Alex Marshall explains how the science of childhood cancer reveals delicate balances in the human body.
Doctors examine the scans of a child, barely one year old. A large tumour presses on one side of his spine. Telling the parents there is nothing that can be done, the doctors send the family on their way without any treatment. This isn’t merely the end of a sad tale, it’s also the start of an unwanted quirk of nature.
Cancer is often considered a disease of the elderly, accompanied by greying hairs and a longing for the good old days – but this isn’t always the case. Cancers can occur at any age, but those found in children and teenagers are often wildly different from their adult counterparts, even forming their own field of research. These cancers can have different survival outcomes, different treatment regimes, and even different mutations.
Cancers are growing masses, ever expanding and selfishly-driven, diverting nutrients and blood from the functioning body and ignoring biological instructions to die despite containing a crumbling jumble of DNA. They do not occur overnight, but in multiple tiny steps, hitting vital cellular mechanisms one at a time. First, the mutations in the DNA stop the cells fulfilling their potential of becoming healthy skin, blood or muscle, instead trapping them in a perpetual cellular puberty – oddly shaped, with a weird diet, and unsure of their place in the world. Then, they increase their growth, the broken cells multiplying exponentially while turning off the mechanisms designed to terminate them. This is a lethal combination. But what happens if many of these mechanisms are already in place, if there is no need for these mutations to occur? This is often the case in children.
Imagine a host which is already primed to grow quickly and even has cells which heal wounds better, because they have yet to determine what they will be for the rest of their adult life. That is a child: fertile soil for a cancer to grow. When you consider that an egg has to transition from a single cell to a fully formed human, it may be more of a shock that we don’t see a staggering number of childhood cancers.
For many childhood cancers, the process can start before the child is even born. In the 1990s, when scientists looked at the blood of newborn twins who would both develop blood cancer, they found the first cancerous mutation existed in both patients. These twins had shared a placenta and a blood supply before being born, allowing the mutant cells to freely flow between the embryos – demonstrating that the first mutations in childhood leukaemia actually started within the womb.
Flash forward to the modern day and researchers have long stopped looking at spots of blood. Instead, they are now mimicking the developing embryo in the lab. Working with induced stem cells, artificially created by genetically manipulating cells from an adult human, scientists have been able to recreate some of the earliest events in embryonic development. Stem cells can continuously reproduce and have the potential to form multiple cell types and organs. By growing these cells in the right conditions, researchers at UCL are able to push stem cells through the various stages of embryonic development towards a desired cell type, dissecting the process of early blood production along the way.
Emma Laycock, a researcher at UCL’s Cancer Institute, works on a mutation found in 1/100 newborn babies and is currently “growing leukaemia in a dish” from stem cells, made from human foreskin. While 1/100 babies are born with the mutation, only 1/10,000 will go on to develop the leukaemia she works on, raising some interesting questions. “We’re trying to figure out how leukaemia develops in children,” Emma Laycock explains. “What happens to the cells that have these mutations? Why are these particular cells vulnerable to the mutations?”
Her work, alongside Dr Charlotta Boiers, has shown that the effect of the mutation is primarily on a rare stage of white blood cell development, unique to the embryo: “Most of the time these errors are detected and, if they can’t be repaired, cells are sent a self-destruct signal. We think mutations, like you get in childhood leukaemia, are these developmental mistakes that managed to escape detection and live past their expiry date.” This means that if the mutation occurs in cells too late, or in cells that do not need to pass through this unique stage, they will function normally and eventually die without ever being noticed.
While blood cancers provided some of the first key evidence for the pre-birth origins of childhood cancer, the link with normal development was evident. Picture a tumour with thin, wiry black hair, teeth protruding at odd angles, a collection of intertwined nerves and muscles and even the odd shrunken limb – a horror of the imagination worthy of Victor Frankenstein. This is a teratoma.
Growing in both adults and children, teratomas are a microcosm of growth, a horrific picture encapsulating all aspects of the human body. Forming from the testis or ovaries in adults, teratomas are an exemplary demonstration of the intimate balance between the programming which controls normal growth and cancer. The cells within the sex organs, which go on to produce eggs or sperm, need to have the innate potential to become any part of the body. When this goes awry, the terrible consequence is a teratoma. If their appearance was not enough of a reason to hate them, these demonic-looking cancers form the most challenging issue towards advancing stem cell therapies. Originally, it was thought that transplanting stem cells could solve many of the ailments facing mankind, due to their ability to become any type of cell. However, in initial experiments, these cells frequently became large teratomas when they were transplanted into mice.
But not everything about childhood cancers is a cause for alarm. Many children respond better to treatment than adults (although there can be some long term implications), and certain childhood cancers can simply disappear. For example, one specific type of cancer, called a neuroblastoma, often starts in the developing nerves of the embryo. Most children are diagnosed before the age of 10, but if a neuroblastoma is diagnosed before the age of one, and restricted to only one side of the body, the child is often left untreated. Incredibly, the outcome is usually that the tumour merely fades away – becoming part of the body or just dying off unnoticed.
It’s a terrible juxtaposition – a trick of fate played by the world – for a child so full of life to be burdened with a cancer. Yet, in many ways, the links between them are intertwined on a deep molecular level. Mutations which are rendered useless at any other time in an adult are only allowed to blossom because they can prey on the quirks of a growing embryo – an embryo which must be able to rapidly grow, avoid death, and take nutrients at the cost of the mother. Unlike other cancers, it is not the specific genetics or mutations that make childhood cancers such an interesting field of study: it’s the oddities that surround them, which arise from hijacking the naturally delicate balance in the fledgling human body.
This article was originally published in Issue 722 of Pi Magazine.