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Taken from The Week

June 3, 2001

ASKING FOR DOUBLE

A maverick cult leader and a team of top-notch scientists compete to clone the world's first human. What will be the consequences of their success?

By Stanley Thomas

With his thinning hair neatly wrapped in a topknot, the milky tunic and trousers lengthening the luminosity of his beatific beam, Rael digs playing the guru of cool. He knows he is hot when he does that. When he picks up his guitar and strums I smell honey and cinnamon...vanilla and love. Or when he takes the wheels of his Porsche GT and burns the tracks on the racing circuit. Now, the guru of cool is getting hotter as he races ahead with another of his passions: to clone the world's first human.

DREAMER AND DOER Rael poses before a model of a UFO. The Raelians believe life originated in alien labs

The guru wants to play God. That was the chorus from critics when the 54-year-old sportswriter-turned-leader of the Raelians sect unveiled his plans for a genetic leap forward. They reacted with disdain when he set up Clonaid, the world's first company to clone a human, soon after the birth of Dolly, the world's first cloned sheep, in 1996. Things have changed since then and the disdain has been replaced by part-disbelief, part-dread.

More so after an American couple approached Clonaid last year with the preserved skin cells of their 10-month-old son who didn't survive heart surgery. Rael's scientists accepted the challenge, and the $500,000 that the couple offered for a cloned child. Boasting the best equipment, geneticists and fertility experts-and now loaded with cash-Rael is moving towards his goal. "We hope to have a pregnancy real soon," Rael told this magazine in an exclusive interview. The unsaid is that the first cloned baby could be born this December, if not earlier.

Unless Dr Panayiotis Zavos delivers first. The Cyprus-born, Kentucky-based doctor has teamed up with Italian fertility specialist Dr Severino Antinori in an international project to clone the first human. Zavos and Antinori, who grabbed headlines six years ago when he helped a 62-year-old Italian give birth, have the same objective as Rael: devising a new technique to help infertile couples have children.

The speed with which the cloners are making progress would have surprised Hans Spemann. Ninety-nine years ago, the German embryologist gingerly extended a sliver of hair from the head of his infant son to splice two cells of a salamander embryo. To his astonishment, the separated cells grew into two robust salamanders.

Spemann's was one of the earliest attempts to prove that every living cell of an animal is loaded with the genetic map for the entire creature. It took another nine decades for Dolly to arrive, then Cumulina the cloned mouse, and Starbuck II the cloned prize bull. A few piglets and some calves followed. Suddenly, it appeared that Aldous Huxley's Brave New World was unfolding before our eyes. The only missing characters from the cloning cast were humans.

Now Rael, Zavos and Co. promise to people the New Age Noah's Ark. "Our project is making progress every day," Zavos told The Week. His international consortium will apply "the human therapeutic cloning technology only for reproductive purposes to help those who have exhausted every possible avenue in having their own biological child."

Five years ago such talk would have tickled the critics. After Dolly, the chuckles have been quieted by the refrain that someone is bound to clone a human sooner than later. Scientists suspect that some underground rebel researcher may have already succeeded. If not, the competing cloners will do it-maybe this year, maybe the next. "It is very much possible," says Dr Indira Hinduja, who helped in the birth of India's first test-tube baby and who is among those who support human cloning.

With every breakthrough since Dolly, researchers have polished the craft of being copycats. So much so that the technology isn't any great shakes today. Everyone knows that cloning involves the creation of a genetic twin from a single cell-such as a skin cell-from an adult. The way Scottish scientist Dr Ian Wilmut went about cloning Dolly was pretty straightforward: the DNA-containing nucleus from the cell of an adult sheep was transferred to a donor egg whose nucleus had been removed. The two were fused with an electrical jolt, activating the growth of the embryo which was then transferred to a surrogate mother's womb to develop. Scientists believe that the process to clone a human will be more or less the same.

Sometimes cloning occurs without any electrical jolt-as in the case of twins-with only the parents receiving a jolt at the double whammy! "Initially there is one egg, but suddenly it bifurcates and they grow into two babies. It does happen naturally," says Hinduja. "Thus cloning a human is quite possible."

Not just possible, says Zavos, but it is "inevitable that human cloning will be done by someone." He argues that it will be better if the procedure is handled by a group like his which will "develop this technology in the most responsible way".

Maybe that's a dig at his competitor in Quebec, but the maverick cult leader nursing a new-born religion could just be ahead in the race. In February, Clonaid's scientific director Dr Brigitte Boisselier revealed her team had started work on human eggs and was practising the technique of enucleation or the removal of the nucleus. Next, they would practise the process of transferring the nucleus of a cell into the enucleated cell. If things went as expected, they would have begun work on the preserved cells of the dead child by early April. Add the gestation period and you know when to expect the results.

