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Scientists Claim Cloning Success
Scientists in South Korea report that they have created human embryos through cloning and extracted embryonic stem cells.

Scientists Claim Cloning Success
By GINA KOLATA

Published: February 12, 2004

Scientists in South Korea report that they have created human embryos through cloning and extracted embryonic stem cells, the universal cells that hold great promise for medical research.

Their goal, the scientists say, is not to clone humans but to advance understanding of the causes and treatment of disease.
But the work makes the birth of a cloned baby suddenly more feasible. For that reason, it is likely to reignite the fierce debate over the ethics of human cloning.

The work was led by Dr. Woo Suk Hwang and Dr. Shin Yong Moon of Seoul National University and will be published tomorrow in the journal Science. The paper provides a detailed description of how to create human embryos by cloning. Experts in the field not involved with the work said they found the paper persuasive.

"You now have the cookbook, you have a methodology that's publicly available," said Dr. Robert Lanza, medical director of a company, Advanced Cell Technology in Worcester, Mass., that had tried without success to do what the South Koreans did.

Although the paper, written in dense jargon and summarizing its findings by saying, "We report the derivation of a pluripotent embryonic stem cell line (SCNT-hES-1) from a cloned human blastocyst," its import was immediately clear to researchers.

"My reaction is, basically, wow," said Dr. Richard Rawlins, an embryologist who is director of the assisted reproduction laboratories at the Rush University Medical Center in Chicago. "It's a landmark paper."

It is what patients with diseases like Parkinson's and diabetes had been waiting for, the start of so-called therapeutic cloning. The idea is to clone a patients cells to make embryonic stem cells that are an exact genetic match of the patient. Then those cells, patients hope, could be turned into replacement tissue to treat or cure their disease without provoking rejection from the body's immune system.

Even though the new work clears a significant hurdle, scientists caution that it could take years of further research before stem cell science turns into actual therapies.

Even before the publication — reported last night by a South Korean newspaper, one day ahead of the embargo imposed by Science — the research was criticized by cloning opponents.

Dr. Leon R. Kass, chairman of the President's Council on Bioethics, called for federal legislation to stop human cloning for any purpose.

"The age of human cloning has apparently arrived: today, cloned blastocysts for research, tomorrow cloned blastocysts for babymaking," Dr. Kass wrote in an e-mail message. "In my opinion, and that of the majority of the Council, the only way to prevent this from happening here is for Congress to enact a comprehensive ban or moratorium on all human cloning."

The House has twice passed legislation that would ban all human cloning experiments, most recently in February 2003. But the bills have foundered in the Senate, where many members who oppose reproductive cloning do not want to ban it for medical research.

Dr. Hwang said he knew that the work would elicit strong responses but that the research was so important it should be done anyway, adding that there was strict oversight by an ethics committee.

"Of course," he said, "we acknowledge that there will be controversy. But as scientists, we think it is our obligation to do this."

The paper describes the successful process in detail, with precise information on how to start the embryos growing and what solutions are best to nourish them. That recipe appears to advance the likelihood of reproductive cloning. When fertility laboratories fertilize eggs, grow embryos to the same developmental stage as the embryo clones and implant them in a human uterus, 40 to 60 percent end up as babies.

The scientists stress that all the research was in the laboratory, in petri dishes. No embryo was implanted in a woman. The women who provided unfertilized eggs that were needed to start the cloning process were not paid.

The research was financed by the government of South Korea, where cloning to create a baby is illegal.

http://www.nytimes.com/2004/02/12/science/12CELL.html?hp

Scientists Get Sought-After Cells from Human Clone
Thu 12 February, 2004 00:20

By Maggie Fox, Health and Science Correspondent

WASHINGTON (Reuters) - South Korean and U.S. researchers said on Wednesday they had cloned a human embryo and extracted from it sought-after cells called embryonic stem cells.

The experiment, the first published report of cloned human stem cells, means so-called therapeutic cloning is no longer a theory but a reality.

Supporters of medical cloning say it can transform medicine, offering tailored and highly effective treatments for diseases ranging from Parkinson's to diabetes. They say it could eventually lead to grow-your-own organ transplants.

The stem cells taken from the tiny embryos, known as blastocysts, have the potential to develop into any kind of cell or tissue in the body.

"Our approach opens the door for the use of these specially developed cells in transplantation medicine," Woo Suk Hwang of Seoul National University in Korea, who led the study, said in a statement.

