Stem cells: Ethical Issues

Stem cell research seems to be provoking a wide range of political, religious and ethical controversy than any other scientific research. Scientist in the field and stem cell research supporters argue that the potential benefits of stem cell research is so immense that there should be an open public debate about its ethical justifications, postulating that legislation and public awareness will help the science grow faster and farther. Opponents of embryonic stem cell research argue that destroying one life to save another is morally wrong. Back and forth the argument goes. There are currently three notable sources of stem cell with varying degrees of effectiveness and flexibility to work with. When it comes to ethical issues, human embryonic stem cells researches are the ones which are causing a storm in the ethical debate. Human embryonic stem cell, scientists argue, possess the special capability of dividing infinitely and growing in to any of the over 200 types of cells in the human body. Most of the problems in the stem cell research ethical issues lie in the definition of the beginning of life. Before progress is made in the field, questions of when and how life begins, the rights of foetuses and how to define a human life should be put to rest. There are three main parties wrangling over the ethical issues in the research. Whatever reason each of the parties have either dogma or science, the debate is likely to continue to rage.

In a bid to document the full sense of the debate, we will discuss the issue in terms of religions, political, and scientific point of view.

When does life begin?

Humans have been grappling with this difficult question using religious or scientific methods. Some scholars have proposed a number of key criteria to determine the person-hood of a foetus. Life begins at

1. conception/ fertilization/ DNA fusion
2. implantation in the uterus
3. start of foetal movement
4. start of brain development
5. formation of human shape in the foetus
6. The gestation period: the period of the development of a foetus while it is still inside a womb, the later the period, the more alive the foetus is presumed to be.

High school biology text books claim that life beings when a sperm cell from a male and an ovum from a female come together in fertilization and form a human zygote. Afterwards, it is a matter of gestation periods. It does not go into the details of other oddities that might work against the normal development of the embryo into a foetus. Modern science indicates that the beginning of life occurs sometimes after the fertilization of an ovum by a sperm cell, yet fertilization itself is surprisingly difficult to define. [1]

Conception brings to life a potential seed with a human DNA. The degree of respect, right and legal status one should give to a collection of about 150 undifferentiated cells (Harris, 2006), just because they have the same genetic make up but do not have in any sense independence or self-awareness, will force society to redefine civil rights and civil laws such that embryos and each cell with the same DNA in our body can be covered. The outlook of embryos progressing beyond only being blastocytes is so grim that the embryologists current estimate for preimplantation failure rate is 50-80% for various sort of biological disorders, an alarming figure due to an inefficient human reproductive system.[2][3]

The argument that life begins at conception fails to answer question of how many lives are in an embryo as some may split early or join to form many or less foetuses respectively, or consider cases of Siamese twins somehow joined down their neck. Currently, laws that protect specifically embryos does not exist except the implication that if corporations are good enough to have legal entities why not embryos with a potential to develop in to a full human beings.

The other arguments for the existence of life and the beginning of personhood are the start of brain development, foetal movement, stage of gestation period. Brain activity or nervous system development does not guarantee a foetus the legal entity that begins with having a birth certificate. These points have been mostly presented in an anti abortion movements but failed constantly to give a foetus the legal entity and the independence it needs to be legally recognized, in fact, in the pro choice side of the argument the woman’s right over her body or to be and not to be pregnant has weighed much more that several states in the world consider it good enough to give abortion upon request. See map. By United Nations Department of Economic and Social Affairs, population Division in 2009.

A foetus in late developmental stage morphs into a human like being by loosing the gills, the tails and most people find it hard to allow abortion in the tri-semester. One paradox to the ethical issues in stem cell research is that states which allow abortion upon request, in any gestation period—to save the life of a mother, the same reason why we need to experiment with stem cells in the long run—found it ethically wrong to collect stem cells from a collection of cells which have no any capacity to feel pain or suffer but offer the potential to relieve millions of people suffering from afflictions such as Parkinson’s and Alzheimer’s disease, brain and spinal cord injuries, diabetes or heart problems.

The Sectarian camp
Religious institutions are in the mix for the debate whether research should be allowed to proceed on stem cell research, with their own version of definition of life, and personhood. Documenting the views and stands of the infinite number of religions is beyond the purpose of this document. But with more than two billion Christians and a billion Muslim in the world today, it would be wise to assess what they have to say. Each religious sect owns its set of standards and codes of conduct that are likely to be different from one another. Christian groups maintain a stricter position against stem cell research claiming that human hood, personhood or life for that matter begins with conception and compromising the future of life for any goal of whatsoever is considered a mortal sin. Christians argue that God recognizes personhood even before conception and believe the bible makes it clear unequivocally. “Before I formed you in the womb I knew you, before you were born I dedicated you; a prophet to the nation I appointed you” Jeremiah 1:5
Moderate Christians suggest that saving a human life is an honourable deed in the eyes of God and conducting a stem cell research to spare humans of suffering and afflictions should be allowed, a line of argument hardliners reject that other life should not be expended to save another life. “Fathers shall not be put death for their children, nor children for their fathers; only for his own guilt shall a man be put to death” Deuteronomy 24:16 In short, embryos should not be prepared and destroyed for another man’s benefit. Possibly one of the reasons many predominately Christian societies find it ethically abhorrent to tinker with embryos.

In contrast, Islam provides two hadiths—the second most important book in Islam next to the Qur’an which details the teachings, deeds and interpretation of the verses of the Qur’an—that might give a blessing to pursue human embryonic stem cell research.[5] In Islam the life span of an embryo is divided into two periods; one is conception, the first 40 days after fertilization; the second is ensoulment that marks the beginning of life and personhood. To rest the case with stem cell research, Muslim scholars indicate that the Prophet Muhammad said “Varily your creation is on this wise. The constituents of one of you are collected for forty days in his mother’s womb; it becomes ‘alaqa (something that clings) in the same period (mithla dhalik), then it becomes mudgha (a chewed lump of flesh) in the same period. And the angel is sent to him with instructions concerning four things, so the angel writes down his provision, his death, his deeds, and whether he will be wretched or fortunate. Then the soul is breathed into him” (Al-Bukhari; Muslim; Ibn Maja; al-Tirmidhi; Abu Dawud). Islam might not have a problem with embryonic stem cell if and only if the age of the embryo is less those 40 days. Proof to that, in 2003—together with the silence of the Qur’an on the matter, the concept of ensoulment in later stages of the embryonic cells and lack of a single centralized policy issuing authority in Islam, just like the catholic church (BBC, 2009)—Iranian scientists were able to develop a human embryonic stem cell line despite Iran being a conservative Muslim nation. [8]

The political camp
One of the major roadblocks to the progress of human stem cell research has been the lack of clear national guidance and policy. In the united states, on August 9, President George Bush promised that federal funding will be provided, only to come with three hard to work with obstacles such as no new embryos are to be collected for destruction, the embryo must be a left-over from fertility therapy and donations are to be collected from an informed donor with consent and no financial payments. [10] Many states follow that line of position, rather than facing the issue head on, sliding off the thorny issue of federal funding seems to normal way to deal with it. With lack of concrete understanding of the science by the public and politicians helped to arrest the growth of the science, and deliberating whether or not to grant permission quickly fades the interests of politicians.

To help matters clear, there are currently around the world four policy cues that are in one form or another are being either considered to be implemented or are semi-implemented.

1. No policy: no clear policy or explicit legislation to conduct any form of human embryonic stem cell research
2. Restrictive: It is prohibited either by law and could lead to a legal action in such countries as Germany, Italy, Lithuania, Poland, Slovakia, for assumed moral or religions point of view.[11]
3. Some research allowed: Research is allowed only on existing and no longer needed embryos such countries include Australia and Canada.
4. Most permissive: Research is permitted on remaining embryos and on embryos created specially for research through SCNT in to non human animals or into human eggs or zygotes such countries are the UK, Sweden, Belgium and China.[8] The United States depicts a patchy picture from permissive to some possibility of research. see map.

What does a living human being have to have, or look like, or be able to do in order to achieve full human-hood or personality with rights to life?

