UK scientists clone human embryo

British scientists say they have cloned the country’s first human embryo.

Cloned embryo

There is controversy around human cloning.

The Newcastle University team took eggs from 11 women, removed the genetic material and replaced it with DNA from embryonic stem cells.

The aim of this kind of work – the subject of fierce debate – is to make cloned embryos from which stem cells can be used to treat diseases.

Meanwhile South Korean scientists say they have created stem cells to match individuals for the first time.

Stem cell lines were created by taking genetic material from the patient and putting it into a donated egg.

The resultant cells were a perfect match for the individual and could mean treatments for diseases like diabetes without problems of rejection.

Therapeutic cloning – believed to have huge potential to treat disease and disability – is allowed in Britain.

Reproductive cloning – the cloning of human embryos with the intention of creating a baby – was made illegal in 2001.

“We are talking about several years before we are talking about a cell-based therapy that can go back into the patient.” Professor Alison Murdoch

The UN recently voted in favour of a ban on all human cloning, but this was non-binding which means the UK can continue to do therapeutic cloning.

The use of embryonic stem cells is controversial, with opponents arguing that all embryos, whether created in the lab or not, have the potential to go on to become a fully fledged human. Others fear there are safety concerns.

Supporters of cloning say it could offer numerous benefits in the future, such as fighting disease, battling infertility or preserving endangered species.

‘Unsafe and inefficient’

Dr Miodrag Stojkovic

Dr Stojkovic: “There is a long way to go”

Criticising the Newcastle research, Julia Millington from the ProLife Alliance said cloning for research purposes was profoundly unethical.

Josephine Quintavalle from CORE said: “No matter how it is created, a human embryo’s destiny should be to live and not to be turned into human stem cells.”

Life said cloning was “unsafe and inefficient”, and involved exposing women to dangerous fertility drugs in order to collect sufficient eggs.

In the Newcastle research, three of the resultant clones lived and grew in the laboratory for three days and one survived for five days.

The critical factor for success appeared to be how quickly the egg was collected and manipulated, Professor Alison Murdoch and colleagues found.

The clone that lasted for five days had been collected and manipulated within 15 minutes.

Other tissues

Stem cells have the ability to develop into virtually any tissue in the body and could, in theory, be used to replace damaged cells in conditions such as Parkinson’s disease and diabetes.

But Professor Murdoch said this was still a long way off.

“We are talking about several years before we are talking about a cell-based therapy that can go back into the patient,” she said.

Colleague Dr Miodrag Stojkovic said: “I’m really happy but I know that this is just the beginning of a long journey so we have to continue to try to derive stem cells that will definitely help us one day to cure diseases.”

The UK research is published in Reproductive and BioMedicine Online.

http://news.bbc.co.uk/2/hi/health/4563607.stm

The Perils of Cloning

The Perils of Cloning

By Alice Park Wednesday, July 05, 2006

Clone: Ten years after Dolly’s birth, scientists are learning that clones may not be such perfect copies after all

ILLUSTRATION FOR TIME BY ANTHONY FREDA

It was 10 years ago this week, on a warm July night, that a newborn lamb with an unique pedigree took her first breath in a small shed tucked in the Scottish hills a few miles south of Edinburgh. From the outside, she looked no different from thousands of other sheep born each summer on surrounding farms. But Dolly, as the world soon came to realize, was no ordinary lamb. She was cloned from a single mammary cell of an adult ewe, overturning long-held scientific dogma that had declared such a thing biologically impossible. Her birth set off a race in laboratories around the world to duplicate the breakthrough. It also raised the specter–however distant–of human cloning.

A decade later, scientists are starting to come to grips with just how different Dolly was. Dozens of animals have been cloned since that first little lamb–mice, cats, cows, pigs, horses and, most recently, a dog–and it’s becoming increasingly clear that they are all, in one way or another, defective.

It’s tempting to think of clones as perfect carbon copies of the original–down to every hair and quirk of temperament. It turns out, though, that there are various degrees of genetic replication. That may come as a rude shock to people who have paid thousands of dollars to clone a pet cat only to discover that their new kitten looks and behaves nothing like their beloved pet–with a different-color coat of fur, perhaps, or a completely different attitude toward its human hosts.

And these are just the obvious differences. Not only are clones separated from the original template by time–in Dolly’s case, six years–but they are also the product of an unnatural molecular mechanism that turns out not to be very good at making identical copies. In fact, the process can embed small flaws in the genomes of clones that scientists are only now discovering. The more scientists have learned about the inner workings of the procedure that created Dolly, the more they are amazed that she survived at all.

“We are still surprised that cloning works,” says Ian Wilmut, the embryologist who led the team that created Dolly. Ten years and 15 mammalian species later, the efficiency of the process is no better than it was at Dolly’s birth: only 2% to 5% of the eggs that start out as clones end up as live animals. For each clone born, hundreds of others never make it past their first days and weeks, the victims of defects in development too severe to allow them to survive.

