Mutants (45 page)

251
His French rival Buffon.
For an account of Geneviève see Buffon (1777)Addition à Particle qui a pour titre, Variétés dans l’espèce humaine,
Supplement à l’histoire naturelle
volume 4 pp.371–454.

253
We are a polychrome species.
For a general review of pigmentation genetics see Sturm et al. (1998). The most common form of albinism is oculocutaneous albinism type 1 or OCA1 (
203100
), which is due to recessive mutations in the tyrosinase gene (
606933
). Albinism with grey eyes is oculocutaneous albinism type 2 or OCA2 (
203200
), due to recessive mutations in the P gene (Durham-Pierre et al. 1994; Stevens et al. 1997).

254
In 1871, en route to his encounter with the Aka.
See Schweinfurth (1878) volume 2 pp.100–1 for his account of albinos in Africa, and Woolf and Dukepoo (1969) for albinos among the Hopi.

255
Those children would have fascinated Buffon.
For the history of Marie Sabina see Buffon (1777) p.557. Pearson et al. (1913) and Dobson (1958). For some of the other eighteenth-century piebalds see Blanchard (1907). For Lisbey’s history see Pearson (1913). Pearson’s insistence on this rather forced account of the inheritance of piebaldism stems, again, from his opposition to the Mendelian theory of inheritance.

261
Molecular devices are required.
Piebald trait, white forelock and bilateral hypopigmentation of the limbs and trunk (
172800
) is caused by dominant mutations in c-Kit (
164920
) which encodes a receptor tyrosine kinase. c-Kit’s ligand is steel (
Sl
) in mouse, but no human disorder has been identified with mutations in this gene. c-Kit and its ligand are thought to help in guiding the migration of the presumptive melanocytes. The other piebald syndromes often only cause white forelock but are associated with deafness or megacolon. These are Waardenburg’s syndromes types I through IV (
193500, 193510, 602229
), caused by dominant mutations in Pax3, Sox10 and MITF (Tassabehji et al. 1992; Watanabe et al. 1998). These genes are transcription factors needed for specification of melanocyte lineages (Goding 2000). All these syndromes manifest variably, all are caused by dominant mutations; homozygotes are probably lethal.

261
What gives us our skin colours?
Africans differ from Europeans, and
East Asians are known to differ in the structure and density of their melanosomes (Szabó et al. 1969; Toda et al. 1972), but very little is known about the genetics – except for a hint it might have something to do with the P gene (Sturm et al. 1998). See Linnaeus (1758) pp.20–1 for his diagnosis of the human species; a translation is given by Robins (1991) p.171.

262
For nearly half a century.
The history of race-classification in South Africa is discussed by Posel (2001). Rita Hoefling’s story is told by Joseph and Godson (1988).

265
Life growth hormone, melanotropins.
Red hair and obesity are caused by mutations in POMC (
176830
), a gene that encodes the ?-MSH and ACTH precusor (Krude et al. 1998).

266
Yet not all redheads are fat.
Red hair (
266300
) caused by recessive mutations in the MC1R gene (
155555
) (Robbins et al. 1993; Valverde et al. 1995; Smith et al. 1998; Flanagan et al. 2000; Healy et al. 2001). Besides the general plausibility arguments that I have given as to whether red hair has been selected or not (Darwin 1871, 1981 volume 2 pp.316–405; Robins 1991 pp.59–72) and is therefore properly thought of as a mutation or polymorphism, there are also elaborate statistical tests which can sometimes detect historical patterns of selection. Such tests have been applied to MC1R, but they are inconclusive (Rana et al. 1999; Harding et al. 2000).

268
Pale, and proud of it.
For a detailed discussion of the pre-PRC history of Chinese anthropology and eugenic thought see Dikötter (1992, 1997, 1998). For a study of Ainu hairiness see Harvey and Broth well (1969).

269
In the collection of the Capodimonte.
For the history and iconography of the Gonsalvus family see Aldrovandi (1642); Siebold (1878); Zapperi (1995); Haupt et al. (1990) pp.92–7 and, especially, Hertel (2001).

273
In 1826 John Crawfurd, British diplomat and naturalist.
For the history of Shwe-Maong and his family see Crawfurd (1827); Yule (1858) and Bondeson and Miles (1996)M.

