John Holter and Roald Dahl both had sons with hydrocephalus. In striving to help their children, their insights and innovations ushered in a new medical era, writes Richard Hayward, winner of The THES science writing prize.
Question: what do a Pennsylvania engineer, an English bestselling author of children's books, breast implants and a condition first described by Hippocrates all have in common? Behind the answer lies the story of a medical revolution.
Charles Case "Casey" Holter was born on November 7 1955 with a severe form of spina bifida. In the lower part of his back, a fleshy mass of disorganised spinal cord tissue could be seen protruding through a midline gap in the skin. As a result, his legs were paralysed and would remain so, and he would never gain proper control of his bladder and bowels.
But the immediate danger facing him was infection. And Casey did indeed develop meningitis, although fortunately it responded to the antibiotics then available. As soon as he recovered, surgeons operated to close his back. But then he developed a new problem. His head started to expand rapidly. His parents were told that he had developed "water on the brain", or, to give it its medical name, hydrocephalus, a term that dates back to the writings of Hippocrates.
Theo Dahl was born five years later, in 1960. He was a fine, healthy baby, but when he was only four months old his nanny was taking him for a walk and a cab hit his pram. He suffered severe brain damage. Instead of recovering as expected, his condition deteriorated. Like Casey Holter, he had developed hydrocephalus.
John Holter, Casey's father, was a machinist working for the Yale and Town Lock Company. Theo's father was Roald Dahl. Both were destined to make significant contributions to the treatment of the condition that afflicted their sons.
Casey and Theo had each developed hydrocephalus for a different reason. For Casey, the diagnosis of spina bifida brought with it a second neurological abnormality - a prolapse downwards of the lowest parts of the brain into the upper reaches of the spinal canal. This was enough to obstruct the circulation of cerebro-spinal fluid (CSF) through this area.
For Theo, the culprit was bleeding in the brain caused by his head injury.
If blood leaks into the CSF in sufficient amounts, it can block the pathways through which the fluid normally circulates.
Without prompt and effective treatment, severe, perhaps fatal, damage to the brain would inevitably occur.
Fifty or so years ago, there were effectively three policies that doctors could pursue to treat the condition: reduce the production of CSF by removing the tissue that produced it - a rarely successful operation with a formidable mortality rate; drain or in some way divert the CSF around the blockage; or do nothing at all because sometimes the hydrocephalic process arrested spontaneously. Draining CSF brought two main problems: where to divert the CSF so that it could be absorbed, and what the tube used should be made of so as to be compatible with the body's tissues as well as resistant to damage from sterilisation. Among the possible destinations for the excess fluid that had by then been tried were the stomach and, for females, the Fallopian tubes. And the substances used in these procedures included polythene, silk threads, as well as the patient's own veins or ureter (a procedure that required the sacrifice of a kidney).
Casey's initial treatment consisted of intermittent withdrawals of CSF using a long needle passed through the skin, through the brain and into the expanded ventricles. He then had two unsuccessful attempts to insert a ventricle-to-abdominal cavity system incorporating tubing made of polythene.
Luckily, where Casey was being looked after in Philadelphia, two surgeons - doctors Spitz and Nulsen - had already demonstrated that a ventricle-to-atrium diversion system could work if it contained an expensive and impractical valve that could control the direction of flow while maintaining an adequate intracranial pressure. They used a rather inflexible polythene tube passed through the jugular vein to the heart.
Holter set about designing a valve for his son that could be used in a ventricle-to-atrium shunt system, and which would be both biocompatible and much simpler to manufacture. But his researches were not progressing quickly enough, so he opted for the old ball-valve model. Unfortunately, the tube tip snagged one of the centres in the heart responsible for rhythm control and the boy suffered a cardiac arrest. The surgeons had to massage his heart back into action for 30 minutes. Ironically, Holter's first valve was ready eight or nine days later, but Casey was not the first patient to try it.
