Scientists have cloned a human embryo, prompting both delight and fear. Trust us, says geneticist Robin Lovell-Badge - rather than doppelganger babies there will be a medical revolution that saves lives
February 16, 2004
I was very excited by the news that a group of scientists, mostly from South Korea, had succeeded in making 30 early human embryos using a cloning technique similar to that used to create Dolly the sheep. These early embryos had been created by taking eggs donated by women, stripping them of the unique DNA at their centre, and replacing it with adult body cells supplied by the same women. The embryos were kept in a Petri dish until they had reached the blastocyst stage, being just balls of 100 or so cells. Then the scientists attempted to isolate the inner cells.
The aim was to generate human embryonic stem cells that would be genetically identical to the donor women. Stem cells are those which create further identical cells when they divide. They can be used for healing purposes as replacements for damaged cells.
The Koreans did not intend to implant the embryos into surrogate mothers. No sensible scientist would consider the use of cloning in order to give birth to living human beings because it is far too dangerous. I personally have no problem with the principle of cloning humans but we do know from work with animals that serious problems develop between the early embryo and birth. There are lots of spontaneous abortions - and the chances are that any babies conceived in this way would be born deformed or develop severe abnormalities. Cloning live people would not be safe.
However, cloning embryos does offer exciting possibilities for medical science, and the news announced on Thursday was of an important achievement. This was good research, conducted well, carefully peer-reviewed and published in Science, a highly rated journal. Critically, it simply says that so-called "therapeutic cloning" is possible in humans.
I have worked with embryonic stem cells from mice for more than 20 years. Because these are derived from such early embryos before any specialisation has occurred, they have the ability to make any cell type in the body. They can do so in the dish, if the right conditions can be found, and they can do so if reintroduced back into a mouse embryo. I know how important they have been for increasing our knowledge about early embryonic development and how particular tissues and cell types form as the embryo develops.
They have allowed us to explore gene function: what does a gene actually do, how critical is it, what happens when the gene is mutated, and so on. They have led to the creation of many models of human genetic disease - mice that can be worked on to search for cures, either short-cutting studies directly on humans or allowing experiments that would be impossible or ethically unsound.
Because human embryonic stem (HuES) cells can probably give rise to any cell type in the body, they offer enormous potential for therapies based on transplanting cells into a patient. This is the same idea as bone marrow transplants, which have also been around for a long time, but with the potential to cure a much broader range of problems, including many degenerative diseases such as diabetes, Parkinson's and multiple sclerosis, or to repair damage due to accidental trauma. HuES cells can be used to better understand how cells make decisions about whether to divide or turn into a specialised cell type - knowledge that could then be fed back into ways of manipulating cells directly within the patient. Stem cells are also found in adult tissue, and there is much excitement about their potential use, but since we do not know nearly enough to even make educated guesses as to whether they, or embryonic stem cells, will provide the best approach for therapies of the future, it seems silly not to pursue both sources with equal vigour.
HuES cells provide an alternative to experiments directly on humans. This must be a good thing. They can be used to study aspects of genetic disease in the culture dish. They can be used to screen for toxicity or effectiveness of pharmaceuticals. They can provide a source of human cells for studying how gene activity is controlled, and ways of controlling this with drugs, or to investigate how pathogens, such as viruses and bacteria, interact with specific cell types. We should be able to use viruses as a vehicle for reintroducing healthy genes to a damaged body - and work on HuES will help us understand how best to do this. These are all potentially very important applications.
So why combine this with cloning? The South Korean scientists managed to produce just one line of cells from their 30 embryos, but it was genetically identical to the woman who had donated the source material. If she developed a problem like diabetes, or suffered an accident that damaged her spinal cord, then specialised cells made from this HuES cell line would not be recognised as foreign by her immune system. "Therapeutic cloning" is essentially taking a biopsy from a patient and turning it into useful cells that can then be used for therapy without fear of graft rejection, which is the most common reason why transplants fail.
