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Spermless fertilization NZ Herald
A technique that uses cells from the body, rather than sperm, has been used to create embryos in mice.
by Roger Highfield
A way to fertilise human eggs without using sperm threatens to make men redundant' The technique which uses cells from any part of the body, rather dm sperm has already been used to create embryos in mice' The research by Melbourne's Monash University auns to help men who have no sperm, or even sperm-raking cells, to father babies that are dleir own genetic offspring. But it could help lesbian couples to have baby girls that are genetically their own. Research team member Dr Orly Lacham-Kaplan said the sperm-free technique could, in theory at least, enable a lesbian couple to have a baby, with one woman contributing an egg and the second a cell to fertilise it. There are theoretical problems to overcome in combining the genes of two women, because aspects of development are controlled by a paternal gene when a maternal copy is tuimed off, and vice versa, as a result of a process called imprinting. "But we have no proof yet that it is or is not a problem," Dr Lacham-Kaplan said. Her team has succeeded in "fertilising" a normal mouse egg by using an artificial gamete, a cell taken from the body of a male. This is remarkable because, unlike sperm, the body cell has two sets of chromosomes. To overcome that problem, the team exploited cellular machinery used by an unfertilised egg to eject a spare set of chromosomes when it meets sperm. During normal fertilisation, two sets of chromosomes in an egg are separated and one set is ejected in a package that biologists call the polar body, leaving a single set to combine with another set from the sperm. After "fertilisation" of the mouse egg, the team used chemicals to persuade the egg to carry out the steps typical of normal fertilisation: it released its spare set of chromosomes into a polar body, only this time the body cen also expelled its spare set into a second polar body.
The embryos go on to develop fairly norrnally in the laboratory and the team is about to transfer them into the wombs of mice. Once offspring from animals have been born, the team will test their genetics, behaviour and ability to reproduce and give birth to viable offspring for a few generations. "Only then we may be able to examine the technique in the human," Dr Lachain-Kaplan said. She admitted that any technique which allowed babies to be created without men could open an ethical can of worms. Fertility expert Lord Robert Winston, of Hammersmith Hospital, west London, said: "These are extraordinarily inteeresting experiments. But the issue of increasing importance with all these developments is whether genes are expressed [used) correctly after fertilisation."
The Monash team's work is just one of a number of startling breakthroughs in reproductive science recently, all of which raised ethical questions.
Last year, a similar proposal to enable homosexual men to have their own children made headlines. It was proposed that a "male egg" would be created by removing the DNA from an egg donated from a woman and replacing it with that from sperm.
A technique has been developed in America which virtually guarantees the sex of a baby by separating out sperm that will 'produce a female embryo. Scientists say the Fairfax procedure has a 90 per cent success rate. It is intended to help couples worried about passing on genetic diseases that are linked to gender, but there is concem that it will be abused by people who want to determine thew baby's sex for purely social reasons.
Scientists at the Wisconsin and Illinois Universities in the United States are working on a device to automate the process of in-vitro fertilisation. They believe the technology may eventually be able to test embryos for genetic flaws. They have designed a device that mimics conditions inside a female reproductive tract. Dr George Seidel, a reproductive physiologist at Colorado State University in Fort Collins, said the work could represent the first step to IVF becoming the norm. "Fifty or 100 years from now, our in-vitro, procedure for parts or even all of pregnancy may end up being safer than dealing with the various things that occur in the body in terms of viruses that the mother comes across, toxins, and so on." TELEGRAPH GROUP LTD, REUTERS
My two mums NZ Herald July 2001
Have genetically engineered children arrived by stealth?
BABIES have been born with DNA from three parents instead of two. They have been described as the first genetically engineered humans, as the added DNA they carry could be passed on down the generations.
New Scientist reported last year that a certain fertility treatment would spawn babies with DNA from more than two parents (2 December 2000, p 16). Now cells from two one-year-old babies born as a result of this treatment have indeed turned out to have a little extra DNA from a donor mother, as well as that from their own parents.
Midway through the 1990s, Jacques Cohen and Jason Barritt at the Institute for Reproductive Medicine and Science of Saint Barnabas in New jersey reckoned that some women couldn't have babies because of defects in the cytoplasm of their eggs-the fluid surrounding the nucleus. So they decided to try adding "healthy" cytoplasm ftom a donor egg.
While the vast majority of our genes are housed in the nucleus, the cytoplasm contains tiny energy-producing structures called mitochondria that have their own set of 13 genes. If you inject donor cytoplasm into an egg, you can transfer mitochondria and their genes as well.
The researchers examined 12 of the 30 babies born with the help of the technique and found that two of them carry donor mitochondria. 'This report is the first case of human germline genetic modification resulting in normal healthy children,' say Barritt and his colleagues in the journal Human Reproduction (vol 16, p 513). These mitochondria could be passed on to future generations. "We won't know till they reach reproductive age,' he told New Scientist.
However, no one knows if the added mitochondria were the reason why the fertility treatment worked in these two cases. Other, non-genetic components of the cytoplasm might have done the trick. "We think every patient is different, and some might need mitochondria for extra energy, and some might need messenger RNA or proteins," says Barritt.
Some researchers want to go further. James Grifo of New York University has been given approval to try to treat infertile women by removing the nucleus from their egg and injecting it into a donor egg whose nucleus has been removed. In this case, all the mitochondria of any baby born would come from the donor.
