Obituary - Sir Graham Collingwood Liggins
World-renowned New Zealand scientist and doctor
Choose the most defining moments of your life. If you're a parent, the birth of your children probably heads the list. Make it a live, healthy baby, please.
Nearly 40 years ago, a Thames-born obstetrician and scientist developed a treatment that made safe entry into this world more likely. It made medical history and has helped prevent the disability or death of hundreds of thousands of premature babies.
Sir Graham Liggins
This extraordinary pioneer, Sir Graham Liggins, died on 24 August 2010, aged 84.
His is a story of intricate surgery on sheep and of saving newborn babies.
Following an Otago medical degree and obstetrics training in the United Kingdom, "Mont", as he was known, took a position at Auckland's National Women's Hospital.
It was an exciting place. Bill Liley - who later became Sir William - was doing groundbreaking work transfusing life - saving red blood cells to sick babies still in the womb.
Mont wrote in a letter, "I asked my friend Bill Liley, of fetal transfusion fame, how to choose a [research] topic. He said to look for a major problem that was potentially solvable. The major problem was easy: prematurity stood out above everything else. I naively thought that all I had to do was solve the ancient question of what controlled the onset of labour at term and the reason for premature onset would become apparent." This became his life's quest.
It had long been believed that the mother’s body instigated labour. But Mont had hints it was otherwise: he had read of animals with very prolonged pregnancies whose fetuses had lacked a pituitary gland.
Enter the sheep. At Hamilton's Ruakura Animal Research Station Mont developed novel techniques to perform surgery on the pituitary gland of unborn lambs. Later, when he was on sabbatical at the University of California, Davis, his surgery led to ewe after ewe failing to go into labour.
On return to National Women's, Mont patched together a laboratory comprised partly of a condemned shed. It was "adequate for my purposes providing that one was careful not to put a foot through the rotting floorboards", he wrote in an unpublished autobiography.
Here the great discovery was made. Mont deactivated fetal lambs' pituitaries, then replaced - not the pituitary itself - but a hormone that it indirectly produces.
The hormone was cortisol. Each time he gave the cortisol, the ewe gave birth about two days later. The signal, it became clear, came from the fetus, not the mother.
But there was much more.
"I remember one morning, there was a lamb lying... with its mother," said Mont in an oral history recording. "A lamb that had been infused as a fetus with cortisol. And to my surprise this lamb was still breathing, not very healthy breathing, but it was alive. It had no right to be. It was so premature that its lungs should have been just like liver, and quite uninflatable.
"I postulated that the cortisol had accelerated the maturation of enzymes in the lung that caused accelerated maturation."
This mattered enormously. In those days premature babies often died of respiratory distress syndrome, their immature lungs unable to inflate.
More than half of all babies born before 32 weeks' gestation died.
Mont was busy on other research at the time but eventually turned to the lung problem after a US colleague with whom he had shared his finding produced definitive answers on how cortisol matures lungs. He teamed up with paediatrician Dr Ross Howie, whom he described as "meticulous". Together they designed and carried out a randomised controlled clinical trial giving synthetic cortisol to mothers in premature labour.
The babies could breathe. Respiratory distress syndrome, overall illness and death rates were dramatically reduced.
The treatment was rapidly taken up in New Zealand and Australia, but the rest of the world took over 20 years to catch up.
Mont's other work included helping to develop and trial the oral contraceptive pill (the seven sugar tablets were his idea), and pioneering fertility treatment for women who don't ovulate.
Mont's childhood in Thames was good preparation for the practical, oily-rag demands of research. Weekends were spent exploring old mine shafts, camping in the bush and detonating the occasional explosion with equipment found in abandoned mines.
The boys of Thames thrilled in the abundance of derelict houses left behind by the gold rush. "Everyone had an old building as a gang headquarters," Mont wrote. "[The buildings] attracted arsonists from far and wide."
In 1980, Mont was made a Fellow of London's Royal Society - arguably the world's most prestigious scientific society, for his scientific contributions. He was knighted in 1991.