If personhood were characteristics to be dole out by society to individuals, the agreement on how one can set the standards for being person would have more negative consequences than benefits. Historically, mankind have been given various forms of personhood depending on membership of a religious sect, race and other artificial social institutions.

The scientist camp
Science puts everything down to simple fact and statistical analysis leaving no room for any superstitious predispositions, assumed point of view or dogma and it is no exception with stem cell research. The scientist camp rejects any injunction based on the basis of religious faith. Scientists claim that religion is based on a groundless hypothesis and can not be a ground to get in the way of scientific progress (Harris, 2006), and want to put religious zealots feet to the fire. On a minimum base, experts ague that research should be allowed and federally funded on a redundant human eggs from fertility clinics, which are anyway going to end up being destroyed. Scientific research generally follows The Nuremberg Code—a 64 year old World War II born document—that dictates ten points of moral guidance. We quote here three in consideration of the purpose of this text. [13]

1. The voluntary consent of the human subject is absolutely essential. This means that the person involved should have legal capacity to give consent; should be so situated as to be able to exercise free power of choice, without the intervention of any element of force, fraud, deceit, duress, overreaching, or other ulterior form of constraint or coercion; and should have sufficient knowledge and comprehension of the elements of the subject matter involved as to enable him to make an understanding and enlightened decision. This latter element requires that before the acceptance of an affirmative decision by the experimental subject there should be made known to him the nature, duration, and purpose of the experiment; the method and means by which it is to be conducted; all inconveniences and hazards reasonably to be expected; and the effects upon his health or person which may possibly come from his participation in the experiment.
2. The experiment should be such as to yield fruitful results for the good of society, unprocurable by other methods or means of study, and not random and unnecessary in nature
3. The experiment should be so conducted as to avoid all unnecessary physical and mental suffering and injury.

Passing through each point one realizes stem cell research rests right in the jurisdiction of two and three that the research is designed to relieve humans of preventable afflictions and the embryo at blastocytes stage does not have any means of experiencing suffering including there is no other means of achieving the intended end.

Philosophers and pro-abortion groups define life as being consciousness of objects, events, having reasoning capacity, being able to conduct self-motivated activity, having the capacity to communicate and self-awareness, which a foetus lacks visibly and fails to fulfil point 1 in The Nuremberg Code. [12]

In the medical world, terminating one life to spare another the misfortune of death is common. According to the United nations department of economics and social affairs population division in 2009, 96% of developed and 97% of developing countries allow abortion to save the life of the mother. In 2003 alone, an estimated 42 million abortions occurred around the world, a grievous genocide when compared to what and why the public finds it wrong to engage in stem cell research. See map.

Sources:

1. The Westchester institute for ethics and the human person, when does life begin? Vol1, Nov1, October 2008 Ed.
2. Preimplantation genetic diagnosis, Joyce C. Harper, Joy D. A. Delhanty, Alan H. Handyside, 2001
3. Fetal medicine: Basic science and clinical practice. Charles H. Rodeck, Martin J. Whittle, 2008
4. Encyclopaedia Britannica 2001
5. Stem Cell Research: An Islamic perspective. Sahin Aksoy, Abdurrahman Elmali and Anwar Nasim 2007
6. Mary Anne Warren, “On the Moral and Legal Status of Abortion,” The Monist, Vol. 57, no.4, 1973. Reprinted in James P. Sterba, op. cit., pp. 159-168
7. United Nations economic and social affairs population division, 2009. http://www.un.org/esa/population/unpop.htm
8. Human Embryonic stem cell research: An Intercultural perspective, Kennedy Institute of Ethics Journal 14.1, 2004
9. British Broadcasting Corporation 2009 http://www.bbc.co.uk/religion/religions/islam/islamethics/stemcells.shtml
10. The National Institute of Health resource for stem cell research, 2009. http://stemcells.nih.gov/policy/2001policy.htm
11. Embryonic stem cell patents: European law and ethics, Aurora Plomer, Paul Torremans, Oxford 2009.
12. Philosophy of Humanism, M. Hillar, F. Prahl, American Humanist Association, 1997, pp. 131-140.
13. The Nuremberg Code 1947
14. The end of faith, Sam Harris, 2006.

Nobel Prize for Stem Cell Research

In 2007, the Nobel Prize in Physiology or Medicine was awarded to the three pioneering scientists Mario R. Capecchi, Oliver Smithies and Sir Martin J. Evans. The trio received the prize due to their groundbreaking discoveries within stem cell research.

Capecchi, Smithies and Evans developed a technique that makes it possible to create specific genetic modifications in mice. The technique involves “knocking out” the functions a single gene. In this process, parts of, or the whole gene will be removed. Knocking out single genes gives information about the normal function of this gene by investigating what has been lost or altered. In order to change the genes of a whole mouse, embryonic stem cells from a mouse embryo are given a specific genetic modification. Furthermore, the modified stem cells are cloned and inserted into a new mouse embryo. A surrogate mother will carry and give birth to the modified mouse embryo. Later on, the genetically modified mouse will give birth to offspring that possess the genetic alteration. The technique developed by the three laureates is called “gene targeting”.

The function of a gene in mice resembles the function of the corresponding gene in humans and other mammals. For this reason, mice can be used as model organisms with the aim of studying human disorders”. Earlier, it was only possible to study the effects of “knocked out” genes in cell cultures. The cell cultures did not give any answers to questions concerning complex organs. Gene targeting now makes it possible to observe the effects on the whole organism when a gene has been modified.

One of the laureates, Sir M. J. Evans, was the first scientist who isolated embryonic stem cells from mice. Together with M. H. Kaufman, he published his work on this subject already in 1981.

Sources:

1. nobelprize.org

2. http://www.bion.no/filarkiv/2010/07/2007_4_s16_nobelprisen_for_maalrettet_genmodifisering_av_mus.pdf

Stem cells today and in the future

The term “stem cell treatment” rises controversy and the term can fill you with everything from disgust to uncontrolled enthusiasm. Some may think that stem cells will bring salvation from diseases, others that the apocalypse is upon us. Maybe this controversy is the reason why it is hard to find an overview of all the available treatments in world which involves stem cells; because often they are covered by other phrasings.

With stem cells we can in theory do “everything”, like grow new organs, cure aids among other things, but where is the research at now? What clinical trials are being conducted, and how promising are the results? What stem cell treatment can you actually get at your local hospital?

Stem cells have a great differentiation potential and can in theory develop into any cell in the body. Ordinary stem cells are divided into two main categories adult and embryonic. The embryonic stem cells can divide into all the adult stem cell lineages, whereas the different lineages of adult stem cells already have a level of specializations and can not differentiate into one another. The embryonic stem cells are the ones concerned with controversy because of the discussion about when life starts. To harvest embryonic stem cells you have to fertilize eggs and destroy them. If an embryo is to be defined as a person you would be destroying a life. An option to this is to harvest stem cells from the umbilical cord. In Norway the storage of stem cells from the umbilical cord is limited to special cases, like when there is a high risk of the person to develop severe illnesses later in life. It is also argued that the amount of stem cells you can get from the umbilical cord is so small that scientific breakthroughs are needed before the cells can be of use to threat an adult.
Clinical use today:
Most of the stem cell treatments are still highly experimental and there is a high risk of complication is great, but there are treatments that are accepted and recommended as standards. The treatments are being closely monitored, and the patients which receive them have to be inspected on a yearly basis by their doctors, through out their life.

Severe combined immunodeficiency disorder a genetic disorder where the immune system is compromised.
Victims are extremely vulnerable to infectiouse diseases. Because of this the disease is also known as bubble-boy syndrome, since the victims have to live in sterile environment (bubble). This makes it difficult to function socially, since the victim limited to the sterile environment. [1.

Box
Leukemia is a type of cancer in the blood, or bone marrow. It is characterized by a abnormal high count of white blood cells. The white blood cells are involved in fighting pathogens, but in leukemia patients these cells do not function properly. In the worst case the white blood cells can attack the victims own body [2.

