1 “Somatic” is a word we will encounter a lot. It simply means “bodily” or “of the body”.
1 Some crystals, and parts of crystals, do “inherit” structure from others, thanks to their ability to act as a kind of template for further growth. It is for this reason that one speculative theory for the origin of life has proposed that clay minerals were able to act as a kind of prebiotic, inorganic carrier of genetic information, while the biologist Hermann Muller suggested in 1921 that the replication of genetic material in cells might parallel the templated growth of crystals. In 1943, physicist Erwin Schrödinger famously proposed that genes might be encoded in an “aperiodic crystal” – one that lacks a regular atomic organization.
2 The same word is used in atomic physics to describe the dense core of the atom, where nearly all of its mass resides. I love the coincidence that Brown’s observation of the dancing motions of pollen grains in water, caused by collisions with molecules, was what led ultimately to experimental proof in 1908 that atoms are real objects and not just a handy conceit for thinking about the structure of matter. Just three years after that, Ernest Rutherford discovered the atomic nucleus.
3 Surprisingly there are still a few advocates of that view – the “protoplasm theory” of life – today. For the fact is that the cell’s wall or membrane is not merely a “housing” for all the machinery. Confinement of the contents, and their isolation from the surrounding environment, are essential for a cell to function as a living thing.
4 Metabolism can, however, be put on hold in some cells and organisms in certain circumstances: they can become quiescent, in a state like suspended animation, which can be a handy survival strategy.
5 A possible exception is viruses: particles still tinier than cells, made of little more than genetic material (DNA or its molecular cousin RNA) enclosed in a sheath of protein – as one biologist famously put it, “bad news in a protein coat”. These infectious agents are able to hijack cells, forcing the cell’s machinery to make copies of the virus. Whether viruses, which can’t replicate and propagate on their own, can be considered truly alive is still argued over, because we lack an agreed definition of life itself. We don’t need to be troubled by that debate. The simple fact is that viruses are an evolutionarily stable way for this form of organized matter to propagate itself, if cellular life is already a given. You could say that cells could in principle exist and persist without viruses, but not vice versa. Yes, you could; but it might not mean very much, since the existence of cells probably make viruses inevitable in the way that money makes moneylenders inevitable. Whether they (viruses, but also moneylenders) are parasites depends on where you stand.
6 I’m putting this all a little more tidily than was apparent to Flemming.
7 Not exact copies of each strand, however, but “complementary strands”. Each molecular building block in one strand is paired with a partner in the other, like men and women matching up in pairs in a quadrille. So during replication of chromosomes, a single DNA strand acts as the template for formation of the complementary strand by mutual recognition of these pairs of building blocks. In this way, the twin strands of a double helix together assemble the strands of another double helix with the same sequence of building blocks.
8 The common quip that we are therefore “one-third mushroom”, or “three-fifths banana” or whatever, is a rather good illustration of the foolishness of equating genomes with organisms, ignoring the unifying principle of the cell. What these equations really mean is that all cells have certain fundamental metabolic requirements, but that slight adjustments to their developmental programmes are enough to guide them into assembling in strikingly different ways: into organisms with very different shapes, behaviours and capabilities.
9 This sounds absurd, because television is far too recent an invention for our watching habits to have resulted in any evolutionary selection among genes. But that’s not the point. Our tendency to watch television will depend on far more general cognitive traits, such as attentiveness and curiosity, that we have every reason to believe have some very ancient adaptive significance.
10 One can sometimes read, in books that are otherwise excellent on the topic of genes and evolution, the assertion that genes are replicators. This is wrong, by any meaningful definition of the word. No gene has ever been shown to be able to replicate autonomously if given the component molecules from which it may be assembled. Aside from human technologies for doing the job, genes get replicated only by enzymes working within the context of cells. Genes are not replicators but replicands: that which is replicated in the course of life.
1 When I was once preparing an exhibition trail at the V&A Museum in London that explored the “science” of some objects on display, the fabrics department curator was horrified at the suggestion that codpieces had anything to do with sexual display. The very idea!
2 Well, we can try starting the tale from here, but children aren’t so easily satisfied. It was no good my telling my three-year-old daughter that the sperm gets into the vagina by coming out of the penis. “No it doesn’t,” she protested. “They’re too far apart.”
