Jim Allison: Breakthrough (2019)

Jim Allison: Breakthrough (2019) is a documentary about the scientist whose work led to a new kind of cancer drug. This page is for viewers who want to know what the film gets right, what it leaves out, and what the science means for patients.

Spoilers throughout. This page says how Jim Allison ends.

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?

The film starts with a loss. The film begins with Allison's family losses to cancer, including his mother.

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.

The film also shows the loss of his brother to 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. CTLA-4 is a molecule that acts as a brake on T cells. If that brake is what stops the immune system attacking a tumor, then blocking it should let the attack happen.

The drug that came out of the work is called ipilimumab. It was approved in the US in March 2011 for metastatic melanoma. It blocks CTLA-4. Other checkpoint drugs, which block PD-1 or PD-L1, are now used for many cancers.

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. 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.

Checkpoint blockade means drugs that block these brakes. 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 skin, lungs, colon, liver, thyroid and other organs can become inflamed. Doctors cannot know for sure when or if side effects will occur, so patients are told to report new diarrhoea, breathlessness, a rash or odd tiredness right away, rather than waiting for the next visit. If you have trouble breathing or severe symptoms, call 911.

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.

Check all of your skin, including the soles, palms and under the nails. Check every part of your skin, including places that rarely see the sun, and tell your doctor about any change.

There is no screening programme for adults at average risk. In 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 says skin exams have not been shown to lower the risk of dying from skin cancer, and they may lead to overtreatment.

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. They also show 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. Book it soon and do not wait. 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 corrections@cancerexplained.org.