Genes

A totipotent cell can differentiate into any cell type, including the extra-embryonic (placental) tissues, and so can give rise to a whole organism (e.g. the zygote).

A pluripotent cell can differentiate into any cell type of the body, but not the extra-embryonic/placental tissues (e.g. embryonic stem cells of the inner cell mass).

A multipotent cell can differentiate into only a limited range of related cell types (e.g. bone-marrow stem cells forming the different blood cells).

Embryonic stem cells, obtained from the inner cell mass of an early embryo (blastocyst), are pluripotent.

Adult (tissue) stem cells, found in tissues such as bone marrow, are multipotent.

Induced pluripotent stem cells (iPSCs), produced by reprogramming a patient's adult body cells (e.g. skin cells), are pluripotent.

Epigenetics is a heritable change in gene expression that does not involve a change in the DNA base sequence.

Unlike a mutation, an epigenetic change does not alter the DNA base sequence (it adds chemical marks such as methyl groups), and it can be reversible.

Mitosis produces genetically identical cells, so every cell contains the same genome — the same complete set of genes.

Cells become different because of differential gene expression: in any given cell, only some genes are switched on (transcribed) while the rest are switched off. The cells do not gain or lose genes.

Which genes are expressed is controlled at the level of transcription. Transcription factors bind to the DNA (e.g. the promoter) and determine whether RNA polymerase can transcribe a gene: activators switch genes on, repressors switch them off. Different cell types contain different transcription factors.

Gene expression is also controlled epigenetically, for example by DNA methylation switching genes off and histone acetylation switching genes on, which fixes the pattern of active genes in a cell.

Because each cell type transcribes a different set of genes, it makes different proteins, which give it a different structure and function — so it becomes a particular specialised cell type.

Transcription factors are proteins that bind to specific DNA sequences, such as the promoter region at the start of a gene.

An activator transcription factor helps RNA polymerase to bind to the gene, so the gene is transcribed — it is switched on and the corresponding protein is made.

A repressor transcription factor binds in a way that prevents RNA polymerase binding, so the gene is not transcribed — it is switched off and no mRNA (and so no protein) is produced.

Because different cell types contain different combinations of transcription factors, they transcribe different genes, which contributes to differential gene expression.

DNA methylation involves adding methyl groups (–CH₃) to the DNA, usually in the promoter region of a gene. This makes the gene inaccessible, so transcription factors and RNA polymerase cannot bind; the gene is switched off and not transcribed. More methylation therefore silences the gene.

Histone modification affects how tightly the DNA is packed around histone proteins to form chromatin. Acetylation (adding acetyl groups to the histones) loosens the chromatin, so the DNA is more accessible and the gene can be transcribed (switched on). In contrast, deacetylation (removing acetyl groups) and histone methylation make the chromatin more condensed and tightly packed, so the transcription machinery cannot reach the gene and it is switched off.

Together, these mechanisms determine which genes are expressed in a particular cell, allowing cells with the same genome to become specialised.

They are described as epigenetic because they change gene expression without changing the DNA base sequence — only chemical groups are added or removed. The marks are copied when the cell divides, so they are heritable through cell division, yet because the base sequence is unchanged they are not mutations and can be reversed.

Sample X (cells from the zygote) is totipotent: it can differentiate into any cell type, including the extra-embryonic (placental) tissues, and so could give rise to a whole organism.

Sample Y (inner cell mass of the blastocyst) is pluripotent: it can differentiate into any cell type of the body, but not the extra-embryonic/placental tissues.

Sample Z (adult bone-marrow stem cells) is multipotent: it can differentiate into only a limited range of related cell types. A named example is that bone-marrow stem cells can form red blood cells (or white blood cells / platelets).

Comparing their potency, sample X (the totipotent zygote cells) could produce the widest range of tissues, because totipotent cells can form every body cell type plus the placental tissues — a wider range than pluripotent Y (body cells only) and far wider than multipotent Z (only a few related blood-cell types). The order of versatility is therefore totipotent (X) > pluripotent (Y) > multipotent (Z).