Stem cell treatment has been implemented and is recommended to several acute diseases such as: severe combined immunodeficiency disorder (SCID) and different types of leukemia. Adult stem cell treatment through bone marrow transplanation has shown to cure these diseases. [3, 4, 5]. By comparison without any treatment people with multiple myeloma, a type of leukemia, have a life expectancy of about one year, and untreated SCID, 6-12months [4, 6, 7]. To go from having one year left to live to complete remission show that great advances in medicine. For SCID other treatments have shown to prolong life, but to this day stem cell tranplantation is the only known cure [5]. Stem cells have also shown to cure other immunodisorders namely, lymphoma and aplastic anemia. In addition stem cells are used in acute cancer types as supporting treatment to allow higher doses of radiation and chemotherapy. An example is to replenish white blood cells destroyed in the treatment, thereby restoring the immune system [8, 3].

Hematopoietic stem cells
In most of the cases mentioned above the treatments are using hematopoietic stem cells. The hematopoietic stem cells can, as the name my reveal (hemato meaning blood), differentiate into all the different blood cells in the body. The cells are situated in the bone marrow where they divide continuously and replenish the red and white blood cells. The hemapotopoietic stem cells were discovered around 60 years ago, and the first successful transplants with these stem cells date back as early as the mid sixties. [3]. The hematopoietic stem cells show great promise in treatment of different autoimmune diseases [9].

Autogenic and allogenic transplant
In the hematopoietic stem cell treatments the adult stem cells are by far the most used [10]. There are two major types of stem cell transplants, the cells can either come from the patients own body or someoneelses. This has huge implication on further follow up and treatment. When the cells come from the patient they are called autogenic, and when they come from someone else than the patient they are named allogenic. In this case autogenic is understood as “derived from sources within the same individual” meaning yourself, and allogenic is interpreted as the source is “individuals from the same species”, aka others [11].

In treatment
The treatment with both allogenic and autogenic stem cells in the case of leukemia and SCID require chemotherapy and/or radiation to destroy the unhealthy cells in the bone marrow. This is an immense stress to the body, the treatments actually is killing the patient. Radiation and chemotherapy are damaging to the whole body so at the same time the healthy white blood cells are dying and the immune system is greatly weakened.

The stem cells are then injected when most of the unhealthy cells are destroyed. The risk of complications in this stage is much higher in the case of the allogenic stem cell transplant. As you remember these cells have not been in your body before, and the already weakened immune system can see the new cells as a threat and start fighting against them. Also the injected stem cells can see the body as a threat and attack it. This is part of what scientists know can give rise to as graft-versus-host-disease.

Not without risk
In allogenic stem cell transplant many patients experience chronic graft-versus-host-disease to some extent [12]. (In the case of SCID the risk of graft-versus-hos disease is low for reasons which are still unclear for scientists [13, 14]). The graft-versus-host-disease can be managed by different immunosuppressent medications [15]. The immunosupressents will at the same time leave the patient more vulnerable towards common diseases as the flu and different infections. Bacterial infections can be treated with antibiotics, but the flu is a viral infection and the patient will be exposed and have to be very careful about his and others hygiene[16]. At the same time, this process is very tyring for the patient and his family both mentally and, in the case of the patient, physically. [17]
Another threat of both allogenic and autogenic transplant is the danger of infection acquired in the hospital and after transplantation [18].

Promising Clinical Trials
There are several clinical trials which show promising results, but even though there is potential it may take decades before the treatment is implemented as a standard at hospitals:

Type 1 Diabetes mellitus [19]
Chronic heart failure [20].
Skin injuries [21, 8]

Type 1 diabetes are near to be cured by stem cells, but since diabetes is not consider a severe illness the risk of complication is still high with respect to what the person can gain from the treatment.

Stem cells from the bone marrow show promising results in treatment of chronic heart failure by having the ability to regenerate damaged heart tissue. Clinical trials have shown to prolong the patients’ life and quality of life in cases of acute myocardial infarction [20]

Somatic stem cells offer the potential to regenerate skin after serious injuries as for example bruns. Perfect skin repair is still a major challenge with regards to fibrosis and scars [21, 8]

What to come:
One of the standard preventive measures regarding stem cells is storage of blood from the umbilical cord to future use. The practice is common as an option for newborns in families with inherited illnesses where the blood (stem cells) may be used to treat future illness. To store the blood the family of the new born can apply to the department of health in Norway [22]. Stem cells from umbilical cord are in use in different countries. In treatments they may be used as a supplement in allogenic and autogenic stem cell transplants. Use of stem cells from the umbilical cord has shown to actually reduce the likelihood of chronic graft-versus-host disease [4].

The great plasticity of the stem cell brings hope for future treatment of a wide range of illnesses. One day sicknesses where we to this day only can treat symptoms, not the underlying cause can one day be cured with stem cells.

Sources:

[1] http://en.wikipedia.org/wiki/Severe_combined_immunodeficiency

[2] http://en.wikipedia.org/wiki/Leukemia

[3] http://emedicine.medscape.com/article/991032-overview

[4] http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2796.2000.00706.x/pdf

[5] http://onlinelibrary.wiley.com/doi/10.1111/j.0105-2896.2005.00223.x/pdf

[6] http://www.ncbi.nlm.nih.gov/pubmed/8410508
Tephan JL, et al. Severe combined
immunodeficiency: a retrospective singlecenter study of clinical presentation and
outcome in 117 patients. J Pediatr 1993;123:564–572.

[7] Buckley RH, et al. Human severe combined immunodeficiency: genetic, phenotypic, and functional diversity in one hundred eight infants. J Pediatr 1997;130:378–387.

[8]http://www.google.com/url?sa=t&source=web&cd=6&ved=0CFEQFjAF&url=http%3A%2F%2Fwww.aftenposten.no%2Fhelse%2Farticle2937416.ece&rct=j&q=stamcelle%20behandling%20i%20norge&ei=N8ViTf2rEorLswaHkai2CA&usg=AFQjCNGJMB5tXjrxcBiIqydk8M3rL-Aw3Q&sig2=FwTMBfgz-TeewpdmpFyq0w&cad=rja

[9] http://www.nature.com/bmt/journal/v32/n1s/pdf/1703935a.pdf

[10] http://www.ebmt.org/4Registry/Registry_docs/slides/slides2009/2009megafile.pdf

[11] http://www.merriam-webster.com

[12] http://www.nature.com/bmt/journal/v45/n4/pdf/bmt2009238a.pdf

[13] Buckley RH, et al. Hematopoietic stem-cell transplantation for the treatment of severe combined immunodeficiency. N Engl J Med
1999;340:508–516.

[14].Antoine C, et al. Long-term survival and transplantation of haemopoietic stem cells for immunodeficiencies: report of the European experience

[15] http://bloodjournal.hematologylibrary.org/cgi/content/full/100/2/415

[16] http://www.nature.com/bmt/journal/vaop/ncurrent/pdf/bmt2010329a.pdf

[17] http://asheducationbook.hematologylibrary.org/cgi/content/full/2010/1/248

[18] http://www.ncbi.nlm.nih.gov/pubmed/21303337

[19] http://www.nature.com/nrendo/journal/v6/n3/full/nrendo.2009.274.html

[20] http://eurjhf.oxfordjournals.org/content/12/7/721.full.pdf+html

[21] http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B8JJJ-4T5BWPT-5-1&_cdi=43728&_user=586462&_pii=S1008127508600450&_origin=search&_coverDate=08%2F31%2F2008&_sk=999889995&view=c&wchp=dGLzVzb-zSkzk&md5=f8bc37cd6a42c039ac0abc71570af725&ie=/sdarticle.pdf

[22] http://olepetergalaasen.wordpress.com/2010/01/11/stamcellebank-for-dyrt-for-norge/ (probably need a better source, btw nice illustration, maybe steal it?)
In norway the umbilical cord

[23] http://onlinelibrary.wiley.com/doi/10.1002/jcb.23028/pdf

[24] http://stemcelltreatments.org/

What kind of baby would you like? -Screening of embryos and “designer babies”

A Los Angeles fertility clinic, The Fertility Institute L.A., advertises their expertise in gender and physical trait selection on their website. The director of the clinic says that they offer what he refers to as “cosmetic medicine”(1). What seemed like science fiction only a decade ago, choosing a baby with certain trait, might be closer to reality than we realize.