Some Raelians are hoping for a December 25 birth because that is the day Rael was conceived in 1945, to be born on September 30 the following year. "Our knowledge on human reproduction, thanks to in vitro fertilisation (IVF), is such that we are very confident on the outcome of this research," says Rael.

The only obstacle seems to be the large number of failed pregnancies during the cloning process. Dolly came after 277 attempts at fusing the donor egg in the womb of the surrogate ewe; Starbuck II was born after 68 tries. Indeed, the cloners will have to make hundreds of attempts to create an embryo and also to implant it successfully. And, most surrogate mothers with bulging bellies face the certainty of an abortion because of defects in the embryo or the placenta.

The numbers game will challenge the cloners, who know that the higher the availability of donor eggs and surrogate wombs, the greater their chances of success. On this score, the Raelians don't have a worry: 50 women followers volunteered to become surrogate mothers. The advantage of such large numbers is that even if one pregnancy is aborted, the experiment will continue through other surrogate mothers instead of having to wait for the woman's next cycle.

A POSITIVE APPROACH

Dr Indira Hinduja believes human cloning has advantages

The Realians have enough wannabe moms because cloning is at the centre of the sect's belief. A belief that set in one fine day in December 1973 when Claude Vorilhon-now known as Rael-had a strange encounter that was to change his life. The young man, then 27, had till then been passionate only about conquering the Formula One racing circuit. On December 13 that year, recalls Rael, he had an encounter with a four-foot-tall alien who emerged from a UFO on a volcano in southern France.

The alien gave Claude a message: all life on earth, including human, was created scientifically in labs by the Elohim, an advanced people from space, using their mastery of genetic engineering and DNA synthesis. Eternal life was possible, the earthling was told, through cloning. The alien flew away after telling Claude that the Elohim would come to Earth to share their knowledge.

Claude changed his name to Rael, meaning the messenger, and launched Raelianism, an "atheistic religion" which has values in tune with the 21st century-including an acceptance of divorce, contraception, abortion, assisted suicide, and marriages for male and female priests. Its biggest achievement, the sect says, is the melding of science and spirituality.

With this kind of talk, it's no surprise that the Raelians have been dismissed as a wacky group and, even after its founder set up Clonaid, labelled publicity-mongers. Rael makes no excuses about his love for publicity. After all, he had handed out condoms outside Catholic schools in 1992; held a seminar on masturbation a year later; and founded a religion powered by aliens, beautiful women, sex and technology. But Rael denies the cloning project is only to draw publicity for his sect. "We are getting people talking while we try to clone," he says. "When we succeed, we will have more people talking."

That's a good line because people are sure talking. Not about how this strange group and Dr Zavos and Co. will clone the world's first human, but about the consequences of their success, whenever that happens. With technology and money in hand, a major impediment is the overwhelming aversion to creating a genetic replica of a human in a lab. A few countries have laws in place to ban human cloning, many others are debating such measures. Last October, the Indian Council of Medical Research published comprehensive guidelines for biomedical research, prohibiting research on human cloning, designer babies and genetic engineering. But the clone rangers have their own way to beat the ban: they have kept the location of their projects secret even as they, at least Rael, benefit from the fact that only four American states have banned human cloning.

There are two types of cloningmedical and reproductive. The medical version involves the creation of a cloned human embryo from which vital cells are extracted by researchers who hope to use it to treat diseases such as cancer and Alzheimer's. Zavos and the Raelians are into the reproductive type of cloning, which involves implanting a cloned embryo in the womb and waiting for the baby's wail.

Supporters of cloning say the benefits are many. Cardiac patients could be treated by cloning their healthy heart cells and injecting them into the damaged areas of the heart. Skin could be grown for burns victims, spinal cord cells for paraplegics, bone marrow for leukaemia patients, as also rejection-proof livers and kidneys.

The immediate benefits, the pro-cloning camp says, will be to infertile couples. The process could help couples who have tried, unsuccessfully, all the available techniques to have a biologically-related child. "There are some men we cannot treat with IVF technology," says Mumbai fertility specialist Dr Aniruddha Malpani. "These include men with no testes, for example. Cloning will be a new treatment option for them."

Similarly, cloning techniques can help women who cannot conceive. "If a woman has hardly any eggs left, is growing old, or did not have eggs from childhood, her embryos can be cloned and kept, so that she can have a baby," says Dr Hinduja.

