Mel Greaves has a simple goal in life. He is trying to create a yoghurt-like drink that would stop children from developing leukaemia. The idea might seem eccentric; cancers are not usually defeated so simply. However, Professor Greaves is confident and, given his experience in the field, his ideas are being taken seriously by other cancer researchers. Based at the Institute of Cancer Research in London, Greaves has been studying childhood leukaemia for three decades. On Friday, it was announced that he had received a knighthood in the New Year honours list for the research he has carried out in the field. “For 30 years I have been obsessed about the reasons why children get leukaemia,” he says. “Now, for the first time, we have an answer to that question – and that means that we can now start thinking about ways to halt it in its tracks. Hence my idea of the drink.”
In the 1950s, common acute lymphoblastic leukaemia – which affects one in 2,000 children in the UK – was lethal. Today 90% of cases are cured, although treatment is toxic, and there can be long-term side effects. Also, for the past few decades, scientists have noticed that numbers of cases have been increasing in the UK and Europe at a steady rate of around 1% a year. “It is a feature of developed societies but not of developing ones,” Greaves adds. “The disease tracks with affluence.” Acute lymphoblastic leukaemia is caused by a sequence of biological events. The initial trigger is a genetic mutation that occurs in about one in 20 children. “That mutation is caused by some kind of accident in the womb. It is not inherited, but leaves a child at risk of getting leukaemia in later life,” adds Greaves. For full leukaemia to occur, another biological event must take place, and this involves the immune system. “For an immune system to work properly, it needs to be confronted by an infection in the first year of life,” says Greaves. Without that confrontation with an infection, the system is left unprimed and will not work properly.”
And this issue is becoming an increasingly worrying problem. Parents, for laudable reasons, are raising children in homes where antiseptic wipes, antibacterial soaps and disinfected floor washes are the norms. Dirt is banished for the good of the household. Also, there is less breastfeeding of infants and a tendency for them to have fewer social contacts with other children. Both trends reduce babies’ contact with germs. This has benefits – but also comes with side effects. Because young children are not being exposed to bugs and infections as they once were, their immune systems are not being properly primed. “When such a baby is eventually exposed to common infections, his or her unprimed immune system reacts in a grossly abnormal way,” says Greaves. “It over-reacts and triggers chronic inflammation.” As this inflammation progresses, chemicals called cytokines are released into the blood, and these can trigger a second mutation that results in leukaemia in children carrying the first mutation. “The disease needs two hits to get going,” Greaves explains. “The second comes from the chronic inflammation set off by an unprimed immune system.” In other words, a susceptible child suffers chronic inflammation that is linked to modern super-clean homes, and this inflammation changes his or her susceptibility to leukaemia so that it is transformed into the full-blown condition.
From this perspective, the disease has nothing to with power lines or nuclear fuel reprocessing stations, as has been suggested in the past, but is caused by a double whammy of interacting prenatal and environmental events, as Greaves outlined in the journal Nature Reviews Cancer earlier this year. Crucially, this new insight offers scientists a chance to intervene and to stop leukaemia from developing in the first place, he adds. “We do not yet know how to prevent the occurrence of the initial prenatal mutation in the womb, but we can now think of ways to block the chronic inflammation that happens later on.” To do this, Greaves and his team have started working on the bacteria, viruses and other microbes that live in the human gut. These help us digest our food, but they also give an indication of the bugs we have been exposed to in life. For example, people in developed countries tend to have far fewer bacterial species in their guts, it has been found – and that is because they have been exposed to fewer species of microbes in the early stages of their lives, a reflection of those “cleaner” lives they are now living. “We need to find ways of reconstituting their microbiomes – as we term this community of microbes. We also need to find which are the most important species of bacteria for priming a child’s immune system.”
To do this, Greaves is now experimenting on mice to find out which bugs are best at stimulating rodent immune systems. The aim would then be to follow up with trials on humans in two or three years. “The aim is to find six or maybe ten species of microbes that are best able to restore a child’s microbiome to a healthy level. This cocktail of microbes would be given, not as a pill, but perhaps as a yoghurt-like drink to very young children. And it would not just help prevent them getting childhood leukaemia. Cases of conditions such as type 1 diabetes and allergies are also rising in the west and have also been linked to our failure to expose babies to bacteria to prime children’s immune systems. So such a drink would help cut numbers of cases of these conditions as well. I think the prospect is incredibly exciting. I think we could use this to reduce the risk not just of leukaemia but some other very debilitating conditions.”
Leukaemia: the facts
Blood cells are manufactured in bone marrow. Red blood cells, which carry oxygen around our bodies, white blood cells, which fight infection, and platelets, which stop bleeding, are created when your body needs them. But when a person develops leukaemia, too many white blood cells are released, which stop the normal cells in your bone marrow from growing. As a result, the amount of normal red cells, white cells and platelets in your blood is reduced – and your health suffers. Of the many types of leukaemia, the most common in young people are acute lymphoblastic leukaemia and acute myeloid leukaemia. Source: Teenage Cancer Trust
Credit: Robin McKie for The Guardian, 30 December 2018.