The human genome project combined with the development of various laboratory techniques have given the possibility of screening embryos in fertility clinics before implantation. Initially scientists intended to use the technique for selection of embryos genetically free of inheritably lethal diseases. However, along came the ability to choose gender and physical traits for cosmetic reasons (2). The technology benefits the fact that all information about the possible individual lies in a cluster of embryonic stem cells. The technology represents stem cell technology at its most powerful: taking control of the genetic recombination. In the following text the general science and technology making this possible will be explained, and the possibility of artificially creating a certain genetic makeup is evaluated.

Preimplantation genetic diagnosis (PGD).
PGD is a scientific term meaning genetic testing of embryos (2). The method is combined with in vitro (made in the laboratory) fertilization and has been offered in selected clinics since 1990 (3). A three day old embryo consists of about 6 embryonic stem cells, and at this stage a single stem cell can be removed for genetic testing. The removed cell will be regenerated by the remaining 5 cells, and the embryo will develop normally. For the testing, two techniques are most frequently in use: polymerase chain reaction (PCR) and chromosome visualization by fluorescence in situ hybridization (FISH). PCR is based on a simple concept, but still represents an advanced technique used to amplify DNA. When multiplied, it is possible to analyze the sequences of genes. In PGD, one uses the knowledge of the composition and function of genes, to identify abnormalities in targeted gene sequences. The following example illustrates how this knowledge is being used in PGD. Cystic fibrosis is an inheritably disease causing reduced lung capacity. In a healthy person, a protein named CFTR controls the transfer of salts across the cell wall. The most common mutation leading to cystic fibrosis, ΔF508, has a three-nucleotide deletion resulting in loss of one amino acid, further resulting in a nonfunctional CFTR protein. This mutation is possible to detect using a PCR test. On the following page, a PCR test has been run on DNA of an embryo originating from a couple both being recessive carriers (heterozygote) of cystic fibrosis. With parents both being heterozygote the offspring is left with a 25% chance of inheriting the disease. The blue colored tops in the diagram represent the CFTP protein. In the affected embryo (genes from both parents are mutated: ΔF508 /ΔF508) the protein is deformed and therefore give a different peak compared to the normal embryo (F508/F508), shown to the left in the following picture (2).

In this way it is possible to select an embryo genetically free of cystic fibrosis. This technique also applies to other single-gene defect diseases such as sickle cell anemia, familial Alzheimer’s disease and breast cancer etc (2, 4, 5). In addition abnormalities in chromosomes can be detected by use of chromosome visualization by FISH. In this technique fluorescent probes attaches to specific targets of the chromosomes. The probes can then be visualized in a fluorescence microscope revealing attachment or not. In a normal embryo each probe will attach twice, indicating one single set of chromosomes (6). As illustrated to the right in the picture, a probe with fluorescent blue dye targeting chromosome 21 has attached to three chromosomes. This reveals that the embryo has trisomy 21, also known as Down’s syndrome. Different probes can bind to different chromosomes and also different parts of targeted chromosomes (6). When having one probe attaching to the sex-chromosome X (female) and one probe attaching to the sex-chromosome Y (male) it is easy to understand how a clinic can predict an embryos gender.

What next?
It seems reasonable to question what other traits scientists can screen for in the embryo. In a survey preformed by researchers at the New York University School of Medicine quite a few provocative opinions were revealed. About 10% of the people participating in the survey said that they would want genetic testing for athletic ability, while 10% said that they would prefer to be able to test their embryo for height. About 13% of the questioned participants also wanted the ability to select for intelligence (1).
The Icelandic company named DeCode Genetics uses what is known as a microarray to screen for sequences in our DNA (1). Matching sequences will attach to the array and reveal if the sequence is present or not. The big advantage of the microarray is the possibility to screen for numerous sequences at the same time (7). Based on samples taken on Iceland and in the Netherlands DeCode Genetics have revealed which sequences that are typically present in DNA representing pigmentation of skin as well as eye and hair color. The sequences are only representative for northern Europe, typically having blond features (1). With this sort of information a microarray can within a blink of an eye give you a baby with the lovely blue eyes just like your grandmother’s.

Designer babies?
It is important to understand that no new genes/traits are added to the embryo. An embryo cannot have preferred genes without any of the parents carrying the same set of preferred genes. A couple with dominating genes for dark hair cannot have a baby with blond hair. Also when it comes to more complex traits such as intelligence and memory no single gene controls the trait alone. Multiple genes are likely to work together in a very complex network, still not understood by scientists. As already stated, PGD only makes it possible to screen for certain genetic combinations arising from the genetic union of a sperm and egg cell. However, in theory it can be possible to extract the genetic material from an embryonic stem cell, modify it and reinsert it, thus creating a genetically engineered embryo. This can then be referred to as a designer baby. But how realistic is a genetically engineered human?
Firstly, one has to consider the ethics and dangers associated with this issue. Looking at the controversy of genetically modification of organisms (GMOs) for production of food (8) and the controversy regarding stem cell research and cloning (9), one might claim that if the question about designer babies were ever to enter the public debate, it would probably create an opposition impossible to ignore. Public opinion is an important limitation; in the UK for instance, a law has already passed prohibition of human cloning (10) because it is considered highly unethical. It is therefore reasonable to believe that public opinion would ban the creation of designer babies if this would become a possibility.

Secondly, there are huge technological challenges associated with genetically engineering of a human embryo. Inserting a gene into the human chromosome has proven to be unpredictable, as some insertions have happened in the wrong site of the chromosome resulting in cancer. Replacing a gene with a different version of the same gene, something one might do if the parents does not have the genes necessary to produce a certain trait, has also been proven to be very difficult when working with human cells (11). Knowledge of the detailed functions and interactions of all human genes is still far, far away.
Considering these two aspects, it is hard to imagine that a baby with a completely artificial genetic makeup, a “designer baby”, will appear anytime soon. However, with the possibility to screen embryos for any trait belonging to a known sequence, it is likely that the use of PGD will expand. Screening of more complex traits, as long as a broader variety of traits are likely to become available, as the knowledge of human genetics expand. This certainly poses ethical challenges, which we will not deal with in this text, but one can imagine in a future society where picking and choosing physical traits for children is normal. Parents telling their kids “you’re perfect just the way you are”, will certainly have different ring to it.

Other issues related to PGD
Another aspect of PGD is the ability to intentionally not choose normal functions of an embryo. An example of such an issue arises with deafness. It is known that most cases of inheritable deafness are due to a mutation referred to as the GJB2 mutation (5). With the ability to screen for this mutation couples with family history of deafness can increase their baby’s chance of having normal hearing. The opposite scenario has appeared as some people argue that a deaf child is better suited to participate in the parents shared culture when deaf (1,5). Even if it is clearly beneficial for a child to have hearing ability, this touches an ethical issue towards the respect of the deaf community (5).

PGD also give rise to concerns of a potentially reduced level of genetic variety. If PGD becomes a routine practice, we will be faced with the fact that certain genes will be lost. By decreasing the genetic diversity we may make ourselves more prone to yet unknown diseases. As we don’t know which genes that will be of advantage when a population experiences changed external factors or threats (such as new diseases), it can be a risk not having a broad genetic variety (1,4).

Not to be forgotten is the financial cost of PGD. The Los Angeles clinic mentioned in the introduction operates with prices ranging from $4800 to $74.120. For the cheapest service of $4800 the company offers a single cycle of IVF and the promise of this being one of the most successful programs in the world (12). $4800, equally about 27.000NOK is a high price, but perhaps well spent money when considering the cost of medical treatment and daily concerns. To be mentioned is the $18.490 (104.420 NOK) price the clinic offers for selection of gender with a 99.9% guarantee (12). It is not hard to imagine how this has the potential to create a socioeconomic split. It is a risk that only couples capable of paying for PGD will be able to choose the genetic inheritance of their offspring(4).

Sources:

1. Naik G., 12.02.09, ”A Baby, Please. Blond, Freckles—Hold the Colic”, The Wall Street Journal

2. Bouffard C. et al., 15.09.2009, “Genetic diagnosis of embryos: Clear explanation, not rhetoric, is needed”, CMAJ, DOI:10.1503, 181 (6-7).