In reproductive cloning, a large number of embryos of similar genetic constitution are produced and used for treatment of infertile couples, explains Dr Satish Patki, a fertility specialist in Mumbai. "However, it can create social problems," he adds. Actually a minefield of ethical and moral issues. "If you are cloning a human, the genetic constitution will remain the same," says Dr Patki. "No two humans match with each other and that is the beauty of nature. Human cloning threatens this core variation in humans."

It is, as opponents of human cloning point out, a huge step away from the normal way of reproduction. Normally, a sperm and an egg from two people unite to create a new individual. With human cloning, one wouldn't even require a man to make babies. Imagine out-of-work dads while human cloners get busy replicating people in the cold labs! The cloners may even enjoy playing the creator.

Other changes could accompany human cloning. During fertilisation, for instance, the sperm and the egg meet bringing together two half sets of genes, thus making a full chromosome. "Cloning may bypass this process," says Dr Pervin K. Meherji, fertility specialist and deputy director of the Institute of Research in Reproduction, Mumbai. Experts point out that when the cloners take a cell from an adult, there is already a full chromosome in existence and you are adding an additional half set to it. "This might lead to some defects in a baby," cautions Dr Meherji.

Besides the possibility of painful miscarriages, all sorts of things can go wrong. Cloned sheep and cattle have been born hideously large, with deformed limbs and protruding organs. Dr Boisselier, whose 22-year-old daughter Marina is among those to volunteer for surrogate motherhood, says such fears are misplaced. Her scientists will carry out diagnostic tests to screen out defects before the embryos are implanted. Even as the clone cuddles in the womb, regular tests will be done to monitor for any malformations.

Among those who are upset with the plans of the human cloners is the original cloner; Dr Wilmut says that it will be "criminally irresponsible" to experiment on humans. The research on animals has indicated a very high failure rate: all but two per cent of the cloned embryos fail to implant or die during pregnancy or soon after birth.

There are others who see a potential to misuse human cloning technology. "The fear that you can clone evil people is theoretically possible," says Dr Hinduja. "But it may not happen that way because so many things play a part." If you clone someone like Hitler, she says, you may not get a replica in thought and behaviour because such characteristics are largely shaped by the environment in which the person grows.

To most people, the whole idea about human cloning makes them turn queasy. There are questions for which no answers are available. What will be the relationship of the cloned child to the mother? A sibling? What happens to the malformed child-will the mother accept it? Psychologists have warned that there could be unreasonable expectations from cloned children. Admittedly, it is a bizarre situation in which the cloners have left ordinary folks like us.

But then, most new ideas seem bizarre when first suggested, says Malpani. When the birth of the first test-tube baby, Louise Joy Brown, was announced in 1978, for instance, critics said that scientists would soon set up baby assembly lines. Some 20,000 test-tube babies later, the prophets of doom have meekly accepted in vitro fertilisation and other techniques of assisted reproduction. "I would say cloning needs to be explored," says Malpani. "The technology by itself is neither good nor bad. It's how we use it!"

Rael hopes to use it step by step. After Cloned Baby No 1 and many more, he hopes to move to the next stage of his plan. Which is, perfecting the technology to directly clone an adult from a single cell. That's a 42-year-old you from a 42-year-old you, sans the blemishes. The third step, says Rael, will be to transfer our memories and personalities into a computer, so that we continue to exist even after death. All that one will have to do is download our personalities into new bodies. That is the eternal life which Rael is dreaming for mankind. He loves crazy dreams. He also loves to sing. And to race.

With Dnyanesh Jathar/Mumbai and N. Bhanutej/Bangalore

Just a wasteful exercise!

By Prof. G Padmanaban

We know about the birth of Dolly. The nuclei which contains genetic material was taken from the udder cell of a sheep and put into the egg cell of another sheep. The resultant embryo was put into a foster mother, and a whole sheep was born.

WHAT ABOUT ETHICAL PROBLEMS? Prof. Padmanaban

Unlike plants, animals do not have totipotency. Any part of the plant can give rise to a whole plant-bark, leaf or any other part. Which means it has memory, and all the genes. In the case of animal cells, they lose this capacity quite early. As soon as the egg and sperm fuse (even at the two-cell stage), it loses this capacity to be totipotent. All we can do is cultivate the cells. Liver cells and intestinal cells can be cultivated, but you cannot generate the whole animal from a liver cell.

While udder cells can be cultivated to make more udder cells, the Dolly experiment was able to generate a whole animal. Animal cells, which we thought were not totipotent, can, under appropriate conditions, generate the whole animal. That is the biological revolution from the Dolly experiment.

