Maud Greep was the mother of Iris du Pré, her only child. Another offspring was born weak and died. A further pregnancy ended in miscarriage. After that, Maud avoided further birth and put all her ambition into Iris who became a talented pianist, playing in music clubs and on the radio. She also taught piano. Married to Derek, she bore a daughter, Hilary in late April 1942. Over fifty years later, a strange story emerged. Hilary wrote in 1997 [10] when her mother was already deceased, that the latter had been unable to conceive a second child so took medical advice. Perhaps she feared the difficulties experienced by her own mother, Maud. However, barely two years after the birth of Hilary, being very ambitious Iris seemed to want children quickly and return to her career. At that time, she lived in Oxford where her husband, Derek a wartime enlistment was seconded by the army to teach at a College of the University. Research was in the University air and perhaps Derek made a suitable contact. Hilary’s report was that a doctor had prescribed pregnant mare’s serum [10] . Hilary probably heard this from her mother when she herself was pregnant. The doctor is said to have joked “This child will be a racehorse winner!”.

By then, injections of PMSG were iv. Even in 2004, a respected, highly experienced researcher still found it necessary to ask “... is it medically prudent and ethically admissible to use preparations derived from urine of untraceable donor source, contaminated with extraneous proteins?” [1] . Did the doctor in 1944 ask himself in relation to PMSG-and also of hCG, if given by him-whether the treatment was necessary? Was the health of his patient his first consideration? Was he concerned also with the fetal outcome of his action? In 1964 the FDA demanded special care, in informed consent of minors. The needs of human fetuses were not mentioned, as supposedly completely excluded from human experimentation. Most tellingly, was the doctor a qualified person under the Nuremberg Code [9] (or did that only apply to alleged war criminals)? If so, he surely would have known in 1944 that the injections were pointless if not followed by injection of hCG at the right time post-PMSG, and if he did also give hCG, that the danger from impurities would be doubled. Presumably he did not know, so was not qualified

That the PMSG injections were indeed given to Iris, is confirmed by a separate, independent report that the mother of a friend of Iris’s was told by Iris that to get pregnant she was getting injections from a pregnant mare [11] . Iris did not become pregnant due to the doctor's injections; they were given in vain. The first mammalian pregnancy to produce offspring was actually in a mouse in 1957, by a protocol developed over years by Fowler and Edwards [12] (the latter notable for the first IVF birth). Hilary also incorrectly reported in 1997 that the serum was “a form of oestrogen” [10] . To prevent possible miscarriage-a reminder from her mother Maud’s bad experiences, when Iris became at last pregnant again, she quite likely received further help from the “up-to-date” doctor: a daily “form of oestrogen”, diethyl stilbestrol DES (of later disrepute [13] ). By 1944 this was the very cheap “latest thing” for sustaining pregnancy; a substitute for very expensive oestrogen extracted from urine. Reporting over thirty years after she heard about the “oestrogen” help, Hilary seems to have mixed up the injections of mare’s serum with the DES.

Iris’s second child, Jacqueline Mary du Pré, was born in an apparently normal order of events, on 26th of January, 1945, but was extraordinary. A child prodigy from five years old, she became one of the best and most loved cellists of all time. Between 1961 and 1973 in London at only sixteen and then globally, in a meteoric career she astounded the public and her profession with a musicality, technique, passion and charisma that exhibited an absolute commitment to music and a unique, personal gift for interpretation [14] [15] . However, from early in adolescence she experienced bouts of depression and self-doubt, that was relieved in 1967 by a marriage apparently made in a musical Heaven to the Jewish pianist/conductor, Daniel Barenboim. That and accompanying conversion to Judaism shocked her narrow-minded, pious and problematic provincial family. This disturbed her deeply. Four years generally of happiness, were followed by three years of serious depressions, declining health, and an abrupt end to her career when diagnosed with multiple sclerosis (MS) in 1973 at age 28. For years after, she taught cello from a chair, before bad years and a tortured death in 1987, aged 42.

A very close friend in her peak musical years said, “Jacqueline du Pré was a creature like non other ... there is no frame of reference ... musically, cellistically, as a personality ... you can’t compare her to anyone” [16] . A colleague regularly playing with du Pré has stated about the ability and musicality which made her immediately ready at any moment, without hesitation to play any music asked of her, that she could not be categorized: “Already it was done; ... I think it was done before she was born” [17] . He may have been closer to the truth than he realized. From early childhood, an exceptional combination of characteristics, anatomic, behavioral, neurological, metabolic, emotional, intellectual and musical distinguished du Pré from all in her family. In adulthood, she was 1.80 meters tall, broad and well built. Her gait was awkward; Hilary thought it unfeminine. Of her square, strong face and attractive but decidedly masculine features, her first flat mate [18] said “If you think of beauty in conventional terms, Jackie should have been a boy”, but she also noted du Pré’s “very mature soul... [and] ... deeply loving, mature and compassionate intellect ...”.