This technique could also help prevent women who have mutations in mitochondrial DNA passing the problem on to their children. Such mitochondrial diseases cause various problems, and can be fatal.
Meanwhile, scientists are still fighting about whether terms such as 'genetic modification" apply to this treatment. Despite what Barritt wrote in Human Reproduction, he maintains it's not germline therapy. 'To be true genetic or germline therapy, you must modify genes in nuclear DNA.'
'My gut feeling is that you're adding mitochondrial DNA, so that is gene therapy," says Norman Nevin, the chairman of Britain's Gene Therapy Advisory Committee. Andy Coghtan and Joanna Marchant
Clamp on plan to clone baby NZ Herald July 2001
WASHINGTON United States federal investigators have uncovered a secret laboratory where members of a religious sect were experirnenting with human cloning. A.grand jury in Syracuse, New York, subpoenaed telephone records and other documents as part of an investigation into a lab run by members-, of the Raelian sect, which believes scientists from another planet created all life on Earth, according to a US News and World Reports article. The Raelian chief scientist, French national Brigitte Boisselier, alorfi@ with Italian gynaecologist Severino Antinori and US doctor Richard Seed lead an intemational consortium that has announced plans to clone a human being. Clonaid, a company with links to the Raelians, seeks to reproduce by cloning a l0-month-old baby that died during heart surgery, at the request of the baby's US parents. Human cloning is forbidden in all but four of the country's 50 states although no federal law exists barring. private financing of such research. AFP
Sexual Selection by David Derbyshire
NZ Herald July 2001
Sperm sorting and gender choice
LAUSANNE Hundreds of couples are using a medical technique to choose the sex of their children, many for social reasons. The "sperm sorting" procedure, which allows gender selection before conception, is particularly valuable in avoiding passing on genetic illnesses that usually affect only boys, such as haemophilia and muscular dystrophy. But Dr Harvey Stem, of the Genetics and IVF Institute in Fairfax, Virginia, said that of 200 couples who had used the procedure, 40 per cent had done so for non-medical reasons. Many of his patients, who paid E1400 ($4625), were seeking to "balance out" families. Dr Stern admitted to having engineered girls for parents who wanted to "buy little dresses." A British couple successfully took part in the American trial after saymg that they had several boys and desperately wanted a girl. Dr Stern told the European Society of Human Reproduction and Embryology in Lausanne, Switzerland, that couples had requested slightly more girls than boys since the service began four years ago. "We are helping couples to have healthy, wanted children," he said. "Couples say, 'I love my sons, but I would like to have a girl because I want to buy little dresses.' "There are concerns that some parts of the world would use it only to have boys ... We only do this for balancing families, not for a first child." The Human Fertilisation and EmbrYology Authority, which regulates IVF and sperm donation in Britain, said the technique was legal, but it opposed using it for nonmedical reasons.
Fertility regulations cover creation of embryos outside the body, storing of sperm and use of donated sperm and eggs.
A spokesman said: "Sex selection for family balance is something that the authority is against because it would engender the idea that one sex is more valuable than the other. "We believe sex selection does have a place in avoiding disorders that affect oWy one sex."
The gender of a child is determined by the genetic makeup of sperm. Eggs fertilised by sperm carrying the Y chromosome will become boys; sperm with the X chromosome become girls. Sperm are sent through a sorting machine one by one and stained with dye. A laser is then shone on @ch sperm to measure its fluorescence and the larger ones are separated out. Because "female" sperm are slightly larger, carrying 2.8 per cent more DNA, it is possible to sort them out before conception.
The treatment is successful for nine out of 10 couples wanting a girl, and for seven of 10 who want a boy. Dr Stem said the technique had been used to create 284 IVF embiws for couples with six X-linked gene-tic diseases. The Daily Telegraph
Mum at 62, pregnant by brother NZ Herald June 2001
PARIS A 62-year woman who this month became France's oldest mother has revealed that her brother was the biological father of the baby. French judicial officials said yesterday that they were looking intq the case, The woman said she got pregnant using her brother's sperm and a donor egg, and that a second baby fathered by her brother a girl was bom to a surrogate mother. The 62-year-old woman, identified in the media only as Jeanine, said she underwent treatment at a Los Angeles clinic and gave birth on May 14 in @ejus in southern France. Prosecutor Christian Girard said officials were studying the baby's "family environment." The woman told Le Parisian newspaper that her child was conceived from her brother's sperm and an egg donated by an American woman. The woman also said her 52-yearold brother's sperm was used to conceive a second baby bom in late May with the sarne egg donor, who acted as a surrogate. Both babies live in Frejus with the woman and her brother, who share their house with their Bo-year-old mother. Jeanine, a retired teacher, said she told the clinic that her brother was her husband. "We are both healthy in mind and body," she told the paper. "I couldn't pass on my genes because of my age, so I wanted to pass on his and give life so our line could continue." The woman and her brother are both single and had been childless. According to a 1994 French law., only couples can have "medically -assisted procreation," and the techniques are forbidden for menopausal women. AP
Moves to prevent genetic means testing NZ Herald June 2001
LONDON The exploitation of genetic testing by insurers is set to be outlawed by the Brltish Government amid fears of creating an uninsurable "genetic underclass." Health Secretary Alan Milburn will signal this week the banning of the use of so-called genetic profiling tests which could predict who will die prematurely or suffer chronic diseases to deny people cover. He is still awaiting final recommendations from the ethical watchdog, the Human Genetics Commission, next month before making a decision, but is known to favour at least a partial moratorium.