3 Sexual dimorphism doesn’t necessarily require rigid division of the species into males and females. Plenty of animals, such as molluscs, are hermaphrodite, possessing both sets of reproductive organs. Some fish, such as clownfish, can change sex. There is typically one dominant female in a group, larger than the males. If she is removed – eaten, say, by a predator – then a male will develop ovaries and take her place, growing accordingly in stature.
4 It’s possible, though, that occasional sex is necessary for the long-term viability of eukaryotes. We don’t know for sure.
5 The maternal and paternal chromosomes can also exchange genes during meiosis, adding to the permutations that may result.
6 It’s not obvious that this rather harsh experiment was needed at all, for as Weismann himself pointed out, “Jewish boys are not born without foreskins”.
7 In fact, as early as 1869 Virchow’s student Ernst Haeckel showed that fragments of the embryos of jellyfish-like organisms called siphonophores can produce complete larvae. Siphonophores are, however, very unusual creatures, being not true jellyfish but colonies of small multi-celled organisms called zooids.
8 This won’t be the outcome for all vertebrates, however. Separate the cells of a two-cell mouse embryo, and in general only one of them will grow into a mouse – showing that in this case there are differences between the cells even at this extremely early stage.
9 If you think that seems a harsh way to put it, bear in mind that some of the important biochemical processes that take place in the placenta involve genes that seem to have originated in viruses.
10 Mangold was Spemann’s graduate student at the University of Freiburg and did the experimental work behind this discovery. She died in a domestic gas explosion while heating milk for her baby before the paper she wrote with Spemann on organizers in embryogenesis was published, and therefore could not share the Nobel prize that Spemann won in 1935 for the work.
11 These too are thought to be a pattern made by morphogens – in this case, by the interaction of at least two morphogens, which control the production of pigment in skin cells. A theory of stripe formation among diffusing morphogens was proposed in 1952 by the British mathematician Alan Turing, and his scheme is now thought to apply to many patterning processes in animals and plants, including the quasi-regular spacing of hair follicles and the formation of ridges on the canine palate. It too invokes diffusion as a means of mapping out positional information, but this time in combination with chemical reactions involving the two morphogens, which introduce feedback into the equation and give rise to more elaborate patterns. Turing’s scheme showed how the basic ingredients of a patterning system can, by their intrinsic nature (their rates of reaction and diffusion), give rise to a pattern with a characteristic length scale and type of symmetry.
12 This “human genome sequence” creates a lot of misunderstanding. It prompts the question “whose sequence?”, because the whole point is that our individual differences are largely genetically determined. But our genome sequences are about 99.9 per cent identical – it is just the small differences in that remaining 0.1 per cent or so of genetic code that make us unique. What’s more, many of those differences involve gene mutations widely shared among different people, albeit in different permutations. And these different variants of a specific gene encode the same function – supplying the blueprint (here, yes!) for a protein enzyme, say. It’s just that the corresponding proteins may differ slightly in their molecular structure and activity. So a universal entity called “the human genome” is a meaningful notion, even if it is a little fuzzy.
13 It’s likely that the incidence of mutations – the error rate – is in fact “optimized” during evolution, since mutations are precisely what evolution “needs” to work at all. In other words, the error rate isn’t necessarily kept as small as it possibly can be but is finely tuned via the efficiency of the proofreading mechanisms to ensure that the resulting genetic variation is as beneficial as it can be. In any case, these variations from cell to cell in our bodies are why, strictly speaking, the idea that we each have a single, unique genome sequence is wrong.
1 All this makes introns sound like a bad thing. But if they were that bad, you’d expect that evolution would have found a way to get rid of them by now. However, the need to edit out introns and splice together the remaining RNA fragments (exons), even though it requires energy to drive the corresponding enzymes, seems to confer benefits. In particular, it creates the possibility of putting together the exons in new permutations, so that a single gene can give rise to more than one protein. This creates more possibility for finding proteins with useful functions. From the 23,000 or so genes in the human genome, around 60,000 different proteins are made. Some genes may give rise to tens or even hundreds of different proteins. And beyond offering opportunities for shuffling protein structures, some intron fragments themselves have been found to have biological functions – for example, they may help to control the growth rate of yeast and to boost yeast’s resistance to starvation.
2 The old image of a tree, suggested by Darwin himself, is now understood to be rather more complex – closer to a bush, but also permitting some exchange of genetic material between different branches: the process called horizontal gene transfer that bacteria are adept at.
