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Cloning and Stem Cells

Cloning, including reproductive and therapeutic cloning, is an emerging technology. In this essay, I focus on the implications of this powerful yet controversial technology and how it can influence our lives. As a scientist working on stem cells, I also feel I have an obligation to discuss these technologies, their potential and the ethical issues they raise.

From Clones to Dolly

Clones are genetically identical organisms. In other words, organisms with the same DNA or genome. Organisms with asexual reproduction, like many microorganisms that merely divide, usually have millions of clones because only rare mutations are a cause of genetic alterations. In mammals, including humans, clones can originate due to divisions of the egg, often called identical or monozygotic twins. Having the same genome does not imply that two organisms will be exactly the same. Even identical twins are different to some degree. During development random events occur, called developmental noise, that are unique to each organism. In addition, changes in education, nurturing, and other environmental factors can lead to noticeable differences between adult organisms with the same genome.

In 1997, Ian Wilmut and colleagues at the Roslin Institute in Scotland developed an artificial method of obtaining mammalian clones from mature animals and thus permit asexual reproduction in mammals. Dolly the sheep was the first such cloned mammal–cloning in other species, like frogs, had been done before. Briefly, clones are generated by extracting the nucleus of a mother cell, which in case of Dolly was a mammary cell, and then injecting it into an egg without a nucleus. Precise cell culture conditions and often an electric shock allow the nucleus to merge with the egg which can then be inserted into a womb and, in some cases, generate a new organism. This procedure–known as nuclear transfer–meant that Dolly featured the same nuclear genome of her “mother”. In recent years, clones of many other mammalian species have been produced using this or similar techniques: calves, mice, monkeys, pigs, cats, etc. Clones from clones have also been created.

Animal cloning has many applications. Cloning pets is already a reality and some companies offer services in this area. In agriculture, researchers have cloned a disease-resistant bull that had died and the cloning of endangered species is an emerging prospect for conservation efforts. Despite some early setbacks, Pasqualino Loi and colleagues have been able to clone a mouflon lamb, a member of an endangered species of sheep, using the same somatic cell nuclear transfer technique used to clone Dolly. Cloning animals is barely controversial, though human cloning has been much attacked, as detailed below.

The Dangers of Human Cloning

The greatest danger human cloning poses is a health risk to babies born through this procedure if it were attempted with current technology. Research in animals has shown that while cloning is possible, the majority of animals die at early stages of development or shortly after birth. Moreover, a number of cloned animals are born with defects. Despite anecdotal claims, human cloning has never been performed, yet one serious possibility is that human clones would also feature birth defects. A possible cause for defects in clones are epigenetic changes. Succinctly, in addition to the DNA, there is another layer of information in the genome called the epigenome. Genes can be turned on and off through chemical modifications of the DNA. Clones derived from adult cells do not have the epigenetic patterns found in a newly born, and so they could carry defects. For this reason, the vast majority of researchers, including myself, opposes reproductive cloning in humans.

There have been other concerns raised, though these are more far-fetched. Can a mad dictator create an army of elite troops using clones? Sure he can. It is, however, a rather clueless thing to do because it wouldn’t be economically viable. It would require a large amount of resources, not to mention years in research and waiting for the clones to grow. Certainly, it is much easier, quicker, and cheaper to recruit and train adults than to create human clones. Or follow the example of dictator Ceausescu of Romania who recruited young orphans to train them for his special forces.

“Cloning may turn out to be less prevalent and less scary than we imagined. Market forces might make reproductive cloning impractical, and scientific advancements may make it unnecessary.” — Robin Marantz Henig

Fortunately, the costs of reproductive cloning are prohibitive for most people and with current legislation aiming at preventing human cloning, it is doubtful that many human clones will be born (if any at all), at least with current technology. It is possible future technological breakthroughs make human cloning a safe and cheap option, but with improvements in reproductive medicine and genetic engineering, it is unlikely human clones will become a reality any time soon. By and large the alarmist concerns associated with human cloning are unfounded.

