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Biotechnology and Society---Part
26
Stem cells and cloning
The trees that are slow to grow bear the best fruits. - Jean Baptiste Poquelin Moliere (1622-1673), French playwright
It is ironic that the world never takes notice of the suffering and death of ordinary citizens from various diseases but if one "prominent" citizen dies of a specific disease there is so much commotion and the world swings into action to address that specific disease. The death of former US president Ronald Reagan in June 2004 after a decade-long struggle with
Alzheimer's disease spurred significant public interest in research using embryonic stem cell (ESC) lines to find cure for several diseases such as Alzheimer's, Parkinson's, multiple sclerosis, muscular dystrophy and
heart attack, just to name a few. Welcome to the world of stem cells and cloning. It takes, sometimes, a political upheaval to goad the
government into changing its policies which are rooted in ideology.
Background: Human embryonic stem cell (hESC) lines were first isolated and grown in the laboratories of the University of Wisconsin, Madison, in 1998. These cell lines were derived from surplus three-to-five-day-old embryos (called blastocysts) that were created from in vitro fertilisation but donated for research purposes. These ESCs are 'pluripotent', i.e., they are capable of developing into any kind of cell of the body and in this capacity they hold great promise for use in transplantation
medicine such as repairing damaged
heart tissue or nerve tissue to treat the various diseases afflicting mankind. This technology is called 'therapeutic cloning', indicating the ability of these stem cells to rectify diseased organs and/or tissues.
As opposed to this therapeutic cloning there is 'reproductive cloning' which implies that humans could be cloned through this technology. Dolly (1996-2003), the sheep which gained international recognition, was cloned in 1996 through transfer of an udder cell of her donor mother into an enucleated (nucleus removed) egg and then transplanting the 'fertilised' egg into a surrogate
mother, thereby creating Dolly which was an exact genetic copy of her mother. The transfer of an adult somatic (non-germline) cell to the cytoplasmic environment of the
egg (from which the genetic material was removed) tricks the somatic cell genome into reactivating embryonic genes and causing embryonic development. From such reconstructed 'embryos' embryonic stem cells can be harvested.
Stem cells are defined by their ability to renew themselves and regenerate tissues but not all stem cells are alike. The ESCs determine the development of the entire organism (pluripotency) while adult stem cells (ASC) function best to regenerate the tissue in which they reside (e.g., bone marrow stem cells can develop only into blood cells). ESCs are capable of becoming any tissue of the body.
What is cloning?: Cloning, in its simplest definition, means copying. Identical twins are clones. Microorganisms 'clone' themselves when they multiply. There is natural cloning in the womb when the fertilised egg divides to make a lot of identical cells up to a point after which the cells start differentiating into different tissue types. When the same process is done in the laboratory to make stem cell lines it takes a different ethical interpretation. Human (reproductive) cloning involves taking someone's
DNA - extracted from a skin cell or hair cell - and inserting it into an unfertilised human egg from which the existing DNA has been removed. Such an egg could theoretically develop into a human being if implanted in a uterus, making an identical copy of the person whose DNA was transferred into the egg. At this point most people - scientists, politicians, religious leaders and many others - oppose the use of cloning to create duplicate human beings. Such an effort is wrought with potential harm whose magnitude is not yet known.
However, therapeutic cloning involves creating healthy adult tissue from stem cells to repair damaged organs to cure diseases such as diabetes, heart failure, or Parkinson's disease. With therapeutic cloning, one's own sample of DNA from a body cell can be put into a human egg and direct the cells to grow into specified tissue to cure the disease, without the incidence of rejection or the need to suppress immune activation in the case of a rejection (which happens when the donor's tissue is incompatible with that of the recipient). It may take years before the technique is perfected. Extensive research on embryonic cells is needed to learn how to develop them into specific tissue types.
