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Jennie Erin Smith (Riverhead Books)

After working in health journalism for over 10 years, I have covered countless drug trials – some runaway successes, others out-and-out failures, and everything in between. But I am ashamed to admit that I have rarely considered how these highs and lows affect the people involved.

In Valley of Forgetting: Alzheimer’s families and the search for a cure, journalist Jennie Erin Smith puts them in the spotlight in her story of a rural community in Medellín, Colombia, hit by early-onset Alzheimer’s disease.

Smith, a contributor to The New York Times, begins with Francisco Lopera, a neurologist at the University of Antioquia, Medellín. Lopera, who died last year, wanted to discover why so many local people experienced memory loss in their 40s, marking the beginning of a dramatic decline until their deaths, typically a decade later.

He found that affected individuals all possessed a mutation in a gene called PSEN1 and that this drove their early-onset Alzheimer’s. The gene is involved in breaking the peptide bonds between amino acids in proteins, and mutations to it can result in the formation of clumps of amyloid protein – the hallmark of Alzheimer’s in the brain.

The researchers also tested the descendants of people with the condition to find out who carried the mutation. The child of someone with the mutation has a 50/50 chance of inheriting it: they either dodge the bullet or almost definitely get early-onset Alzheimer’s.

With this knowledge, Lopera and his team decided to test the monoclonal antibody crenezumab. They hoped it would prevent or slow this amyloid clumping, thereby delaying or easing Alzheimer’s symptoms in people who were genetically predetermined to develop the condition.

However, the researchers didn’t reveal the results of the genetic tests until their drug trials (some of which were paused or ended due to a lack of efficacy) had concluded. The participants could then choose whether to learn their fate.

For many of them, learning their genetic status was why they signed up. But finding out meant an interminable wait for many, like the 38-year-old woman who wanted to know whether she might pass the mutation to the baby she yearned for. This was no hypothetical situation: Smith later learned of a woman around this age who developed dementia after starting a family.

The tribulations didn’t stop there. Smith also met a woman called Lina whose mother, Amparo, had Alzheimer’s and suddenly disappeared. Lina claims that trial staff made no effort to help find her. She said that when researchers had needed anything – from an MRI scan to a cognitive test – Amparo showed up. But in her moment of need, they weren’t there for her.

In the end, crenezumab was no better than a placebo at slowing Alzheimer’s. This was announced in a press conference with no relatives of the participants present – and it was held in English, which most of those involved didn’t understand. They found out via WhatsApp.

The affair also raises the question of how things could have played out. Drugs are free for trial participants, but if crenezumab had been effective enough for approval, who would have been able to continue paying after the trial ended? How would Colombia have ensured participants who benefitted had continued access? Most of them weren’t well off – some signed up only because they received free diapers for incontinent relatives.

The book left me aching and enraged for what they and others have endured in the name of scientific research. Clinical trials are essential, but we must not ignore the turmoil of the participants – people to whom Smith has finally given identities.

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