Milburn will also pledge legislation to ban human reproductive cloning - likely to be highlighted by the Labour party's manifesto - to allay public fears about scientists playing god.
He will warn that the benefits of gentic testing discoveries must not be used to divide patients into a genetic underclass who are likely to become ill and a healthy superclassThe Practice is already outlawed by another watchdog, the Human Fertility and Embryology Authority, but Milburn wants to ensure that this ban could not be reversed in future. He will use a speech on Friday to highlight Potential benefits of genetic testing, such as new screening programmes for those found to have inherited a risk of serious treatable disease, and promise funding for developing accurate tests.
But he will warn that discoveries must not be used to divide patients into a "genetic underclass," who are likely to become ill, and a healthy "genetic superclass.11 British ministers may make a regulatory distinction between "essentials"such as life insurance needed for mortgage cover, where genetic discrimination could have disastrous consequences, and "luxuries" such as extensive private health insurance, where patients could rely on the National Health Service instead .
Milburn knows discussing such a sensitive issue close to an election is risky. But he fears that unless patients are sure that test results will not be used against them, scientific progress will be hampered as they refuse to take tests.
"There are huge potential health gains to be had from genetic advances, but until we address these public concerns we can't create the necessary space," said one source close to Milburn. "We want to make sure these advances are to the benefit of all, not the cost of a few."
The Health Department has approved as reliable only one genetic test, for the rare and fatal Huntington's chorea. Others are in the pipeline.for approval, but already being used by insurers. So far the industry has handled fewer than 100 cases involving genetic testing. But numbers will soar over the next decade as researchers develop susceptibility tests for more common illnesses such as cancers, Alzheimer's or heart disease. Britain is well placed to lead research because of its role in the Human Genome Project, which mapped the genes in DNA. Insurers argue that using genetic testing to calculate premiums is little different from asking about family medical histories and helps spread risk. They agreed not to use results in applications for life insurance linked to mortgages of under F,100,000 ($353,000) but a recent survey found this widely flouted. A parliamentary committee on science and technology has condemned the voluntary code as "inadequate" and warned that insurers were placing a significance on tests "that cannot at present be justified." OBSERVER
by Naomi Larkin
Secret Pregnancies reignite
MPs call for "rent a womb" bill.
NZ herald June 2001
Calls for laws preventing "rent a womb" cases have been reignited following news of the country's first surrogate IVF pregnancy. The identity of the in-vitro fertilised woman, and the parents for whom she is acting as a surrogate, are secret. Officials and fertility experts have refused to say how advanced the pregnancy is, where the people involved live, or what relationship exists between them. Labour MP Dianne Yates yesterday said the case showed the need for laws to regulate IVF and surrogacy and stop any "rent a womb" situation arising. Surrogacy using IVF treatment in New Zealand is ruled by guidelines drawn up by the National Ethics Committee on Assisted Human Reproduction. Since July 1997, the committee has approved 11 IVF surrogacies but this was the first to result in a pregnancy. "The ethics committee has no clout. It's got no means of enforcing any of its decisions," Dianne Yates said. In Australia people had flouted a similar committee's rulings and "nothing has happened to them." Her Human Assisted Reproductive Technology Bill has been before the health select committee since 1996 and a version of it is due to be debated this year.
The bill calls for fertility clinics to be licensed, a central
record system to be established and human cloning to be outlawed.
The bm would also ban sperm and eggs as a commercial commodity.
"I don't believe women are just 'rent a wombs.' "There
needs to be rules around these things. We are deamg with the future
of human beings. "It's not as ff you're conb7acting for a
commodity and it's not just the people who are contracting or
thb mother there's the rights and the future of the child and
a whole range of other things that have to be considered,"
she said. . Dr Rosemary de Luca, chairwoman of the committee,
said that legislation could strengthen the powers of the committee.
"Although having said that, it does seem to be working in
terms of self-regulation with ethical input." Under the guidelines
IVF surrogacy in New Zealand must be carried out on a "non-commerc@
altruistic" basis and the birth mother cannot be paid. One
or both of the commissioning parents need to be the potential
child's genetic parents and the birth mother must be either a
family member or a close friend. Fertility experts are required
to submit every case for individual consideration by the committee
before they are allowed to proceed with it.
Timebomb Threat to Cloned Humans
Telegraph / NZ Herald july 2001
Many cloned animals die in the womb or develop serious defects in later life. Human clones could carry similar hidden agendas.
