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freemartins The freemartin, an occasional anomalous development in domestic cattle, has long been recognized. It was observed at least as long ago as the Roman Empire that when a cow bore male and female twins the apparent female did not develop as a cow should, could not be bred from, and did not give milk — there was a Latin term ‘taura’ (female form of taurus, a bull), meaning a barren cow, and a similar expression in Greek. In many other ways the freemartin resembled a bull, or a spayed heifer, more than a normal cow, and was also readier to mount other heifers when they came into oestrus. The term ‘freemartin’ (and its variants) in English, for this anomaly, can be traced back to the seventeenth century. It is often suggested that the term derives from the butchering of cattle around Martinmas (11 November) to preserve for the winter: these particular cattle, unsuitable for breeding or dairy production, would be prime candidates for not keeping throughout the lean months. This may, however, be purely coincidental, given that the word ‘martin’, a generic term for cattle, can be traced in variant forms back to the thirteenth century, and that ‘ferry’, ‘farrow’, and related words are found in both English and Scottish dialects to mean a barren or dry cow.

Although the external genitalia of the freemartin may appear normal, the internal organs are abnormal in greater or lesser degrees. In a few cases, one in ten or twelve, a heifer born as twin to a bull calf will be normally fertile, but these odds are such that stockbreeders discourage breeding for the trait of mixed-sex twins. The condition occurs as a result of the placentas of the two embryos uniting during pregnancy, allowing the two embryonic circulations to combine. A hormonal substance which organizes the development of the reproductive system of the male enters the bloodstream of the female. This inhibits the development of the ovaries and causes abnormal development of the heifer's reproductive tract, affecting the oviducts, uterus, cervix, and parts of the vagina. The degree to which the reproductive system of the heifer is affected relates to the stage at which the placentas join: the earlier, the more extensive the masculinization which occurs. Other abnormalities — two cervixes, absence of one uterine horn, or blockage of the oviducts — have also been reported as a result of this uterine exposure to male hormones. Stockbreeders are advised to have a veterinarian examine suspected freemartin heifers by rectal palpation to ascertain whether the reproductive organs are present and functional. If they are not, culling of the heifer for beef is usually recommended — although freemartins were sometimes used as draught animals in the past, this is no longer relevant to modern agriculture. Freemartins are sometimes employed as oestrous detectors, being readier than normal females to mount other cows when these become ready for breeding.

Freemartins became an object of particular interest to anatomists in the seventeenth century, and were the subject of correspondence between A. M. Malsalva and G. Baglivi, pupils of the great Italian anatomist, Malphigi, in 1692. In 1779 John Hunter reported to the Royal Society of London on his dissection of three freemartins. The specimens, which were retained in the internationally-renowned anatomical collections of Hunter and his brother William, excited the interest of another Italian anatomist, Antonio Scarpa of Modena. Scarpa acquired a freemartin to dissect on his own behalf, and generated a considerable stir in Italian scientific circles. However, the major advances in the elucidation of this fascinating but mysterious condition did not take place until the twentieth century and the early investigations into the sex hormones. Following morphological investigation by Tandler and Keller of Vienna, F. R. Lillie of Chicago established that the freemartin was a genetically female embryo which had been affected by the circulation of the male hormones of its twin via the joined placenta, and he published this conclusion in a paper in the Journal of Experimental Zoology in 1917. This conclusively overturned the arguments of some contemporary scientists that freemartins were in fact defective genetic males, and had far-reaching implications for the development of embryology and in particular for the relationship between the gonadal hormones and sexual differentiation. The exact nature of the hormonal influence remains a little obscure, since attempting to replicate the condition experimentally by injecting testosterone into pregnant cows does not produce the same effect. A similar effect in rodents, however, does seem to be due to transfer of testosterone or oestradiol. Freemartin births have sometimes been reported in other mammals, e.g. sheep. This phenomenon of one normal and one sterile twin may possibly be responsible for the superstition that, in human twins, only one will be capable of childbearing, but as this is said to apply to identical twin females, perhaps not.

Freemartin cattle (and their male twins) played an important role in the work by P. B. Medawar and his colleagues on skin grafting. He had assumed that grafts between heterozygous twins (which mixed-sex twins are) would be rejected whereas those between monozygotic (identical) twins would not (transplantation between identical twins having already been proved to be possible). In fact, it turned out that skin and other tissue could be transplanted between such a twin pair of cattle at any stage in their lives, since they were tolerant of each other's tissues as a result of exposure to one another's tissue antigens as embryos. This demonstrated a state of acquired tolerance. Two papers describing this unexpected result and its implications were published in Heredity (Billington, Lampkin, Medawar, and Williams, 1951; Anderson, Billingham, Lampkin, and Medawar, 1952). Equivalent tolerances were subsequently induced in new-born mice: given skin or bone marrow transplants from unrelated animals, they became permanently tolerant of the new tissue. This work led to the award of the Nobel Prize to Medawar in 1960 and heralded the dawn of a new era in immunology with wide-ranging implications for the prevention and treatment of diseases in humans and animals.

Lesley A. Hall