Less than a year after a Wisconsin team helped discover a major alternative to human embryonic stem cells, the Madison scientists say more than 800 labs have begun using the approach, suggesting that many stem-cell researchers are starting to move beyond controversial embryonic sources for their work.
Such shifts may reframe the emotionally fraught debate over stem cells--an issue that has ignited passions across the political spectrum. Both presidential candidates have indicated they would lift President George W. Bush's restrictions on research funding, though Sen.Barack Obama has been more adamant than Sen. John McCain.
The biologist doing more than anyone else to stir the debate is University of Wisconsinresearcher James Thomson, who co-discovered human embryonic stem cells a decade ago, in November 1998. Last year Thomson shook the field again when his lab and a Japanese team showed a way of genetically reprogramming adult skin cells to act like stem cells, including the ability to form any of the body's tissues.
Some groups that oppose destroying embryos for research have hailed the new cells, called induced pluripotent stem cells, as a way to eliminate the need for stem cell research based on embryonic material. In a rare extended interview, Thomson said he shares some of their qualms but believes the issue's moral and scientific contours have never been more complex.
Recently in Stem Cells Category
Reoved cells and MHC antigens from a human donor trachea, which was then readily colonised by epithelial cells and mesenchymal stem-cell-derived chondrocytes that had been cultured from cells taken from the recipient (a 30-year old woman with end-stage bronchomalacia). This graft was then used to replace the recipient's left main bronchus.
Result: Functional airway!
I also received this report regarding Bishops from Spain from hat seems to be a catholic news site.
Rapid translation: I'm disobedient.
Rapid translation: Too strong. Makes me mad.
Rapid translation: I'm selfish?
Specially disturbing, they said, is parents choosing a specific embryo because the child's tissues or organs might save the life of a sick sibling.
OOPS.
The Vatican isn't much for trying to save sick children's lives with embryonic stem cell research or PGD because they both mess with embryos and an embryo deserves the same respect as any adult. This is an old argument.
The best response is a perhaps over-used hypothetical scenario:
A building is burning down. Twelve small children are inside screaming for help. The building also contains a freezer storing a dozen or so frozen embryos. Which do you save first?
Same should apply for stem cell research. The goal is to cure devastating diseases as soon as possible.
Chemical found to simplify production of stem cells
Harvard team hopes technique cuts tumor risk
By Maggie Fox
Reuters / October 13, 2008
WASHINGTON - Researchers trying to find ways to transform human skin cells into stem cells said yesterday that they found a shortcut by adding a chemical to the cells.
The chemical allowed the team at the Harvard Stem Cell Institute to use just two genes to transform skin cells into more powerful induced pluripotent stem cells, or iPS cells.
"This study demonstrates there's a possibility that instead of using genes and viruses to reprogram cells, one can use chemicals," said Dr. Doug Melton, who directed the study published in the journal Nature Biotechnology. That could reduce the risk of tumors developing in the cells.
Melton said Danwei Huangfu, a postdoctoral researcher in his lab, developed the new method.
"The exciting thing about Danwei's work is you can see for the first time that you could sprinkle chemicals on cells and make stem cells," said Melton, a researcher at the Howard Hughes Medical Institute.
Huangfu tried treating the cells first with valproic acid. After she did this, she found it took only two of the four usual genes to reprogram the human skin cells into iPS cells, which resemble embryonic stem cells.
Huangfu said the valproic acid unraveled the chromatin - the physical structure of the chromosomes - making it possible to get in and alter the DNA more easily.
"We may need two types of chemicals, one to loosen the chromatin structure, and one to reprogram. We are looking for that reprogramming chemical, and it should be possible to find it eventually," she said.
Stem cells are the body's master cells, giving rise to all the tissues, organs, and blood. Embryonic stem cells are considered the most versatile kinds of stem cells.
Doctors hope to someday use stem cells to transform medicine. Melton, for instance, wants to find a way to regenerate the pancreatic cells destroyed in type 1 diabetes and perhaps cure that disease.
But embryonic stem cells are difficult to make, requiring the use of an embryo or cloning technology. Many people also object to their use, and several countries, including the United States, limit funding for such experiments.
In the past year, several teams of scientists have reported finding a handful of genes that can transform ordinary skin cells into iPS cells.