3 That’s not the same as suggesting that we are descended from such sponges. One can probably never too often issue the reminder that there is no organism extant today from which we and other complex creatures were descended. Rather, all living organisms exist at the tips of evolution’s branches, and we all at various points share common ancestors in organisms that are now extinct.
4 This is a generalization. Evolution relies on random mutations, and so changes appear (mostly) at random. The question is really why particular changes persist. Generally that is because of the evolutionary advantage they convey, but it is possible also for change and variety to appear simply because there is no good reason to eliminate it: it conveys neither adaptive benefit nor deficit. Varieties of pigment marking patterns on seashells might be examples of this neutral variation.
1 There are in fact hundreds of different types of nerve cell in the brain, each with its own characteristic branching shape – as different as a poplar tree is from an oak.
2 It is odd that Harrison never won a Nobel prize for pioneering tissue culture. He was considered many times, but in 1933 the committee considered his work of “rather limited value”. To call this a misjudgement – even then – would be too kind.
3 I can’t forego piling on the grotesquerie by pointing out that Strangeways’s middle name was Pigg.
4 The island trope used by Wells and Huxley goes back to Gulliver’s Travels and Robinson Crusoe, if not indeed to Thomas More’s Utopia, as a vehicle for imaginative exploration unfettered by the normal rules of civilization. Aldous Huxley used it for his final novel Island (1962), which describes a utopian society where the sexual repression and taboos that he regarded as so corrosive in the West have been overcome.
5 After the discovery of HeLa cells, a laboratory was set up to mass-produce them. It was based at Tuskegee.
6 The name, as you doubtless guessed, makes reference to Stanley Gartler and his studies of the “invasive” nature of HeLa.
7 Despite being legally vindicated, Golde seems to have remained deeply troubled by the incident. In 2004, he committed suicide. That the shadow of the court case weighed heavily on him was implied in a statement by the Chair of Medicine at Harvard Medical School: Golde, he said, “deeply respected the rights of patients and their integrity but he also believed that science should be unfettered with regard to what amounted to discarded tissue.”
1 The rather random names that genes acquire tells a story in itself. Myc was first isolated from a virus that triggers a certain sort of tumour growth called myelocytomatosis in birds. The naming invites the idea that Myc and its oncogenic form do very specific things related to this viral condition. That’s far from the case. There is in fact a whole family of Myc genes, and it’s not possible to say concisely what they do except that they have an extremely general role as transcription factors that regulate the expression of a whole suite of other genes, some related to cell proliferation. It’s a common situation in molecular biology: genes first identified in a very specific context get named for that, only to turn out to have generalized functions far downstream of that particular role. The (mis)naming of a gene for what it is first observed to “do”, or for where it does it, is partly just pragmatic. But it can also be confusing, and surely reflects the prevailing view attested as recently as the late 1990s by cancer specialist Robert Weinberg that “each human gene [is] assigned the role of organizing a distinct body trait.” Given that false assumption, it is no wonder the genetics of cancer seemed so perplexing for so long.
2 Some immune cells are unique among normal somatic cells in being able to reactivate telomerase genes too, because the immune system depends on being able to renew its cells.
3 This proportion used to be set much higher, but it now seems that was an overestimate.
4 It seems likely that some genes from an organism’s microbiome can find their way into the genome of the host.
1 Much of the groundwork for this achievement was done by biologist Gail Martin, who figured out how to isolate and sustain a kind of stem cell from tumours of germ cells.
2 The regeneration of neurons in humans was discovered only recently by researchers at the Karolinska Institute in Sweden. In 2013, they used radiocarbon dating in the human body to show that some neurons in the brain’s “memory centre”, the hippocampus, are relatively young. About 700 new neurons are thought to arise in the hippocampus each day.
3 There were actually some restrictions already in place since 1996 on the use of US federal funds for research involving human embryos. This meant that, for his breakthrough research on the culturing of human ES cells, James Thomson had to rely on private funds from Californian biotechnology company the Geron Corporation, and had to perform most of the work himself in an off-campus lab at Madison.
4 You could also argue that his experiments on separating cells in a salamander embryo using a “noose” (see here) were also a kind of cloning, producing genetically identical “twins” artificially from a single embryo.
5 There is a small but important exception. A few genes in mammal cells are contained not in the nuclear chromosomes but in the mitochondria, which are where energy-storage molecules are produced. These mitochondrial genes are inherited solely from the mother.
