Cloning
by Dr Amin Abboud
All Life Matters, September 2001

     On 24 February 1997 the pin-up girl of the world’s newspapers was a sheep. It was an historic moment. Scientists at the Roslin Institute in Scotland had cloned a sheep named Dolly from a ewe’s udder. Dolly had no genetic father and she was genetically identical to her mother. Along with a profusion of jokes and cartoons, this major scientific development sparked a fierce debate about the possibility of cloning humans. Within days of the news, US President Bill Clinton announced a ban on human cloning and French President Jacques Chirac asked the Group of Seven nations to do the same. Why all the fuss?
     
What is cloning?
     The word clone is used in many different contexts in biological research but in its simplest and strictest sense, a clone is a precise genetic copy of a molecule, cell, plant, animal or human being.
      In molecular cloning pieces of DNA containing genes are duplicated in a host bacterium. This process is the mainstay of recombinant DNA technology and has led to the production of such important medicines as insulin for treating diabetes, tissue plasminogen activator (tPA) for dissolving clots after a heart attack, and erythropoietin (EPO) for treating anaemia associated with dialysis for kidney disease.
      In cellular cloning, copies are made of a cell which give rise to cell lines, identical cells which are grown in a laboratory culture. The genetic make-up of the resulting cell line is identical to that of the original cell. This, too, is a highly reliable procedure which is used to test and sometimes to produce new medicines such as treatment for diabetes and therapies for haemophilia.
      Since molecular and cellular cloning do not involve germ cells (ova or sperm), the cloned cells are not capable of developing into a baby.
      Lower down the chain of the plant and animal kingdom, cloning is still part of the natural process. Many people clone plants in their homes when they cut rose branches and replant them. Genetically identical copies of whole plants are commonplace in the plant breeding world, although they are termed "varieties" rather than clones. Valuable horticultural or agricultural strains are maintained solely by vegetative propagation from an original plant. The ease of cloning plants is proportionate to their relative simplicity in the life chain.
      Animals are another story. Simpler invertebrate species, such as certain kinds of worms, are capable of regenerating a whole organism from a small piece of tissue, although they do have their own mode of reproduction. A starfish can grow from the limb of a previous starfish. Vertebrates have lost this ability, even though regeneration of limbs, organs, or tissues can occur in some animals.
      There are two processes of animal cloning in a laboratory: blastomere separation and nuclear somatic transfer.
      Everyone is familiar with blastomere separation, because this is the process which results in identical twins. However, twinning is a chance occurrence in humans and other mammals. A single embryo separates into genetically identical halves at an early stage of development. The resulting offspring derive from a single zygote, which itself is the result of the fertilisation of one egg by one sperm.
      IVF reproduces this process in a laboratory. The developing embryo is split very soon after fertilisation when it is composed of two to eight cells. Each cell, called a blastomere, is totipotent, that is, it can grow into an individual organism. Totipotency allows scientists to split animal embryos into several cells which become genetically identical organisms. This capability has tremendous relevance to breeding cattle and other livestock.
      The process that resulted in Dolly, nuclear somatic transfer, is different. The nucleus of a cell from one individual is placed in the egg of another individual from which the nucleus has been removed. This nucleus can come from an embryo, foetus or adult (as in Dolly). In Dolly’s case the nucleus came from the frozen tissue of a ewe which had died years before.
      Although the birth of Dolly was lauded as an amazing success, nuclear somatic transfer is far from perfect. Of the 244 nuclei which had been prepared in Dolly’s case, only 34 developed enough to be transferred into ewes. Of those 34, 15 were not developing properly in the lab and were discarded. Of the remaining 19, five genetically identical lambs were born. Two of these died within 10 days.
      It is still not clear whether Dolly is a normal, healthy sheep. She may have subtle problems that will lead to serious diseases. Later experiments have resulted in sickly animals and many have died soon after birth. A number of scientists, including Dr Ian Wilmut, have warned that using this technique on humans might produce a diseased or malformed child.
     
