scientific fraud. By December, it was conclusively shown that all the claimed cloned stem cell lines were fakes. To date, no one has successfully demonstrated that it is indeed possible to clone human embryos, and, based on the failed attempts of Hwang and others, human cloning is not likely to be a simple task, should it prove possible at all.
The scandal surrounding Hwang’s audacious fraud raised multiple concerns about the ethics of embryonic stem cell research. Investigations revealed that Hwang had used thousands of human oocytes for his unsuccessful attempts, not the hundreds as he had originally claimed. The medical risks associated with egg donation (the potential complications include both sterility and death) raise serious questions about the morality of conducting basic research on human cloning. Given that Hwang pressured junior female colleagues into donating eggs for his research, how can the interests of female scientists be protected from such professional exploitation? Given that thousands of human eggs from more than a hundred women were used by Hwang and not even a single viable cloned human embryo resulted from this research, how can the medical risks to women entailed by this research possibly be justified?
The technical challenges encountered by Hwang are not particularly surprising. Experience from multiple laboratories over the past decade confirms that it is extremely difficult to clone any animal. Cloned embryos are generally quite abnormal, with those that are sufficiently normal to survive to live birth typically representing between 0.1 and 2 percent. The problems do not end with the technical difficulty of somatic-cell nuclear transfer itself. Extensive evidence indicates that even the cloned animals that make it to birth are not untarnished success stories. Following Ian Wilmut’s production of Dolly the sheep, the world’s first cloned mammal, it was almost immediately evident that Dolly was not normal; she experienced a number of medical problems that resulted in her being euthanized, due to poor health, at the age of six years, about half the lifespan of a healthy sheep. Dolly was the only clone to survive to live birth out of the 277 cloned embryos Wilmut’s group generated, yet this success did not prove that cloning can produce a normal sheep. Dolly was merely normal enough to survive to birth.
In the past five years, a number of studies have carefully examined patterns of gene expression in mice and other cloned animals that survived to birth. Not one of these animals is genetically normal, and multiple genes are aberrantly expressed in multiple tissues. Both the severity and the extent of these genetic abnormalities came as a surprise to the cloning field, and yet, in retrospect, they are not surprising at all. The fact that most cloned embryos die at early stages of development is entirely consistent with the conclusion that somatic-cell nuclear transfer does not generate normal embryos, even in the rare cases where clones survive to birth. Thus, the optimistic contention that “therapeutic cloning” would fix the immune problem facing potential embryonic stem cell–based therapies for humans seems thus far entirely unsupported by the scientific evidence.