The truth about why kids get leukaemia

Mel Greaves is ob­sessed with beat­ing child­hood leukeamia – and hopes to cre­ate a drink that will stop the dis­ease


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. Last month it was an­nounced that he had re­ceived a knight­hood in the UK 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. In ad­di­tion, for the past few decades, sci­en­tists have no­ticed that num­bers of cases have ac­tu­ally been in­creas­ing in the UK and Europe at a steady rate of around 1% a year.

“It is a fea­ture of de­vel­oped soci- eties but not of de­vel­op­ing ones,” Greaves adds. “The dis­ease tracks with af­flu­ence.”

Acute lym­phoblas­tic leukaemia is caused by a se­quence of 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 floor­washes are the norm. Dirt is ban­ished.

In ad­di­tion, 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 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 over­re­acts 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.”

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 last year.

Cru­cially, this new in­sight of­fers sci­en­tists a chance to stop leukaemia from de­vel­op­ing, 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 germs 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.”

Greaves is now ex­per­i­ment­ing on mice to find out what best stim­u­lates 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 10 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 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 a num­ber of other very de­bil­i­tat­ing con­di­tions.”

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