Science and scientists
     The media have cast scientists amongst the heroes of our age – and they deserve to be. Science is basically the struggle of our human intelligence to understand better the physical world. In view of the immense services they have rendered to mankind, we should respect scientists and encourage their work. But it must always be remembered that the true marvel is not the scientific mind but nature.
      Consequently, the glamorous quest for scientific knowledge is not an end in itself. It must be governed by respect for the ecology (the laws of nature) and the laws governing human behaviour (ethics). Science can never be neutral; it is good or bad depending on whether or not it operates within these boundaries. It would be wrong to destroy a rainforest to test a nuclear bomb and it would be wrong for someone to experiment with man-animal hybrids like H.G. Wells’s character Dr Moreau.
      Admittedly, what scientists at the Roslin Institute did is impressive, but even more impressive is the cell’s incredible ability to develop into something unique and complex. Scientists merely manipulate inbuilt programs which have an awesome capacity to grow, multiply and differentiate into a new creature.
      The process that resulted in Dolly required intense work. But it was a bit like giving a broken machine a kick to get it going again. An egg cell (phased in its cell cycle and complemented with some added genetic material) was given an electrical kick-start. But it was not the scientists who conferred reproductive capacity upon the cell; it was there already, a gift of nature.
     
Dolly’s contribution
     Dolly is a milestone in reproductive technology. Similar experiments had been conducted over the last 40 years, but Wilmut and his team were the first to use adult cells to produce a clone.
      The difficulty scientists faced was this: the nucleus of somatic cells is diploid — that is, it contains two sets of genes, one from the mother and one from the father. Germ cells, however, contain a haploid nucleus, with only the maternal or paternal genes. In nuclear somatic transfer, the nucleus is removed from a haploid egg and replaced with the diploid nucleus sucked out of a somatic cell. Equipped with the complete genetic tool kit, the egg is now programmed to develop into a mature organism, even though it has a single genetic "parent".
      The first experiments of this type were successful only when the donor nucleus was taken from an early embryo. The problem was that the nuclei from embryos which had developed beyond a certain number of cells seemed to lose their totipotency. This limited the number of clones which could be produced to the handful of cells which could be split off a blastomere.
      Before Dolly, many biologists believed that the somatic cells of an adult mammal could not be made totipotent. They had already differentiated and specialised into specific tissue such as muscle, bone or neurons, and could not revert to the totipotency of blastomere cells.
      What Wilmut and his colleagues did was to successfully use donor nuclei from fully developed adult cells, thus ensuring a virtually unlimited number of clones. His work was stunning evidence that cell differentiation and specialisation are reversible. Mammalian genes can be reprogrammed. Large scale animal cloning is possible.
     
Ethical concerns
     In simple terms, ethics is the study of the rightness or wrongness of actions. It is a science and like other sciences it is guided by fundamental principles in nature which we can discover and reflect upon rationally. But our instinctive reactions also play a role in ethical reasoning. By reflecting upon why we shudder at murder, theft or rape we begin to discern those moral principles which are inherent in our make-up and which form the foundation of the science of ethics. For this reason, it is folly to dismiss the misgivings of many experienced and learned people around the world about cloning. The "yuk factor" is not ethical reasoning, but it is evidence that something is seriously amiss.
      Within certain limits the cloning of plants and animals does not pose serious ethical problems for anyone who believes that the animal and plant kingdoms exist to serve the human race. This is just common sense. To argue otherwise would make eating an egg for breakfast an ethically questionable practice.
      However human cloning raises a host of ethical difficulties for anyone who believes that human beings are more than complicated plants or animals. These have been recognised by a long list of countries and institutions, beginning with the United Nations and the European Commission. The National Bioethics Advisory Commission in the United States has urged a Federal ban on human cloning and US President George Bush recently threw the weight of his authority against cloning. Even Ian Wilmut has said "that no good reason exist[s] to clone people". The creation, manipulation and destruction of human life in a laboratory mean that a scientist is interfering with nature itself. If the community regards so simple an issue as genetically modified crops with suspicion, it should be a thousand times more cautious about cloning.
      Many observers, both secular and religious, have offered cogent objections to cloning. Since most cloning techniques create embryonic human beings in order to destroy them, it can be rejected on this basis alone. However, there are many other issues, ranging from the creation of parent-less children to the possibility of creating humans whose destiny is merely to serve as tissue banks. A society which allows cloning, almost everyone feels, is a society which has lost its moral bearings and which has an impoverished notion of personhood.
      Without expanding upon these arguments, ask yourself: would I choose to be born as a clone? What kind of life would be mine? Even if you were healthy (and this is far from certain), you would almost certainly be emotionally unbalanced as a result of your unique origin.
      Nonetheless, rogue scientists are experimenting with human cloning. They plead that they want to create children for childless couples, but scientific thrill-seeking is more likely to be their ultimate motivation. Thankfully, nearly every government in the world has banned their work. To some degree, at least, politicians recognise that scientific inquiry cannot be exempted from ethical concerns. Reproductive science, like nuclear energy technology or bacteriology, is a human activity and has to be judged by ethical standards. Nuclear energy may be used to generate power, but not bombs. Bacteriology may be used to cure diseases, but not to create them.
     