But critics say it involves destroying a human embryo, however tiny, and is thus unethical. The administration of President Bush and supporters in Congress are seeking to outlaw the technology both in the United States and worldwide.

Writing in the journal Science, Hwang and colleagues said they created the clone using eggs and cumulus cells donated by Korean women.

Cumulus cells are found in the ovaries and in some species have been found to work especially well in cloning experiments.

Scientists have cloned sheep, cattle, mice and other species but have had trouble cloning a human being. Last year a Massachusetts company, Advanced Cell Technology, said it had created a human cloned embryo but it had not grown enough to become a source of stem cells.

The company is still trying but has not reported publicly on its progress.

POWERFUL MASTER CELLS

Stem cells are found throughout the body and are a kind of master cell. But adult stem cells are difficult to find and to work with.

Many scientists believe blastocysts -- stem cells taken from days-old embryos -- have much greater potential. Each one, when grown correctly, can be directed to become any kind of cell or tissue at all.

Outside experts on cloning praised the work. "It is a very impressive study. It obviously represents a major medical milestone," said Dr. Robert Lanza, who has helped lead cloning experiments at Advanced Cell Technology.

"I think it could help spur a medical revolution."

Working with Hwang was Dr. Jose Cibelli, formerly of Advanced Cell Technology and now a researcher at Michigan State University.

They used a process called nuclear transfer, which involves removing the nucleus from an egg cell and replacing it with the nucleus of a so-called adult cell -- in this case a cumulus cells.

They cloned each woman using her own egg cell and her own cumulus cell, so the clones were 100 percent copies of each woman.

They activated the egg cells using a chemical process, which started the eggs growing as if they had been fertilized by a sperm and got 30 embryos to grow to the blastocyst stage.

At this stage, approximately 100 cells, the stem cells should be removable.

They pulled stem cells from one of the blastocysts and managed to get them to grow into a variety of different cells including eye cells, muscle cells, bone and cartilage.

Lanza said it is now important that laws be passed banning reproductive cloning -- using cloning to create a human baby.

He noted that some researchers, notably Kentucky fertility expert Dr. Panos Zavos, have been at least trying to clone a baby. "He's got the cookbook now. It's scary. We really need to move as soon as possible," Lanza said.

http://www.reuters.co.uk/newsArticle.jhtml?type=scienceNews&storyID=4339416&section=news

Human Clone Produces Stem Cells

Korean researchers have created a human clone and derived the first cloned stem cells from it -- a significant advance toward using the cells to replace those damaged by diseases like diabetes and Alzheimer's.

A Korean woman now has a set of cells that could one day replace any damaged or diseased cell in her body with little worry of rejection, if researchers can get stem cells to work therapeutically

The study, which will be published in the Feb. 13 issue of the journal Science, will be presented Thursday at the annual meeting of the American Association for the Advancement of Science in Seattle.

While researchers have cloned animals like sheep, cats and cows before this study, researchers had been unable to make the jump to monkeys or humans and believed cloning primates posed a unique obstacle. Now, the Korean researchers show they have perfected a cloning technique, also known as somatic cell nuclear transfer, that works in humans and potentially other primates.

"When I saw the first version of this manuscript back in June 2003, it came like any other e-mail you get," said Jose Cibelli, a professor of animal biotechnology at the University of Michigan who co-authored the paper. "They wanted me to comment on the manuscript and recommend where to submit it, and when I saw the data I almost fell off my chair."

The Korean researchers, led by veterinary cloning expert Woo Suk Hwang and gynecologist Shin Yong Moon of Seoul National University in South Korea, not only created a robust clone that divided into hundreds of cells, but also extracted a stem cell "line," or a group of cells that can potentially replicate indefinitely. So far the line has copied itself 70 times.

Scientists have extracted stem cells from embryos in the past, hoping to one day use them as medicine. But they worried that the patient's body would reject stem cells taken from someone else. So for the past several years, various groups around the world have been trying to first create a clone, which would be a patient's exact biological match, then take stem cells from it.

Researchers have said they believe that some stem cells taken from embryos can be coaxed to become almost any type of cell in the human body, a characteristic known as "pluripotency." The stem cells in the Korean study differentiated into retinal, bone and other types of cells when implanted into mice.

Advanced Cell Technology, a private company in Worcester, Massachusetts, announced in a splashy Wired magazine cover story in January that it had cloned an embryo to the 16-cell stage. But the company apparently didn't extract stem cells from the embryo, and it wasn't clear how long the clone survived.