276
We are born with about five million hair follicles.
For a general review of hair (and feather) specification see Oro and Scott (1998). For the role of BMPs and FGFs, Jung et al. (1998) and Noramly and Morgan (1998). Reynolds et al. (1999) carry out the trans-gender transplantation experiment.

280
The one thing that many of us.
Most of the anecdotal material here comes from Segrave (1996) – a delightful social history of balding. Male pattern balding or androgenetic alopecia (
109200
). See Cotsarelis and Millar (2001) for a general biology of the dying hair follicle, and Kuester
and Happle
(1984) for a review of the genetics of the androgenetic alopecia.

282
One fact is, however, known: to go bald you need testosterone.
See Aristotle
Historia animalium
in
Collected works
pp.983–4. Hamilton (1942) recounts the experiments with testosterone. Knussmann et al. (1992) discuss the relationship between testosterone levels, virility and balding.

283
Is there any hope for the bald?
Trotter (1928) discusses the relationship
between hair growth and shaving. Sato et al. (1999) and Callahan and Oro (2001) discuss the role of sonic hedgehog in rejuvenating hair follicles; Huelsken et al. (2001) discuss (?-catenin.

285
One can still, occasionally.
The portraits of the Ambras family were first described in the modern scientific literature by the physiologist C. Th. Siebold (1878). He proposed that they were atavistic, a claim echoed by Brandt (1897), who points out that the Burmese family have the same disorder. Both men recognised that the surplus hair in the two families was lanugo (Siebold explicitly compares Petrus Gonsalvus’s hair to that of a foetal orangutan), but suppose that lanugo is more ‘primitive’ – a conflation between phylogeny and ontogeny that is typical of German workers of the time, who were deeply influenced by Haeckel. Felgenhauer (1969) gives a summary of nineteenth-century views on hairy people. More recently, there has been a great deal of debate about just how many surplus-hair syndromes there are, and who had what (see Garcia-Cruz et al. 2002 for one point of view). I argue that Petrus Gonsalvus’s and Shwe-Maong’s families both have the same condition: hypertrichosis lanuginosa (
145700
), the mutant gene of which may reside on chromosome 8. The hair of at least one man with this syndrome (a Russian named Adrian Jewtichjew) has been examined microscopically and seems to have been lanugo. The most famous modern pedigree of hairy people, the Gomez family of Mexico, have another, unrelated, disorder: X-linked hypertrichosis terminalis (
145701
); Figuera et al. (1995). See this paper and Hall (1995), recent – and perhaps reasonable – claims that this latter kind of hairiness is indeed atavistic.

286
Darwin himself knew of the Burmese hairy family.
See Darwin (1871; 1981) volume 2. p.378 for his account of sexual selection and hairiness of the Burmese family; see Darwin (1859; 1968) pp.183–4 and Darwin (1882) volume 2, pp.319–21 for the homology between skin organs, the Burmese family and the ‘Hindoos of Scinde’. See Thadani (1935) for a later account of the same pedigree (the ‘Bhudas’) who have a syndrome called ectodermal dysplasia 1, anhydrotic or ED1 (
305100
) caused by a mutation in ectodysplasin (EDA) (Kere et al. 1996). The Mexican hairless dog’s mutation is still unknown (Schnaas 1974; Goto et al. 1987) but is probably this gene or its receptor, EDAR (
224900; 604095
) (Headon and Overbeek 1999; Monreal et al. 1999). The scaleless variety of Medaka has a mutation in the EDAR gene (Kondo et al. 2001). For ectodysplasin’s proposed role in establishing hair papillae see Barsh (1999). See Sharpe (2001) on the evolutionary history of the hair follicle.

288
The use of a single molecule in the making.
For hens’ teeth see the classic experiments by Kollar and Fisher (1980), a commentary by Gould (1983) pp.177–86, and recent experiments showing that chicken mandibles are BMP4-defective (Chen et al. 2000).

289
Perhaps it is also the retrieval of an ancient signalling system.
Nipples,
supernumerary or polymastia (
163700
). For a review see Cockayne (1933) pp.341–5; Japanese polymastia, Iwai (1907). I thank Alan Ashworth and Beatrice Howard for telling me about
Scaramanga.