Human clones could be "ticking timebombs" with hidden health defects that emerge only later in life, says a leading medical ethics expert. Dr Guido de Wert, of the University of Maastricht in the Netherlands, says reproductive cloning should be ruled out until scientists can ensure the procedure is safe. "Cloning carries substantial medical risks," he told the European Society of Human Reproduction and Embryology annual meeting in Lausanne, Switzerland, this week. "Many animal clones die in the womb or develop serious deformities, including diabetes, bad kidneys and enlarged tongues. Even clones that look healthy may be ticking time bombs. "Human adult cloning would probably have similar adverse outcomes. Clones might also be predisposed to a decreased life span." But Dr de Wert said there might be an argwnent for making hunian cloning legal if it could be made safe. "It could be used, in principle, to treat some types of infertility, for instance, when a nian is unable to produce any germ cells in his sperm." Clones are at risk of genetic dainage because they are created from adult cells that may have acquired DNA mutations and damage as they grow older in their hosts' bodies. Dr Severino Antinori, who runs a fertility clinic in Rome, has announced plans to clone a baby within a year. This week Professor Hans Evers, the new head of the society, accused him of "irresponsibly" raising the hopes of infertile couples. Researchers in the United States have found serious abnormalities in cloned mice, a finding that strengthens the belief that the technique used to clone Dolly the sheep should not be used on humans. The findings, which are based on the use of embryonic stem cells in cloning, appear in the journal Science. "This study conflrms the suspicions of many of us that cloning of humans would be really dangerous," said Professor Rudolf Jaenisch, senior author of the study. David Humphery, fu-st author of the study, said that many of the cloned mice appeared normal, including having normal genes, but there was evidence that during embryonic ahd foetal development the genes did not work properly. "It is quite likely that just the animals that are most nearly nomal make it to birth [in cloning], but our study shows that doesn't mean they @re completely normal," he said. There may be changes in gene expression that could affect them later in life." In cloned humans, Dr Jaenisch said, the gene expression flaws could affect personality, intelligence and other human attributes. Dr Humphery said there was no evidence that the genes in the cloned animal were altered, but that the way in which the genes made proteins was flawed and unstable. In effect, the researchers found that even though the biological blueprint was intact in the cloned animals, the way that the blueprint was read and interpreted was flawed. This could result in abnormal tissues and organs. The authors said that a number of scientists doing cloning experiments with mice, pigs, sheep and cattle have reported that even apparently nominal animals develop disorders later in life. Dr Jaenisch said that extreme obesity had developed in many cloned animals, including Dolly, the first mainmal cloned from an adult cell. Dr David A. Prentice, an Indiana State University professor of life sciences, said the MIT-Whitehead study showed the hazards of the present cloning technology. "Development is a finely orchesteated ballet of cells forrning tissues and organs at the right place and titne," said Prentice. "It takes only one going awry at the wrong tune and place to have a seriously flawed individuaL" In the study, the researchers made the mouse clones using embryonic stem cells, the primordial cells known to be able to form virtually any tissue in the body. The DNA from the cells was removed and inserted into a mouse egg that had been stripped of its, DNA. The resulting embryos were then implanted in mother mice and allowed to grow to birth. The researchers monitored th6 expression, or action, of genes that play a role in embryo and foetal development. They found -that the genes, even from nearly identical stem cells-," worked differently. In fact, said Dr Humphery, stem cells are unstable in gene expression even in the laboratory dish. This instability raises the Dossibility that using stem cells to t*t health disorders might not work & well as some scientists have suggesffd, said Dr [email protected] Boughman, vreepresident of the American Society of Human Genetics. "When we grow [embryonic stow cells for a curative situation, we wfll need to precisely control the procet she said. "IMis paper shows that we've got a very long way to go to fully understand this whole process." TELEGRAPH GROUP
Outrage at Lab Killing of Embryos
US scientists admit creating human embryos to harvest stem cells for experiments. NZ Herald July 2001
WASHINGTON United States researchers have admitted producing human embryos in laboratory killing them to use their stem cells in research. "The fact that living, human embryos would be deliberately destroyed in order to obtain their stem cells is absolutely appalling," said Tom Delay, the House of Representatives Majority Whip. "Once we begin justifying the killlng of human beings at one stage of development, we invite extensions of this reasoning to include other, even more troubling applications. "Stem cell research from human embryos establishes a bad precedent and is ethically wrong" he said. In an article in Fertility and Sterility, scientists from the Jones institute for Reproductive Medicine in Norfolk, Virginia, said they had performed in-vitro fertilisation of donated egg cells with donated sperm, to create human embryos, ,
The scientists created a five to six day old blastula an embryo with only one layer of cells around a cavity and removed from it the embryonic stem cells they needed for research. Until now, scientists have harvested embryonic stem cells only from aborted foetuses or foetuses rejected by fertility clinics. Some scientists have criticised the practice of creating embryos and cutting them up for research. "This research demonstrates the urgent need for federal oversight of stem cell research," said Lawrence Soler, chairman of the Coalition for the Advancement of Medical Research, which groups-50 universities and US research centres. But Dr Susan Lanzendorf, who led the researchers, wrote in the report: "These findings demonstrate that the future Production of human embryonic stem cell lines for therapeutic use is possible with the use of donated gametes."