Therapeutic cloning
     However, most scientists and politicians do not baulk at so-called therapeutic cloning. This is a terrible mistake which must be resisted.
      In reproductive cloning the clone is allowed to progress to birth. In therapeutic cloning the new life is terminated at an early stage and its embryonic stem cells are "harvested" to create medicines or to serve as research material. Why are scientists so keen on this inhumane procedure?
      Embryonic cells are totipotent and can differentiate into all types of cells (such as bone cells, blood cells or reproductive cells). Theoretically they can be used to treat diseases, repair organ damage and heal severed spinal cords. They can also be used in other scientific research to understand the development of cells and errors in development. This makes them very interesting (and potentially profitable) for scientists and biotechnology companies.
      Interesting, indeed, but is it ethical? Not at all. Therapeutic cloning is thoroughly unethical and ought to be banned for the exactly same reasons as reproductive cloning. People are produced in order to be dismembered to obtain their cells. The main difference between reproductive cloning and therapeutic cloning is that the clones produced in therapeutic cloning are too small to protest.
      The distinction is the same kind of Orwellian doublespeak that has given rise to phrases like "collateral damage" instead of "killing innocent civilian bystanders" or "corporate downsizing" instead of "sacking long-serving employees". The terms "therapeutic cloning" (which sounds good) and "human cloning" (which sounds revolting) are bandied about so freely that people think them as different as killing time and killing Thais. But, in practice, there is no genuine distinction. Both involve liquidating scores of embryonic human beings.
     
Personal business
     A person who has been cloned with nuclear somatic transfer is as fully a person as a person who is produced from natural fertilisation. He or she has begun the life cycle which we all have passed through and which continues up to the present moment. Human dignity needs to be respected always and at all stages of this cycle, from conception to death. We must resist all pressure to put brackets around certain stages in the life cycle which are deemed unworthy of human dignity and human rights.
      The personhood and inherent dignity of the embryo pose questions which Australian society has never adequately addressed. The answer to your child’s question, "When did I begin?", is not "when you were born" or "when you reached 20 weeks of gestation". Arbitrary limits such as these are pragmatic compromises.
      From the very beginning of human life, as Professor Dianne Irving has written in "When Do Humans Beings Begin? (International Journal of Sociology and Social Policy, 1999): "This new human being, the single-cell human zygote, is biologically an individual, a living organism, an individual member of the human species."
      Ultimately the ethical argument against cloning comes down to who we are, when we began and why we should be respected. We are persons from the moment that our life’s journey begins – and those who cannot articulate their human status are no less human for all that.
      As a society we claim to be committed to protecting the vulnerable and the defenceless. We protect children from abuse even if they are too young to articulate a complaint. Embryos and the unborn are also silent when they are abused. The fact that the abuse takes place at the hands of a white-coated lab technician instead of the fist of an angry father makes very little difference.
      The dignity of embryos, whether they come to exist naturally or in a laboratory, must to be upheld firmly and compassionately. When we uphold that dignity, we are defending what is human and we are truly humane.
     
Adult stem cell research
     In any case, therapeutic cloning of embryos is probably completely unnecessary. There is a large and growing body of evidence which indicates that all the benefits of harvesting embryonic human beings can be gained from stem cells obtained from the everyday blood, brain or muscle cells of adults – without killing anyone.
      Stem cells are unspecialised cells which can transform themselves, in varying degrees, into many other types of cells. Thus a single stem cell could become a skin cell, a hair cell, a liver cell and so on. All of us were once stem cells, and our bodies still hold many forms of these cells.
      Adult stem cells can be acquired without harming the person they are taken from. They may even be superior to embryonic cells because, if they are taken from the person to be treated, they form an identical match and there will be no rejection problems.
      Adult stem cells can also be taken from cord blood at birth. Every day thousands of placenta, which are a good source of these cells, are discarded. In the United States there are companies that store the cord blood of babies in case the child develops some illness. With so many alternative sources of stem cells, why do we need to destroy embryos?
      Research on adult stem cells is well advanced. Among the many exciting possibilities are these, all documented in leading international journals:
      • Surgeons in Taiwan have restored vision to patients with severe eye damage by using stem cells from the patients’ own eyes. Their vision improved from 20/112 to 20/45, according to results published in the New England Journal of Medicine.
      • British scientists found that adult stem cells in bone marrow can turn into liver tissue, a first step toward developing new treatments for liver damage. Their work was reported in the journal Nature.
      • Two recent studies have shown that adult stem cells in bone marrow transplanted into the brain of mice can develop into neurons. Previous research had shown this transformation was possible in cultured cells, but these studies, one of which was published in the journal Science, show it can happen in living animals.
      • Scientists found that adult stem cells in bone marrow injected into a damaged mouse heart could become functional heart muscle cells, and that these new cells partially restored the heart’s pumping ability. One of the scientists predicted that after successful follow-up studies, human clinical trials could start in three years. The results were published in Nature.
      These findings have all been reported within the past year or so. And they are only a few examples of breathtaking medical breakthroughs. Many others can be expected: stroke victims’ brains repaired, new cartilage for damaged knees...
     
