It has finally happened – the technique used in 1996 to make Dolly, the world’s first cloned mammal, has finally been used in 2013 to make the world’s first cloned human embryo. Despite a history in the years after Dolly of nuts, crackpots, frauds and charlatans announcing that they had either cloned embryos or cloned babies--who can forget the Raelians with their star fleet uniforms announcing the creation of multiple clone baby births to a credulous press core—we have an announcement that is the real deal. A team of experts in cloning at Oregon Health Sciences University who have extensive experience and success with primate cloning have announced the cloning of human embryos.

This announcement is sure to set off a heated debate about the morality of what they have done and what could be done with cloned human embryos. But while there is some reason for concern, there is more reason for excitement.

The Oregon team has been trying to clone human embryos for many years. Why? Not to produce cloned people but to have a source of stem cells useful for the treatment of diseases.

Those who oppose manipulating embryos to generate stem cells -- and their number is huge -- will be blasting away at what has been achieved.

But before they try to freak you out with terrifying images of clone armies directed by despots (think “Star Wars: Episode II - Attack of the Clones”), the unmourned dead coming back to life via cloning (think Osama bin Laden) or the creation of multiple copies of particularly odd or dangerous people (think of dozens of versions of Lindsay Lohan or Charlie Sheen in your neighborhood), remember that the whole point of cloning research is to come up with stem cells that have the same genetic makeup as the person who needs them.

Stem cells can be obtained from human embryos at fertility clinics. But the cells that are made from them will not match those to whom they might be transplanted to repair macular degeneration, spinal cord injury or diabetes. Through cloning you can take a disabled or sick person's DNA from one of their body cells, insert it into a human egg from which the DNA has been removed, fuse the cell electrically (the technique used in Oregon) and create an embryo from which cells can be grown that are identical matches to what the sick or disabled person needs.

There are certainly crucially important ethical issues that cloning raises.  Should anyone be allowed to try to make people using cloning? Most assuredly not until cloning efforts with animals prove far safer then they currently are. Many animals made via cloning die in utero, are stillborn or have a variety of serious health issues as did Dolly, the first cloned sheep. For now, banning human reproductive cloning—not cloning for stem cell research, as many nations have already done -- ought to be a legislative priority in the U.S. and around the world.

If we are going to need eggs to clone human embryos, then where are they coming from? Most likely in the short run from donors who will have to fully understand what their eggs will be used to create. Whether paid sellers of eggs will be needed in the future remains to be seen, but that is not yet likely to be a problem.

And some will say we don’t need to make cloned embryos to get stem cells because there are other ways to get them. There are other ways but this may prove to be the best way medically to get the regenerative cells that so many could benefit from.

Cloning a human embryo to create stem cells has been a dream for many scientists since Dolly was born. Cloning a human embryo has been a source of ethical nightmares for many theologians, ethicists and scientists since Dolly was born. It has now time to decide if we can manage a technology that holds great promise while assuring those who fear its abuse that their concerns will be fully addressed.

Arthur Caplan, Ph.D., is the head of the Division of Medical Ethics at NYU Langone Medical Center.

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Oregon Health&Science University

Donor egg held by pipette prior to nuclear extraction.

Researchers say they have finally managed to use cloning technology to make human embryos and grow stem cells from them in the hopes of making perfectly matched grow-your-own tissue transplants.

They used a human egg cell and parts of a human skin cell to grow a very early human embryo, then transformed cells from this ball of cells into beating heart cells and skin cells. The process may eventually help treat a range of diseases, from Parkinson’s to rare inherited conditions, they reported Wednesday in the journal Cell.

The researchers, at Oregon Health & Science University, say their embryos almost certainly could not grow into living human babies or even start a pregnancy – they’re deficient in a key way. But they admit also that they haven’t quite overcome ethical qualms about working with human embryos.

However, the work opens another route to treatments using human embryonic stem cells, the body’s master cells. “These stem cells are kind of very early unprogrammed cells but they have the capacity to become any other cell type,” says Shoukhrat Mitalipov, who led the research.

These cells are very different from so-called adult stem cells, like those taken from bone marrow. Adult stem cells cannot give rise to cells of other tissue types -- blood cells cannot be used to make brain cells, for instance.

Dr. George Daley, a stem cell expert at Harvard Medical School, called it a "beautiful piece of work".

When human embryonic stem cells were first discovered in 1998, scientists immediately dreamed of using cloning technology to help people grow their own organ and tissue transplants, and to use them to study disease. They’d be perfect genetic matches for each patient, meaning an end to a lifetime of taking dangerous immune-suppressing drugs after an organ transplant.

But in the many years since, no lab’s been able to do the work easily. It seems it is much harder to clone a human being than it is to clone a sheep, a frog or a mouse. And then there are the ethical concerns, not only concerns about cloning human beings but over working with human embryos. A federal court has only just ruled in the past year that government funds may be used in the research.