6 HIV is somewhat different: the virus does actually attack the immune system, killing off a type of white blood cell that protects against infection and thereby leaving the body exposed to secondary infections.
7 Even if the viruses used here are ostensibly harmless, there is always a danger that they could introduce other changes into the cells’ DNA, potentially making them apt to develop into tumour cells. That’s not a problem in the petri dish, but it is if you’re planning to use the cells in medicine. So researchers are looking for other ways to get the right factors into somatic cells. One is to add the respective proteins directly, not the genes that encode them. But the efficiency of reprogramming is typically lower in that case: fewer cells are switched to a stem-cell state.
8 The word “glia” comes from the Greek for glue, a translation of the German word kitt given to them by Rudolf Virchow in the 1850s. Virchow and his contemporaries thought these cells were merely a kind of passive matrix – a “nerve-glue” (nervenkitt) – binding neurons together. It is now clear that they have a much more active role, fine-tuning the properties of nearby neurons and forging or pruning synaptic connections between them. They have been called a “brain homeostat”, maintaining the function and integrity of the neural network.
9 You might remember that Sox2 is one of the transcription factors in Yamanaka’s cocktail for turning fibroblasts into iPSCs. So why is it here making neurons? This illustrates again the subtlety within the black box of genetic circuitry. Sox2 is evidently not by any means a “stem-cell-making” gene – it has a more general but hard-to-define influence on cell development that depends on the company it keeps.
1 Although Maximow was working at that time at the University of Chicago, medical historian Duncan Wilson points out that his disquiet about the anarchy of anti-Bolshevik uprisings in his homeland around this time might account for the quasi-political overtones in this choice of words.
2 Any human tissue thicker than about a few tenths of a millimetre needs to have a vascular system (blood vessels) to keep the cells well supplied with oxygen and nutrients.
3 Note that the mice with pancreases made earlier from embryonic stem cells taken from a different mouse embryo were also chimeras, but not trans-species chimeras. Such chimeric mice were first made in the 1960s by IVF pioneer Robert Edwards and others, by allowing embryos to fuse together before the blastocyst stage.
4 This general approach of growing human stem cells within animal embryos with a prepared niche had been demonstrated previously. In 2016, for example, Rudolf Jaenisch and his co-workers made chimeric albino mice from embryos into which they added human “neural crest” cells derived from either iPSCs or embryonic stem cells. Neural crest cells are progenitors of a range of different mature cells, among which are melanocytes: pigment-producing cells, which cause hair colouration. The human cells survived in the developing mice, which, once born, had black patches of hair courtesy of their “humanized” tissues.
1 This was no coincidence. The understanding of the role of hormones in the female ovulation cycle that emerged from research on assisted conception and IVF informed work on artificial ways to control that cycle for contraceptive purposes. Some scientists were engaged in both fields at the same time.
2 “Donor sperm” is something of an anachronism here. Accounts say that the sperm came from one of Pancoast’s students, who was generally agreed to be the most handsome. The students were sworn to secrecy.
3 The reasons for not telling her are unknown. While the ethics of the procedure seem rightly to be horrifying today, that has tended to foreclose any deeper enquiry about the affair. Was it thought that the mother would not love her child if she knew the truth? That she would find the process too shocking and shameful? That she would denounce and condemn the doctor and students? Was this paternalistic chauvinism pure and simple? The truth would surely provide a useful datum in the evolution of public attitudes to assisted conception.
4 It complicates the story even more to note that Rock was a devout Catholic, albeit one who evidently disagreed with the church’s views on birth control and attempts at assisted conception. His search for fertilized eggs in utero could be regarded, after all, as a kind of abortion.
5 When you bear in mind that animal IVF experiments had shown no such thing, it becomes more clear that these fears were coming from some source other than their informed scientific judgement.
6 The paper was published on Valentine’s Day, a gift to press interest. That could hardly be the authors’ doing but was precisely the sort of canny decision for which Nature’s then editor John Maddox was renowned, and I have my suspicions.
7 Even newborn babies were not always perceived as yet fully human – a fact occasioned by the high rates of infant mortality before the twentieth century, which perhaps even demanded a degree of psychological distancing in the early days of infancy.