Of course, this type of treatment is a long way off widespread use, and it is not going to be cheap. We also need to know how reliable the method will be. Moreover, if it is to be used clinically, it will have to be as personalised medicine: we are not talking about pills from the pharmacist. But this could be a once-only treatment that will improve the quality of life for an individual and extend life in a productive way.
The current cost of treating someone with diabetes and the complications that can arise from this are huge, as are those for cardiovascular problems, or any degenerative disease that requires long-term care. Using cloned cells may make it all unnecessary. And if we can put somebody's life back together after a traumatic accident using this technology, then how can we not justify some expense?
However, I think the first applications of this exciting research will be for studying disease or the interactions of genes and drugs. "Therapeutic cloning" can allow scientists to establish HuES cell lines from individuals with genetic diseases, giving us a chance to understand better how that disease develops. For example, we could study what is wrong with motor neurons in patients with motor neurone disease, which cannot be done in the patients themselves. It may help us find the genetic cause of rare diseases where there are simply too few patients to work with. And it can allow drug companies to better test potential pharmaceuticals for their effects on different people - why some respond well and others adversely or not at all - and to do this before marketing the drug. All of this explains my excitement, which I am pleased to share.
Dr Robin Lovell-Badge is head of the division of developmental genetics at the MRC National Institute for Medical Research
The case for caution
Cut the hype, says Britain's favourite medical scientist, Robert Winston. Enthusiasts for cloning are asking for trouble if they make exaggerated claims on behalf of a technology that is undeveloped and fraught with dangers
It is difficult to understand the massive media interest in cloning. Mere mention of this seven-letter word seems to send many of my journalist friends into a complete spasm. It can't be because of alarm at the prospect of making identical people - there are at least 25,000 human clones in Britain already. These are, of course, identical twins - and these naturally produced clones are closer to their twin sibling than any that might be made artificially. This is because identical twins are conceived at the same time and in the same environment, are nurtured in the same womb, and born into an identical milieu. As likely as not, they will eat the same meals and share the same bedroom, at least during the most formative part of their life: childhood. Apart from the fact that artificially made clones would not be genetically identical to their progenitor, their nurture would be wholly different - and nurture is vitally important in how we turn out.
Perhaps the latest report of human cloning is of interest to newspapers because it emanates from Korea. There is a perception that experiments happening in that part of the world are faintly mysterious and controversial, and are less likely to be subject to ethical scrutiny. But this is not true of the medical science in South Korea, where this work was done. I have just returned from a conference on stem cells and cloning in Colorado, in the US. Some 17 papers read there were from South Korea and all demonstrated excellent work carried out to scrupulous ethical standards. Indeed, the latest report on cloning is legitimate research and would be perfectly legal in Britain. But this work was not done in the UK. Sadly, we have such a diminishing science base and spend so much time worrying about regulation that the temptation is for British scientists to avoid this area. Work that might have been completed here has again been done by skilful colleagues elsewhere.
The Government's regulatory body, the Human Fertilisation and Embryology Authority (HFEA), is not blameless. Applying for a licence is a bureaucratic process, even after gaining ethical approval from institutional ethics committees. And these committees are strict. Moreover, the HFEA, with the Medical Research Council, insists that a condition of any licence for generating human embryonic stem cells is that a proportion of the cells (derived with or without a cloning procedure) must be donated to a "stem cell bank".
This means that patients donating their embryos often feel their genetic privacy might be invaded in future. This has contributed to the grave shortage of embryos for legitimate research. The HFEA should never forget that women who donate embryos, created as a by-product of their IVF treatment, are genuinely altruistic. Women often fear that, in giving up a randomly selected embryo for research, they may relinquish the very embryo that might give their best chance of pregnancy.
The announcement of the Korean research was greeted with much enthusiasm. The press, doubtless encouraged by the scientists concerned, announced that this cloning experiment holds huge hope for the treatment of an extraordinary mix of serious disorders, such as Alzheimer's and heart failure. Some exaggerated claims are being made. Of course, we now know that human embryonic cells are likely to have the potential to develop into a complete range of different tissues. But while such so-called stem cells may eventually help palliate some brain disease, it seems unlikely that complex and incompletely understood degenerative conditions such as Alzheimer's will be cured with them.