Professor Sir Peter Gluckman, another Royal Society Fellow and chief science advisor to the Prime Minister, says Mont is without doubt the most distinguished medical scientist New Zealand has ever produced. "His work is idolised throughout the world of paediatrics and obstetrics," he says.
But Mont's main legacy is his work on saving premature babies. Says one of the mothers from the original trial: "We have a delightful child (well, she’s [over] 30 now but still 'my child') who has given us much joy; we are ever thankful for all the help given at her premature birth."
Thank you, Mont Liggins.
New Zealand Listener
September 4-10 2010 Vol 225 No 3669
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Doctor gave premmies the breath of life
Graham Liggins developed a lifesaving treatment for premature babies, after showing that foetal lung maturation could be speeded up by administering a steroid. His research changed medical practice and saved hundreds of thousands of lives.
He used to tell the story of his farming neighbour in New Zealand, knowing he was an obstetrician, asking why lambs so often die after premature delivery when dogs worry the ewes. Liggins did not know, but he realised the question mattered and he wondered if it might have something to do with the stress-response steroid cortisol. He tested his hypothesis in a series of experiments and eventually proved that, at least in sheep, foetal cortisol release triggers labour.
This was important, but he had also noticed something else. The lungs of premature lambs normally sank in water because they had failed to fill with air. However, if the ewe had been given corticosteroids before delivery, the lungs inflated normally and floated - the steroids had stimulated production of a soapy substance, surfactant, which was vital for lung aeration.
Premature human babies also lack surfactant, and can develop an often fatal condition known as respiratory distress syndrome (RDS). Over the next few years Liggins and Ross Howie, a paediatrician, randomly allocated steroids or placebos to more than 1000 women in premature labour. Both RDS and mortality fell dramatically in the experimental group, and that simple treatment now saves the lives of many thousands of premature babies.
Graham Liggins was born on June 24, 1926, in Thames, NZ, the fourth son of a doctor. From 1944 to 1948 he studied medicine in Dunedin, where he later worked as a GP to save up enough money to travel to Britain for specialist training. He met his wife, Celia, later Auckland's first female obstetrician, in Newcastle and together they worked for a time in Cumbria.
In 1959, he returned to NZ as a consultant at the National Women's Hospital, in Auckland, where he met Bill Liley, another obstetrician, who suggested preterm labour as a topic for study. After minor projects on fertility treatment, Liggins developed his experimental techniques, in particular his methods for studying the physiology of lambs in utero.
A natural outdoorsman, Liggins epitomised the Kiwi "No. 8 wire man" mentality: someone who can fix anything with whatever is to hand. For the next 30 years he combined clinical practice with animal physiology performed in his laboratory, a small wooden hut in the hospital grounds, and with Geoffrey Dawes in Oxford led the science of foetal physiology.
Liggins was a scrupulously honest researcher. Studying in California, he blew the whistle when he discovered a colleague fabricating data. When his steroid discovery paper was praised for the careful trial design he always acknowledged his debt to Howie. His treatment was not accepted overnight, though. The first report, in the journal Paediatrics in 1972, is now a citation classic but, incredibly, The Lancet had rejected it on the grounds that it would be of little general interest. Liggins probably suspected they were reluctant to advocate a treatment developed in a small, faraway country such as New Zealand.
It took nearly 20 years before everyone realised that Liggins had been right all along. Steroids work in all premature babies, and cost a few cents. The systematic review that finally pulled together all the evidence relating to their effectiveness is now a classic in its own right, and even forms the basis of the logo of the Cochrane Collaboration, the worldwide evidence-based medicine organisation.
Liggins was professor of obstetrics and gynaecological endocrinology at the University of Auckland from 1968. When, in 2001, the university established the first major research institute dedicated to developmental research, it was named the Liggins Institute. He was elected a fellow of the Royal Society in 1980, appointed a Commander of the British Empire (CBE) in 1983 and knighted in 1991. He retired from clinical practice and from his chair in 1987, but never from his "No. 8 wire man" role; shortly before his death, he had rigged up a solar panel to run a watering system for his vegetable patch.
Graham Liggins is survived by his four children and several grandchildren. Celia predeceased him.
Jim Thornton, Guardian News & Media
The Sydney Morning Herald, 9 September 2010