3. Verlinsky Y. et al., 1990, “The preimplantation genetic diagnosis of genetic diseases.”, Journal of assisted Reproduction and Genetics, Vol. 7, No. 1, pages 1-5.

4. Klipstein S., 05.2005, “Preimplantation genetic diagnosis: technological promise and ethical perils”, Fertility and Sterility, No 5, DOI: 10.1016.

5. Robertson J.A., 2003, “Extending preimplantation genetic diagnosis: the ethical debate”, Human Reproduction, Vol.18, No.3, pages 465-471.

6. Ye Y. et al., 20.09.2004,”Identification of embryonic chromosomal abnormality using FISH-based preimplantaion genetic diagnosis”, Journal of Zhejiang University Science, Vol. 5, No. 10, pages 1249–1254.

7. Yu X. et al., 14.01.2010, “Protein microarrays for personalized medicine”, Clin Chem Journal, Vol. 56, No. 3, pages 376-87.

8. http://www.johnlang.org/pubs/NationalStudy2003.pdf

9. http://poq.oxfordjournals.org/content/68/1/131.full.pdf+html

10. http://www.legislation.gov.uk/uksi/2001/188/contents/made

11. Principles of genetics 5th ed., Snustad & Simmons, 2010, John Wiley & Sons, USA.

12. The Fertility Institute home webpage: http://www.fertility-docs.com/fertility_fees.phtml

The Hwang scandal

The story of the South-Korean researcher Hwang Woo-Suk is a tragic, yet fascinating example of scientific fraud. His publications, first giving hope and promise to the world for a bright future of stem cell treatment, was a disappointment for the global scientific community.

Background and quick rise to national fame
Hwang Woo Suk grew up without a father in a poor, remote town in South-Korea, and worked hard to finance his own education. He started his career as a scientist after getting his PhD at Seol National University(SNU), and specialized in the reproduction of cattle. Working with in vitro fertilization and cloning of animals for years at SNU, he became a famous scientist in South-Korea, claiming to have cloned cows and pigs and genetically engineering a pig to produce human organs (among other accomplishments). He then began research on stem cells, and acquired powerful friends in the government, most notably the president himself, apparently demonstrating how he cured a sick dog using stem cell treatment. He also gained popularity in the puclic by appearing in media with sensational demonstrations. This led to his research being heavily financed, through government funds and donations from the public (1, 3, 6).

Hwangs Science articles
In 2004, Science published an article by Hwang and colleagues, where they claimed to have created a line of pluripotent embryonic stem cells using somatic cell nuclear transfer(SCNT) and 242 human egg cells. The stem cell line was claimed to have been created using genetic material from the egg donors own somatic cells, and apparently showed all characteristics of embryonic stem cells. The experiment claimed to have created one blastocyst for approximately every fourth egg cell, an efficiency comparable to earlier experiments on cattle and pigs (2). This was the first time anyone could seemingly prove having created stem cells from cloning (3). In 2005, Hwang and his colleagues published another article in Science, claiming to have created eleven lines of pluripotent stem cells using the same technique, using 185 human egg cells – and again the stem cell lines showed all characteristics of pluripotent embryonic stem cells. This time, however, the lines were created using the genetic material from somatic cells of people of different ages and sex(and even people with diseases that were potential targets for stem cell treatment), not the egg cell donors own genetic material. The efficiency of creating blastocysts had also risen dramatically (4). These articles, being published in the highly respected journal Science, and the fact that he had collaborated with Dr. Gerald Schatten (a famous American scientist) on the two papers, was seen as evidence for his earlier unpublished experiments.

The following paragraph explains the method of cloning allegedly used in Hwangs experiments, and cloning in general, but I am unsure whether it should appear here, in Idas article or an article about cloned animals.
(the first step in cloning an organism, therefore also known as “research cloning”. This technique involves removing the nucleus of an egg cell, thereby stripping it of its genetic material, and injecting the nucleus from an ordinary (somatic) cell. Using a mature egg cell (an egg cell which is ready for fertilization), the environment inside the egg cell then automatically reprograms the genetic material injected, creating a cell which theory will be almost identical with the fertilized egg that gave rise to the organism from which the somatic cell nucleus was harvested. After artificially stimulating the egg cell, this cell will divide to give a blastocyst, from which embryonic stem cells can be harvested. As embryonic stem cells have the potential to become any kind of tissue of an organism, they have great therapeutic potential. The SCNT technology would, if successful, also create stem cells with identical genetic material and therefore not be rejected by the immune system (5).

Downfall
Soon after the 2005 Science article, Hwang published an article in Nature describing the cloning of an Afghan dog, named Snuppy. This was regarded as probably being more difficult than cloning a human being, because of the nature of the egg cells and pregnancy in dogs. Hwang was already a national hero in South Korea. South Korea was now regarded as the leading country of stem cell research, and the Korean people placed high expectations for him and his work. A survey showed that 30 % of women said they would donate egg cells for Hwangs research. The South Korean postal service produced 1,6 million stamps depicting stem cells together with a man rising from his wheel chair after getting stem cell treatment to hail his achievements, and public posters celebrating his success appeared on public transport (3, 5).

However, already in 2004, an article in Nature reported that two junior scientists working with Hwang had donated eggs for the for the 2004 Science paper, which is considered unethical. However, this article was not given much attention. In Later, in 2005,
Dr. Shatten suddenly ended his collaboration with Hwang because of unethical procedure in getting eggs for his research. Then, a South Korean investigative TV-show started doing research about his methods, reported that he had forced these junior scientists into donating their eggs, and that DNA-test showed that of one of the cell lines in the 2005 paper did not match the DNA of the somatic tissue donor. Science reported that a review board for Seol National University in an investigation found out that donors had received payment for the eggs (which is illegal). Hwang still had massive support amongst the general public, and more importantly the scientific community in South Korea, and although Hwang admitted egg donations by his junior scientists, it did not affect his status as a star scientist (6,7,8). Then, things started to fall apart. Following accusations of fabrication, Hwang informed Science that some of the pictures in the 2005 article were taken from another article (the pictures were later admitted to be faked). Dr. Schatten requested to have his name removed from the paper. One of Hwangs collaborators then
told a news network that “there are no cloned embryonic stem cells”. Hwang and Dr. Schatten later retracted their article from Science, stating that analyzing the data had led to the conclusion that “the results could not be trusted”. An investigation of Hwangs work by Seol National University concluded that large amounts of the 2005 Science paper had been fabricated, and that there had only been 2 lines of embryonic stem cells, not 11 – and later that these two lines had been created using in vitro fertilization, not cloning. It was also later revealed that he in total had used 2,200 eggs, not 427, in his 2004 and 2005 articles. In the end, Hwang first apologized for bringing shame to the nation, and then publicly admitted to have fabricated data for the 2005 article (3, 8).

Hwangs contribution to science
The Hwang scandal highlights how important regulations and close inspections are in the field of stem cell research, and in general the importance of preventing fabrication of scientific data. First of all, researchers spent time and money trying to replicate his research. In addition, publications of false data might lead to researchers and medical practitioners to make decisions not based on true findings. Also, the revealing of the fraud was a huge disappointmend to both researchers and people in general, and gave the South Korean research a bad reputation. In addition, with the exploitation of hwang’s junior scientists, this case provides a real life example of how easily ethical wrongdoings can occur in this research (3). Even though his two Science papers were almost completely (and intentionally) fabricated, Hwang undoubtedly made important contributions to science and stem cell research. The cloning of Snuppy appears to be genuine, and his nuclear extrusion technique was also used by Dr. Schatten and colleagues successfully cloning a monkey. The Hwang affair is therefore a remarkable story about a talented researcher that ended up wasting his career and talent (3).

It is interesting to note that Norway has suffered from a similar scandal, namely the case of Dr. Jon Sudbø, a former researcher at Radiumhospitalet in Oslo. Interested readers can have a look at “What can we learn from the Hwang and Sudbø affairs” (Paul gerber, 2006, Medical Journal of Australia) and http://en.wikipedia.org/wiki/Jon_Sudbø.

