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The great stem cell debate

Should research be encouraged just because something is possible, even if we are not clear about the consequences? Who sets the boundaries, and how does society conduct an informed debate on this subject? The promise of stem cell research is too valuable to be undermined because these ethical concerns are not posed and addressed adequately, says Amit Sengupta

Stem cell research has been in the public discourse for contradictory reasons. Advances in research hold out the promise of treatments for conditions that were hitherto seen as incurable. Stem cells, many believe, can become an almost inexhaustible source of spare organs. Already, research is advanced enough to project that stem cells will play a role in the treatment of ageing disorders such as Alzheimer’s, Parkinsonism, cardiomyopathy, diabetes, etc.

On the flip side, stem cell research is faced with numerous ethical concerns. While the most prominent critics of stem cell research have been neo-conservative elements in the George Bush administration in the US (led by George Bush himself [1]), critics of stem cell research are not limited to conservatives who oppose stem cell research on grounds of ‘immorality’. Interestingly, one of the first actions taken by Barack Obama after assuming the US presidency was to reverse the US government’s opposition to embryonic stem cell research (2).

However, no matter which side of the debate one may be on, the genie is out of the bottle; stem cell research is clearly here to stay.

What is stem cell research?

In order to understand the contours of this debate, it is necessary to understand what stem cell research is all about. Stem cells are cells from the human body that have still not become specialised in their function, that is, they have not formed into cells in the muscle, or skin, or intestines, or any other part of the body performing a specific function. These cells are thus called ‘pluripotent’ -- they have the potential to develop into any kind of cell with a certain specialised function.

Stem cells have two important characteristics that distinguish them from other types of cells. In addition to being unspecialised cells, they react to certain ‘triggers’ that induce them to become cells with special functions. Research is being conducted on two kinds of stem cells from animals and humans: embryonic stem cells and adult stem cells.

Stem cell research is not really new, but the major advance came in 1998 when methods to isolate stem cells from human embryos and grow the cells in the laboratory were discovered (3). These are called human embryonic stem cells. Human embryos are now routinely formed by the fertilisation of a human egg by a sperm under laboratory conditions -- what we call in-vitro fertilisation, used as a means to treat infertility in couples. Normally, the number of embryos formed for a couple is much larger than required to induce pregnancy; these can be used as a source of embryonic stem cells.

Stem cells can be harvested from a three-to-five-day-old embryo, called a blastocyst. The opposition to stem cell research centres around the use of human embryos. In the US, ‘anti-abortion’ and ‘pro-life’ lobbies have been in the forefront of the campaign against stem cell research.

Stem cells are grown in the laboratory through a process known as ‘cell culture’. In the case of embryonic stem cells (still the preferred source of stem cells), the cells are transferred from the blastocyst into a culture dish that contains nutrients known as ‘culture medium’. The cells divide and spread over the surface of the dish. Over the course of several days, the cells divide and multiply in the culture dish. They are then transferred into fresh culture dishes -- this process is called ‘sub-culturing’. After six months, 30 of the original cells can yield millions of stem cells. Stem cells that have proliferated in cell culture for six or more months without differentiating, are pluripotent, and appear genetically normal are referred to as an ‘embryonic stem cell line’. Once cell lines are established, batches of them can be frozen and shipped to other laboratories for further culture and experimentation.

Challenges for stem cell research

Stem cells are also found in the adult body, in different organs like the bone marrow, brain, etc. These cells remain non-specialised for years and start to become specialised in function to repair some damage or to replace old specialised cells that die out. These are called ‘adult stem cells’.

These stem cells, later in life, give rise to the multiple specialised cell types that make up the heart, lung, skin, and other tissues. Scientists are now engaged in determining how stem cells remain unspecialised and are able to multiply for many years; also in identifying the signals and triggers that cause stem cells to become specialised cells. If this can be done, the cells can be artificially introduced into the body to repair damaged organs like a damaged heart, or brain, or liver -- the potential is virtually unlimited.