Embryo hype
     The urgent need for embryonic stem cells to heal irreversible disease and irreparable injuries is a media beat-up. The only experiments with embryonic stem cells have been on people with Parkinson’s disease. The patients became worse and the trial was stopped.
      The argument for the superiority of embryo stem cells over adult stem cells is based on three premises: they are easier to harvest; there are more stem cells in embryos than in adults; and they can be more easily changed into every organ and tissue in the body.
      The first two claims are misleading. Harvesting is a non-problem. Scientists have been extracting some types of human adult stem cells for almost a decade (for example, with bone marrow transplants), while human embryo stem cells were not successfully isolated until 1998. Several biotech companies have developed proprietary methods to make adult stem cell isolation and extraction even easier.
      Associate Prof. Mark Kirkland and his team at the Douglas Hocking Research Centre in Melbourne have worked on adult cells for many years with excellent results.
      While it is true that embryos have a higher ratio of stem to non-stem cells, that does not mean much. Scientists have discovered stem cells in adults in virtually every major organ, including the brain. In Italy scientists are taking them from the olfactory bulb in the brain to treat spinal cord damage. Last year researchers identified conditions that would allow a billion-fold multiplication of adult stem cells in just a few weeks.
      The most attractive feature of embryo stem cells is they are more plastic; – that is, easier to change into other types of cells. While this claim has some basis, technology is improving so rapidly that it is hard to maintain. The US National Institute of Health recently noted that "the field of stem-cell biology is advancing at an incredible pace with new discoveries being reported in the scientific literature on a weekly basis". Any unique benefits of embryo stem cells trumpeted today may be trumped tomorrow by new research on adult stem cells.
      Indeed, scientists have already proved adept at turning adult stem cells into a variety of seemingly unrelated cells. Jonas Frisen, a scientist working at NeuroNova AB, a Stockholm-based biotech firm, published some exciting work in Science (June 2000). "We have demonstrated that the potency of these [adult stem] cells was far greater than expected and what seemed to be a fairly restricted cell type can give rise to many different types of cells. These recent findings may turn some previous concepts upside down,"; Dr. Frisen said in a press release. Already, human adult stem cells have been transformed into cartilage, muscle, bone, cardiac tissues, neural cells, liver tissues and blood vessels. Research with animal adult stem cells indicates the ability to transform them into kidney, heart, lung, intestine and nervous system tissues.
      While adult stem cells may never be as completelyplastic; as embryo stem cells, they will almost certainly be plastic enough for all practical applications. "These adult tissues don’t appear to be as restricted in their fate as we thought they were," Dennis Steindler, a professor of neuroscience and neurosurgery at the University of Tennessee-Memphis, told Blood Weekly magazine in May. "In some ways they may not have the same potential as embryonic cells, but once we figure out their molecular genetics, we should be able to coax them into becoming almost anything we want them to be."
      Diane Krause of the Yale School of Medicine, a supporter of embryonic stem-cell research, said she was "surprised" by her own research on adult stem cells which appeared in the New England Journal of Medicine. It went against our dogma," Dr. Krause said. Stem cells found in the liver were believed to be limited to making liver tissue, stem cells in the skin more skin and so on. "But at least for stem cells found in bone marrow, that is not true." Scientists are "searching for a new paradigm," she added.
      Investors also feel that research with embryonic stem cells is unlikely to succeed. In the words of one medical researcher, "If you look at some of the medical and scientific indications, adult stem cells are much closer to therapeutic applications; embryonic cells still have a variety of obstacles that need to be overcome." Of the 15 or so major companies in the United States doing stem cell research, 13 are working with adult stem cells.
      Nevertheless, some scientists are lobbying hard to use stem cells taken from embryonic human beings. They say that Australian research will fall behind or that talented researchers will migrate overseas to countries with a more relaxed attitude towards embryo experimentation. Pressure from these gung-ho scientific cowboys should be resisted. We must shape science to our ethical standards, not our ethical standards to our science. That was the lesson taught by Dr Frankenstein, and after nearly 200 years, it is high time that we learned it.
     