Now people are thinking of doing this in humans. There are technical and ethical issues involved. We still do not completely understand the developmental biology of the human foetus-from the time the egg and sperm fuse. In the sheep, the cytoplasm was able to reprogramme. How long the developmental phase lasts is crucial. Whether that time factor is applicable to humans, we do not know. How long it takes for the human cells to lose totipotency has to be figured out. It may take many years to understand the processes involved.

Recently, Dolly's creator Dr Ian Wilmut wrote that all the animals generated by this process were not normal. Even if they look normal, there are some defects which are not apparent. Their susceptibility to disease cannot be known unless an illness strikes.

The other point is the success rate: in cloning it is one in 300-plus embryos. Let us not be under the impression that they used one sperm and one egg and produced an animal clone. Only one fusion has succeeded in 300-plus fusions. There is no reason to believe that the success rate in humans will be higher. Though the Italian group involved in human cloning says it has an expert embryologist working on improving the efficiency, it cannot be done.

Even if such experts attain 5 per cent success rate, is it ethically correct? How many fusions, how many embryos, how many eggs are you going to fuse? You have to super-ovulate the woman (to make her produce more eggs than one) by giving some hormone injections. The eggs have to be taken, their nuclei have to be removed. Then, a skin cell or some other cell will become the donor nuclei. (Even in the case of test-tube babies, they prime the woman to produce more eggs. After hormone injections, she can produce two or three eggs, not more than that).

Then, if there are defective babies-which may not be apparent at the time of birth-it leads to ethical problems. What is the guarantee that the baby, even if it is generated from one in 100 fusions, is perfect? The experts themselves say the clones thus produced are defective.

I don't think humans should be cloned. People believe we can generate our own copies. Someone who has lost a child believes scientists can bring back the same child through cloning. Others say a grandmother can see herself growing again!

Even without cloning, the DNAs of all human beings are identical to the extent of 99.99 per cent. Yet we are different physically, mentally and behaviourally. So it is not the DNA sequence that decides. What matters is how the expression is taking place and that is a highly complex phenomenon. It is the protein that acts, not the gene. And the way one human being produces the various proteins is different from another's.

If you clone yourself and get identical DNA, the person could look like you but behave totally differently. It is the environment that plays a very important role. The expression of the gene is controlled by the environment.

These technical and ethical issues are not trivial. Cloning a human will be a wasteful exercise. The saving grace is that these processes can be used to clone organs. We can clone the liver, the heart and so on. This becomes very useful in transplantation. More than 40 per cent of the population suffers because of lack of donors. Imagine a situation where your own cloned organ is available in the freezer!

It is not possible to bring to life a dead child, let's accept that. Instead, why not give a good life to an orphan?

(The writer is former director of the Indian Institute of Science, Bangalore.) As told to N. Bhanutej

Interview/Dr Panos Zavos, human cloning project leader

'A human can be cloned safely'

Do you believe that a human can be cloned? Or is it all a dream?

The project is on its way to being executed and therefore it is not just a dream. A human can be cloned and can be cloned safely. Please do not forget that the effort of our consortium is to apply the human therapeutic cloning technology for reproductive purposes only and to those who have exhausted every possible avenue in reproducing their own biological child.

What is the progress of your project?

It is well under way and we're making progress every day.

Experts have criticised your project, not only because of the ethical issues but because of the possibility that a cloned human will have serious malformations.

The so-called experts in the field of animal cloning have created a monstrous opinion about reproductive cloning. Since they have been unable to execute their efforts successfully, because of a variety of reasons, they believe that nobody else should attempt to apply this development in humans.

Most of the animal cloners have carried out their so-called experiments in a "hit and miss" configuration and are driven by fame and fortune. We are not driven by any of those qualities but rather by our desire to help our fellow men and women to have a better life. [Zavos will be debating Dr Ian Wilmut on this subject at Oxford Union on June 5.]

Experts say that serious malformations have occurred in all species cloned so far, and they are sure it will happen in humans too. Are their fears justified?

With further experimentation our consortium will be able to develop the proper technology to bypass and overcome any of the so-called difficulties that the animal cloners are referring to. We do not live in a perfect world and therefore there will be mishaps and risks taken like any other technology that is currently available for use in humans. The consortium will not step on dead bodies and deformed babies to develop and apply this technology. Furthermore, we will not do this unless it is safe. This is the responsible way of going about it. ST

Someone stop those nuts!