Scientists have found several other routes to harnessing the power of these master cells, which can give rise to any tissue type in the body, from nerve cells to muscle, bone and skin. There are cells taken from embryos left over at fertility clinics – currently being tested as treatments for blindness by a company, Advanced Cell Technology of Massachusetts.

Oregon Health & Science University

Researchers at Oregon Health & Science University have successfully developed a method for converting human skin cells into embryonic stem cells.

Other groups have learned how to “trick” ordinary skin cells into re-modeling themselves into different tissues. These so-called induced pluripotent stem cells, iPS cells for short, might also some day be used to grow transplants perfectly matched to a patient. But again, the technique isn’t easy and there have been many stumbling blocks.

Several other scientists said the science was sound, but said the field had mostly moved on from the pursuit of cloning technology. "IPS cells are easier to produce and have wide applications in research and regenerative medicine, and it remains to be shown whether (cloned embryonic stem cells) have advantages over iPS cells," Daley said by e-mail.

Cloning almost got left in the dust with the work on the other techniques. But the team at OHSU had been perfecting the technique in monkeys, and now they’ve managed to make it work with human cells. The advantage, they say, is that the donated human egg provides fresh and rejuvenating DNA.

The technique they use is called somatic cell nuclear transfer – the same method used to make Dolly, the sheep who was the first mammal cloned from the cell of another adult mammal, in 1996. Scientists remove the nucleus from a normal cell, usually a type of skin cell. They do the same with a human egg cell, then inject the nucleus from the skin cell into the egg.

Various chemical or electrical tricks can be used to start the egg growing as if it had been fertilized by sperm. The method’s been used to make sheep, dogs, horses, and mice – but never human beings.

None of these clones are precise copies because the egg contains an important source of DNA, called mitochondrial DNA. And defects in this DNA cause many diseases, including diabetes and a condition called Leigh syndrome, which causes seizures and dementia.

Mitalipov hopes that replacing the mitochondrial DNA as part of the cloning process might help make tissue that could correct these diseases. His team tested cells taken from a patient with Leigh syndrome, a neurological disorder, and made stem cells using the technique.

“It allows you to produce genetically corrected cells,” he said. “There are a variety of age-related diseases that we believe are caused by acquired mitochondrial mutations.”

Lots of testing lies ahead and because of laws banning the use of federal money to directly make human embryos, Mitalipov’s lab uses private funds instead. But he believes the method cannot be used to make human babies.

“We have been doing it for years in primates and the embryos never implant,” he said. The blastocysts appear to lack a key layer of cells, he said, that give rise to the placenta and that are needed for a normal pregnancy.

Nonetheless, he admits that is unlikely to reassure people who object to experimenting on human embryos. “They’ll say ‘oh, you are just creating a disabled embryo’,” he said.

O. Carter Snead, a bioethicist and professor of law at the University of Notre Dame, called it sad news. “The use and destruction of living human beings – at any stage of biological development – for scientific research is a terrible injustice.  Human cloning for biomedical research is a particularly aggravated form of this harm," Snead said in a statement.

Another barrier --- human eggs are not easy to come by and there are also ethical questions about whether women should be paid to donate their eggs for this kind of research.

The work will almost certainly be used to study diseases in lab dishes at first. But Daley, who heads the bone marrow transplant program at Boston Children's Hospital, said using a patient's own cells offers potentially huge advantages. "A lot of patients don't have an optimal donor," he said. So bone marrow transplants are done only for the patients in the most dire need.

"If we could make every patient their own donor ... we would bypass the transplant barrier," he said. "Everyone could be a donor for themselves."

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• Ethicist: Cloning offers more cause for excitement, not concern
• Supreme Court lets embryonic stem cell research go forward
• Court rules on controversial human research
• Stephen Hawking visits stem cell lab

A team of scientists at the Oregon National Primate Research Center and the Oregon Health & Science University are reporting a remarkable advance in the treatment of inherited genetic disease in the journal Nature.

They show it is possible to repair a tiny part of a human egg cell that, when broken, causes a host of awful inherited genetic diseases.  Those diseases cause disability and the death for many children and adults.  What is equally remarkable is that the treatment they report is illegal in Britain, Germany, Costa Rica, Norway and Sweden and would be illegal to provide using federal dollars in the United States.

What did the Oregon scientists do?  And why is it so ethically controversial?

Mitochondria are the batteries of human cells.  They convert oxygen and nutrients into a chemical that is the source of the energy that allows chromosomes to move and recombine and, once a sperm arrives, a fertilized embryo to grow.  Every cell in your body has mitochondria inherited from your mother’s egg.  When these little cellular engines have a genetic problem,  it can make for terrible diseases in any child that inherits them. 