"Many ethical issues were considered before the initiation of this study, and it was our goal to ensure that both oocyte and sperm donors understood the nature and purpose of the research before their participation in the study," the researchers said. While suspicions about the practice of harvesting stem cells from specially created embryos have existed for some time, this is the first time a group of private sector scientists has admitted creating human embryos for laboratory experiments. The acknowledgment came as President George W. Bush prepared to make his decision on whether public funds would be made available for medical research into embryonic stem cells. "This is not good timing," said Robert Lanza of Advanced Cell Technologies in Worcester, Massachusetts, a pioneer company in stem cell research. White House spokesman Ari Fleischer said that Bush would "decide this matter on his own timetable." "It will be a decision that recognises the deep complexities that this matter raises for our society," he said. Senate Majority Leader Tom Daschle said he hoped Bush would authorise stem cell research, thereby opening the doors to federal funding. "I don't think there's anything more important to research in science than the promotion of sterh cell, and I believe that there is overwhelming support in the country for taking this action," Daschle said. "I will say that if the President fails to make that decision, that it would be our intention to offer legislation and to pass it on the Senate floor in the not too distant future." He declined to comment on the Jones Institute revelations. AFP
Embryonic Dilemmas Newsweek
/ NZ Herald July 2001
Science, ethics and stem cell research
THEY'RE NOT much to look at, really. To see the cells of a fourday-old human embryo, you stain them with a few drops of dye, slip them under a 20 to 40-times magnification microscope and peer through the eyepiece. There they are: a hollow sphere of roundish balls, snuggled up against each other like sticky blueberries, pollen grains or vibrant red r-aspberty drupelets (depending on which stain you used). The 40 or so cells that constitute the embryo look a little fuzzy, dusty even, as if they had been rolling around on a dirty floor. But that is only the beginning. If you are a right-to-life activist, you see an incipient humeri life, one deserving the rights and respect of any other human, chief among those the @t not to be destroyed or used as a nieans to an end. If, though, you suffer from an incurable disease such as Parkinson's or Alzheiiner's, or love someone who does, then those cells look very different: they look like the seeds of hope, tiny miracles able to dance on the head of a pin. In those two clashing views lie the makings of the latest embryo war. This time it's not about abortion. The embryos whose stem cells hold the promise of treating often fatal illnesses come not from clinics where pregnancies end, but from those where they begin: in vitro fertilisation ( IVF centres, which fuse sperm with eggs in a petri dish, and where spare" embryos, too numerous to implant, are otherwise discarded.
Even though stem cells do not come from aborted foetuses (which are defined as older than nine weeks, with a shape and incipient organs), the moral and theological issues inherent in using human embryos in research press the same buttons. The fire has been stoked with the disclosure that a private fertility clinic, the Jones Institute for Reproductiv(' Medicine in Virginia, had created human embryos specifically to harvest cells for research. Richard Doerflinger, a leading Catholic critic of stem-cell research, called it "a grotesque practice." Religious broadcaster Pat Robertson said, "Once you begin this concept of utilitarian use of cells then everything is up for grabs." Arthur Caplan, a medical ethics specialist at the University of Pennsylvania, says, "The tuning of this has been somewhere between disastrous and horrific."
As a result, the White House has been dragged into the heart of an issue it very much wanted to avoid. It had hoped it had done its right-to-life duty by paft financial support for organisations that offer abortion counselling overseas and by supporting every piece of pro-life legislation introduced in Congress. But sometime in the coming weeks, President George W. Bush is expected to decide whether to allow federal funding for research on stem cells taken from hwnan embryos. So far he has remained true to his campaign stance opposing the research. In February he ordered a review of the Clintonian compromise under which federal money could be used to conduct research, but not to obtain the embryonic cells in the first place. And this Spring the administration cancelled the inaugural meeting of a National Institutes of health (NIH) committee that was to review applications for federal grants to study human embryonic stem cells. As long as Bush puts off a decision, the status quo under which the research in the US has come to a virtual standstill, except in labs ftmded by biotech fmm and other private money will continue. David Stevens, executive director of the Christian Medical Association, last week compared working with stem cells to Josef Mengele's experiments at Auschwitz. That infuriates many politicians, as well as ordinary people who have decided that 'pro-life" need not mean "no stem-cell research." In recent polls, 57 per cent of abortion opponents have &-ud they support embryonic stem-cell research. So have 72 per cent of Catholics. Senator Orrin Hatch, as anti-abortion as they come, argues that "a frozen embryo stored in a refrigerator in a clinic" just isn't the same as "a foetus developing in a mother's womb."
