We finally know what causes childhood leukemia — and how to prevent it

A number of different things have to happen for a child to develop leukemia.

The cause of the most common type of childhood cancer has been a century-long debate among those in the medical community. Now, thanks to the work of Prof. Mel Greaves, of the Institute of Cancer Research in London, the mystery is at its end. Acute lymphoblastic leukemia (ALL) affects 1 in 2,000 children. Ironically, it's our modern germ-free lifestyle, particularly our high level of cleanliness, that contributes to the disease's formation. What's really exciting is that we may even have the knowledge we need to make ALL a thing of the past.


To make this breakthrough, Prof. Greaves conducted a meta-analysis, combing through 30 years of medical literature and gathering data from colleagues all across the globe. His search included research on genetics, epidemiology, immunology, cellular biology, and much more. Along this journey, Prof. Greaves ruled out chemicals in the environment, ionizing radiation, electromagnetic waves, and the influence of high tension wires (electrical cables) as possible causes.

Putting together so many disparate puzzle pieces and eliminating false causes allowed him to formulate a “unified theory of leukemia." Although a horrifying condition for a child and parents to endure, Prof. Greaves' analysis, published in the journal Nature Reviews Cancer, has a bright spot. This type of leukemia may be wholly preventable.


A lack of exposure to microbes in the environment contributes to ALL. Image credit: Donnie Ray Jones, Flickr.

This exhaustive work supports the “delayed infection theory." According to Prof. Greaves, “The research study strongly suggests that acute lymphoblastic leukemia has a clear biological cause and is activated by a variety of infections in predisposed kids whose immune systems have not been properly primed."

Children born with a certain genetic mutation have merely the potential for developing ALL. This mutation takes place by accident within the womb. It will remain latent until the second “hit" comes, when the immune system fails to encounter enough microbes during the first year of life to prime it, or in other words train it.

A healthy amount of germ exposure allows the immune system to learn how to deal with pathogens correctly. If the infant grows into childhood without exposure to microbes from the environment or other children, they may develop ALL. But it takes a run-of-the-mill infection later on to ultimately trigger this form of leukemia. All told, full-blown ALL only occurs in 1% of cases where the mutation is present. The absence of pathogens as a factor explains why this form of childhood leukemia is common in wealthy, developed countries, but nearly absent in developing ones.


Allowing young children to play with older ones and be exposed to microbes in the environment could prevent ALL. Image credit: Pixababy.

What's fascinating is some of the disparate pieces of the puzzle Prof. Greaves put together to formulate this discovery. For instance, one clue was an outbreak of swine flu in Milan, which resulted in seven children developing ALL. Another clue was that infants born vaginally over cesarean section have a lower risk of developing this form of cancer.

That's because infants passing through the vaginal canal are exposed to more microbes than those born through c-section. Also, infants who are breastfed have less of a risk, as they often pickup healthy bacteria this way. On another front, animals, particularly mice, when living in an environment devoid of pathogens, often develop leukemia.

Prof. Greaves urges parents not to worry too much about keeping a clean house, and he offer some tips for preventing the disease, which include being less worried about normal, run-of-the-mill infections, and allowing young children to play with other kids, especially older children.

This research may even someday help us prevent the onset of other autoimmune disorders, including type 1 diabetes and allergies. In the future, giving young children a special yogurt drink or somehow purposefully exposing them to healthy microbes could help prevent ALL and perhaps other autoimmune conditions as well.

To hear Prof. Greaves explain his breakthrough himself, click here:

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Researchers hope the technology will further our understanding of the brain, but lawmakers may not be ready for the ethical challenges.

Still from John Stephenson's 1999 rendition of Animal Farm.
Surprising Science
  • Researchers at the Yale School of Medicine successfully restored some functions to pig brains that had been dead for hours.
  • They hope the technology will advance our understanding of the brain, potentially developing new treatments for debilitating diseases and disorders.
  • The research raises many ethical questions and puts to the test our current understanding of death.

The image of an undead brain coming back to live again is the stuff of science fiction. Not just any science fiction, specifically B-grade sci fi. What instantly springs to mind is the black-and-white horrors of films like Fiend Without a Face. Bad acting. Plastic monstrosities. Visible strings. And a spinal cord that, for some reason, is also a tentacle?