Corporate ethics
     Powerful commercial interests have now become involved in the biotechnology industry. It is projected that if attempts to produce spare human body parts and other medical treatments via stem cell research are successful, the profits that will accrue to businesses involved in the biotechnology industry will run into tens of billions of dollars annually. Stem cell technology promises to displace the dot.com boom on Wall Street.
           University of Chicago ethicist Dr Leon Kass, who was recently appointed by US President George Bush to oversee stem cell research, has said that those who are opposed to new technologies such as therapeutic cloning are fighting "against an enormous amount of money, against the general liberal prejudice that it is wrong to stop people doing something and, in many cases, against everybody’s quite rational fear of death (Economist, April 14).
           It was the glitter of money, jobs and prestige which moved the UK to become the first country in the world to allow therapeutic cloning. In a speech to the European Bioscience Conference, UK Prime Minister Tony Blair said that Britain was "well placed" to keep its "lead in Europe". He attributed Britain’s competitive advantage to its "sophisticated capital markets and venture capital industry, as well as to the large number of skilled scientists" and managers in its pharmaceuticals sector. After pointing out that "three-quarters of the biotechnology drugs in late stage clinical trials in Europe are produced by British companies," Mr Blair went on to warn that the "German biotechnology sector is growing fast". However, Mr Blair expressed confidence that Britain could meet this challenge from Germany: "I want to make it clear: we don’t intend to let our leadership fall behind and are prepared to back that commitment with investment."
     Biotechnology companies have clever marketing strategies. Realising that they must win the ethical debate in order to win the political debate, they have shopped around for pliable bioethicists. Nowadays a conference on cloning is not complete without an address from an ethicist who praises its benefits. In Australia the situation is much the same. Biotechnology companies sponsor seminars on therapeutic cloning and fly in overseas experts to convince the politicians and the public.
     Bioethicists are serving on company boards or working as paid consultants. Whether these tame watchdogs can give objective advice about the work of their employers is an open question. "In recent years, the biomedical industry has given at least US$2 million to bioethics centres and offered lucrative contracts to academic researchers to study ethical issues in the field," according to the magazine U.S. News & World Report. In a few cases, firms have allegedly even offered bioethicists stock options. Consulting fees range from US$200 per day... to contracts worth tens of thousands of dollars. Companies have long tempted scientists and physicians with sweet rewards. But for bioethicists, it’s something new, and the potential risks cut to the profession’s quick."
     "This is a semi-scandalous situation for my field," Dr Daniel Callahan, co-founder of the Hastings Center, a medical ethics institute, acknowledged to the London Times. These companies are smart enough to know that there are a variety of views on these subjects, and with a little bit of asking or shopping around you can find a group that will be congenial to what you are doing."

How should we respond?
     Our response to cloning needs to be firm and clear. Human cloning undermines our society’s moral foundation. Science must be governed by ethics, not ethics by science. And ethics must be governed by human dignity, not profit. The Federal President of Germany, Johannes Rau, recently stated that "where human dignity is at stake, economic arguments have no value". This is wise advice to all legislators in Australia.
           We need to support medical science in areas which promise cures without harmful side effects. Our governments need to back adult stem cell research to find treatment options for people with Alzheimer’s and other conditions. The possibilities are enormous and for the sake of those who are suffering we need to do more.
           At the same time we cannot allow human beings to become quarries for medical researchers. As Dr Joerg-Deitrich Hoppe, chairman of the Federal Chamber of German Doctors, stated last year, the legalisation of therapeutic cloning would be "the first time in history that humans themselves will be used to supply raw materials."
           All Australians need to take and active role in the public debate on this vital matter. We cannot allow a few glib scientists and entrepreneurs to dominate the discussion. We should write to politicians and the media. Human cloning is the goal of a handful of scientists, businessmen and naive journalists. A public which understands the facts and which has not been bamboozled by a smoke-screen of half-truths will reject cloning out of hand.
     

Acknowledgements
Pence, Gregory E., Who’s Afraid of Human Cloning? Rowman and Littlefield, 1998.

The Science and Application of Cloning, National Bioethics Advisory Commission, June 1997.

Miniter, Richard, Hard Cell — Science Does Better With Adult Stem Cells, Wall Street Journal, 23 July 2001.

Keanne, Eamonn, The Brave New World Of Therapeutic Cloning,Foundation for Human Development, Sydney 2001.

Corporate Bioethicists: Watchdogs... or Show Dogs? www.zenit.org 4 August 2001