How to Build a Human: Adventures in How We Are Made and Who We Are. Philip Ball

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СКАЧАТЬ rise to different cell types and tissues, on the other hand, are generally systematic and preordained in the genes – not in the sense that they will happen come what may, but that they are destined to be a part of the developmental programme so long as it proceeds without mishap. Some epigenetic changes aren’t preordained at all, though. They may take place in response to the contingent environment of a cell or organism, including unpredictable events arising from randomness within the network of interacting genes themselves. This is one reason why identical twins, who have the same genomes, may look rather different later in life. They have different environmental nudges, and this affects the epigenetic programming of their genes. Some dietary chemicals such as curcumin (found in curry spices) and resveratrol (in grapes) seem to have epigenetic effects on the folding-up of chromatin in cancer cells, while deficiencies of folate (a chemical in pulses and grains) can alter epigenetic patterns of methyl attachment to DNA. (Whether this means that red wine and tikka masala protect against cancer is another matter.) Drugs and pollutants can also act, for better or worse, via their influences on the epigenetic (as well as genetic) programming of cells.

      Given that Waddington proposed the idea of an “epigenotype” – which he called a “whole complex of developmental processes between the genotype and phenotype” – in 1942, it is a little odd that epigenetics has been portrayed in recent years as a field that is “revolutionizing” biology. Perhaps that’s just how it looks if you’re starting from a simplistic view in which cells are nothing more than player-pianos orchestrated by their punched-hole genetic scripts – that’s to say, if you had a faulty story to begin with.

      All the same, it is only in the past several decades that we have had a more detailed understanding of how epigenetics works at the scale of cells and molecules. There are still many holes in that understanding. Some researchers now talk in terms of an epigenetic code that imposes itself on and modulates the “all-powerful” genetic code. But epigenetics is a dynamic process, for which a “code” might be the wrong metaphor. Sure, there may be an epigenetic signature characteristic of, say, a fibroblast cell. But the epigenetic status of a human being is constantly changing and depends on our personal history.

      It is the recognition of contingency in a cell’s epigenetic state that underpins the real revolution in biology. For, as the growth of my mini-brain from skin cells attests, the specification of cell fate is not irreversible. If we cling too strongly to the evolutionary metaphor of cell lineage, that sounds crazy: it’s like saying that you could be transformed back to a pre-human Australopithecus (more properly, to the common ancestor we Homo sapiens shared with that early hominid).

      But for cells, such things are possible. The history of our flesh can be reversed and revised, and this completely transforms the possibilities for what it can become – and what we might do with it. We will see later how this can be achieved.

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      It should come as no surprise that there’s plenty of contingency and circumstance involved in the way genes, epigenetics and cell interactions combine to create a human being. Of course the environment can play a major and perhaps even catastrophic part. Drugs (licit and otherwise), alcohol, hormones and environmental contaminants entering the mother’s bloodstream during pregnancy can disrupt the process, for example, in ways that are transformative to the embryo or fetus.

      We might tend to imagine that this is just a matter of a “plan for a person” that either proceeds as it should or gets thrown off course. But I will end this chapter by looking at one more way in which a simplistic picture of the person being a kind of “read-out” of the genes in a zygote can be profoundly misleading. The person – their body, their chromosomal inheritance of propensities – is not so easily condensed into a single type of cell. For just as human societies can be diverse, so can the cell societies that comprise a human individual.

      Non-identical twins, for instance, may each have a mixture of red blood cells from both twins. Red blood cells are unique in the human body in having no chromosomes: they are produced not by cell division but by transformation of a special kind of cell in bone marrow. They fall into particular general classes – blood groups – depending on the chemical structure of protein molecules on the surface of the cells. Normally, each individual has red blood cells of a specific blood group, but twins can have a mixture of each twin’s blood group.

      This was first discovered in non-identical twinned cattle calves by the American biologist Ray Owen in the 1940s. In 1953, British physicians Ivor Dunsford and Robert Race found a similar case of two distinct blood groups in a human, a patient denoted Mrs McK who was tested before donating blood. Mrs McK had no living twin, but she told the puzzled doctors that she had had a twin brother who had died at three months old. The mixture of blood types here come from the fact that twins share a blood circulation system in the uterus, and so may exchange blood-forming cells that continue to produce blood long after birth and perhaps for a lifetime.

      This presence of cells from more than one “biological individual” persisting and carrying out their biological function in a single organism is said to make it a chimera. Robert Race coined the term in describing the case of Mrs McK, admitting that he was simply looking to give his paper a catchy title.

      People can be chimeric in much more dramatic ways than this. Their entire bodies can be patchworks of cells that seem to come from two different people. One way this can arise is by the fusing, at a very early stage of development, of non-identical twin embryos in utero. In a demonstration of how our cells can adjust to “unforeseen circumstances”, these fusions can give rise to an anatomically normal individual whose cells got their genetic material from two different pairs of gametes: they are said to be tetragametic. This can happen even if the embryos that fused were of different sexes: the reproductive organs will then be decided by which set of cells in the merged embryo happens to produce them. But the chimeric person’s body as a whole is not specifically gendered one way or the other in terms of the usual XX/XY chromosomal distinction: it is a bit of both.

      Chimerism can also arise from exchange of cells between an embryo and the mother carrying it. These two “individuals” are conjoined via the placenta, which, as I explained earlier, is a mixture of cells from both of them. But the placenta is a rather leaky barrier. So cells from the mother can become incorporated into the embryo and fetus, while the developing child’s cells may enter the body of the mother.

      In fact, some degree of exchange, known as microchimerism, is normal. Many women who are pregnant with sons, for example, acquire some cells with Y chromosomes. What surprised researchers when this exchange came to light in the 1990s is that these fetal cells may persist and remain active, albeit at a low level, in the mother for many years after the child is born. But while microchimerism affects just a small proportion of the body’s cells, a process like embryo fusion to create a tetragametic chimera makes a person who is genetically heterodox through and through: some organs and body parts come from one embryo, some from another.

      If I were a mixture of the flesh of “two people”, what would that make me? It is tempting to say that such an individual is indeed a mixture of two people in one. But that seems a profoundly odd and unhelpful way to look at the matter, for in what meaningful sense were those twin embryos “people” before they fused? These clusters of cells have only given rise to a single individual. This is just one of the ways in which quirks of developmental and reproductive biology undermine a simplistic determination to invest an embryo with unique personhood. A “person” is a higher-order concept, not to be reduced to genes or cells.

      Still, our habits of thought and even our laws are challenged by these discoveries. DNA analysis of a tissue sample from a tetragametic woman may fail to confirm that her biological children are “hers”, if the sample does not happen to share chromosomes with her gametes. Such cases have come to light through genetic testing to confirm maternity in applications for social welfare benefits in the United States, leading to harrowing accusations of false claims of parentage. СКАЧАТЬ