The valve system was based on a chance observation of Holter's - that, when the nurses in the hospital punctured the plastic tubing of a patient's intravenous drip, the slit in the tubing produced by the angle at which the needle had been introduced appeared to seal itself as the needle was withdrawn. Holter surmised that if the pressure of the fluid were raised, this sealing effect would be overcome and fluid would leak out. His valve had two slit valves. But it was in his choice of material that Holter made an even more lasting contribution to medical history.
During his researches, Holter learnt that silicone incorporated into rubber produced a compound that was strong, heat-resistant, flexible and did not excite a tissue reaction when implanted. He promoted its refinement to a grade suitable for medical use. It was patented and manufactured as Silastic, which is now used for all hydrocephalus shunt systems as well as devices such as heart valves and breast implants.
Holter made all the first valves by hand at a cost of $40 each, including catheter. His revolutionary invention was soon recognised by the medical community, and he formed a company with Spitz and another partner to manufacture the valves. It is estimated that during the 1960s, about 100,000 Holter valves were implanted into patients with hydrocephalus.
As for Theo, as Jeremy Treglown reports in his biography of Roald Dahl, his early treatment in the US for hydrocephalus had been with the type of valve developed by Holter. But it kept blocking, and every time it did so, the pressure of the water inside his head rose to dangerously high levels - high enough to threaten his eyesight - requiring an emergency operation.
The family lived in a state of constant fear.
In 1961, they moved back to England and Theo's care was taken over by neurosurgeon Kenneth Till at Great Ormond Street Hospital in London. He identified the silicone rubber slit valves of the Holter valve as the cause of the trouble - they became too easily clogged with the debris that can accumulate in the hydrocephalic ventricles, particularly when (as in Theo's case) there had been bleeding in the brain. He, Dahl and Stanley Wade, a hydraulic engineer friend of Dahl's, set about designing a new valve.
In the Wade-Dahl-Till (WDT) valve, the mechanism took the form of two metal discs, one set in a restrictive housing at each end of a short length of silicone rubber tubing. Movement of fluid under pressure from above moved each disc to an open position, but any pressure from below pushed the discs back and prevented retrograde flow.
Like the Holter valve, the early prototypes and the first commercial models were assembled in a home workshop and had a rather Heath-Robinson look: the Silastic tubing was secured to the valve housing at each end by a strong tie - black silk in the case of the WDT. By 1962, the WDT valve was ready for implantation.
However, while Wade, Dahl and Till were working on their prototype, for reasons unknown, Theo's hydrocephalus entered a state of arrest.
Casey's hydrocephalus did not arrest. Instead, 14 months after he had received the second Holter valve ever implanted, his shunt blocked and the lower end had to be transposed from the heart down into the abdominal cavity. One further revision was needed when he died after an epileptic fit at the age of five.
Both Casey and Theo had fathers who were exceptional men and who, despite - or perhaps because of - their intense emotional involvement in their child's care, had the courage to take a step back from their feelings and do something to help. For John Holter, there is no doubt that he helped launch a new era in the treatment of hydrocephalus. Today there are more than 40 different valve systems available, including variations on the original Holter valve - and the name itself is still in everyday use.
But Holter's greatest contribution was to change our attitude towards children with the condition. No longer is it considered, with rare exceptions, a hopeless condition. Now the world is full of children who owe their lives to the Holter valve revolution.
The WDT valve was popular for a while in the UK, particularly for hydrocephalus caused by bleeding in the brain, but it offered too little resistance to flow and patients could experience overdrainage of CSF, sometimes with catastrophic results. In more entrepreneurial hands, perhaps, the problems would have been addressed and the valve would have been more than a footnote in the history of water on the brain.
Richard Hayward is a paediatric neurosurgery consultant at Great Ormond Street Hospital, London. This is an edited version of the essay that won him first prize in The THES /Oxford University Press Science Writing Prize 2003.