The current controversy: The US Congress placed a moratorium on funding research on all forms of activated human eggs in 1996. The President, in 2001, extended the moratorium to include funding for stem cell research using the 'leftover' human embryos. There are some limited numbers of ESCs that are available in the research community which are exempt from this moratorium. Of the existing cell lines, many are either duplicates or not viable for research, according to several scientists. Hence, development of new embryonic stem cell lines can go on only in privately funded laboratories. Currently, the research remains legal but not fundable by federal dollars. There are still attempts by various segments to declare such research illegal.
Religious leaders, pro-life caucuses and bioethicists argue that life begins at conception (at the embryo stage) and hence any research on ESCs is immoral and unethical. They suggest research on adult stem cells as an alternative. However, adult stem cells are characterised as "multipotent" (capable of developing into a few other cell types) but not 'pluripotent' (capable of developing into any cell type) and hence are not that useful.
The British government approved the use of human therapeutic cloning for medical research recently. The technique involves removing the nucleus of a human egg and replacing it with the nucleus from a human body cell (such as a skin cell). The 'fertilised' egg is then artificially stimulated causing it to divide in a manner similar to a standard embryo fertilized by sperm.
The French parliament passed legislation in July 2004 banning human cloning for reproduction purposes as well as therapeutic cloning. It, however, allowed embryo research to continue.
The science: A true stem cell must be capable of unlimited self-renewal and after a stage, capable of asymmetric division (one daughter resembling the mother and the other a differentiated form - representing the three primitive embryonic germ layers called the
ectoderm, mesoderm and endoderm). ESCs have to be coaxed into specialised cells such as insulin-making cells (to cure diabetes), or brain neurons (to cure Parkinson's, Alzheimer's and other nervous system diseases). For example, it is known that the ectoderm cells develop into skin cells, nerve cells and stomach layer cells. The mesoderm develops into muscle and bone. The endoderm develops into tissues that constitute the various organs in the body such as lungs, intestine, liver, pancreas, etc. The conditions for such developments that automatically take place in the foetus are not easy to reproduce in the laboratory and will take years to perfect.
In a recent test of the therapeutic potential of ESCs, dopamine-producing neurons (nerve cells) were derived from ESCs. When they were injected into the brains of rats with symptoms of Parkinson's disease, motor function improved with no associated tumour formation. Researchers have also had some success instructing ESCs in mice to become insulin-secreting cells.
There is still the danger that cultures of ESCs may engender rare 'cancer' stem cells which may then proliferate. Other uncertainties remain such as at what point in the culturing process the stem cells lose their pluripotency and what are the exact conditions that are necessary to keep them viable until developing them into specific tissue types.
So far, only one US company, Advanced Cell Technology of Worcester, Massachusetts, has claimed to have cloned a human embryo for stem cell research. Other companies such as Infigen in Wisconsin and Geron Corporation in California have cloned animal embryos.
Prometheus's vulture: When Prometheus, the Titan in Greek mythology, stole fire from Olympus and gave it to humankind (to teach them civilisation and arts) in defiance of Zeus, he was chained by Zeus to Mount Caucasus where a vulture tore at his liver daily. However, his liver would regenerate as quickly as it was devoured. While ordinary human beings do not have the same regenerative capacity, the body is capable of healing itself from wounds caused by cuts and other injuries. Wound healing involves proliferation of cells that can restore the original function of tissues and organs. These cells obviously retain a memory endowed with them during the development stage when the tissue was first constructed as a foetus. It is surmised that there are still some primitive undifferentiated cells floating around the human body which are capable of recovering their original functionality on demand. Thus, the stem cell functionality is already available in the human body. The problem is that it is not universally capable of curing the body of all ills in all organs. The stem cell promise is alive but has to be nurtured.
Note to readers:
This article brings us to the end of the series of articles under the banner of Biotech Corner. I started writing these articles with the intention of educating the general public on the benefits of biotechnology. I am satisfied that I have had a reasonable success in my mission, judging from the responses from many of you. With that satisfaction I am giving rest to my keyboard and my pecking fingers. So long, then!
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