To get these genes into the cells, they have had to use retroviruses, which integrate their own genetic material into the cells they infect. This can be dangerous and can cause tumors
A breakthrough, then a surge, in stem cell research
A year after report, research into new type of stem cells continues to grow
Some scientists cite this potential in saying the true moral course is to accelerate research on embryonic cells because it might produce transplant tissue for illnesses like diabetes and Parkinson's disease. But Thomson also said many arguments for expanded federal funding have exaggerated the field's short-term promise. Perfecting such techniques could take many decades, he said. "It's certainly going to happen, but it's going to be hard, and people are not prepared for how hard it's likely to be."
The most profound effect of stem cells in the meantime could be to screen new drugs for safety and to gauge a medication's effectiveness on real human tissue without using patients as guinea pigs.
"It simply means that for the very first time we have access to the human body in the lab," Thomson said. "And for drug screening and drug discovery that's going to make a huge difference. When you use one of those drugs you won't know that human embryonic stem cells or iPS cells were involved. It won't make the front pages at all."
With a day's stubble on his chin and flip-flops on his feet, Thomson does not look like the sort of person who could change the world once, much less twice. He grew up in Oak Park and still keeps a beat-up dart board in his office that dates to his high school days. Thomson said he recently found a pay stub for $14 from his first job--delivering copies of the now-defunct Chicago Daily News.
One of his key skills as a biologist is the patient, constant nurturing of cells that other labs have found difficult to master.
"Things grow for me," Thomson said, gesturing to a set of flourishing staghorn fern plants in his office.
He said he's amazed at how quickly scientists have begun exploring the use of the reprogrammed skin cells he reported on last year. "People are jumping in very rapidly, much more rapidly than they did 10 years ago" after the initial discovery of embryonic stem cells, Thomson said.
In all, 812 labs in dozens of countries have requested the materials needed to reprogram ordinary cells into iPS cells, said Addgene, a Massachusetts-based repository for research supplies. By contrast, a half-dozen or so labs started working with embryonic stem cells in the months after his landmark 1998 paper, Thomson said.
In recent months Thomson has been racing other labs to grow an improved form of iPS cells that potentially could be used in human patients. The original method probably could not be tested in people because it relied on a retrovirus to activate a few genes that reprogram the cells.
The first successful attempt to make iPS cells without such potentially dangerous viruses was published online recently in the journal Science. A group from Massachusetts General Hospital grew the cells using relatively safe viruses that can be cleared from the cells once they do their jobs, though the method was not as efficient as existing techniques.
Already, researchers said, iPS cells have proved easier for individual labs to make than embryonic stem cells, fueling the intense interest.
Before the iPS papers, stem-cell research "was still a select fraternity," said Evan Snyder, director of the stem cells and regenerative medicine program at the California-basedBurnham Institute. "Now it's been kind of opened to the masses."
To use embryonic stem cells, labs must either make their own--which requires the destruction of human embryos--or get them from a lab like Thomson's that already has made its own cell lines. Only cell lines made before August 2001 qualify for federal funding under Bush's research restrictions.
With iPS cells, Snyder said, "you can do a skin biopsy on yourself if you want" and use that tissue as raw material for the stem cells.
Many scientists said the absence of ethical concerns over iPS cells also is a draw. "As soon as you have a cell type that is relatively free of this black cloud, then obviously there's huge pent-up interest," said George Daley, director of the stem cell program at Children's Hospital Boston.
Yet no one knows whether iPS cells can fill the same roles as embryonic stem cells, most researchers said. Some believe iPS cells may work differently depending on the type of tissue they came from--that skin cells might be difficult to transform into blood cells, for example.
That's a major reason why Thomson still refers to his original embryonic stem cells as a "gold standard."
"My belief is that if iPS cells turn out to be completely biologically equivalent [to embryonic stem cells], scientists will just migrate to them because they're easier to deal with," Thomson said. "But that may not be true, and we should simply let the science play itself out."
THE EMBRYO DILEMMA
Donating embryos for research may be easier said than done
By Shari Roan, Los Angeles Times Staff Writer
October 6, 2008
CHRIS AND TANYA Bailey of Mission Viejo have a 3-year-old and triplet toddlers, all conceived through in vitro fertilization. After the birth of the triplets, they had 13 embryos left over in cryopreservation.
The idea of discarding them made the couple uneasy.
"I thought of them as potential life, but I don't think of them as children," says Chris Bailey. "They are definitely more than sperm and egg."
After much discussion, the couple decided to donate the embryos to research.
"We felt we were so lucky that research had been done and [that it] gave us the opportunity to have children," says Tanya Bailey. "So why not give our embryos to research as well to help somebody else out?"