8 I use that terminology precisely to emphasize the politicized language; the phrase is not descriptive.
9 I tell that story in my book Unnatural.
10 Haldane indulges the unfortunate tendency to use “fertility” to mean the actual number of offspring, rather than the potential to bear offspring. This confusing usage is pretty much universal now, but with no lessening of its liability to mislead.
11 This is a reference to Jacques Loeb, a German-American biologist who was alleged to have created life chemically when, in experiments in the United States in the 1890s, he discovered how to induce parthenogenesis in sea urchins by treating them with chemical salts.
12 His birth didn’t involve IVF, negating the common preconception – no more, in fact, than an ancient, quasi-magical prejudice – that a person conceived “artificially” would be infertile.
13 Jesus’s was not the Immaculate Conception, however – that was the conception of the Virgin Mary, which was occasioned by sex between her parents but granted special, pre-emptive exemption from original sin.
14 The global figure is hard to pin down. But it will be larger still if we include all those people whose parents were conceived by IVF, and who would not otherwise have come into existence. Louise Brown’s sister Natalie, who was also conceived by IVF, became in 1999 the first such person to have their own child.
15 The role of Jean Purdy, in particular in the early work with Edwards and Steptoe, has been afforded too little attention. She was a central member of the team.
16 Conservative critics of putative ARTs in the 1920s seemed more alarmed by the prospect that they would make men redundant. In the face of new ways of making people, we are all insecure.
17 The 14-day rule is adopted in law by several other countries, including Canada, Australia and Sweden. Some others, including the United States and China, make it a guideline, and it is advised in that sense also by the International Society for Stem Cell Research.
18 I’m being rather vague about exactly when and where the PGCs first form because, in humans, we simply don’t know. It might be before or after gastrulation. And whereas the PGCs appear in the primitive streak in pigs, they are located elsewhere in monkeys.
19 The abbreviation stands for “bone morphogenetic protein 4”, because this protein, and others in the BMP family, were first found to play a role in the formation of bone. But BMPs are now known to have a host of roles in development, some – as here – having nothing to do with skeletal growth. This is yet another indication that many genes don’t have well-defined and easily summarized jobs, but induce different effects depending on when and where they are expressed as the body grows.
20 You could call it the ultimate form of incest – and it would incur all the same hazards of inbreeding that have made that a near-universal taboo.
1 Percy was widely assumed to be the author when the book was first published. Some others have suggested that he had as much to do with it as Mary, but that’s not true. His edits are ornamental: little modifications of style, no more. And in any case, the roughness of Mary’s prose and plotting is ultimately Frankenstein’s gain, giving it the space in which myth can flourish.
2 Yes, the play is prescient in many ways; robot ethics is now a very active field.
3 The Scripps researchers in fact used several different iPSC lines to make each embryo, each with distinct genomes – so the resulting mice were chimeras.
4 I’m talking here about an experiment with reproductive goals. Creating a blastocyst that contains human iPSCs (which would be a chimeric embryo) for research within the 14-day limit is quite another matter.
5 I’m making the claim rather casually that this or that cell becomes a particular type: mesoderm, primordial germ cell and so on. How do we know, given that most cells look largely alike at this stage under the microscope? Researchers use the same methods that Chris Lovejoy and Selina Wray did to look at the cell types in my mini-brain. They deploy molecular tags that stick to particular proteins and emit fluorescent light when illuminated. Certain of these proteins serve as fingerprints of the cell type: they are known to be made only by particular cell types. In this way, these cell structures become gorgeous kaleidoscopic patterns of coloured blobs, showing exactly which types of cell are present, and where.
6 In other words, signals from the human cells are governing development in the chick embryo. Here’s another reminder that, at the cell level and at this early stage of embryo growth, the apparently major differences between species don’t much matter: the key genes and proteins involved are much the same in humans and chickens.
7 By no means all mitochondrial diseases with genetic roots are caused by the mitochondrial genes themselves, however; around 85 per cent of them are caused by mutations in the nuclear DNA.
8 Including, I’d hope it goes without saying, a child with whom they share no genetic relationship.
9 One sees “gene editing” and “genome editing” used interchangeably, and there is no hard-and-fast definition. It is possible in principle both to edit an individual gene by switching a few base pairs, perhaps turning a disease-causing variant into a healthy one, and to replace an entire gene or set of genes to the same end. Both are done. Alterations to genes that are intended to change the phenotype of a cell or organism – in effect, to change a trait – are best described as genome editing, acknowledging that very few genes act in isolation.