But like any good science fiction, it's only a matter of time before some manner of it seeps into our reality. This week's Nature published the findings of researchers who managed to restore function to pigs' brains that were clinically dead. At least, what we once thought of as dead.

What's dead may never die, it seems

The researchers did not hail from House Greyjoy — "What is dead may never die" — but came largely from the Yale School of Medicine. They connected 32 pig brains to a system called BrainEx. BrainEx is an artificial perfusion system — that is, a system that takes over the functions normally regulated by the organ. The pigs had been killed four hours earlier at a U.S. Department of Agriculture slaughterhouse; their brains completely removed from the skulls.

BrainEx pumped an experiment solution into the brain that essentially mimic blood flow. It brought oxygen and nutrients to the tissues, giving brain cells the resources to begin many normal functions. The cells began consuming and metabolizing sugars. The brains' immune systems kicked in. Neuron samples could carry an electrical signal. Some brain cells even responded to drugs.

The researchers have managed to keep some brains alive for up to 36 hours, and currently do not know if BrainEx can have sustained the brains longer. "It is conceivable we are just preventing the inevitable, and the brain won't be able to recover," said Nenad Sestan, Yale neuroscientist and the lead researcher.

As a control, other brains received either a fake solution or no solution at all. None revived brain activity and deteriorated as normal.

The researchers hope the technology can enhance our ability to study the brain and its cellular functions. One of the main avenues of such studies would be brain disorders and diseases. This could point the way to developing new of treatments for the likes of brain injuries, Alzheimer's, Huntington's, and neurodegenerative conditions.

"This is an extraordinary and very promising breakthrough for neuroscience. It immediately offers a much better model for studying the human brain, which is extraordinarily important, given the vast amount of human suffering from diseases of the mind [and] brain," Nita Farahany, the bioethicists at the Duke University School of Law who wrote the study's commentary, told National Geographic.

An ethical gray matter

Before anyone gets an Island of Dr. Moreau vibe, it's worth noting that the brains did not approach neural activity anywhere near consciousness.

The BrainEx solution contained chemicals that prevented neurons from firing. To be extra cautious, the researchers also monitored the brains for any such activity and were prepared to administer an anesthetic should they have seen signs of consciousness.

Even so, the research signals a massive debate to come regarding medical ethics and our definition of death.

Most countries define death, clinically speaking, as the irreversible loss of brain or circulatory function. This definition was already at odds with some folk- and value-centric understandings, but where do we go if it becomes possible to reverse clinical death with artificial perfusion?

"This is wild," Jonathan Moreno, a bioethicist at the University of Pennsylvania, told the New York Times. "If ever there was an issue that merited big public deliberation on the ethics of science and medicine, this is one."

One possible consequence involves organ donations. Some European countries require emergency responders to use a process that preserves organs when they cannot resuscitate a person. They continue to pump blood throughout the body, but use a "thoracic aortic occlusion balloon" to prevent that blood from reaching the brain.

The system is already controversial because it raises concerns about what caused the patient's death. But what happens when brain death becomes readily reversible? Stuart Younger, a bioethicist at Case Western Reserve University, told Nature that if BrainEx were to become widely available, it could shrink the pool of eligible donors.

"There's a potential conflict here between the interests of potential donors — who might not even be donors — and people who are waiting for organs," he said.

It will be a while before such experiments go anywhere near human subjects. A more immediate ethical question relates to how such experiments harm animal subjects.

Ethical review boards evaluate research protocols and can reject any that causes undue pain, suffering, or distress. Since dead animals feel no pain, suffer no trauma, they are typically approved as subjects. But how do such boards make a judgement regarding the suffering of a "cellularly active" brain? The distress of a partially alive brain?

The dilemma is unprecedented.

Setting new boundaries

Another science fiction story that comes to mind when discussing this story is, of course, Frankenstein. As Farahany told National Geographic: "It is definitely has [sic] a good science-fiction element to it, and it is restoring cellular function where we previously thought impossible. But to have Frankenstein, you need some degree of consciousness, some 'there' there. [The researchers] did not recover any form of consciousness in this study, and it is still unclear if we ever could. But we are one step closer to that possibility."

She's right. The researchers undertook their research for the betterment of humanity, and we may one day reap some unimaginable medical benefits from it. The ethical questions, however, remain as unsettling as the stories they remind us of.

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