Last week, I was told my other brain is fully grown. It does not look like much. A blob of pale flesh about the size of a small pea, it floats in a bath of blood-red nutrient. It would fit into the cranium of a fetus barely a month old.
Still, it is a “brain” after a fashion and it is made from me — from a piece of my arm, to be precise.
I am not going to pretend that this is not strange, but neither is it an exercise in gratuitously ghoulish biological engineering, a piece of Frankensteinian scientific hubris 200 years after Mary Shelley’s tale.
Illustration: Yusha
The researchers who made my mini-brain are trying to understand how neurodegenerative diseases develop. With mini-brains grown from the tissues of people who have a genetic susceptibility to the early onset of conditions such as Alzheimer’s disease, they hope to unravel what goes awry in the mature adult brain.
It is this link to studies of dementia that led me to the little room in the Dementia Research Centre of University College London (UCL) last July, where neuroscientist Ross Paterson anesthetized my upper arm and then sliced a small plug of flesh from it. This biopsy was going to be the seed for growing brain cells — neurons — that would organize themselves into mini-brains.
The Brains in a Dish project is one of many strands of Created Out of Mind, an initiative hosted at the Wellcome Collection in London and funded by the Wellcome Trust for two years to explore, challenge and shape perceptions and understanding of dementias through science and the creative arts. Neuroscientist Selina Wray at UCL is studying the genetics of Alzheimer’s disease and other neurodegenerative diseases and she and her doctoral student Christopher Lovejoy gamely agreed to culture mini-brains from cells taken from four of the Created Out of Mind team: artist Charlie Murphy, who is leading Brains in a Dish, BBC journalist Fergus Walsh, neurologist Nick Fox and me.
It was a no-brainer. Well, you know what I mean. Who could resist the narcissistic flattery of having another brain grown for them? I was curious how it would feel. Would I see this piece of disembodied tissue as truly mine? Would I feel protective of, even concerned for, a tiny “organoid” floating in a petri dish? Most of all, I was attracted by the extraordinary scientific feat of turning a lump of arm into something such as a brain.
However, mini-brains are not blobs of neurons identical to a small chunk of my cortex. One can fairly say that the neurons “want” to make a brain but, lacking proper guidance, do not quite know how to go about it. So, they make a reasonable but imperfect approximation.
As the embryo grows, some cells become committed to particular fates — they become skin cells, liver, heart, brain or bone-forming cells and so on. This differentiation springs from a modification of the cells’ genetic program: the switching on and off of genes. As they differentiate, cells can change their shapes as well as their functions.
Neurons grow the long, thin appendages that wire them into networks, the ends equipped with synapses where one cell sends an electrical signal to others. That signaling is the stuff of thought.
It was believed that cell differentiation was one-way — that once a cell was committed to a fate, there was no going back and that the silenced genes were switched off forever. It came as a surprise to many researchers when, in 2007, Kyoto University biologist Shinya Yamanaka and his colleagues used viruses to inject into the mature cells some of the genes that are highly active in embryonic stem cells, and found that just four of these were enough to switch the cells into a pluripotent state, becoming, to all intents and purposes, like stem cells. These became known as induced pluripotent stem cells (iPSCs).
Creating organs involves knowing how to guide iPSCs toward the appropriate fate. This might involve giving them an extra dose of the genes that are highly active in that particular tissue type.
However, Chris turned my own iPSCs into neurons simply by changing the nutrient medium. Such stem cells seem to have a preference for becoming neurons, so they only need a nudge to get them going.
Yet, cells can do a lot of it themselves. The biologist Madeline Lancaster discovered this when she was studying the growth of neurons from stem cells as a doctoral student in Vienna with the neuroscientist Jurgen Knoblich in 2010. She found that the neurons, left to their own devices, would start to specialize and organize into mini-brains.
The plan, Lancaster — who now runs her own lab at the University of Cambridge — told me, was that she would make flat neural structures called rosettes, which had been done before.
However, the mouse stem cells she worked with would not stick well to the surface of the dishes.
Instead, Lancaster said that “they formed these really beautiful 3D structures.”
“It was a complete accident,” she added.
Lancaster and others are now seeking to find ways to supply mini-brains with more of the environmental cues that they would get in a developing fetus, enabling them to become even more brain-like.
“You don’t need a completely well-formed human brain in a dish to study biological questions,” she said.
However, if you can improve the resemblance in the right respects, you can get a better picture of the process in real bodies.
Lancaster uses brain organoids to investigate how the size of the human brain gets fixed. She has studied microcephaly, a growth defect that results in abnormally small brain size, and is also interested in what can make brains grow too big, which, contrary to what you might expect, is not a good thing and is linked to neurological disorders such as autism.
Other researchers are using these mini-brains to study conditions such as schizophrenia and epilepsy.
At UCL, Wray is making them to understand the neurodegenerative process in two types of dementia: Alzheimer’s disease and frontotemporal dementia. The atrophy of brain tissue can start when two proteins called tau and amyloid beta switch from a normal form to a misshapen form. These forms stick together in clumps and tangles that accumulate in the brain and cause neurons to die.
By culturing mini-brains from the cells of people with a genetic predisposition to these diseases — who account for about 1 percent to 5 percent of all cases — Wray hopes to find out what goes awry with the two proteins as neurons grow.
“We are making mini-brains to try to follow the disease in real time,” she said. “We hope to see the very earliest disease-associated changes — that’s important when we think about developing treatment.”
She has found that the tau proteins for the disease samples are different from those in healthy samples. My cultures might eventually be anonymized and used as one of those control samples.
Yet, I do think of these brain organoids as “mine,” although not with any sense of ownership or pastoral duty. That is probably a common response in people whose cells are cultured in the lab.
The cancer cells taken in 1951 from the patient Henrietta Lacks at Johns Hopkins University Hospital in Baltimore, Maryland, just before she died, and used for research — without her consent, which was not then required — are still regarded by Lacks’ surviving family as in some sense “her,” as Rebecca Skloot described in her bestselling 2011 book The Immortal Life of Henrietta Lacks.
These “HeLa” cells are now the standard cell line for studying cancer and millions of tonnes of them have been grown worldwide: a piece of a person turned into a mass-produced commodity.
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