The decision to donate to research, says Chris Bailey, "was a logical choice."
Even after grappling with the decision, however, many people find that donating to research is easier said than done. People wishing to donate to research must complete detailed paperwork and may even be asked to select the type of medical research for which they want their donation used. Others find they cannot proceed with their donation if they used egg and sperm donors who would not consent to the donation. Still others simply can't find a medical research organization to accept their donation.
For Californians, at least, donating unused embryos to research has become somewhat easier in the last two years. The launch of the state's stem cell research program and the opening of a dedicated tissue bank at UC San Francisco has opened at least one clear path for donation by providing a place for families to send their embryos where they will be available to researchers.
"As stem cell research moves forward and viable treatments emerge, there will be a greater demand for the use of frozen embryos," says Lois Uttley, director of the MergerWatch Project, a patients' rights organization based in New York City. "That could raise the profile of this issue."
The few states that fund stem cell research are more likely to be able to connect donating families to specific research programs that need embryos. People in other states do not have a clear pathway to donation, says R. Alta Charo, a professor of law and bioethics at the University of Wisconsin at Madison. "Most IVF clinics are not hooked up to a research team and they may not be able to refer couples to a clinic who can do it for them," she says.
Research options
At the UC San Francisco IVF Tissue Bank, which opened in 2005, couples have some choices as to the type of research they will be assisting. In cases where families donate to a specific research program, they often do not have the ability to specify the kind of research they wish to support.
There, however, Level 1 allows donated tissue to be studied but doesn't allow for the creation of stem cell lines. Level 2 allows all Level 1 research and the creation of a stem cell line. Level 3 allows Levels 1 and 2 research and, in addition, allows tissue to be used for stem cell nuclear transfer, which is also known as therapeutic cloning. In this type of research, stem cells are extracted from the embryo and are allowed to grow into a piece of tissue or organ, but never a human being.
Individuals who donate do not incur any costs, but they should be prepared to spend a lot of time on paperwork, says Denise Bernstein, coordinator of the bank. The packet sent to donors from UCSF contains pages of information as well as numerous forms, some of which must be notarized. In addition, the tissue bank conducts a telephone interview with the donors. The process' goal is to fully inform the donor or donors and to gather information scientists may need for their research.
"Some people say, 'You know what? It's easier to discard them,' " Bernstein says. "They have to be motivated to want to do this."
Though the UCSF bank's paperwork may be especially laborious because of the options for stem cell research, most research groups have a detailed consent process, says Dr. David Diaz, an infertility doctor with offices in Fullerton and Fountain Valley.
"The bureaucracy can be overwhelming." In his clinic, says Diaz, fewer than 1% of patients with frozen embryos have donated to research over the last three years.
And a sizable number of potential donors are turned away because of consent questions.
People who used donor eggs or donor sperm to create their embryos must obtain the consent of those donors before embryos can be released to researchers -- something that may be impossible if the gametes (eggs or sperm) were donated long ago, especially if anonymous donors were used. About 15% of all IVF cycles involve donor eggs.
Egg and sperm donors may also be asked to provide some personal health information. Researchers often want to know about the donor's personal and family medical history. Donors may be asked if they can be contacted in the future if the research yields information that could be useful to them or to see if any health changes have occurred since the donation.
Moreover, many research organizations -- including California state-funded research groups -- will not accept frozen embryos in which an egg donor was compensated in any way, which is often the case with anonymous donors.
Protecting gamete donors' rights is critical, says Nanette Elster, director of the Health Law Institute at DePaul UniversityCollege of Law in Chicago.
"Someone may have donated with the idea that he or she is donating to help a woman build a family," she says. "But if that is not what the family is going to use it for, maybe they wouldn't get consent. The donors are individuals with concerns and a stake in the process."
Many uses for embryos
Researchers hope that as the process becomes more familiar, more couples will donate. Evolving research suggests that stem cell researchers may have a need for many embryos.
For example, some studies show that individual stem cell lines have a preference for the way they develop, Charo notes. "Some differentiate more easily into heart tissue. Some seem to differentiate more easily into neurological tissue." Having a broad range of stem cells will help develop lines that can be used more efficiently.
Moreover, some people may have an immune reaction to tissues made with specific stem cells, she says. Thus it may be necessary to have a large variety of stem cell lines to get a variety of immunological matches. Disease-specific stem cell lines are also needed, researchers say. For example, cell lines may be created from an embryo that carries the gene for a specific disease or a high risk of developing that disease.
