had shifted the paradigm, allowing researchers to think of hypoxic-ischaemic damage as a treatable disease. apoptosis however, it was still a mystery how and why cells triggered by hypoxia-ischaemia should die hours or days later, particularly when it became clear that glutamate levels were not particularly high during secondary energy failure. the next critical idea came with the discovery of programmed cell death, a novel form of cell suicide. originally observed as a pathological appearance and named apoptosis ("falling off", as of leaves) in the 1970s, horvitz, raff and evan provided a molecular understanding and showed that apoptosis could be triggered by cellular insults. the radical idea that hypoxia-ischaemia triggered a cell suicide programme which could explain the perplexing phenomenon of delayed cell death was soon supported by experimental and human data, and many researchers believe this helps explain why neural rescue works in the newborn. however the picture is complex: both apoptosis and necrosis are present in variable proportions; and there seems to be prolonged neurodegeneration after an insult. research into this problem continues. neonatal neural rescue these ideas flowed through the perinatal research community, producing a new belief that neural rescue after birth asphyxia should be possible. amongst the first to have attempt neonatal neural rescue in animals were ingmar kjellmer and henrik hagberg in gothenburg, and michael johnston in baltimore. the potential began to draw in other neonatal researchers from diverse fields to begin neuroprotection research, including those who came to form the informal neonatal hypothermia research group: peter gluckman and tania gunn were endocrinologists in the university of auckland new zealand and interested in cooling for its effect on thyroid function; they had first cooled a sheep fetus for endocrine studies in 1983. denis azzopardi, john wyatt and david edwards, then young researchers working for reynolds, were using reynolds's sophisticated mrs approach to replicate secondary energy failure in newborn piglets and immature rats; in gluckman's laboratory alistair gunn and chris williams developed a simple and elegant biophysical method using cerebral impedance to do essentially the same thing in fetal sheep. marianne thoresen, who was working on cerebral perfusion, was prompted to think about neuroprotection by stories of children who fell through the norwegian ice and suffering prolonged drowning in iced water but emerged with preserved cerebral function. there were many potential therapies around which might achieve neural rescue, and most of these workers did not immediately move to hypothermia. magnesium was an appealingly simple excitoxin receptor antagonist that protected cells in culture: the reynolds group tested it in their piglet model without success. gluckman and gunn started by looking unsuccessfully at flunarizine, a calcium entry inhibitor. edwards picked on nitric oxide synthase inhibition which was also a failure. gluckman had success with his innovative studies of igf-1, but could not immediately translate this to clinical practice.