Cloning, Stem Cells, and Their Impact on Medicine

“Therefore to him that knows to do good, and does it not, to him it is sin.” — The Bible (James 4:17)

The future of cloning is really at the cellular level, also called therapeutic cloning. It is possible to obtain blastocysts, which are a mass of undifferentiated cells, from eggs generated via nuclear transfer techniques like the one used to create Dolly. (Although scientists at Advanced Cell Technology succeeded in creating human embryos from clones, for therapeutic cloning this is not necessary.) Each of the cells in the blastocyst has the potential to generate an individual, a clone of the patient. Strikingly, these undifferentiated cells, also called embryonic stem cells, can give rise to any type of tissue. Therefore, cloning makes it possible to obtain these stem cells from an adult patient which can then used to treat a myriad of diseases. Because cells created using therapeutic cloning are genetically equal to the patient’s there are few or no problems of immune system rejection.

Mouse embryonic stem cells

Mouse embryonic stem cells derived from the inner mass of the blastocyst. The large aggregates are colonies of cells. These cells can be used to create transgenic mice or they can be differentiated into different types of tissues, including neurons, pancreatic insulin-secreting cells, etc.

Much research is being done in therapeutic cloning and stem cells to develop treatments for life-threatening disease such as AIDS, Parkinson’s disease, Alzheimer’s, diabetes, etc. Therapeutic cloning is part of the broader emerging field of regenerative medicine, which also includes using stem cells derived from adult tissues, and has applications in various injuries and debilitating conditions. The general strategy involves collecting cells from the patient, creating totipotent cells from the blastocyst using nuclear transfer techniques, differentiating the cells into the necessary tissue type, multiplying the cells, and implanting the cells back again. For instance, it may be possible to use cells obtained this way to replace the dying neurons in Alzheimer’s disease and even aging may be amenable to treatments with stem cells. It is also possible to correct genetic errors in the stem cells and therefore provide new treatments for patients with genetic diseases. Overall, the potential stem cells have is enormous and as engineering problems are progressively solved, this field has the capacity to change the face of medicine.

Many politicians and bioethicists have opposed research using embryonic stem cells by drawing parallels between the methods used to derive stem cells and abortion. These comparisons are misleading, though. Unlike in abortions, an individual is not destroyed to generate embryonic stem cells. The blastocyst is not an embryo as it will not give rise to an individual. Instead, it is a cellular mass that has the potential to yield one, two, three, or more individuals. As such, the blastocyst cannot be considered an individual. Misleading criticism of therapeutic cloning is particularly unfortunate because it is hindering research that can save thousands of lives.

For some tissues it is possible to derive stem cells from adults without the need of a blastocyst. These adult stem cells are, however, less powerful than embryonic stem cells and have more limited applications and that is why researchers prefer to use embryonic stem cells. Another alternative to avoid ethical concerns regarding the use embryonic stem-cell research is a technique called induced pluripotency (iPS) which allows adult cells to be transformed into pluripotent cells. This revolutionary technique developed by the lab of Shinya Yamanaka in Japan has generated great excitement, though it should be said that stem cells created with iPS are not yet proven to be safe for the clinic.

No doubt much more research is necessary to fully exploit the potential of therapeutic cloning to generate patient-specific undifferentiated stem cells. A number of technical hurdles remain, though clinical trials for a variety of conditions, including cardiovascular and neurological diseases, are ongoing. The strict requirements for extensive clinical trials imposed by governments mean that years will be necessary to bring these treatments to patients. In that sense, I do think (and many other scientists agree) that for serious, untreatable conditions more relaxed clinical trials would allow for faster progress. In many cases of terminal diseases patients have nothing to lose and many would volunteer to participate in trials, hence governments should allow companies and researchers to take more risks with experimental treatments in such extreme conditions.

In conclusion, I’m convinced that human cloning and genetics are going to play a critical role in the future of medicine. My lab already conducts research on stem cells and I feel lucky to have the opportunity to embark on this exciting journey. I hope politicians and the public in general see the benefits of stem cell research are much greater than its problems.

Clonaid; controversial company that claim to be the first to offer human cloning.

Bio Arts; pet cloning.

Copyright © 1997 – 2001, 2004, 2006, 2012 by João Pedro de Magalhães. All rights reserved.

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