Saving infants' lives with iron

ETH pharmaceutical sciences graduate Nicole Stoffel has shown that iron deficiency reduces vaccine efficacy. Her research is now helping to improve the health of children in developing countries – yet becoming a researcher was not originally part of her plans.
Nicole Stoffel received this year’s Lopez-​Loreta Prize in recognition of her work. (Photograph: Daniel Winkler / ETH Zurich)

Nicole Stoffel doesn’t mind her busy travel schedule – in fact, she welcomes the variety: “I actually work really well when I’m travelling, so it doesn’t bother me at all,” she says with a smile. She has just popped back to Switzerland for a few days after a visit to England. The 31-year-old senior scientist conducts research in the Laboratory of Human Nutrition at ETH Zurich, but she also does much of her work at Oxford University: “I’m very grateful to be working at two such prestigious institutions.” She also makes several trips a year to Kenya and spends time in countries including Thailand, Mexico and the Philippines, where she supervises various studies.

Stoffel’s research focuses on the effects and treatment of iron deficiency, especially in developing countries. Together with researchers from the group led by ETH Professor Michael Zimmermann – as well as researchers from Kenya, the UK, the US and the Netherlands – she was able to show that iron deficiency reduces vaccine efficacy.

Some 40 percent of the world’s children, many of them just infants, suffer from anaemia caused by a lack of iron, so understanding the link to reduced vaccine protection is crucial, particularly in developing countries. The problem begins before birth: many pregnant women are themselves iron-deficient, so their baby’s iron stores are not adequately filled up in the womb. These newborns begin life with depleted iron reserves – and they exhaust what little they have after just a few months.

Saving children’s lives

This puts children’s health at risk, because one consequence of iron deficiency is a significant reduction in the efficacy of vaccines against childhood diseases such as measles, diphtheria, whooping cough and pneumococcus. This was confirmed by two clinical trials that Stoffel conducted on Kenyan children. The results of these trials showed that this cohort had a two to five times higher risk of failing to produce protective antibodies after vaccination.

In contrast, the effects of vaccination are significantly improved in children who receive iron as a dietary supplement – more antibodies are produced, and these antibodies are also more potent. Even though other factors are likely to play a role in vaccine effectiveness, one thing is clear: “Combating iron deficiency could save the lives of many, many children,” Stoffel says, noting that one and a half million children worldwide still die from vaccine-preventable diseases each year.

In recognition of her work, Nicole Stoffel received this year’s Lopez-Loreta Prize, which is awarded on an annual basis to outstanding graduates of four universities, including ETH Zurich. The young researcher intends to use the one million euros of prize money to carry out further studies over the next four years. These will once again take place in Kenya, and her goal will be to investigate whether the link between iron levels and vaccine efficacy extends to adults – for example after receiving a COVID-19 vaccine. “The pandemic has made this issue even more pressing, because many developing countries have been hit really hard,” Stoffel says.

Optimum dosage

Stoffel’s greatest concern, however, is how to ensure that the iron that is so crucial to infants’ health is administered safely and efficiently. In many African countries, children are given a powdered nutritional supplement that contains iron alongside various micronutrients. However, this sometimes has unwanted side effects, since too much free iron in the intestine can accelerate the growth of harmful bacteria, potentially leading to inflammation and diarrhoea.

One way to avoid this is by adding a type of prebiotics known as galacto‑oligosaccharides (GOS) to the powder. As well as promoting “good” gut bacteria that protect children against gastrointestinal diseases, GOS prebiotics also improve iron absorption. Stoffel is now experimenting with different doses of iron and GOS to find the optimum mix.

In addition to the clinical trials that she plans and coordinates from her office at ETH, Stoffel also investigates the relationship between iron and the immune system on a molecular level. “It’s tremendously exciting to be able to incorporate both these areas into my work,” she says. She carries out her molecular biology research in Hal Drakesmith’s lab at Oxford University.

Using modern cell analysis methods, her goal is to observe the response of different immune cells in cell cultures and animal models. Initial results from her British colleagues show that certain immune cells can defend themselves efficiently against a viral infection only if they have enough iron available to them.

An unexpected path into research

Nicole Stoffel originally intended to work in her parents’ pharmacy after completing her degree in pharmaceutical sciences. Purely by chance, however, she discovered that the ETH Laboratory of Human Nutrition had an opening for a doctoral student. “I thought I could at least take a quick look,” she says. Somewhat to her surprise, she found the topic genuinely interesting – and her training as a pharmacist had given her the right skill set for supervising clinical trials.

She ended up accepting the position which, in retrospect, was exactly the right decision: “I quite simply fell in love with research!” Nowadays, Stoffel can’t imagine doing anything else. She takes particular pleasure in planning and evaluating clinical trials, though she also enjoys interacting with local teams in different countries. “We’re lucky to be working with some amazing people,” she says. She also firmly believes in transferring knowledge to these partner countries to provide a lasting boost to their own research work.

Taking setbacks in stride

Yet however well things have turned out for Stoffel, her path hasn’t always been a smooth one. During her doctoral project, Stoffel initially planned to carry out a study on the iron levels of overweight pregnant women. Unable to find enough subjects for the study, her thesis soon ground to a halt.

Fortunately, she was able to take over a different project that ran a lot more smoothly. “You never know how things will turn out – and that’s what makes scientific research so exciting,” she says. The important thing is learning to take setbacks in your stride and remaining open to new opportunities.

This attitude has certainly paid off: in 2018, she completed her doctoral thesis and was promptly awarded the ETH Medal for her outstanding work. The doctoral project she had switched to involved developing a new regimen for taking iron tablets. She was able to show that young women with an iron deficiency experience fewer side effects and absorb more iron if they take iron tablets orally only once every other day.

The previous recommendation was to take iron tablets on a daily basis. A number of doctors and hospitals have now amended their prescriptions to reflect Stoffel’s findings. The World Health Organization is also considering changing its recommendation, though not until it sees the results of a long-term study that is currently being conducted by one of Stoffel’s doctoral students.

Teamwork on ice

Sport is the perfect antidote to Stoffel’s mentally demanding work, and she always takes her running shoes with her on trips to Kenya, England or anywhere else: “Running is a great way to get to know new places.”

She also enjoys a sport that is still relatively unknown in Switzerland: synchronised figure skating, which involves teams of between 12 and 16 people who glide over the ice performing complicated choreography. Stoffel does her best to attend as many training sessions as she can in her hometown of Rapperswil, enjoying the outdoor exercise in the fresh wintery air and the beautiful views of Lake Zurich: “Some of my best ideas come to me at moments like that!”