Moreover, stem cell technology faces huge problems. Scientific papers read in Colorado emphasised how difficult it seems to be to guarantee pure, healthy tissue from stem cells, whatever their source. Many tissues derived from these cells do not function normally; others seem to have the potential for developing cancers. And cloning, the particular technology to produce stem cells used by these Korean scientists in an attempt to avoid problems of transplant rejection, has additional hazards.
It is doubtful whether any scientific group anywhere in the world has definitely produced an entirely normal cloned animal. Whether sheep, mice or other species, most clones seem to have genes that don't work properly. A cloned sheep may occasionally look normal, but many have had obvious abnormalities. Many of their genes, such as those concerned with vital cellular functions such as growth and development, don't function correctly.
And what is true of the genes of intact animals is likely to be true of genes in their organs. So cloned animals such as pigs are unlikely to be a good source of healthy kidneys or hearts to be used as donor organs for human treatments. Cloned human embryos could be expected to present similar problems. Just as any child born from cloning is at risk of being abnormal, so cloned embryos may well produce abnormal cells or tissues that would be too dangerous to use for transplants. It would be unthinkable to inject cloned embryonic nerve cells into the brain of somebody suffering from Parkinson's disease, only to find that they develop cancer, or that their brain cells stop working.
Perhaps the most exciting opportunity held out by stem cell research is unexpected. Understanding stem cells offers possibilities for new cancer treatments. Many cancers, such as the common ones of the breast and bowel, may be caused by changes in stem cells we all carry in different parts of our body. While the embryo is the richest source of stem cells that can develop into any cell type, many adult organs have cells capable of maturing into a considerable range of tissues. A rich source of stem cells is our skin. Human skin stem cells carried at the base of the epidermis can form the scaly protective cells we all know as "skin". But equally, skin stem cells form follicles that grow hair, and glandular cells producing oil or sweat. The breast and bowel both contain stem cells, and there is increasing evidence that most cancers of these organs may develop from their stem cells. So by understanding how to regulate the growth of these stem cells we are likely to discover effective methods for many cancer treatments in the future.
I remain worried about the bizarre hype surrounding cloning. The Korean research is useful because it will add to our understanding of stem cells. But it is a long way from contributing to a successful medical treatment for anything. People are mistrustful of scientists and are reluctant to accept scientific advice. We have seen mistrust demonstrated in the reluctance to accept the safety of the measles vaccine. The outcome is that there may be a serious epidemic and children may die unnecessarily. And if we scientists are foolish enough to exaggerate what we might be able achieve with other projects, public mistrust will increase. We can be sure that the backlash will be huge when our exaggerations concern controversial areas like cloning.
Robert Winston is professor of fertility studies at Imperial College London, and director of NHS research and development for Hammersmith Hospital
Timeline
1984 Danish scientist Steen Willadsen, working for the British Agricultural Research Council, clones a lamb from sheep embryo cells, using a technique known as nuclear transfer, the placing of a cell nucleus into a hollowed-out unfertilised egg.
1995 Ian Wilmut and Keith Campbell at the Roslin Institute near Edinburgh clone a sheep (named after country singer Dolly Parton) using cells taken from the mammary of a six-year-old ewe. Six years later Dolly is put down, suffering from progressive lung disease, a condition only usually found in much older animals.
1998 Advanced Cell Technology says it has cloned primitive human embryonic stem cells by fusing a human somatic cell with a cow's egg, opening the possibility of supplies of stem cells for transplant medicine.
2002 His Holiness Rae, leader of the Raelian Movement, which believes humans are cloned aliens, claims to be behind the birth of Eve, the world's first cloned human baby. No proof has since been forthcoming.
2003 Millionaire John Sperling funds the first cloning of a pet, a calico kitten called Cc (Copy Cat). Other animals, including three pigs who died of heart attacks, have since been cloned.
2004 Woo Suk Hwang and his team at the Seoul National University announce they have cloned the first human embryo, using a similar technique to the one that produced Dolly the sheep.
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