Former Florida senator Connie Mack, a pro-life Catholic and a Republican, has broken with his church and his party to support the research. "For me, as long as that fertilised egg is not destined to be placed in a uterus, it cannot become life," he says. But it can, perhaps, bestow life. "Anyone who would ban research wiu be responsible for the harm done to real, alive, postnatal, sentient human beings who might be helped by this research," argues biologist Irv Weissman, of Stanford University. "Opponents are sacrificing these people to keep from destroying embryos in fertility-clinic freezers that will be thrown out anyway." The cells that make up days-old embryos embody a world of potential. Four days after fertffimtion, the embryo is a hollow ball of cells called a blastocyst. Cells in the outer layer are destined to become the placenta. Those in the irmer layer have not yet decided what they will be when they grow up: they are "pluripotent," able to differentiate into any of the 220 cell types that make up a human body, from the kidney, heart and liver to the skin, neuronal and pancreatic. These are the famous embryonic stem cells. For a few short days they are blank slates waiting for destiny (or the complex interplay of genes and biochemistry) to write their future. And that is the source of their power. A decade ago research on lab animals revealed that stem cells taken from animal embryos are very versatile. They grow in the lab, proliferate and develop into specialised cells such as neurons. But no one had turned the same trick with human cells. Then, in November 1998, researchers at the University of Wisconsin at Madison and at Johns Hopkins University announced they had independently cultured stem cells taken from human embryos. In particular, they had stopped human embryonic stem cells from differentiating and, instead, kept them merrily growing in lab dishes while maintaining their pluripotency it was as if someone had fired the starter's pistol. The next month John Gearhart, the lead Hopkins scientist, testified before Congress that embryonic stem cells might one day treat Alzheimer's disease, Huntington's disease, stroke and spinal cord iwury, as well as diabetes and muscular dystrophy. In each case, stem cells would be coaxed to turn into the appropriate cell and transplanted into a patient. But one early hope that embryonic stem cells could be used to seed organ farms, growing livers, hearts and other body parts is fading. Organs have intricate structures, with ducts ond valves everywhere, so will probably be tough to grow outside a body. Stem cells implanted into a patient, however, are another story. In the more than two years since the discovery that human stem cells can be grown in the lab, their potential has only expanded, according to the National Institutes of Health. I Injecting stem cells into a liver could produce new liver cells, rejuvenating an organ decimated by cirrhosis or hepatitis. Stem-cell therapy might cure rheumatoid arthritis and osteoarthritis by replacing wrecked cartilage. It could supply new skin to treat life-threatening bums. Stem cells could replace cells damaged by chronic heart disease. "It is not unrealistic to say that [stemcell] research has the potential to revolutionise the practice of medicine," says Harold Vannus, former NIH director. How soon? Clinical trials in which cells grown from human embryonic stem cells are implanted into patients are at least three years away. So far, stem cans have proved a godsend to rats and mice. Transplants of embryonic stem cells have enabled animals that suffered spinal cord injuries to move their legs and partially support their body weight, the stem cells, taking a cue from their new surroundings, morphed into neurons. The cells have enabled rats that suffered strokes in the brain's motor cortex to move again by homing in on the lesion, maturing into neurons and fanning the connections necessary for movement. Rats with the rodent versions of Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis and Gehrig's disease) improved somewhat In a big surprise, scientists have discovered that even cells that smmed hTevocably committed to one job were capable of a midlife career switch. They have long known that many kinds of tissue include adult stem cans whose job it is to produce more cells of that kind: adult liver stem cells give rise to liver cells and adult Ain stem mUs give rise to skin. The cell divides, producing one differentiated cell (skhi, say) and one stem cell, thus maintaining its biological seed com. But lately, "multipotent" adult stem cells capable of turning into more than one kind of cell have been popping out all over. In mice, adult bone-marrow cells have produced neurons, liver cells, lung cells and gastrointestinal cells. In September last year researchers at Italy's San Raffaele Hospital research institute demonstrated that stem cells from the brams of adult rats could be used to generate muscular tissue. Why "kill anybody," as Kansas senator Sam Brownback put it, referring to stem cells from IVF embryos, when you can instead tap into willing adults with hardly more fuss than drawing bloods But adult stem cells may not live up to their name. They seem to proliferate more slowly than the embryonic ones, and so might not provide an ever-renewing source of new cells. Also, studies on human adult stem cells may be flawed. One biologist even calls them "crap science" although scientists think that they induced bone-marrow cells to become brain or bone cells, precursor cells of those tissues might have been present in the bone marrow all along. "No paper shows definitively any adult stem cell in humans tummg into anything else," says Stanford's Weisman. "It's baloney that adult stem cells are all we need to make regenerative medicine real," says Okarma. A new NIH report concludes that embryonic stem cells may be superior to the adult variety. Which is why scientists covet the six or so colonies of human embryonic stem cells growing m labs around the world, says Jaines Thomson, whose Wisconsin lab started one of the first colonies. These lines might provide endless quantities of stem cells, obviating the need to harvest mor-e embryos. "You can imagine a system where you don't have to keep going back to embryos," says Harvard's Snyder. But until enough such cell lines are established, Thomson says, "if the destiny of embryos at IVF clinics is to be thrown out, and couples are willing to donate them to research instead, it's hard for me to believe that throwing them out is a better ethical decision." NEWSWEEK
Built-in Health Insurance Observer / NZ Herald July 2001
WHEN gynaecologist Dr Derek Tuffnell takes a tiny specimen of of blood from the umbilical cord of a newborn baby in Britain's Bradford Royal Infirmary, he is doing an operation that seems safe and familiar. Yet the removal of the sample from the minutes-old infant, containing only a few dozen miflilitres of blood, could have profound medical significance. tf experts are right, such an operation is the start of a medical revolution that will ensure future generations of children lead lives free from serious illness. In other words, it could realise every parent's dream: the safegutrding of their children against fatal illnesses in later life. This is the promise of stem-cell storage, which was launched in Britain this year and which offers father,-, and mothers the chance to create what has been called "the ultimate in health insurance." For a fee of about $2130, parents will be able to have blood taken from their baby's umbilical cord. This sample rich in special stem cells will be stored for up to 20 years in liquid nitrogen to provide the child with the means to restore damaged organs, blood or tissue. "Stem cells are the progenitors of all other cells in our bodies," Tuffnell says. "They develop into blood, bone, brain and other cells. That is why they are important. "if a child or adolescent gets a disorder for example, leukaemia their stem cells will give us the means to replenish their bodies with healthy blood and save their lives."
Scientists have orfly recently discovered how to isolate stem cells, which are now viewed as the holy grail of medicine because they can develop into any kind of cell that the body needs.