Clones are vulnerable throughout the cloning process, from their first days in a culture dish to their final moments in the womb to their first weeks after birth. (By contrast, embryos created by in vitro fertilization, which also start out in a petri dish, are pretty much home free if they make it past the first month in the womb.) Dolly, in fact, was the sole survivor of 277 cloning attempts. Clones, as the scientists who make them are fond of saying, are the exception rather than the rule.

It’s not hard to appreciate why. Mammalian cloning is an intricate process involving at least three animals, hundreds of eggs, hundreds of more mature cells and not a single sperm. The key challenge is to undo the development of an adult cell–which, like all cells, contains in its DNA the genetic blueprint of the entire organism–that has been programmed or “differentiated” to be one kind of cell (skin or bone or nerve) and no other kind. Somehow, scientists must trick this mature, fully developed cell into resetting its genetic clock so that it can begin life anew as an embryo.

The process by which that is achieved is called nuclear transfer. The first step is to remove the nucleus from an egg and replace it with the nucleus of an adult cell (in Dolly’s case, a cell from a ewe’s udder). The two components are electrically fused and chemically activated to trick the hybrid cell into dividing like an embryo. Not surprisingly, the process doesn’t always go right. “I call it a lottery,” says Wilmut. “Even if you use the same method as consistently as you can, you may get some clones with severe abnormalities and some that have only minor ones.”

The most common defect–seen across most of the species that have been cloned so far–is a condition known as large-offspring syndrome. Those clones are born larger than normal and have trouble breathing in their first few weeks. Most of the surrogates that gave birth to them experience prolonged pregnancies and sluggish, difficult labors, which may have something to do with their distended and enlarged placentas. Some of Wilmut’s cloned sheep were born with incomplete body walls, with muscles and skin around their abdomen that failed to properly join. Other scientists have reported abnormalities in kidney and brain function. In still other clones, the heart does not develop normally, and the walls that are supposed to separate fresh blood from deoxygenated blood do not form.

The good news, as far as cloning’s future is concerned, is that those problems seem to be limited to the clones and are not passed on to the next generation. When clones mate with ordinary animals, their offspring are created by the natural merging of egg and sperm–not by the reprogramming of a mature cell–which may erase any reprogramming errors in the clone. The proof is that Dolly gave birth to five healthy lambs. Cloned cows, pigs and mice are also bearing normal offspring. But when clones mate with other clones, all bets are off. Mice created this way appear to accumulate more abnormalities with each generation.

Most of the errors in reprogramming, scientists say, can be traced to a process known as DNA methylation. During normal development, molecules called methyl groups attach themselves to DNA in precisely timed patterns that regulate which genes are expressed at which times. During cloning, however, those patterns are not always reconstructed in exactly the same way. It’s a bit like taking all the words in a novel, jumbling them up and then trying to re-create the original book, putting sentences, pages and chapters back in the right order. The chances of that happening with 100% accuracy are minuscule, which helps explain why cloning is so inefficient. Rudolf Jaenisch, a geneticist at the Massachusetts Institute of Technology, estimates that 4% to 5% of the genes in a cloned animal’s genome are expressed incorrectly–probably because of faulty methylation. “If you reprogram, it affects the whole genome,” he says. “From what we know, I would argue that cloned animals cannot be normal. They can be closer to normal, but not normal.”

The mammalian body is surprisingly forgiving and can often compensate for minor programming errors. That’s why some genetic changes in clones may not have any measurable functional effects on the animals.

Dolly seems to have been one of those lucky ones. She showed just two signs of her unusual provenance. One was the arthritis she developed at an early age. The other was shortened telomeres in her cells. Telomeres are bits of DNA that sit at the ends of chromosomes and serve as a biological clock chronicling a cell’s age. In general, the shorter the telomeres, the older the cell. Dolly, a clone of a 6-year-old ewe, had cells whose telomeres were closer in length to those of her biological mother than to those of a baby lamb. We will never know, though, whether her shortened telomeres would have shortened her life. In 2003 Wilmut and his team decided to put Dolly to sleep after she developed lung cancer caused by a viral infection common among sheep. An autopsy revealed that she was otherwise normal.

But the fact that clones have defects–however minor–only bolsters the arguments that scientists have made against human cloning. Based on his studies of the faults introduced by reprogramming, Jaenisch, for one, thinks human cloning is now out of the question. “I think we cannot make human reproductive cloning safe,” he says. “And it’s not a technological issue. It’s a biological barrier. The pattern of methylation of a normal embryo cannot be re-created consistently in cloning.”