290
Breasts bring us back to Linnaeus.
The ancient iconography of Artemis Ephesia is discussed by Fleischer (1984) and Linnaeus’ use of it by Gertz (1948) – for the translation of which I am indebted to Lisbet Rausing.
Nosce te ipsum –
the slogan that meant so much to Linnaeus is rarely attributed to Solon, but rather (as in Plato) to the seven wise men of Protagorous who wrote it on the temple of Apollo at Delphi.
The Oxford dictionary of quotations
gives its source as ‘Anonymous’.

CHAPTER IX: THE SOBER LIFE

297
Huntington disease is one of the nastier.
Huntington disease, also Huntington’s Chorea or HD (
143100
), is caused by dominant mutations in the huntingtin gene. Rubinsztein (2002) reviews the molecular basis of the pathology; Bruyn and Went (1986) review the history and spread of the disease.

298
How can so lethal a disorder?
See Haldane (1941) pp.192–4.

300
Were it not for ageing’s pervasive effects.
Ricklefs and Finch (1995) give estimates of longevity in the absence of ageing.

302
But it was another British scientist.
See Medawar (1952) and Williams (1957) for the seminal papers on the evolutionary theory of ageing. Rose (1991) gives an incisive historical review. Albin (1988) discusses the fecundity of women with Huntington’s based on data collected by Reed and Neel (1959).

304
In his declining years, flush with cash and fame.
Alexander Graham Bell (1918) analyses the Hyde family; Quance (1977) discusses Bell’s interests in the genetics of longevity.

306
In the 1980s the evolutionary account of ageing.
See Rose (1984) for the original experiment; Rose (1991) for a review; and Sgrò and Partridge (1999)for a more detailed analysis of a similar experiment.

308
Since Aristotle.
Aristotle
On length and shortness of life
in
Complete Works
volume 1 p.743. See Diamond (1982) for the cost of reproduction in marsupial mice and Westendorp and Kirk wood (1998) for the cost of reproduction in British aristocrats. See Leroi (2001) for a sceptical treatment of cost of reproduction data.

309
Is there a recipe for long life?
See Cornaro (1550,1903) for a translation of the
Vita sobria
, and Gruman (1966) for a review of Cornaro’s thought and its influence.

311
The worst of it is that there is an element of truth.
See Finch (1990) pp.506–37 for a review of the earlier literature on caloric restriction;
ibid.
pp.20–1 for mortality rates of the Dutch during the
Hongerwinter.
See Holliday (1989) and Chapman and Partridge (1996) on reproductive costs and caloric restriction. Several experiments in flies and mice have been done
to look at the effects of caloric restriction on ‘whole genome expression profiles’. The best is a study on flies (Pletcher et al. 2002); the mouse studies (Lee et al. 1999) are more difficult to interpret.

313
We term sleep a death.
See Beckman and Ames (1998) and Ames et al. (1993) for a review of the free radical theory of ageing. See Rose (1991) for SOD in gerontocratic flies. Parkes et al. (1998) for overexpression of superoxide dismutase in
Drosophila
motorneurons; Finch and Ruvkun (2001) for a general review of SOD and ageing.

316
Our genomes contain three genes.
Familial amyotrophic lateral sclerosis or ALS1 (
105400
) is caused by dominant mutations in Cu/Zn superoxide dismutase or SOD1 (
147450
) (Rosen et al. 1993). Deleting this gene in mice seems to have little obvious phenotypic effect, although longevity does not seem to have been examined (Reaume et al. 1996). For the experiments excluding free radicals and hydrogen peroxide as a cause of ALS see Subramaniam et al. (2002); for a review, Orr (2002). For a more general discussion on the causes of ALS see Newbery and Abbott (2002). For the role of SOD1 in Down’s syndrome see Epstein et al. (1987) and Reeves et al. (2001).

319
Wrinkling is a manifestation.
Werner’s syndrome (
277700
) caused by recessive mutations in RECQL2 (also known as WRN) helicase (
604611
) (Yu et al. 1989) reviewed by Martin and Oshima (2000).

319
As we age.
For two reviews of the proposed role of cellular senesence (or Hayflick’s limit) in ageing see Rose (1991) pp.126–36 and Shay and Wright (2000). Bodnar et al. (1997) show that overexpression of telomerase in human cell lines confers cellular immortality. There are some reports that the neuronal cells of mice do not undergo cellular senesence
in vitro
(Tang et al. 2001; Mathon et al. 2001). There are also strong suggestions that the proliferation of mouse cells
in vitro
is not telomere limited (Shay and Wright 2000).