At the American Association for the Advancement of Science in San Francisco, scientists have reported that patients stnick down by strokes and other brain injuries could be cured using stem cells. Professor Paul Sanberg, an expert in ageing from the University of South Florida, has revealed that retinoic acid, a form of vitamin A, caused stem cells to develop into immature brain cells, and in animal experiments dramatically restored mental functions in rats that had suffered stroke damage.
However, like other transplanted tissue, stem cells have to be matched so that donor and recipient are compatible. If not, rejection will occur. "It is exactly the same problem that you have with bone marrow," says Tuffnell. "You have to get a precise match with a donor, and that does not happen very often." And that is where stem-cell storage offers a key advantage it gets round the problem of rejection by using a person's own stem cells.
Shamshad Ahmed, of Cryo-Care UK, which is pioneering the service in Britain, says bone marrow cannot be removed from a newborn baby, but stem cells can. It means individuals in middle age, or even in old age, might be able to exploit their own infant blood. For example, if they contract a serious illness such as leukaemia, doctors could use radiotherapy to destroy their wayward blood system and then restore it using the tiny stem cell specimen that was taken at their birth. Their parents, possibly long dead, will have saved their lives. It is a startling prospect, although Tuffnell counsels caution. "There is the issue of the size of the sample," he says. "The umbilical corxl contains only about 50 ml to 60 ml of blood. That wffl be enough to save a child or adolescent but may be too small for a full-grown adult. "However, in a couple of decades we may well have found ways to multiply stem cells before returning them to patients' bodies." Tuffhell has no doubts about the value of the technique. "I already have two chjl&en, and when I heard about this technique I asked my wife who is a midwife if she thought it was a good idea. We agreed that if we ever had a third we would certainly pay for it. It gives such comfort and hope." OBSERVER
Bush on Horns of Stem Dilemma The NY TIMES
July 4, 2001
Embryonic Cell Research
By SHERYL GAY STOLBERG and DAVID E. SANGER
WASHINGTON, July 3 - As President Bush nears a decision on
whether the government should pay for research on stem cells extracted
from human embryos, his advisers are struggling to mold a compromise
that would satisfy both patients' advocates, who say the experiments
may save tens of thousands of lives, and religious conservatives,
who say the studies are tantamount to murder.
The White House is considering several options, people familiar with the debate say. One choice is permitting federally backed experiments on a handful of cell types, called lines, that have already been identified, but banning public money to develop more. Another option is allowing the research to proceed until scientists are satisfied they have a sufficient number of lines to study. Yet another choice is giving government grants to groups that finance medical research, thus freeing their private money to pay for the stem cell work.
But reaching any compromise will be tricky. One option, pushed by conservatives, would be to maintain the ban on embryonic stem cell research while increasing financing for experiments on adult stem cells, which are obtained from blood and bone marrow and therefore pose no ethical objections.
Many scientists, however, argue that any restrictions on federal
financing would restrict their ability to pursue promising treatments
and potential cures for Alzheimer's disease, juvenile diabetes,
Parkinson's disease and a number of other disorders.
At the same time, the issue is creating strange political bedfellows in the capital, where some Republicans who fervently oppose abortion are calling on Mr. Bush to support the research.
"This doesn't fit into neat categories," said one senior White House adviser who often works with Karl Rove, Mr. Bush's top political adviser, who has argued strongly against federal financing.
"There are different types of coalitions forming."
Asked today when he would make a decision, Mr. Bush said simply,
"In a while."
His advisers are even split on the question of when to make the decision. Mr. Bush meets with Pope John Paul II on July 23. The Roman Catholic Church is deeply opposed to experiments involving human embryos, even those created outside the womb, and Mr. Bush may want to have the matter settled beforehand so that he would neither offend Catholics by appearing to ignore the pontiff's entreaties nor appear to be influenced by the pope. But others in the administration are arguing that the president should take his time, because the decision is both scientifically and politically complicated. "There's no reason to rush this," one White House official said.
Tommy G. Thompson, the secretary of health and human services, and an advocate of financing the research, has told associates that he believes time is on his side, and the longer the president takes to make a decision the more likely he is to allow some kind of research. With Mr. Bush's approval ratings in the polls dropping, in part because the public views the president as too conservative, the stem cell decision has taken on greater significance.
So Mr. Bush and his aides are now re-examining Mr. Rove's initial
advice. Before the issue turned into a heated political debate
- with some, but not all, of the Republican leadership of the
House writing Mr. Bush on Monday to urge that he reject federal
financing - Mr. Rove had sided with the arguments of religious
conservatives, who argue the experiments destroy nascent human
Mr. Rove's current view is something of a mystery. He has declined to return reporters' telephone calls, and while there are reports that he is involved in the search for a compromise, his views are being gleaned from tidbits of conversation.