By Prof. B.J. Rao

For a long time, biologists have been trying to comprehend the molecular mystery of how a single cell-a fertilised egg-of an animal develops specifically into that animal with such mind-boggling precision. Early experiments suggested that the compartment of the cell which carries the genetic material, the nucleus, is mainly responsible for the precision, and not the cytoplasm, the cellular content outside the nucleus.

Soon it became clear that embryonic cells are endowed with the ability to differentiate into any type of adult tissue-totipotent, as they are called in biology-following appropriate cues from their surroundings. In fact, it is this precise patterning of cues in the early development of an animal that specifies the precise development of an animal. A developing animal, therefore, is a self-contained programmed unit requiring essentially nutrients from the surrounding medium.

THE CLONING PROCESS MIGHT LEAD TO DEFECTS IN THE BABY, CAUTIONS DR PERVIN MEHRJI.

This new knowledge took a giant leap with Dolly. It was a major event in animal biology, as a clone (a genetically identical animal) was developed from a chosen adult animal. This led to the technical feasibility of being able to clone any higher mammal. So far attempts on five species of higher mammals have been successful, leading to the big question: why not clone humans?

It is important to know what actually cloning an animal involves. Typically, the genetic compartment (the nucleus) is extracted out of a somatic tissue cell of a donor adult (who is to be cloned) and transplanted into an enucleated recipient egg (whose nucleus is removed), followed by its growth in a surrogate mother's womb.

The process sounds fairly simple. But it involves many areas of biology where our understanding is rather poor. For example, it is not clear how to efficiently deprogramme the genetic information of a donor nucleus from its original differentiated state and reprogramme to a totipotent state, so that it can successfully develop into a full and flawless animal following its placement in the enucleated egg. This is perhaps the biggest reason why cloning success rates are frustratingly low, as ill-defined procedures were followed to achieve this very crucial step.

The molecular facets of reprogramming associated with early embryonic cells are a very active area of biological research and new findings have suggested that the nucleus is involved in a complex control of not only genetic (specified in DNA-sequence) modifications, but also epigenetic modifications (those that are not specified in DNA-sequence, but are conveyed to the genome by other means, the nature of which is not fully clear).

The real challenge is to mimic these genetic and epigenetic events as faithfully in cloned early embryos as they would have been during the natural embryogenesis of the donor animal. Until biologists can guarantee this precision, animal cloning is going to be an exercise with little quality control.

This is only the tip of the iceberg. We do not know, as yet, how experimental manipulations involved in cloning might disturb the natural steps of development and how residual genetic programme from the donor nucleus might adversely affect the process.

Animal cloning experiments had their origins primarily in two quests:

1. To understand the basic biology associated with development and differentiation, the two most fundamental issues in biology;

2. To exploit commercially the beneficial traits of livestock through cloning the animals with such traits. Until the human cloning possibility was realised, this issue was not really beset with any ethical dilemma. The situation is now threatened by a few groups who have proclaimed their intent to perform human cloning experiments. These 'human nuts' (as Dr Jaenisch, a renowned biologist at the MIT, calls them) are essentially misleading society and jeopardising important biological research by creating a public backlash.

We are beset with three challenges on human cloning:

1. Is there a case for allowing human embryo cloning to harness the benefits of embryonic stem cells that can potentially alleviate suffering in diseases such as diabetes, Parkinson's and Alzheimer's? In a patient, replacement of disease tissue with a healthy one of an identical genetic match (and therefore immunological match) will go a long way in disease treatment. It is here that stem cells retrieved from a human embryo cloned from the patient's normal cells will be therapeutically very useful, as they provide the required tissue of perfect genetic match.

2. Is there a good case for allowing human embryo cloning to help infertile couples with cloned babies? This is a mischievous and devious proposition. Firstly, the cloning success rates are so abysmally poor that it is no match for conventional, high success rate methods such as in-vitro fertilisation. Secondly, even if a baby is born out of a cloning experiment (which is going to be prohibitively expensive in view of a very low success rate!), it is unclear whether it is going to be normal with respect to future development as deprogramming and reprogramming events of donor nucleus are unlikely to be authentic. Thirdly, cloning of a specified human being would throw up enormous ethical issues that are far more serious for society as a whole than an infertile individual's freedom of designing one's babies (through the so-called "reproductive human cloning" strategy).

Perhaps one can make a case for "therapeutic" rather than "reproductive" human cloning. Societies have to quickly wake up to this challenge, and make appropriate laws to prevent reproductive human cloning efforts. (The writer is professor of molecular biology at the Tata Institute of Fundamental Research.)

 


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