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The spaces between facts

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William Halsted is revered among surgeons. He died in 1922, and yet is still considered one of the most influential surgeons ever, with many of his innovations – such as the use of rubber gloves and a surgical procedure on the digestive tract – still in use in operating theatres today.

He also developed the radical mastectomy procedure after some women he operated on for breast cancer relapsed when the cancer spread to other parts of the body. Halsted was convinced that the operation wasn’t ‘clean’ and had left behind some of the tumour, so he began to remove the breast, lymph nodes and chest wall muscles to ensure no trace of the cancer was left behind.

Radical mastectomy quickly established itself as the standard operation for breast cancer even though it was never tested, and surgeons were happy to go along with Halsted’s strange ideas about ‘unclean’ surgery. Even when surgeons like Sir Geoffrey Keynes questioned the approach in the 1940s, they were shouted down and ignored.

In 1980 – around 80 years after Halsted introduced the procedure – the first-ever randomized trial was carried out and tested against conservative, breast-saving surgery. But it was hard to find surgeons prepared to try out this latter alternative, so convinced were they that radical mastectomy was the only ethical and effective response to breast cancer.

Eventually the researchers found enough recruits to test the more conservative approach – and, to their amazement, they discovered that the death rate among women who had a radical mastectomy was the same as those who had the conservative surgery.

As no one could believe the results, the researchers took another look in the 1990s and then again in 2000. Eventually, everyone had to agree that radical mastectomy had been a false direction. Sadly, by then, more than 500,000 women had undergone the unnecessary surgery in the US alone.

Halsted had got it seriously wrong. It wasn’t that some of the cancer had been left behind after surgery: long before the women had gone under the knife, their cancer had already spread and that’s why they suffered a relapse.

The story of Halsted has now been told by leading oncologist Siddhartha Mukherjee in a TED talk and subsequent book, The Laws of Medicine (Simon & Schuster, 2015). It’s an example of how doctors work with incomplete knowledge and sometimes fail. It’s the space between the facts, as he describes it.

These spaces, rich with quantum uncertainty, can make a ‘typical’ case of cardiovascular disease suddenly veer into unknown terrain, or a drug that’s been effective in thousands kill the next patient, or convince an eminent surgeon of ‘unclean’ surgery.

Far from being a science, medicine is “a lawless, uncertain world. I wondered if the compulsive naming of parts, diseases, and chemical reactions was a mechanism invented by doctors to defend themselves against a largely unknowable sphere of knowledge,” said Mukherjee.

As if trying to put a Band-Aid across the chasms created by a massive earthquake, Mukherjee has come up with ‘three laws’ to help guide him through medicine’s otherwise lawless landscape.

His first law reminds us that strong intuition is much more powerful than a weak test. No test is perfect and all will throw up their share of false positives – seeing a disease that’s not actually there – and false negatives – where it fails to see a disease that really is there. So how can you know the result is true? Without prior knowledge, you can’t, but a fair slice of common sense and a little bit of information about the person being screened can reduce the odds.

The second law states that ‘normals’ teach us rules, while ‘outliers’ teach us laws. Most diseases and treatments follow a similar pattern – these are the normal – but it’s the unusual and unexpected that teaches doctors something new. Outliers are also known as ‘anecdotal’, a term that sends a shiver down the spines of most researchers, because the anecdotal is the exception to the rule – but it shouldn’t be ignored.

The third law, inspired by Halsted and his unclean surgery, tells us that, for every perfect medical experiment, there is a perfect human bias.

All of this suggests that, despite the progress that’s been made, Voltaire’s caustic view of medicine still holds true three hundred years on: Doctors are men who prescribe medicines of which they know little, to cure disease of which they know less, in human beings of whom they know nothing.

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