It's significant that the Korean research went through a stringent peer-review process in order to be published in Science, scientists say. Advanced Cell Technology has published just one study in an online scientific journal on its human-cloning experiments. In that study, the researchers -- including Cibelli, who worked there at the time -- achieved a clone with only six cells.

The Korean advance also rekindles ethical protests from some religious and anti-abortion groups. Since the embryo is destroyed when stem cells are extracted, they contend the process is murder. A handful of bills to ban cloning have languished in Congress for the past several years. None has passed, however, because therapeutic cloning is often tied to reproductive cloning, which rogue scientists have threatened to use to produce babies -- although they offer no scientific proof that they're close to reaching their goal. Most researchers agree legislation should ban reproductive cloning and support therapeutic cloning.

"In this case there was no sperm, no uterus, there was no vision for this to be a human being," said Bernard Siegel, director of the Genetics Policy Institute. "This is entirely something with the potential to create cures, understanding and treatment of medical conditions, and it's a real step in the right direction."

To create a clone, researchers take an egg from a woman and remove the nucleus. They replace it with a cell from the person to be cloned. They then use chemicals or zap it with electricity to kick-start cell division.

The Koreans had 242 eggs to work with, donated from 16 unpaid healthy women who underwent hormone treatment to stimulate their ovaries to produce more eggs than normal.

With so many eggs to work with, the researchers were able to tweak their process to optimize their methodology. First, instead of sucking the nucleus out with a pipette, which in other experiments sometimes damaged proteins that control cell division, the team nicked a small hole in the egg and gently squeezed the nucleus out.

In their fourth and most successful protocol, the researchers got 19 of 66 cloned eggs to develop into blastocysts -- the embryonic stage when it becomes possible to derive stem cells.

In the United States, President Bush announced in August 2001 that federally funded researchers would be prohibited from creating new embryonic stem cell lines, and would be allowed to use only the limited number of lines that already had been created. Researchers in the United States believe the mandate has severely limited progress in stem-cell research here.

"At the pace we're going we're never going to get there, because we don't have enough funding," Cibelli said. "The federal government will have to put up more money. These cells definitely have the potential to be treatments for many diseases."

The Korean researchers wrote that they could not rule out the possibility that their eggs might have begun spontaneously dividing and were not true embryos, a phenomenon called parthenogenesis. It's a type of reproduction found in many life forms, including flies, ants and lizards, but it doesn't create an embryo in mammals. It's not clear that stem cells from human parthenotes would be useful in therapies.

But genetic tests indicated the Koreans very likely had true embryos, not parthenotes.

"I have no doubt they have done somatic cell nuclear transfer," Cibelli said.

http://www.wired.com/news/medtech/0,1286,62254-2,00.html?tw=wn_story_page_next1

Scientists create human embryos through cloning, extract embryonic stem cells

By DAVID WAHLBERG
Atlanta Journal-Constitution Staff Writer

For the first time, scientists have achieved human "therapeutic cloning," creating human embryos through cloning and extracting stem cells that were then morphed into other kinds of cells.

The stunning announcement, being made today by Korean scientists at a major American science conference in Seattle, boosts hope for stem-cell therapies for diabetes, Parkinson's disease, spinal-cord injuries and other diseases -- though such treatments remain years away.

The news is also certain to ratchet up the ethical debate over cloning.

Others have claimed success at human cloning, including a biotech company, a Kentucky researcher and a religious sect. But scientists have largely dismissed those declarations because they were not reviewed by their peers and published in major journals.

The unprecedented research, by a team from Seoul National University, is being reported in today's edition of the journal Science, published by the American Association for the Advancement of Science, which is currently meeting in Seattle.

The Korean group's work goes beyond basic cloning to producing viable stem cells from the embryos, essential to developing potential therapies.

"I'm staggered," said Gerald Schatten, a University of Pittsburgh researcher who has been trying to accomplish the feat in monkeys. "This means we're in a new era of medical promise for generating embryonic stem cells for treating diabetes, spinal-cord injury and Parkinson's disease."

Many researchers applauded the findings, but some cautioned that scientific, financial and ethical hurdles remain, putting clinical trials of embryonic stem cell treatments at least five years away.

Jose Cibelli, a cloning and stem cells researcher at Michigan State University who helped the Korean team verify the findings, said therapeutic cloning has been accomplished in cows and mice, but few scientists realized anyone was close to achieving it in humans.