Link
Although stem cells may one day be derived by other methods, those derived from embryos are, for now, the gold standard in research, says Dr. Marie Csete, chief scientific officer for the California Institute for Regenerative Medicine.
"There is absolutely no need to take every frozen embryo and make a stem cell line," she says. "But the science is changing a lot. We need diverse human stem cell lines to really understand the biology of a stem cell at a baseline."
SD2008: What is your position on government regulation and funding of stem cell research?
Obama: I believe that the restrictions that President Bush has placed on funding of human embryonic stem cell research have handcuffed our scientists and hindered our ability to compete with other nations. As president, I will lift the current administration's ban on federal funding of research on embryonic stem cell lines created after August 9, 2001 through executive order, and I will ensure that all research on stem cells is conducted ethically and with rigorous oversight.
More here.
Scientists Reprogram Adult Cells' Function
Advance Stirs Up Debate on EmbryosBy Rob Stein
Washington Post Staff Writer
Thursday, August 28, 2008; A01
Scientists have transformed one type of fully developed adult cell directly into another inside a living animal, a startling advance that could lead to cures for a variety of illnesses and sidestep the political and ethical quagmires
associated with embryonic stem cell research.
Through a series of painstaking experiments involving mice, the Harvard biologists pinpointed three crucial molecular switches that, when flipped, completely convert a common cell in the pancreas into the more precious insulin-producing ones that diabetics need to survive.
The experiments, detailed online yesterday in the journal Nature, raise the prospect that patients suffering from not only diabetes but also heart disease, strokes and many other ailments could eventually have some of their cells reprogrammed to cure their afflictions without the need for drugs, transplants or other therapies.
"It's kind of an extreme makeover of a cell," said Douglas A. Melton, co-director of the Harvard Stem Cell Institute, who led the research. "The goal is to create cells that are missing or defective in people. It's very exciting."
The work was hailed as a welcome development even by critics of research involving embryonic stem cells, which can be coaxed to become any tissue in the body but are highly controversial because they are obtained by destroying embryos.
"I see no moral problem in this basic technique," said Richard Doerflinger of the U.S. Conference of Catholic Bishops, a leading opponent of embryonic stems cell research. "This is a 'win-win' situation for medicine and ethics."
Researchers in the field, who have become accustomed to rapid advances, said they, too, were surprised by the advance.
"I'm stunned," said Robert Lanza, chief scientific officer of Advanced Cell Technology in Worcester, Mass., a developer of stem cell therapies. "It introduces a whole new paradigm for treating disease."
Melton and other researchers cautioned that many years of research lay ahead to prove whether the development would translate into cures.
"It's an important proof of concept," said Lawrence Goldstein, a stem cell researcher at the University of California at San Diego. "But these things always look easier on the blackboard than when you have to do them in actual patients."
Although the experiment involved mice, Melton and other researchers were optimistic that the approach would work in people.
"You never know for sure -- mice aren't humans," said George Q. Daley, a stem cell researcher at Children's Hospital in Boston. "But the biology of pancreatic development is very closely related in mice and humans."
Melton has already started experimenting with human cells in the laboratory and hopes that within a year he can start planning the first studies involving people with diabetes. "I would say within five years, we could be ready to start human trials," Melton said.
Other scientists have begun trying the approach on other cells, including those that could be used to treat spinal cord injuries and neurogenerative disorders such as Lou Gehrig's disease.
"The idea to be able to reprogram one adult neuron type into another for repair in the nervous system is very exciting," said Paola Arlotta, who is working in the Center for Regenerative Medicine at Massachusetts General Hospital-Harvard Medical School in Boston.
The research is the latest development in the explosive field of regenerative medicine, which seeks to create replacement tissues and body parts tailored to patients. That objective appeared within reach after scientists discovered stem cells. But stem cell research has been hampered by objections from President Bush and others who believe that the earliest stages of human life have moral standing.
Scientists last year shocked the field when they announced they had discovered how to manipulate the genes of adult cells to turn them back into the equivalent of embryonic cells -- entities dubbed "induced pluripotent stem" or "iPS" cells -- which could then be coaxed into any type of cell in the body.
The new work takes further advantage of the increasing ability scientists have developed in harnessing the once-mysterious inner workings of cells -- this time to skip the intermediary step of iPS cells and directly transform adult cells.