But Jaenisch and Wilmut both see a role for cloning in treating human diseases–and perhaps someday conquering some of man’s most intractable conditions. Wilmut and others have already created cow, sheep and pig cells genetically engineered to produce a particularly beneficial human protein, then cloned those cells to generate live animals able to make copious amounts of the target protein in their milk. It may be another 10 years or more before that approach yields anything safe and reliable enough to be used in real patients, and there is no guarantee that it will ever be successful. But as Wilmut points out, nobody thought Dolly was possible until she made history that warm July night 10 years ago.

http://www.time.com/time/magazine/article/0,9171,1209937-3,00.html

Cloning scientists create human brain cells

Cloning scientists create human brain cells

Scientists in Edinburgh who pioneered cloning have made a technological breakthrough that could pave the way for better medical treatment of mental illnesses and nerve diseases

doll the sheep

Scientist Ian Wilmut with Dolly, the worlds first cloned sheep, at the Roslin Institute near Edinburgh in 2001. Photograph: Murdo Macleod

The news that Edinburgh scientists had created the world’s first cloned mammal, Dolly the sheep, at the university’s Roslin Institute made headlines around the world 16 years ago. Her birth raised hopes of the creation of a new generation of medicines – with a host of these breakthroughs occurring at laboratories in the university over the following decade.

And now one of the most spectacular has taken place at Edinburgh’s Centre for Regenerative Medicine, where scientists have continued to develop the technology used to make Dolly. In a series of remarkable experiments, they have created brain tissue from patients suffering from schizophrenia, bipolar depression and other mental illnesses.

The work offers spectacular rewards for doctors. From a scrap of skin taken from a patient, they can make neurones genetically identical to those in that person’s brain. These brain cells, grown in the laboratory, can then be studied to reveal the neurological secrets of their condition.

“A patient’s neurones can tell us a great deal about the psychological conditions that affect them, but you cannot stick a needle in someone’s brain and take out its cells,” said Professor Charles ffrench-Constant, the centre’s director.

“However, we have found a way round that. We can take a skin sample, make stem cells from it and then direct these stem cells to grow into brain cells. Essentially, we are turning a person’s skin cells into brain. We are making cells that were previously inaccessible. And we could do that in future for the liver, the heart and other organs on which it is very difficult to carry out biopsies.”

The scientists are concentrating on a range of neurological conditions, including multiple sclerosis, Parkinson’s disease and motor neurone disease. In addition, work is being carried out on schizophrenia and bipolar depression, two debilitating ailments that are triggered by malfunctions in brain activity. This latter project is directed by Professor Andrew McIntosh of the Royal Edinburgh Hospital, who is working in collaboration with the regenerative medicine centre.

“We are making different types of brain cells out of skin samples from people with schizophrenia and bipolar depression,” he said. “Once we have assembled these, we look at standard psychological medicines, such as lithium, to see how they affect these cells in the laboratory. After that, we can start to screen new medicines. Our lines of brain cells would become testing platforms for new drugs. We should be able to start that work in a couple of years.”

In the past, scientists have studied brain tissue from people with conditions such as schizophrenia, but could only do so once an autopsy had been carried out. “It is very difficult to get primary tissue to study until after a patient has died,” added McIntosh.

“Even then, that tissue is affected by whatever killed them and by the impact of the medication they had been taking for their condition, possibly for several decades. So having access to living brain cells is a significant development for the development of drugs for these conditions.”

In addition, ffrench-Constant is planning experiments to create brain cells from patients suffering from multiple sclerosis, a disease that occurs when a person’s immune system turns on his or her own nerve cells and starts destroying the myelin sheaths that protect the fibres that it uses to communicate with other nerve cells. The condition induces severe debilitation in many cases.

“The problem with MS is that we cannot predict how patients will progress,” said ffrench-Constant. “In some, it progresses rapidly. In others, the damage to the myelin is repaired and they can live quite happily for many years. If we can find out the roots of the difference, we may be able to help patients.”

The brain cells that make myelin and wrap it around the fibres of nerve cells are known as oligodendrocytes. “We will take skin samples from MS patients whose condition has progressed quickly and others in whom it is not changing very much.

“Then we will make oligodendrocytes from those samples and see if there is an intrinsic difference between the two sets of patients. In other words, we will see if there is an underlying difference in people’s myelin-making cells that explains, when they get MS, why some manage to repair damage to their brain cells and others do not.”

Once that mechanism is revealed, the route to developing a new generation of MS drugs could be opened up, he added. “It is only a hypothesis, but it is a very attractive one,” said ffrench-Constant. “Crucially, stem cells will be the means of proving it.”

The technology involved in this work is a direct offshoot from the science involved in making Dolly the sheep. Dolly showed that adult cells in animals were more flexible than previously thought. This paved the way for research that allows scientists to turn adult cells, such as those found in the skin, into stem cells that can then be converted into any other type of cell found in the human body.

Four basic uses for stem cells have been found: to test the toxicity of drugs; to create tissue for transplanting, for example for Parkinson’s disease; to try to boost levels of a patient’s own population of stem cells in order to improve their defences against diseases; and to make models of diseases that will lead to the development of new drugs, as is being done with the Edinburgh research on brain cells.

“That is why the stem cell revolution is so important,” said ffrench-Constant. “It has so much to offer, not just in the area of creating material for transplants but in areas such as making models of diseases which should then allow you, hopefully, to develop all sorts of new treatments for a condition.”

http://www.guardian.co.uk/science/2012/jan/29/brain-cloning-breakthrough-mental-illness