About 4,000 U.S. children are born each year with mitochondrial diseases.  They may become blind,  paralyzed or suffer severe cognitive impairment.

The Oregon team showed that they could fix the problem of damaged mitochondria in an egg cell by transplanting the DNA in the nucleus of eggs with diseased mitochondria into eggs with healthy mitochondria that had the nucleus removed.  They did this both in monkeys and humans.  A child born as a result of this genetic transplant—referred to as a spindle transfer-- would be the genetic offspring of two mothers.

The child would have healthy mitochondrial DNA from the egg of a donor mom. He or she would also have DNA from the mom with the mitochondria problem. 

This is amazing genetic engineering.  Gene transfer in human eggs has and will provoke a lot of controversy.

When the Oregon team did their studies they proved the transplanted genes would work in a human egg by making them into viable embryos.  Those embryos were studied in various ways to prove they were normal -- and then destroyed.  There is no other way to prove that transplanting genes between eggs could someday cure children of terrible diseases without the kind of experiment the Oregon group did.

While monkeys have been used in the past, this is the first paper reporting success in the genetic engineering of human eggs.

But to go forward, more such experiments will need to be done to ensure the safety of the technique.  Currently there is a ban in the U.S. on doing this kind of research with federal funds. Federal law forbids using federal taxpayer dollars to pay for any research involving the destruction of a human embryo.

This experiment also crosses a bright ethical line. Changing genes in the lungs of people with cystic fibrosis or in the eyes of people with retinitis pigmentosa or macular degeneration may fix the broken body part, but the change is not passed on to future generations.

When you change genes in an egg, even in the mitochondria of an egg, you make a change that is inherited by every single offspring of any child created from that egg.  That is called germline engineering -- meaning changing inherited genetic material.

And germline engineering of mitochondria crosses the line from using genetic engineering to fix our body parts into directly engineering the traits of our children.  It is a road that could lead, in the distant future, toward eugenics.

So should we celebrate or condemn this first step into reproductive cell or germline genetic engineering?

I think the price of experimenting on embryos to find a solution to disease, while high, is morally acceptable.  Creating embryos in the future by means of a mitochondrial transplant that will not be used to make babies on a limited basis seems to appropriately value children and adults over possible children and adults.

And while I, too, worry about where genetically engineering eggs might lead, I think doing so to find cures is ethically noble.  Those nations that say no to any form of germline engineering, including the U.S., should revisit those policies to permit research that is clearly intended as therapy.

The brave new world has now appeared in print.  We need to be brave enough to avail ourselves of the good it can bring.

Arthur Caplan is the head of the Division of Medical Ethics at NYU Langone Medical Center.

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“Right now I am talking to you from bed, wrapped up in blankets because I can’t regulate my body temperature,” says Stefani Bush, a Chelmsford, Mass., mother. Bush, 35, has a gene mutation, one in a galaxy of mutations that causes often devastating conditions known collectively as mitochondrial diseases. She has been hospitalized about 16 times this year. She can’t walk more than about 20 yards and has a host of cardiovascular and gastrointestinal symptoms.

A study published Wednesday in the journal Nature might offer a way to prevent children from inheriting such conditions in the future. Scientists in Oregon have found a way to remove the damaged genetic material and replace it with healthy DNA. The catch is it’s controversial, and children born using the technique would, technically, have three genetic parents. It’s just the kind of ethical debate that stopped such science dead in its tracks a decade ago.

Bush wasn’t aware she carried her mutation until she was pregnant with her daughter, now 7. Her son, 9, has been diagnosed with the same mutation, and her daughter is showing signs she has it, too. On a recent family dream trip to Disney World, the little girl spent an entire day having seizures.      

Mitochondria are tiny organelles in every cell of our bodies except red blood cells. They’re the cells’ power plants, converting glucose to energy. Mitochondria has DNA of its own – human mitochondria has 13 genes – that is passed down virtually unchanged from mothers to babies.

If mitochondria don’t do their jobs properly, a wide variety of health troubles can result, especially in parts of the body, like muscle and brain, that have high energy requirements.

An estimated 1 in 4,000 children born in the U.S. are affected by some version of mitochondrial disease, according to the United Mitochondrial Disease Foundation.

Many children born with mitochondrial mutations don’t live past age 4 or 5. Mutations can cause blindness, deafness, strokes, seizures and cardiovascular problems. Often, as in Stefani Bush’s case, people go undiagnosed for many years.

Researchers have been trying for years to find ways to repair damaged mitochondria to give the kids a chance.

Shoukhrat Mitalipov at the Oregon National Primate Research Center and Oregon Health and Science University and colleagues found a way they think might work. Most of a person’s DNA is found in the nucleus of the cell, carried on structures called chromosomes.