10 There is little to be gained by spelling out the acronym, which refers to the types of DNA sequences that are involved in the natural gene-editing process in bacteria.
11 Curiously, the Cas9 enzymes here were guided to the faulty MYBPC3 gene in the paternal DNA by RNA made from the normal gene on the maternal DNA, rather than by the guide strands that the researchers provided for it. They figured that the CRISPR process thus happens rather differently for embryos than for somatic cells.
12 Gene variants that cause single-gene diseases are often “recessive”, which means that you’ll only get the disease if you have the variant on both of the respective chromosomes – inherited from both parents. If you have one “disease” variant and one copy of the normal gene, the normal form is “dominant” and you don’t suffer from the disease. Indeed, you might not ever know you are a carrier: it’s thought that everyone is a carrier of some recessive disease-related gene varieties. But carriers of such genes sometimes do know it, because a relatively high risk of incurring the disease runs in the family. Some disease-related genes, though, are dominant – you need only one copy of the wrong variant to get the disease. The MYBPC3 gene edited out of embryos by CRISPR as described earlier is like this.
13 According to one estimate in 2008, around one in 20 cases of PGD in IVF clinics in the United States involves selection of embryos for conditions shared by the biological parents that are generally classed as disabilities, such as dwarfism and deafness.
14 Many wealthy pet owners, most famously Barbra Streisand, have since availed themselves of that facility. Some, however, have learnt the hard way that cloning does not guarantee identical copies. Entrepreneurs John Sperling and Lou Hawthorne were dismayed to find that the first cat cloned in a project in Texas, in which they invested in the hope of tapping a lucrative market, did not look like the donor. Inevitably dubbed CopyCat, it was black and white, lacking the orange of the tortoise-shell “original”. This is because the fur colour of cats is controlled not genetically but epigenetically. It was a vivid illustration of how misguided is any notion that all that we prize in ourselves or other beings is genetically determined.
15 Some countries, including the UK and Australia, permit non-reproductive therapeutic cloning to make human blastocyst embryos for research purposes – as Hwang claimed to have done.
16 Actually this work used embryos with an excess of chromosomes, which meant there was no guarantee that the divided cells were genetically identical clones.
17 Stapledon’s book – I hesitate to call it a novel, because it is a dense but plotless chronicle of humankind’s far future – is a remarkable flight of the imagination. In an anticipation of the technologies discussed in this book that some might consider chillingly prescient, Stapledon explains that the super-brains of the Fourth Men are produced by “manipulation of the hereditary factors in germ cells (cultivated in the laboratory), manipulation of the fertilized ovum (cultivated also in the laboratory), and manipulations of the growing body.” Stapledon suggests, however, that the Fourth Men eventually come to realize that their life of pure intellect is constrained and devalued precisely by the lack of a body. For that reason, they engineer their successor from the remnants of the embodied Third Men: “he was to be a normal human organism, with all the bodily functions of the natural type; but he was to be perfected through and through.”
18 I contemplate the old floppy disks at the bottom of my drawer, crammed with data that are useless, inaccessible and no doubt degrading, and I wonder how long-lived a hypothetical “virtual self” would truly be if hosted digitally.
1 Who, for that matter, can forget Marty Feldman admitting to Gene Wilder’s doctor in Young Frankenstein (1974) that the bottled brain he has purloined belonged to “Abby Normal”?
2 It’s a tragic tale for sure, but one can’t discuss the legalities of an individual being perpetuated in their isolated and preserved brain without mentioning this court exchange allegedly reported in the Massachusetts Bar Association Lawyers’ Journal:
Lawyer: Doctor, before you performed the autopsy, did you check for a pulse?
Doctor: No.
L: Did you check for blood pressure?
D: No.
L: Did you check for breathing?
D: No.
L: So, then it is possible that the patient was alive when you began the autopsy?
D: No.
L: How can you be so sure, Doctor?
D: Because his brain was sitting on my desk in a jar.
L: But could the patient have still been alive, nevertheless?
D: It is possible that he could have been alive and practising law somewhere.
1 The most notable exception was the work of the late Derek Parfit, whose Reasons and Persons is becoming the starting point for philosophical reasoning about many of the implications of new technologies of people-making, from computer simulation to artificial reproductive technologies and cloning.