Sources

1. “Profile: Woo-Suk Hwang”, Apoorva Mandavilli, (http://www.nature.com/nm/journal/v11/n5/full/nm0505-464.html)

2. Hwang WS et. al, “Evidence of a pluripotent human embryonic stem cell line derived from a cloned blastocyte”, Science, 2004.

3. Saunders R, Savulescu J, “Research ethics and lessons from Hwanggate: what can we learn from the Korean cloning fraud?”, J. Med. Ethics., 2008.

4. Hwang WS et. al., “Patient-specific embryonic stem cells derived from human SCNT blastocysts”, Science, 2005.

5. Rusnak AJ, Chudley AE, “Stem cell research: cloning, therapy and scientific fraud”, Clinical Genetics, 2006.

6. Hong S, “The Hwang scandal that “shook the world of science””, East Asian Science, Technology and Science: an International Journal, 2008.

7. Steve Connor, “Dr Hwang and the stem cell swindle”, The Independent, October 2009.

8. “Timeline of a controversy”, Nature (http://www.nature.com/news/2005/051219/full/news051219-3.html)

Human stem cell cloning – what’s taking so long?

As mentioned in Stem Cells: the fundamentals earlier in this magazine, stem cell cloning generally refers to the creation of an embryonic stem cell from a somatic cell nucleus and an egg cell. This is done by somatic cell nuclear transfer (SCNT). The reason why Hwang and colleagues gained so much temporary fame for the 2005 and 2006 stem cell cloning articles (the story of Hwang and his fraudulent papers are described earlier in this magazine), is the great potential that lies in mastering this technology. However, this has been practiced for over a decade already, namely in the cloning of animals.

Since the birth of Dolly the sheep in 1996, the first cloned mammal, the list of species which have been cloned has grown long; cats, dogs, mice, fish, horses, pigs and rats to mention a few (1, 2). The birth of a cloned animal always gets news coverage, and is of great interest to the general public. More importantly, every animal clone that is born is evidence that the researchers have managed to create a cloned embryonic stem cell from a somatic stem cell. Despite this long list of the successes of animal cloning using SCNT, and the great interest in the scientific community in creating cloned human embryonic stem cells, the first real evidence of a human blastocyst cloned from a somatic cell came in a 2008 article in the journal Stem Cells. (3) (see pic 1). This is twelve years after the first cloned mammal. Apparently, scientists are already mastering SCNT for numerous species, so why is human stem cell cloning progressing so slowly? Indeed, animal cloning has to a certain degree served as pioneering research for human stem cell cloning-research. This is evident in the heavy citation of animal embryonic cloning articles in the human stem cell cloning articles (3, 9). However, the first animal clones were probably not projects with human stem cell research as primary underlying motivation.

The creation of Dolly was the result of a long and labourious process, with many unsuccessful implantations. Before Dolly was created, scientists was even unsure as to whether or not they would manage to clone a mammal (4). The amount of trial and error associated with the first years of animal clonings would have been unacceptable given the high value a human egg cells (there is a risk of death associated with donation of egg cells). These points taken together, it is reasonable to assume that human stem cell cloning has actually been made possible by the accumulating experience and skill in animal cloning, and that this has happened the last 4-5 years. Another reason for the rather slow pace is the fact that laws, regulations and paperwork associated with research on human stem cells naturally are much more complex than for stem cell research with animals. Western countries are also the strictest. In the US, for example, federal funding of research on cloned embryos is not even permitted, and a lot of the embryonic stem cell research has been taking place in Asian countries (5). It is therefore rather illustrative of the situation (at least in the western world) that the 2008 ground-breaking paper mentioned above was published by three private stem cell research companies – Stemagen, The Reproductive Sciences Center and Genesis Genetics (6, 7, 8)
(Genesis Genetics also offers preimplantation genetic diagnosis (PGD), discussed in the article What kind of baby do you want? in our magazine).

A mystery in the science of cloning is that the results are not always reproducable (of course, the non-reproducable results of Hwang are rather easy to explain). The same scientist might try to repeat his/her own cloning experiment using the same procedure, and fail to produce a viable clone. After the cloning of Dolly, for example, scientists in other countries were first unable to clone sheep using the same protocol. A possible explanation for this is that cells are very sensitive to minute differences in concentrations in both the external (growth media) and internal (inside the cell) environment. This means that success or failure is dependent not only on very precise external conditions, but also that the same cell type in different individuals might respond differently to the same conditions (11). One might conclude from this discussion that cloning is a rather new science, and that the slow progress of human stem cell cloning is due to the complexity of the science itself, and the regulations and precautions necessary for this research field. It is also reasonable to suspect that human stem cell cloning only has been a feasible project after knowledge and skills from animal cloning accumulated. Again, the prospects of human stem cell cloning are exciting, and the research is guaranteed to give very interesting results.

Sources:

(1)http://library.thinkquest.org/20830/Frameless/Manipulating/Experimentation/Cloning/longdoc.htm

(2) http://www.businesspundit.com/20-animals-that-have-been-cloned/

(3) ”Development of Human Cloned Blastocysts Following Somatic Cell Nuclear Transfer with Adult Fibroblasts”, French AJ, Adams CA, Anderson LS, Kitchen JR, Hughes MR, Wood SH., Stem Cells, 2008.
(http://onlinelibrary.wiley.com/doi/10.1634/stemcells.2007-0252/pdf)

(4) “Death of Dolly marks cloning milestone”, Nigel Williams, Current Biology, 2003. http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6VRT-4861XN1-1-1&_cdi=6243&_user=586462&_pii=S0960982203001489&_origin=gateway&_coverDate=03%2F18%2F2003&_sk=999869993&view=c&wchp=dGLzVtz-zSkWb&md5=d0712861ad290406e3fee87d9556b800&ie=/sdarticle.pdf

(5) “The case for cloning humans”, Ian Welmut, The Scientist, 2005. http://www.the-scientist.com/article/display/15421/

(6) Stemagen Homepage: http://www.stemagen.com/

(7) Reproductive sciences center homepage: http://www.fertile.com/

(8) Genesis Genetics homepage: http://www.genesisgenetics.org/

(9) http://www.liebertonline.com/doi/pdf/10.1089/clo.2008.0041

(10) http://www.explorestemcells.co.uk/TherapeuticCloning.html

(11) Thanks to Prof. Atle M. Bones at Institute of Biology, NTNU, for a very informal chat about cloning.

(12) http://www.newscientist.com/article/dn1931-cloners-create-worlds-first-copycat.html

Stem Cells – the fundamentals

Stem cells are unique
The human body is a complex mixture of various specialized cell types, each with its own characteristics and functions. Examples of such specialized cell types are nerve, muscle, bone, blood, cartilage and fat. These cells are also called differentiated cells, which means that they have been transformed into a certain cell type through a special process called differentiation. Differentiated cells are produced from populations of immature cells called stem cells (Becker et al 2009). Stem cells have three important properties that distinguish them from other body cells: they are unspecialized, they can renew themselves by infinite cell division and they can mature into specialized cells with a certain morphology and function (Store Medisinske Leksikon 2011).

Division and differentiation
Five thousand cells in our body die every second, but as long as we stay healthy, new cells will continuously replace the dead cells. This phenomenon can be explained by stem cells. Stem cells have a unique potential to develop or differentiate into many different cell types during early life and growth. They also serve as an internal repair system in many tissues where they divide infinitely to replenish other cells while the person or animal is still alive.
A normal stem cell divides to give two new cells. Each of these cells has the potential to remain a stem cell or to differentiate through several stages into another cell with a specialized function such as for instance a red blood cell (Alberts et al 2004). The differentiation process is unidirectional, meaning that once the stem cell has morphed into a more specialized state, it normally cannot reverse the process and become a stem cell again. Induced pluripotent stem cells, iPSCs, are an exception. They are artificially derived adult cells that have been induced to express certain genes in order to adopt a stem cell-like state (National Institutes of Health 2006).