From the age of just five when she heard a cello on the radio and declared she wanted 'to make that sound' [10] , she concentrated an obsessive focus on her cello, was utterly immersed in music, and apart from other children. During puberty the instrument was her only real friend and its music her only real language. Though not a delayed speaker, she did not converse, was socially awkward and at school between the ages of 8 - 14, did not make one truly special friend. A classmate [19] cannot “remember her having any special close friend. She seemed not to need anybody. We never really knew her ... we never took her into our lives” [20] . Another said: “I don’t remember ever playing with her during break ... I suspect that she was extremely lonely, that she found it extremely hard to make friends ... schoolmates were simply not up to understanding her most important aspect.” Another girl [21] remarked: “... she wasn’t really there in spirit. Watching her play you ... [knew] ... where she really was. She came alive when she played.”

Between seven and thirteen, du Pré spent much time with the only girl who thought herself a close friend [22] . However, the latter remarked “We never shared our feelings” ... “We couldn’t communicate with her through music, and she couldn’t communicate with words ... a strange creature .... to this day I have no idea who she was-a remarkable and telling conclusion. Generally, in late adolescence du Pré communicated more successfully, but even in adulthood, she could veer suddenly from chatter to a “cut off” mode, or from a long silence into sometimes inappropriate laughter [11] . Though her limits in social know-how have been ascribed to missing ordinary schooling, the descriptions above by adults and children and her exceptional hearing, perfect pitch and remarkable musical memory, suggest a deeper source.

This view is augmented by comments made by Daniel Barenboim, her husband, a pianist/conductor who probably knew her personally better than anyone: “... you felt like a mere mortal faced with somebody who possessed some kind of ethereal dimension”. “[She had an] ... almost physical contact with music”. “[Even as a teenager] she played with incredible intensity ...”. Telling is Barenboim’s comment. “She had a capacity to imagine sound such as I never met in any other musician [23] ”. Such comments, like others above, may indeed suggest a unique fetal neurodevelopment. This was unfortunately unbalanced and incorporated eventually devastating pathological elements.

The injections of PMSG were given by Iris’s doctor in an unknown, intravenous protocol about the time Iris conceived. The glycoproteins persist in the circulation for up to two to three months [1] . In 1944, knowledge of immunity was very limited, and we do not know if the doctor was aware of two important monographs that had already been independently published in 1942: “Antigonadotrophic substances” [24] and “The antigonadotrophic factor with consideration of the anti-hormone problem” [25] . Both claimed that gonadotrophins from animal origin produced “anti-hormones”, which decreased ovarian responsiveness in humans. Indeed, the latter monograph mentioned that already in 1930 it was noted during chronic treatment with gonadotrophic hormone the ovary maintained its response for a limited period, at the end of which the response becomes increasingly weaker and finally disappears. They further stated: “Chronic treatment of animals with gonadotrophic hormones evokes ... a new blood substance called an anti-hormone ... capable of inactivating gonadotrophin [s] ... in vivo and in vitro”. Indeed, in 1956 a hog pituitary hormone precipitated in women an anti-hormone to itself [26] . Thus long before immunological phenomena were recognized, “anti-hormone” to animal gonadotrophins in women were known but the clinical consequences were uncertain. Another issue was worrying.

The immunological potencies of the different molecular species of gonadotrophins have now been known for well over two decades [27] , but how did du Pré’s body behave towards the 95% of other, so-called “inert” proteins injected together with the PMSG? Whether they precipitated negative factors or not, did they interfere with normal neurodevelopment? Could it really be doubted that Iris's fetus was exposed immediately to many severe and possibly harmful challenges? The placenta is now known to be a hormonal organ and at a very early stage for a short period, the placenta and not the mother supplies the fetus with serotonin, a neurotransmitter important in neurodevelopment [28] . What if that mechanism was disturbed ever so slightly by just one of the protein “imports” influencing a genetically controlled pathway, or epigenetically? In some young autists, for example, accelerated maturation of white matter [29] , disrupted neural synchronization [30] or dissociations of white matter volume [31] or defects in neurogenesis or neural migration are found [32] . Could such genetic changes, or unspecified environmental damage due to autoimmunity, inflammation or immune dysfunction have challenged also the fetus of du Pré?

What too, if Iris’s fetus was indeed also exposed to DES? What of a possible synergism between DES and a mare’s protein? Small studies after exposure to DES, indicated increased risk of auto-immune diseases or diseases involving impaired immune function in animals and humans, including abnormal natural killer cell activity, T cell-mediated immunity and thymic development [33] . In the first study assessing directly prenatal DES exposure and risk of MS despite limited statistical power due to very rare exposure, there was modest support for a positive association [34] .

Some foreign effects imposed on du Pré’s fetal development may also have had a less dramatic effect than the eventual MS. Circulating thyroxine is balanced by hypothalamic-pituitary-thyroid feedback in the fetus and is important for correct fetal neurodevelopment and growth [35] . Du Pré suffered regular discomfort and inconvenience from wide swings between excess and lack of circulating thyroxine. From childhood she was known to suffer from sudden loss of energy, even on holiday [10] , yet was also known at times to suddenly run “like a great big colt” [11] . Though she was comfortable swimming in very cold waters, she perspired exceptionally when playing the cello, even when her movements were minimal, so she had special garments made to absorb the perspiration [11] . However, she also felt an increasing need to warm hands before performances.