Jim Allison: Breakthrough (2019)

Bill Haney's documentary follows Jim Allison out of Alice, Texas, a small farming and oil town in the south of the state. He spends a lab career on one question that most people thought was a dead end. Could the immune system be set loose on cancer?

Spoilers throughout. This page says how Jim Allison ends.

The film starts with a loss. Allison's mother died of lymphoma in the summer of 1960, when he was eleven. Her radiation treatment left burns on her neck. In his Nobel autobiography he describes sitting at her bedside and holding her hand as she died. He also says he did not know at the time that it was cancer, because people did not speak of such things.

The tension in the rest of the film is not about science. It is about money and habit. Years of rejection from drug companies. A cancer field that was sure this approach was finished. A drug that almost never reached trials at all.

Allison plays harmonica in a band of cancer scientists called the Checkpoints. He is filmed learning he has won the 2018 Nobel Prize in Physiology or Medicine, shared with Tasuku Honjo. His brother Mike died in 2005. Allison counts him among the family he lost to cancer, and notes that his own drug does not work for prostate cancer.

The science is worth setting out plainly, because the film can leave you with the idea of one flash of insight.

T cells are the immune cells that kill infected and faulty cells. Allison's lab showed that a molecule called CTLA-4 acts as a brake on them. It was the first brake of its kind ever described. If that brake is what stops the immune system attacking a tumor, then blocking it should let the attack happen.

In March 1996, Leach, Krummel and Allison published that result in Science. Antibodies against CTLA-4, given to mice, made established tumors shrink away. The mice were then immune when the tumor cells were given again. That paper is the hinge of the whole story.

The drug that came out of the work is called ipilimumab. The US Food and Drug Administration approved it on 25 March 2011, for advanced melanoma. Honjo worked on a second brake, called PD-1, and that led to the drugs now used far more widely.

This is a warm film about a likeable man, and it is shaped accordingly.

The discovery took a great many people, and the film squeezes that into one man's stubbornness. Students, junior researchers, company scientists and the doctors who ran the trials get little room. Nor do the scientists behind PD-1, whose work matters at least as much to patients today. Years of trial design and failure become a short run of turning points.

The film puts the striking cases first, which is what films do. These are patients who were expected to die and did not. That can leave you thinking this is the normal result. For most cancers and most patients it is not. Cost, access and the long list of failed trials barely feature.

The honest summary is the one the film half tells and then moves past.

These drugs take the brakes off the immune system. For a minority of patients with certain cancers, the results are striking and long-lasting in a way older drugs never were. For many others they do nothing at all, and nobody fully knows why. Working out in advance who will respond is still an open problem.

They are also not gentle. An immune system without brakes can turn on healthy organs. The bowel, the liver, the thyroid, the lungs and the skin can all become inflamed. These effects can show up weeks or even months after treatment. That is why patients are told to report new diarrhoea, breathlessness, a rash or odd tiredness straight away, rather than waiting for the next visit. Caught early, most are manageable. Left alone, some are not.

Ipilimumab was first approved for advanced melanoma, so the sensible thing for a viewer to do with this film is check their own skin.

The CDC's ABCDE prompt describes what to look for in a mole or spot:

• Asymmetrical shape, with parts that look different.
• Border that is jagged.
• Color that is uneven.
• Diameter larger than a pea.
• Evolving: it has changed over the past few weeks or months.

The CDC also describes the other skin cancers, which look different. Basal cell cancer can show up as a shiny bump, a pink or red scaly patch, or a sore that does not heal and is crusty or bleeds. Squamous cell cancer usually shows up as a firm red or skin-coloured bump, a scaly patch, or an open sore that bleeds.

Melanoma also turns up on skin that rarely sees the sun. The soles of the feet. The palms. Under the nails. Those sites are relatively more common on darker skin, and they are a frequent reason for late diagnosis, because nobody thinks to look there.

There is no screening programme for adults at average risk. In April 2023 the US Preventive Services Task Force looked at whether a doctor checking your skin does more good than harm in people with no symptoms. It found there was not enough evidence to say. That is called an I statement, and it means unproven rather than useless. NCI puts it more bluntly: skin checks used as screening have not been shown to cut deaths.

Some people are still offered regular skin surveillance by a specialist. That includes people with many unusual moles, heavy sun damage, or melanoma in themselves or their family.

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Films about research are good at one thing. They show that treatments come from decades of dull work, and that whoever pays decides which questions get answered. They are bad at odds. If you have cancer, the useful question is not whether immunotherapy is remarkable. It is whether it is an option for your disease, and what is honestly known about how often it helps people like you. And if a mole has changed, that is a separate appointment, worth making this month. Jim Allison: Breakthrough cannot tell you what to watch for, but screening and possible warning signs can.

This page discusses Jim Allison: Breakthrough for education. It is not medical advice, and nothing here is a judgement of anyone's real medical care. Spotted an error? Please email [email protected].