"This experiment proves you don't have to go all the way back to an embryonic state," Daley said. "You can use a related cell. That may be easier to do and more practical to do."
Doerflinger argued that the discovery was the latest evidence that research involving human embryos is no longer necessary. "This adds to the large and growing list of studies helping to make embryonic stem cells irrelevant to medical progress," Doerflinger wrote in an e-mail.
But other researchers disputed that, saying it remains unclear which approach will ultimately prove most useful.
"Embryonic stem cells offer a unique window in human disease and remain a key to the long-term progress of regenerative medicine," Melton said.
For their work, Melton and his colleagues systematically studied cells from the pancreas of adult mice, slowly winnowing the list of genes necessary to make a "beta" cell that produces insulin. After narrowing the candidate genes to nine, the researchers genetically engineered viruses known as adenoviruses to ferry the genes into other pancreatic cells, known as exocrine cells, which normally secrete enzymes to help digest food. That finally enabled the researchers to identify the three crucial genes needed take control of the rest of the cell's genes to convert an exocrine cell into a beta cell.
"It was a mixture of work, luck and guessing," Melton said. "We achieved a complete transformation, or re-purposing, of cells from one type to another. We were delighted."
When the scientists tried the approach on diabetic mice, the animals became able to control their blood sugar levels.
"It didn't cure the mouse, but they were able to reduce their blood sugar levels to near-normal," Melton said.
Melton and others said it remains to be seen whether it will be necessary to use genetically engineered viruses, which could face obstacles obtaining regulatory approval because of concerns about unforeseen risks, or whether chemicals might be found to do the same thing.
If preliminary studies in the laboratory are promising, Melton said he might first try converting liver cells to insulin-producing pancreatic cells, because that would be safer than using the pancreas. An alternative strategy would be to use the approach to grow beta cells in the laboratory and transplant them into patients.
Lanza said he is optimistic.
"One day, this may allow the doctor to replace the scalpel with a sort of genetic surgery," Lanza said. "If this can be perfected, it would represent one of the holy grails of medicine."
Scientists produce stem cells for 10 diseases
NEW YORK (AP) -- Harvard scientists say they have created stems cells for 10 genetic disorders, which will allow researchers to watch the diseases develop in a lab dish.
This early step, using a new technique, could help speed up efforts to find treatments for some of the most confounding ailments, the scientists said.
The new work was reported online Thursday in the journal Cell, and the researchers said they plan to make the cell lines readily available to other scientists.
Dr. George Daley and his colleagues at the Harvard Stem Cell Institute used ordinary skin cells and bone marrow from people with a variety of diseases, including Parkinson's, Huntington's and Down syndrome to produce the stem cells.
The new cells will allow researchers to "watch the disease progress in a dish, that is, to watch what goes right or wrong," Doug Melton, co-director of the institute, said during a teleconference.
"I think we'll see in years ahead that this opens the door to a new way to treating degenerative diseases," he said.
The new technique reprograms cells, giving them the chameleon-like qualities of embryonic stem cells, which can morph into all kinds of tissue, such as heart, nerve and brain. As with embryonic stem cells, the hope is to speed medical research.
Research teams in Wisconsin and Japan were the first to report last November that they had reprogrammed skin cells, and that the cells had behaved like stem cells in a series of lab tests. Just last week, another Harvard team of scientists said they reprogrammed skin cells from two elderly patients with ALS, or Lou Gehrig's disease, and grew them into nerve cells.
Melton said the new disease-specific cell lines "represent a collection of degenerative diseases for which there are no good treatments and, more importantly, no good animal models for the most part in studying them."
A new laboratory has been created to serve as a repository for the cells, and to distribute them to other scientists researching the diseases, Melton said.
"The hope is that this will accelerate research and it will create a climate of openness," said Daley.
He expects stem cell lines to be developed for many more diseases, noting, "this is just the first wave of diseases." Other diseases for which they created stem cells are Type 1, or juvenile, diabetes; two types of muscular dystrophy, Gaucher disease and a rare genetic disorder known as the "bubble boy disease."
Daley stressed that the reprogrammed cells won't eliminate the need or value of studying embryonic stem cells.
"At least for the foreseeable future, and I would argue forever, they are going to be extremely valuable tools," he said.
The reprogramming work was funded by the National Institutes of Health and private contributions to the Harvard Stem Cell Institute.
On the Net:
- Harvard Stem Cell Institute: http://www.hsci.harvard.edu