Mitalipov’s team took the chromosomes out of one set of human egg cells. They replaced them with chromosomes from human donor eggs. Then they used fertilization techniques to inject sperm and fertilize the eggs – about 65 in total.

Mitalipov Lab / Oregon Health & Science University

Researchers have found a way to removed damaged DNA from a woman's egg cell and replace it with healthy DNA from another woman.

When the resulting embryos developed into balls of cells called blastocysts, they took out a few of the embryonic stem cells and tested them to show they were healthy and would have developed into normal embryos. Only about half did.

Even so, Mitalipov told a news conference, the process worked “pretty well. Mitochondrial DNA can be replaced efficiently.”

Three years ago, the same team announced they’d used the technique to create reconstituted eggs from monkeys called macaques, fertilize those eggs, and implant them into females. Three babies were born.

“At three years follow up,” Mitalipov said, “the study showed these are normal” juvenile monkeys.

By doing such manipulations, scientists hope to prevent mitochondrial disease by removing chromosomes from the eggs of affected women, and putting them into donor eggs. Any children that would be born would not carry the mother’s mitochondrial mutations – but would have the mitochondrial DNA from the woman who donated her eggs.

“From my point of view, this has big implications in women who have some type of mitochondrial DNA mutation,” said Carla Koehler, a mitochondrial biologist at the University of California Los Angeles who has been studying ways to repair the mutations. She uses some of the same kinds of techniques to make what she calls “cybrids.”

“I’d hate to rush this technique and start using it in women,” she added. “We should always have a high bar.”

In 2010, a team from Newcastle University in Britain published results of their own, similar, chromosome transfer. On behalf of that team, Mary Herbert issued a statement applauding the work of the Oregon scientists and noting that it “confirms our previous work published in Nature, showing that, in principle, it is possible to use IVF-based techniques to reduce the risk of transmitting mitochondrial DNA disease from a mother to her child.”

The team hasn’t yet shown that an embryo made this way could be used to make a woman pregnant.

Mitalipov said the scientists think they’ve figured out why most of the manipulated eggs didn’t develop normally. He hopes to start human tests. “I say it is safe enough to proceed,” he said.

Dr. Jamie Grifo, director of the division of endocrinology and infertility at the New York University Fertility Center, agreed. “It’s a great paper,” he told NBC News. “This is a kind of orphan group of patients, but they are out there, and the only thing we can offer them now is donor eggs.”

But Grifo also predicted that the Food and Drug Administration (FDA) would be very reluctant to approve any human trials

Grifo knows, because, in 1999, he published results of a similar technique in his effort to improve success rates for infertile patients.

“I think this study confirms what we were doing a long time ago,” he said.

But Grifo was working at a time when there were great concerns over the issue of human cloning. He wasn’t trying to clone anybody, just trying to make a healthy egg.

After media reports of Grifo’s work were published, “I got a personal phone call from the assistant surgeon general of the United States who wanted to know why I was doing it and said I should not be doing it,” he recalled. “Then I got a letter from FDA telling me to stop.”

Grifo turned his data and research over to Chinese scientists so it wouldn’t go to waste.

In fact, there are already children born with two genetic mothers. In the mid 1990s, Jacques Cohen, at St. Barnabas Medical Center in New Jersey, began transplanting cytoplasm from donor eggs into eggs from infertile women as a way to “rescue” those eggs.

In 2001, Cohen announced that he’d found mitochondrial DNA from both the mother and the donor in the cells of babies born using this cytoplasmic transfer technique.

It was the first time the human germline – the genetic information that’s passed down from one generation to the next – had been deliberately altered and resulted in the birth of children.

In response, the FDA said it would require researchers to file an Investigational New Drug (IND) application, and conduct clinical trials under that IND. In the 11 years since, FDA has not issued any such INDs, according to FDA spokesperson Rita Chappelle. Given fears over altering the human germline, and the idea that any babies would be born with DNA from three people, some question if FDA will change policy now.  

“I’m not sure what FDA’s stand is on this treatment,” Mitalipov said. “Last time I heard, this topic was under active discussion in the FDA’s Division of Cellular and Gene Therapies department.”

Chappelle would say only that “any proposed process of mitochondrial transfer would be carefully evaluated before FDA could make a determination as to whether an IND would be required to conduct clinical research.”

Bush understands the concerns, but has no doubts the science should move forward. If she’d known what she risked passing on to her children, “I would do it,” she said. “If I could have spared my children one ounce of what they have gone though, I would.”

Brian Alexander (www.BrianRAlexander.com) is co-author, with Larry Young Ph.D., of "The Chemistry Between Us: Love, Sex and the Science of Attraction," (www.TheChemistryBetweenUs.com), now on sale.

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