"When I first saw their manuscript, I almost passed out. This was it," Cibelli said. "This paper proves that you can take a cell committed to being one type of tissue and make it go back in development. This is the first time it was done in humans."

Stem cells are primordial cells that can theoretically develop into all of the body's 220 cell types -- possibly replacing patients' damaged or defective cells -- but exactly how they can be coaxed into desired cell types and ensured to function properly in a patient largely remains to be seen.

"Embryonic stem cell research is still at the Wright brothers' stage," said Arthur Caplan, a biomedical ethicist at the University of Pennsylvania. "This shows that it's possible to get into the air, but it's not a jumbo jet."

The Korean team, led by Woo Suk Hwang, collected 242 eggs from 16 women who signed consent forms and were not paid.

After removing the genetic material from the eggs, the researchers said, they inserted cumulus cells -- which nurture developing eggs in the ovary -- from the same women into their own empty eggs. An electric pulse fused the genetic material from the cumulus cells with the eggs.

After about five days, early-stage embryos known as blastocysts formed with more than 100 developing cells, including stem cells along the inner wall of the blastocysts. The researchers removed the stem cells and grew them into other basic kinds of cells in a lab dish. They also injected some stem cells into mice. After six weeks, those stem cells became skin, muscle, bone, cartilage and other specific kinds of cells, the researchers said.

Michael Manganiello, senior vice president at the Christopher Reeve Paralysis Foundation, said the development is especially hopeful because the cumulus cells and egg cells came from the same women. That could lead to cell therapies that wouldn't cause immune system rejection, he said.

"The idea that someone with spinal-cord injury could essentially cure themselves without having to take immune suppressant drugs is a wonderful potential of this discovery," he said.

Several scientific obstacles must be overcome before therapies are realistic, said Arlene Chiu, a program director at the National Institute of Neurological Disorders and Stroke in Bethesda, Md., one of the National Institutes of Health.

It's one thing to inject stem cells into a patient with a spinal cord injury and hope the cells become motor neurons, Chiu said. It's quite another to make sure the cells go to the right place, become the right kind of cell and connect with the right network.

"If some of the cells form aberrant circuits, will they cause adverse events like seizures?" Chiu asked.

Steve Stice, a cloning and stem cells researcher at the University of Georgia, said regulators are concerned that stem cells injected into patients could turn into benign but grotesque-sounding tumors called teratomas -- a dynamic mass of dozens of different cell types, from teeth to kidney to brain.

"It's pretty evident that stem cells will be effective, but the question of safety may take the most time to answer," Stice said.

The Korean experiment also raises questions of cost, Stice said. The team from Seoul collected 242 eggs to produce one active stem cell line. In the United States, procuring a single egg costs about $3,000.

"The cost is going to be way too prohibitive for most patients," Stice said.

Another issue is access to stem cells. Under a 2001 decision by President Bush, federal funding for stem-cell research is limited to the 78 stem cell lines in place at the time, four of which were created by Stice and his colleagues.

But only 15 of those stem-cell lines have proven useful so far, said James Battey, chairman of the NIH Stem Cell Task Force. In 2002, the NIH awarded just $11 million in grants for embryonic stem-cell research, with $170 million going to research on adult stem cells, which some scientists say are promising but not as malleable.

The new study also reignites ethical issues, experts say. The Korean women donated eggs specifically for research, not for any potential reproductive benefit for themselves. In the United States, stem-cell research has primarily involved leftover eggs from fertility clinics, where the original intent of collecting eggs is to have babies.

"We may need to analyze whether eggs should be taken for non-reproductive purposes," said Schatten, of the University of Pittsburgh.

Abortion opponents also raise concerns. By discarding hundreds of embryos to get one stem cell line, the researchers abused human life, said Richard Doerflinger with the U.S. Conference of Catholic Bishops.

"This is creating new human life solely to destroy it, and in an especially wasteful way," he said.

The U.S. House of Representatives has approved a ban on cloning for reproductive or therapeutic purposes. The bill has been bogged down in the Senate, where supporters of therapeutic cloning want to prohibit only reproductive cloning.

In December, the United Nations delayed a decision on whether to ban cloning for at least a year, after a debate over an all-out ban versus a partial one. The United States urged the U.N. to prohibit both varieties.

http://www.ajc.com/news/content/news/0204a/12clone.html