The stem cells in different organs behave differently. Stem cells in the bone marrow divide regularly to repair and replace damaged or worn out tissues, while neural stem cells only divide under special conditions. Stem cells are organized into four categories based on the degree of differentiation.
A totipotent stem cell is a cell that can differentiate into any cell and tissue in the body in addition to the placenta. A fertilized egg cell is an example.
A pluripotent stem cell is a cell that can give rise to all the cells of the body except the placenta. Embryonic stem cells, (will be explained later) are pluripotent.
A multipotent stem cell is a cell that can specialize into several related cells in a certain tissue. Blood stem cells can for instance give rise to red blood cells, white blood cells and blood platelets.
A unipotent stem cell is a cell that can only develop into a specific cell type. A muscle stem cell is a unipotent stem cell (Store Medisinske Leksikon 2011).

The three major sources for stem cells in humans are the embryonic stem cells, the adult (or somatic) stem cells, and stem cells that can be derived from the umbilical cord.

Embryonic stem cells
As the name reveals, embryonic stem cells are derived from embryos. In research however, these embryos are usually derived from eggs that have been fertilized in vitro, that is, outside the body. If an egg cell is fertilized in vitro in the laboratory, the fertilized egg can be used as a source for stem cells instead of developing into a foetus. Five to six days after the fertilization, a blastocyst is formed. A blastocyst is a preimplantation embryo of about 150 cells produced by the cell divisions that follow the fertilization. The blastocyst is a sphere containing an outer layer of cells, a fluid-filled cavity and a cluster of cells on the interior. A few embryonic stem cells are found in the inner cell mass of the blastocyst. The embryonic stem cells are called pluripotent because of their capability to differentiate into many cell types (“pluri” is latin and means “more”). Scientists have proved in the laboratory that stem cells from blastocysts formed by in vitro fertilization can produce different cell types including blood, nerve, skin and heart muscle (Bioteknologinemda 2010).

Adult stem cells
Adult stem cells are undifferentiated cells that can renew and repair the tissue in which they reside. They are also called somatic stem cells. Adult stem cells are either multipotent or unipotent. They are found in a “stem cell niche” among other differentiated cells that make up the specific tissue or organ. The ability to renew and repair tissues makes the adult stem cells interesting in order to perform transplants. However, the number of stem cells in each tissue is limited, so scientists have difficulties with generating large quantities of cells that are needed for research. The term “adult stem cells” covers several types of stem cells. The bone marrow contains at least two different types of stem cells. The hematopoietic stem cells form all the types of blood cells in the body, while the stromal stem cells (sometimes called mesenchymal stem cells) can generate bone, cartilage, fat, cells that support blood formation and connective tissue. Another example of adult stem cells are neural stem cells that can give rise to astrocytes, oligodendrocytes and neurons, which are the three major cell types in the brain. (National Institutes of Health 2006).

Stem cells from the umbilical cord
When a child is born, the umbilical cord contains blood from the placenta and the foetus. This blood has a high concentration of stem cells. Most of these stem cells are hematopoietic and stromal stem cells that can be used to treat children suffering from leukaemia. The number of stem cells that can be isolated from one umbilical cord is estimated to be too low to treat adult humans, so scientists are currently investigating the possibilities to enhance the number of cells in order to treat adults as well. It is now possible to keep the umbilical cord blood when the child is born and store it in special banks for potential future use. Such banks have been established in some countries in order to offer stem cells to children who do not have access to stem cells from bone marrow (Bioteknologinemda 2010).

Similarities and differences between adult an embryonic stem cells
The major difference between adult and embryonic stem cells is the range of cells that can be produced from each stem cell type. Because of the pluripotency of the embryonic stem cells, they can produce all the approximated 200 cell types that exist in the human body. Adult stem cells are thought to be more limited because they only differentiate into the different types of cells of the tissue in which they reside.
A large number of cells are needed for stem cell research and replacement therapies. When culturing stem cells, the embryonic stem cells are grown more easily than the adult stem cells. The extraction of adult stem cells is a complex process due to the small amount of cells in the mature tissue, and an efficient method for enhanced proliferation is still not worked out (National Institutes of Health 2006).

Stem cells and cloning
Dolly, the first cloned mammal, was born in 1996. She had the exact identical set of genes as her biological mother. After Dolly, several other animals have been cloned in the same way. The cloning method used in these cases is called somatic cell nuclear transfer (SCNT). This technique involves removing the nucleus from an egg cell, thereby stripping it for its genetic material. A nucleus from an ordinary (somatic) cell is then injected into the mature egg cell. By using a mature egg cell (a cell ready for fertilization), the environment inside the cell automatically reprograms the injected genetic material from the somatic cell. The egg cell will be almost identical with the fertilized egg that gave rise to the organism from which the somatic cell nucleus was harvested. After artificially stimulating the egg cell with the injected nucleus, the cell will divide to form a blastocyst, from which embryonic stem cells can be harvested (Rusnak and Chudley 2006).

If the blastocyst is used as a source for stem cells for treatment, the process is called therapeutic cloning. If the blastocyst is inserted into a uterus, it can develop into a foetus. The latter process is called reproductive cloning. (Bioteknologinemda 2010)

Therapeutic cloning has great potential within the field of medicine. Cells, tissues and possibly whole organs can be produced and tailor made to fit each patient. Since cells and tissues with the recipients own DNA can be derived from therapeutic cloning, the risk for immunogenic rejection after transplantation can be reduced.

Potential applications of stem cells
Currently, scientists are using stem cells in the laboratory to study normal growth and development, identify causes of birth defects and to screen and test how new drugs affect the cells. Another important application of stem cells is within the field of regenerative medicine. Regenerative medicine is based on the fact that cells derived from stem cells can generate replacements for cells that are lost or injured. Through cell or tissue regeneration and transplantation, stem cells offer possibilities for treating diseases such as diabetes, Alzheimer’s disease, Parkinson’s disease and muscular dystrophy. Scientists hope that regenerative medicine based on stem cells can be offered as an important supplement to existing treatments for a range of diseases in the future.

Sources

1. Becker, W. M. et al, “The World of The Cell”, seventh edition, Pearson International, 2009

2. Store medisinske leksikon
http://www.snl.no/.sml_artikkel/stamcelle

3. Alberts, B. et al, “Essential Cell Biology”, second edition, Garland Science, 2004.

4. The National Institutes of Health (U.S.)
http://stemcells.nih.gov/info/2006report/
http://stemcells.nih.gov/info/basics/

5. Bioteknologinemda
http://www.bion.no/filarkiv/2010/0/2004_09_stamceller_og_kloning.pdf

6. Rusnak AJ, Chudley AE, “Stem cell research: cloning, therapy and scientific fraud”, Clinical Genetics, 2006.

Stem cell regulations in Norway

Norway is not considered a leading stem cell research country, possibly as a result of the limiting regulations set by the government. Neighboring countries such as Sweden, Denmark and England have allowed research on embryonic stem cells for several years, leaving Norwegian research behind (Solberg 2009). All though, cases in recent years have led to a slight loosening of the strict regulations, bringing optimism and enthusiasm about Norway’s stem cell research. The stem cell research is associated with high expectations, shown by the Norwegian government’s 28 million kroner investment in a public stem cell research center in 2008/2009 (Dagens medisin 2009).

Stem cell research concerning bone marrow, tissue and brain puts Norwegian scientist on the global map, while research on embryonic stem cells seems stalled. This might be due to a legislation from 2003 stating a strict ban towards research on fertilized eggs, an extension of a regulation accepted in 1994. The 1994 regulation was first changed in 2002, to ensure that the legislation also covered the ban of research on human embryos and cell lines originating from fertilized eggs or human embryos. The arguments supporting this ban were they believe in humans as well as the protection of the evolving human life. In 2008 a new legislation cancelled this ban and opened the possibility to perform research on redundant embryos (Helse og omsorgsdepartementet 2006-2007).