But it is clear that some of the president's advisers fear that following Mr. Rove's initial inclination to satisfy Catholics and the right could further alienate moderates and independents who have already been disaffected from the administration. So they are giving greater consideration to the views of Mr. Thompson, who some aides say has been periodically dealt into the negotiations. "The secretary and the president and his advisers are talking regularly," Tony Jewell, Mr. Thompson's spokesman, said today. "Beyond that, what the final result will be, is too soon to talk about." Embryonic stem cells are generating great excitement among scientists because they have the potential to grow into any cell or tissue in the body, and therefore hold promise for repairing and replacing damaged tissues and organs. But the embryos, typically obtained from fertility clinics with the consent of couples who have created them, are destroyed. The intense debate over the cells was merely a theoretical abstraction until three years ago, when Dr. James Thomson at the University of Wisconsin became the first to isolate them. Dr. Thomson's work was paid for by a biotechnology company, Geron, of Menlo Park, Calif. Federally financed scientists could not jump into the field, because of a Congressional ban on using taxpayer money for research on human embryos. Last summer, to get around that ban, the Clinton administration issued a ruling that said the government could pay for research on cells derived from the embryos, so long as federally financed scientists did not work on the embryos themselves.
The Bush administration must now decide whether to overturn that ruling, let it stand or choose a course that is somewhere in between. "I'm not surprised they are looking for a compromise," said Michael Werner, who advises the Biotechnology Industry Organization on bioethics issues. "But I think this is an issue where it will be very difficult to craft a compromise, because it means so much to both sides, so neither wants to concede much."
Indeed, part of the difficulty of reaching a decision is that no matter what the White House concludes, it will alienate some constituency. One plan that is generating discussion is the one to permit research only on existing cell lines. But abortion opponents say they would be outraged by such a move. "We think it is unethical to use cells obtained by killing human embryos," said Douglas Johnson, legislative director for the National Right to Life Committee, "whether the killing is done yesterday or next week." Scientists and patients' groups, meanwhile, would be outraged by that same plan, but for different reasons. They note that only about a dozen cell lines have been developed and say many more are needed to ensure that the cells have enough genetic diversity to be useful. In addition, such a plan might greatly enrich Geron, because that company holds intellectual property rights to six of the existing cell lines. "This is not a compromise," said Dr. Gerald Fischbach, dean of the faculty of medicine at Columbia University and a former official of the National Institutes of Health.
No matter what the administration decides, the subject may end up in Congress. Senator Arlen Specter, Republican of Pennsylvania, has introduced legislation to authorize the National Institutes of Health to pay for embryonic stem cell research, including experiments that involve the destruction of embryos.
And in an interview last week, Senator Orrin G. Hatch, the Utah Republican who has stated his support for stem cell research, said that while he would not go as far as Mr. Specter, he believed most senators would vote in favor of allowing some kind of research to go forward. "If Congress, in its infinite wisdom, chooses to intervene," Mr. Hatch said, "well then, I think we are getting pretty close to that magic 60- vote number."
Science Stymied by a Moral Debate Newsweek / NZ Herald July 2001
THE PACKAGE Wolfgang Franz received at his laboratory at the University of Lubeck was nondescript, but its contents were explosive. The molecular biologist had ordered a sample of 100,000 stem cells to use in his medical experiments. In particular, he wanted to flnd out whether the cells could repair heart damage from cardiac arrest. But now it looks like he won't get a chance, at least not soon. Word of the shipment got out and immediately ignited a controversy. Last week the German Government called for a voluntary halt to all research involving human embryonic tissue, including stem cells. Under that kind of pressure, Franz had no choice but to put his stem cells in liquid-nitrogen storage and his research on ice,
In Germany, embryos are protected under one of the strictest such laws in the world: the 1990 Embryonenschutzgesetz embryo-protection law. It says that life begins at conception and that every fertfiised egg has a right to survive. Since stem cells are harvested from human embryos only a few days old, producing them is Megal in Germany. Scientist,s have turned to outside firms for the cells they need. Franz, for instance, received his from WiCell, a Wisconsinbased company.
Even though Franz and his colleagues have broken no laws, the issue is so controversial they have tried to keep quiet about the practice. It's easy to see why. Once the news got out, the scientists received some heavy flak. They were guilty of a "shameless gold-digger mentality" and "Wild West manners," said Thomas Goppel, a conservative firebrand from the Christian Social Union Party. An alliance of conservative Christians and technophobic Greens has maintained that it is immoral to destroy embryos even a few days old to harvest stem cells..
The debate in Germany is also overshadowed by painfuj memories of the Nazis' genetic experiments in the Second World War. Afraid of drawing fim from religious headers and conservative politicians, the Government has passed the issue to a newly commissioned National Ethics Council that is due to make its recommendation in October.
As the debate goes on, competitors 'm other countries are getting a jump on the research. In Britain, Parharnent gave the go-ahead to stem-cell production and research last January, rulmg that human life doesn't start until an embryo is 14 days old.
In Israel, where Jewish tradition says an embryo doesn't become human until it is nestled in the mother's womb, Haifa's Rambam Medical Center has taken a lead in stem-cell research and export.
In the United States, projects are going ahead even as the Congress considers a ban on federal funding for stem-cell research.
And the French Government is considering a law banning the production of stem cells, Arhile still allowing, research to continue. The progress abroad only frustrates German scientists all the more. "Now we're falling behind," says Oliver Brstle, a University of Bonn scientist who made medical history when he proved that stem cells could cure multiple sclerosis in rats. "It's a sad situation for us." The threat of another scientific brain drain is not lost on politicians. "There's no question that we have a moral imperative to protect embryos," German Chancellor Gerhard Schroeder said recently. "But it's also part of our moral responsibility to care about jobs and prosperity." Nevertheless, he won't review the law until late this year, at the earliest. At that rate he may find that German biotech researchers will have voted on their own with their feet.