A key area of research is also to understand the signals in a mature organism that cause a stem cell population to proliferate and remain unspecialised until the cells are needed for repair of a specific tissue. Many related questions still remain to be answered. For example, are the internal and external signals for cell differentiation similar for all kinds of stem cells? Can specific sets of signals be identified that promote differentiation into specific cell types?

Adult stem cells

Attention is now also turning to the use of adult stem cells. Adult stem cells typically generate the cell types of the tissue in which they reside. A blood-forming adult stem cell in the bone marrow, for example, normally gives rise to the many types of blood cells such as red blood cells, white blood cells and platelets. Until recently, it had been thought that a blood-forming cell in the bone marrow -- called a ‘haematopoietic stem cell’ -- could not give rise to the cells of a very different tissue, such as nerve cells in the brain. We now know, however, that this is not true. For a long time, most scientists believed that new nerve cells could not be generated in the adult brain. It was not until the 1990s that scientists agreed that the adult brain does contain stem cells that are able to generate the brain’s three major cell types.

Such new insights now suggest that certain adult stem cell types are pluripotent. This ability to differentiate into multiple cell types is called ‘plasticity’ or ‘transdifferentiation’. Haematopoietic stem cells in the bone marrow may differentiate into three major types of brain cells (neurons, oligodendrocytes, and astrocytes); skeletal muscle cells; cardiac muscle cells; and liver cells. Similarly, bone marrow stromal cells may differentiate into cardiac (heart) muscle cells and skeletal muscle cells, and brain stem cells may differentiate into blood cells and skeletal muscle cells. Current research is aimed at determining the mechanisms that underlie adult stem cell plasticity. If such mechanisms can be identified and controlled, existing stem cells from a healthy tissue might be induced to repair a diseased tissue.

Comparative advantages of adult and embryonic stem cells

Human embryonic and adult stem cells each have advantages and disadvantages regarding potential use for cell-based regenerative therapies. Embryonic stem cells can become all cell types of the body because they are pluripotent. Adult stem cells are generally limited to differentiating into different cell types of their tissue of origin. However, as discussed earlier, we now know that some adult stem cells can exhibit plasticity. Another difference is that, while large numbers of embryonic stem cells can be grown in a culture medium, adult stem cells are rare in mature tissues, and methods for culturing them in large numbers are yet to be standardised. A potential advantage of using stem cells from an adult is that the patient’s own cells could be expanded in culture and then reintroduced into the patient. Use of the patient’s own adult stem cells would mean that the cells will not be rejected by the immune system. This represents a significant advantage, as immune rejection (where the body’s immune mechanism fights and kills cells from a different organism) is a difficult problem one would encounter if embryonic stem cells are introduced into a person. The ‘rejection’ can only be circumvented with immunosuppressive drugs which have other toxic side-effects.

Potential applications for stem cell research

There are many ways in which human stem cells can be used in basic research and in clinical research. Human stem cells could also be used to test new drugs. Today, human volunteers are used to test for safety and efficacy of new medicines. In the future, new medications could be tested on cells generated from cell cultures obtained from stem cells. Thus, for example, a medicine to treat a heart condition could be tested on cells artificially grown in a laboratory and made to differentiate into heart muscle cells. In order to do that, we would need to be able to precisely control the differentiation of stem cells into the specific cell types on which drugs will be tested.

Perhaps the most important potential application of human stem cells is the generation of cells and tissues that could be used for cell-based therapies. Today, donated organs and tissues (for example, in cases of heart, kidney, cornea or liver transplant) are often used to replace ailing or destroyed tissue, but the need for transplantable tissue and organs far outweighs the available supply. Stem cells, directed to differentiate into specific cell types, offer the possibility of a virtually unending source of replacement cells and tissue to treat diseases including Parkinson’s and Alzheimer’s, spinal cord injury, stroke, burns, heart disease, diabetes, osteoarthritis, rheumatoid arthritis, blindness, kidney or liver failure, etc. It may, for example, become possible to generate healthy heart muscle cells in the laboratory and then transplant those cells into patients with chronic heart disease. Preliminary research in mice and other animals indicates that bone marrow stem cells, transplanted into a damaged heart, can generate heart muscle cells and successfully repopulate the heart tissue. Other recent studies in cell culture systems indicate that it may be possible to direct the differentiation of embryonic stem cells or adult bone marrow cells into heart muscle cells.