(a) As promoter methylation increases, the amount of protein produced decreases. In healthy tissue methylation is low (8%) and protein is high (100 units); in cancerous tissue methylation is much higher (71%) and protein is far lower (12 units). So there is a negative correlation between methylation and protein level — methylation rose by about 63 percentage points while protein fell to about 12% of the healthy value.

(b) The added methyl groups in the promoter make the gene inaccessible, so transcription factors and RNA polymerase cannot bind. The tumour-suppressor gene is therefore not transcribed, so little or no mRNA is made, and so very little protein is produced. With the tumour-suppressor protein switched off, cell division is no longer properly controlled, which can contribute to cancer.

(c) This is an epigenetic change because the DNA base sequence has not been altered — only methyl groups have been added to the DNA. The gene itself is unchanged; what has changed is whether it is expressed. (In principle the methylation could be removed and the gene reactivated, unlike a mutation in the base sequence.)

Because stem cells can divide and differentiate into specialised cells, they could be used to replace cells or tissues that are damaged, lost or not working. Examples include using bone-marrow (multipotent) stem cells to replace blood-forming tissue in leukaemia, replacing the dopamine-producing neurones lost in Parkinson's disease, replacing insulin-producing β-cells in type 1 diabetes, repairing heart muscle after a heart attack, treating spinal-cord injury, and growing skin for burns. Stem cells are also valuable for testing new drugs and studying how diseases develop.

iPSCs are made by reprogramming a patient's own adult cells (e.g. skin cells) back to a pluripotent state, so they can form any body cell type — the same versatility as embryonic stem cells.

They may be preferred to embryonic stem cells for two main reasons. First, they are produced without destroying an embryo, so they avoid the main ethical objection. Second, because they are derived from the patient's own cells, any tissue grown from them is genetically identical to the patient, so it is less likely to be rejected by the immune system. These advantages make iPSCs an attractive route to safe, individualised stem-cell therapies.

Stem-cell therapy using embryonic stem cells raises strong ethical arguments on both sides, and a balanced judgement must weigh them against each other.

Arguments against. Embryonic stem cells are obtained from the inner cell mass of an early embryo, and harvesting them usually destroys the embryo. People who believe that human life begins at fertilisation regard the embryo as a potential human being with the right to life, so destroying it is seen as ethically equivalent to ending a human life. There are further objections: the embryo cannot give consent; some object to embryos being created or used as a means to an end; and there are safety concerns about a new technology (for example, the risk of stem cells forming tumours) and fears of a "slippery slope" towards reproductive cloning.

Arguments in favour. Stem-cell therapies have the potential to relieve great suffering and save lives by treating conditions that are currently untreatable, such as Parkinson's disease, type 1 diabetes, spinal-cord injury and the after-effects of a heart attack. Many of the embryos used are "spare" embryos left over from IVF that would otherwise be discarded, so some argue it is better to use them for research that could benefit others. Supporters also point out that an early embryo is a tiny ball of unspecialised cells with no nervous system, and so does not experience suffering.

Reducing the conflict. Importantly, adult (tissue) stem cells and induced pluripotent stem cells (iPSCs) can provide many of the same benefits without destroying an embryo at all, and iPSCs additionally reduce immune rejection because they come from the patient's own cells. This offers a route that respects objections to using embryos while keeping most of the medical benefit.

Conclusion. The central conflict is between the potential to relieve enormous human suffering and respect for the moral status of the embryo. Given that iPSCs and adult stem cells increasingly offer comparable therapeutic potential without destroying embryos, a reasonable conclusion is that research should prioritise these sources, restricting the use of embryonic stem cells to cases where no alternative exists and where embryos are donated with informed consent. Whatever stance is taken, it should follow logically from the balance of arguments above.