The history of Australian medical research is an unabashed good news story: it’s led to many astounding yet common medical treatments and to better understanding of disease.
In fact, as a society we benefit every single day from this innovation and growth in human knowledge. Yet so many of the stories behind the science remain hidden: we know so little about how we came to know what we know.
1. Lithium as a treatment for mania
The first is about a young psychiatrist from Melbourne who had no research training whatsoever – John Cade.
Cade was particularly interested in bipolar disorder. He was convinced that the horrendous manic phase, where the person goes completely mad, must have been due to some toxin and he thought it would be secreted in the urine, particularly uric acid.
He was completely wrong. But his hypothesis led Cade to inject the urine from manic patients into guinea pigs. Because he knew lithium salts could help dissolve the uric acid crystals, Cade gave these salts to the guinea pigs. When he did that, he noticed they became calm and lethargic.
Not wanting to hurt anybody, Cade decided to take lithium himself. And then published an excellent clinical trial on ten patients in the manic phase of bipolar, six patients with schizophrenia and one with depression.
His results for mania were excellent, but there was no effect on schizophrenia or depression. In the best traditions of medical research, he published the paper in the Medical Journal of Australia. Sadly, the journal was not very widely read at the time and the findings lay silent.
But in the late 1960s, a Swedish group picked up the findings and and gave a young man by the name of Mogens Schou the job of investigating further. He did a double-blind trial and got regulatory approval for the drug in 1970.
Lithium remains one of the best treatments for bipolar disorder. In fact, what started as an experiment with a few guinea pigs and urine absolutely revolutionised treatment of the manic phase of bipolar.
2. Analgesics and severe kidney disease
For those of you not old enough to remember Bex and Vincent’s powders, they were painkillers that made a pleasant fizzy sound when put in a glass of water. You could go to the supermarket and there would be all these nice packets of the powders at the exit. And you would see people with four or five of these packets at the checkout to give them a bit of a pick-me-up.
Priscilla Kincaid-Smith began her studies in the Royal Melbourne Hospital in 1962. As a pathologist, she noted there were these tiny little black spots in the urine of some patients with chronic renal failure.
She put these samples under the microscope and saw they were the papillae (small nipple-like structures) of the kidneys that had been sliced off.
Early on, it was thought just one of the powders, or powders that contained aspirin, another painkiller called phenacetin, and caffeine, affected the kidneys and that phenacetin in particular was the problem.
Kincaid-Smith began testing with rats by giving them different painkillers. She found salicylates (an acid used for pain relief) alone could cause the kidney disease, but so could aspirin, panadol, paracetamol, a strong painkiller called indomethacin and other non-steroidal anti-inflammatory drugs.
But then she did her real work. With extensive activism and advocacy, gradually and over quite some time, Kincaid-Smith persuaded authorities that the sale of the painkillers should be restricted and that advertising should be abated.
A set of recommendations from the National Health And Medical Research Council (NHMRC) in 1970 achieved many of these goals. Advertising for these drugs as “pick-me-ups” disappeared and, with them, the disease essentially disappeared too.
3. Colony stimulating factors
Now we come to Don Metcalf and his large team of collaborators. This story begins in 1965 when Ray Bradley brought a little agar dish across the road from Melbourne University to the Walter and Eliza Hall Institute (WEHI).
In this dish, he had some large colonies of bone marrow cells that were growing: he had learnt how to grow them. Ray Bradley and Don Metcalf then published this discovery in 1966. They very quickly realised that the growth of these large colonies of cells depended on a variety of soluble hormonal factors, which were named colony stimulating factors (CSFs).
This story showed immense fortitude of the researchers involved because these CSFs are present in vanishingly small amounts. In one instance, all the workers at WEHI had to pee into a big bucket, and the urine was purified to get tiny amounts of CSF.
Later on, when the gene cloning era dawned, CSFs were made by genetic engineering in harmless bacteria. They have come to be amazing therapeutic substances, especially for people with cancer.
There are dose-limiting factors in cancer chemotherapy, usually either gut toxicity or bone marrow toxicity. If you have no white cells because the bone marrow is not making them you’ll die of an infection, it’s as simple as that.
So what these CSFs do is act as a bone marrow tonic to restore white blood count to normal. They’re an immensely important adjunct to cancer radiotherapy. Over 20 million cancer patients have received CSFs.
4. Sleep apnoea
Now we come to Colin Sullivan from the University of Sydney and Royal Prince Alfred Hospital. He was a respiratory physician interested in sleep apnoea.
At least 4% of men and 2% of women suffer from obstructive sleep apnoea. It’s a serious problem that means when they fall asleep, they stop breathing. In the worst cases, there might be 500 such attacks a night.
Sleep apnoea causes daytime sleepiness, but more worryingly evidence now shows it leads to increased incidence of coronary artery disease, hypertension and stroke.
Colin Sullivan developed a “continuous automatic positive airways pressure kit” or CPAP to prevent the upper airway from closing. He then founded a firm called ResMed in 1989.
Since then, each model has been improved and they’re now mass-produced portable, home-use CPAP devices consisting of a small, light, comfortable nasal mask connected via light tubing to quiet, unobtrusive ventilator. This sits on your bedside table delivering ideal temperature and humidity-controlled pressurised air.
It’s such a good treatment that it brings in revenue of $1.6 billion per year.
5. Spina bifida
In 1981, UK scientists conducted a double-blind clinical trial showing folic acid supplementation in early pregnancy could lower the incidence of spina bifida. But it was Fiona Stanley who first showed, in a case-control study, that the more folate in your diet during pregnancy, the less spina bifida.
Since this discovery, Stanley has promoted mandatory fortification of flour with folic acid. This was finally enacted in 2009.
Stanley has another string to her bow. She is an epidemiologist and neonatologist and she’s responsible for showing that cerebral palsy is only very rarely due to birth trauma (5% to 10% of cases). The rest, and in the vast majority of cases it’s due to infections, blood incompatibilities, genetics or unknown causes.
That’s important because of the litigiousness of patients who are dealing with the terrible burden of having a cerebral palsy child against obstetricians. It’s legendary. And in fact, many people refrain from going into the field of obstetrics because they’re so frightened of this litigation.
This article is based on a speech delivered by Sir Gus Nossal at Celebrating Australian Science: Past, Present, Future, a symposium held by the Australian Academy of Science. You can watch his full presentation here.