Redundant embryos appear as a result of fertilization of more eggs than needed for artificial insemination. In addition, appearance of low-quality eggs not suited for further insemination also goes to waste. It has been estimated that Norway annually destroys about 15000 redundant embryos (Dagens Næringsliv 2006). It is a paradox that Norwegian hospital workers are expected to perform high quality artificial insemination, without being allowed to practice on human fertilized eggs. It is reasonable to believe that Norwegian hospital workers have received their training outside of Norway (Berge 2009). One aim of the 2008 legislation is therefore to make it easier to improve skills and aim a higher degree of quality of artificial insemination.
Further, a case from 2004 became a trigger for a change included in the 2008 legislation. 2004 became a year with media storm followed by public debate as a result of the “Mehmet case” (Andersen 2004).

A six year old boy named Mehmet is born with the inherited disease Thalassami. The disease makes the boy dependent on monthly blood transfer, unfortunately resulting in accumulation of iron in target organs such as brain and liver. These circumstances give Mehmet a limited life expectancy of 40 years. The disease can be cured if the patient receives stem cells from a suitable donor, most likely a sibling (Andersen 2004). This case raised the ethical question: Is it acceptable to raise donor siblings? Mehmet could be saved if Norway allowed pre implantation genetic diagnosis (PGD). This means that in vitro (outside the body) fertilization must be performed, followed by selection of the most suitable embryo.

In this case, most suitable meaning an embryo genetically free of Thalassami combined with tissue matching Mehmets tissue. Despite split views among Norwegian politicians the government decided to allow PGD with the purpose to find suitable stem cell donors (Andersen 2004). The legislation came with a limitation though, each case must be considered independently by a selected committee before accepted. To be evaluated, one or both parents must genetically carry a seriously or possibly lethal disease. The legislation was officially accepted in 2007, and took effect 1^st of January 2008 (Norsk Lovdata 2007). Besides from improving skills on PGD and artificial insemination, the 2008 legislation states the allowance of research on stem cells with the aim of gained knowledge. This knowledge about stem cells might give clues in future treatment for diseases such as Alzheimer, Parkinson, diabetes and cancer. The 2008 legislation emphasizes that research on stem cells is only allowed for the mentioned purposes. Research resulting in inheritable genetically changes are still considered illegal (Norsk Lovdata 2007).

Norway’s stem cell research regulation might seem strict from a stem cell enthusiast’s view. But the Norwegian government’s regulation also seems to be precautionary and based on carefully evaluated decisions.

Sources:

1. Solberg Berge, 30.03.2009, ”Nasjonale lover og internasjonal forskning på stamceller”, Forskningsetisk bibliotek, Oslo

2. Dagens medisin, 27.11.2009, ”Åpner stamcelle-senter”, Dagens medisin.

3. Helse og omsorgsdepartementet, ”Om lov om endringer i bioteknologiloven (preimplantasjonsdiagnostikk og forskning på overtallige befruktede egg)”, nr. 26, 2006/2007, Oslo

4. Dagens næringsliv, 26.01.2006, ”egg og etikk”, Dagens næringsliv, Oslo

5. Andersen K. Elisabeth, 23.03.2004, ”Hva er det med Mehmet?”, Forskning.no, Oslo

6. Norsk lovdata. Nr.6-2007, lov nr 31, side 678: ”Lov om endring i bioteknologiloven”

Important discoveries within the history of stem cell research

The beginning of stem cell research
From 1958 and up until today the research and discoveries within the stem cell field has evolved a lot. This article will give an insight on the research done within the field. Stem cell is a research field getting a lot of publicity. One hops that in the future stem cells can be used to create new organs and body parts. A lot today’s medicine can give side effects which reduces the patient’s life quality, and scientists hope that stem cells can provide an entirely new kind of medicine, without any side effects.

Stevens working at a laboratory in Maine was the first person to identify pluripotent tendencies in cells. The same year he also published his work on mouse teratocarcinomas. In 1970 Stevens sees that the mouse primordial germ cells that gave rise to teratomas, resemble cells of earlier embryos and when transplanted into adult mice tissues can differentiate into teratocarcinoma cells. In 1975 Beatrice Mintz and Karl Illmensee, from the institute for Cancer Research in Philadelphia, determines that ES cells can give rise to organisms, as well as teratomas (Garland Science).

Early development of in vitro fertilization
In 1934 doctor Gregory Pincus at the Harward University managed to achieve in vitro fertilization of rabbits. This achievement suggested that a similar type of technique can be applied to humans. By achieving this in 1934 he was ahead of his time and as a result, he got a negative reputation. He was even described by the media as a modern Dr. Frankenstein. Twenty-five years later, in 1958 Dr. Min Cuheh Chang published a study showing that rabbit eggs developed in vitro could develop as rabbits born conventionally. The study led to the acceptance of in vitro fertilization in humans, as a clinical infertility treatment. During the 1950 to 1970 Dr. Chang studied a variation of animals, such as rabbits, rats, mice and hamsters. In this period he identified main assumptions for in vitro fertilization to be successful, especially related to reproduction. The ten years from 1950 to 1960 were said to be the most significant time in the history of in vitro fertilization (Bavister 2002).

Pluripotent stem cells, what?
The rapidly moving research on stem cells is built upon already existing knowledge that is being modified to create new facts and principles. The isolation of pluripotent stem cells, meaning cells that have the potential to differentiate into almost any part of the body, was a major discovery. The isolation of pluripotent stem cell provided the possibility to produce a full range of cell types at an early stage of the embryos development. Scientist have in less than a decade made huge progress in the possibilities of pluripotent stem cells. The opportunities have expanded from being able to isolate and grow pluripotent stem cell from early embryos in the laboratory to regenerate the pluripotent cells. The advanced research within stem cell therapy makes it now in principle possible to reconstruct or replace diseased tissue as well as for gene therapy. Pluripotent stem cells, also known as embryonic stem cells have set and will continue to set the standard for pluripotentiality research. But the promise is being held by the induced stem cells, which is a type of pluripotent stem cells that are forced to express a specific gene (Trounson 2009).

Hematopoietic and embryonic stem cells
Studies on hematopoietic stem cells have uncovered that the hematopoietic stem cell contains a lot of unique properties, not yet found in other cell types. It has for example a self-renewal division and a division inhibiting the structures that pull a cell apart when it divides leading to a production of the same stem cells. An important founding on adult hematopoietic stem cells is that they give rise to many other cell types in the blood. Biologist have through the development of embryos searched for an answer on how a complex organism evolves from a single cell to the fertilized egg. One frequent used strategy in the development of embryonic stem cells is to see the use of embryonic stem cells to help generate and maintain a given tissue or organ (Rossant 2009).

In the future
To treat patients using stem cells, preclinical studies of animals is being conducted to understand the patients clinical condition. It is highly desirable to understand the biological mechanisms underlying the observed therapeutic effect, before treating a patient. One of many fascinating aspects within stem cell research is that it could lead to the development of new therapies for human disorders that currently can not be effectively treated. All fields within stem cell research is now quickly progressing. At the same time it is important to point out that stem cell therapy can only treat a very small number of human conditions. So far there are hematopoietic stem cell transplants, leukemia and stem-cell-based treatments for burns and corneal disorders. All other clinical applications are now still in the experimental state. A big issue concerning the stem cell identity has been brought up and questioned whether stem cells exist as a defined clone in each organ is whether they are being sustained throughout the development of the organ, or if stem cells are a product of organ function to maintain each organ.

Sources:

1. Garland Science
http://www.garlandscience.com/textbooks/cbl/stemcell/corematerials/timeline.html Hentet 21 februar 2011.

2. Bioteknologinemda
http://www.bion.no/temaer/stamceller/#s2 2010, hentet 31. januar 2011.

3. Bavister B, “Early history of In vitro fertilization”, Department of Biological Sciences, University of New Orleans, and the Audubon Center for Research of Endangered Species, New Orleans, 2002.

4. Il-Hoan O, Dong-Wook K, “Three Dimensional Approach to Stem Cell Therapy”, J Korean Med Sci, 2002.

5. A Trounon, in Lanza R, “Essentials of stem cell biology”, 2nd ed. Academic press, Canada 2009.

6. Rossant J, in Lanza R, “Essentials of stem cell biology”, 2nd ed. Academic press, Canada 2009.

7. Lindvall O, in Lanza R, “Essentials of stem cell biology”, 2nd ed. Academic press, Canada 2009.