Ethics of stem cell research

Research on stem cells involves something very different from what many believe it to be -- human cloning. No serious researcher on stem cell research is engaged in producing a whole human being from stem cells. Rather, the effort is to standardise the method of producing cells in the laboratory that are able to perform specialised functions.

However, as in many new areas of research, new ethical concerns need to be addressed. What singles out stem cell research for special attention is that it deals with human tissue. This raises ethical issues regarding ownership of the basic material on which the research is conducted. For example, at present, most researchers working to produce human embryonic stem cells use embryos that were created but not used during in-vitro fertilisation procedures (4). The use of unused embryos -- the by-products of in-vitro fertilisation -- being used for stem cell research is a grey area. Many countries discourage payment for egg donation if they are to be used for research (5). At the same time, a large number of ‘unused embryos’ are picked up by those engaged in stem cell research. What remain unresolved are ethical issues regarding the use of eggs ‘donated’ for an entirely different purpose.

While no mainstream research programme works on human cloning, it does not mean that human cloning is not possible. In fact, human cloning -- if undertaken with resources and available expertise today -- is likely to be much easier to crack than many other problems that stem cell researchers are grappling with. Scientists have produced clones of many mammalian species, and there is no particular reason why humans would prove more difficult to clone. There is, however, a fair level of consensus that human cloning is a boundary that should not be crossed. We know too little about cloned animals to predict their long-term futures and possible genetic instability. We know even less about the social consequences if humans were to be cloned.

In science, as we nudge at the frontiers of the hitherto unthinkable, we shall increasingly be faced with dilemmas. Should research be encouraged just because something is possible, even if we are not clear about the consequences? Who sets the boundaries for such research? How does society conduct an informed debate on such research? There are no definite answers to these questions. But what is clear is that they will need to be answered soon if we are not to see a face-off between science and the public it seeks to benefit. A better public understanding will definitely help. So will better levels of social consciousness among scientists. In the case of stem cell research, we need a debate that is neither coloured by the likes of the neo-cons in the US nor by ‘big’ science with big funding, big interest lobbies and big corporate backing. The promise of stem cell research is too valuable to be undermined because ethical concerns are not posed and addressed adequately.

(Amit Sengupta is with the All-India People’s Science Network/Jan Swasthya Abhiyan (People’s Health Movement-India))

Endnotes

1 In 2006, President George W Bush vetoed the House Resolution 810 Stem Cell Research Enhancement Act, a Bill that would have reversed the Dickey Amendment which made it illegal for federal money to be used for research where stem cells are derived from the destruction of an embryo
2 ‘Obama Reverses Bush-Era Stem Cell Policy’. Associated Press. http://www.msnbc.msn.com/id/29586269
3 Thomson J A, Itskovitz-Eldor J, Shapiro S S, Waknitz M A, Swiergiel J J, Marshall V S, Jones J M (November 1998). ‘Embryonic Stem Cell Lines Derived From Human Blastocysts’. Science (New York) 282 (5391): 1145-7. doi:10.1126/science.282.5391.1145. PMID 9804556
4 Our Bodies Ourselves, ‘Egg Donation for IVF and Stem Cell Research: Time to Weigh the Risks to Women’s Health’, http://www.ourbodiesourselves.org/
5 For example, in the US, the 2005 guidelines of the National Academy of Sciences for human embryonic stem cell research discourage paying for eggs for research

Infochange News & Features, December 2010