It is a rainy Wednesday morning and Andrew Affleck is driving more carefully than usual on his way to the Neuroscience Research Australia (NeuRA) building in Randwick, a suburb in Sydney, Australia.
It is not just the slick, crowded roads putting the edge on his caution; in the boot of his car, cocooned in several layers of protective container and nestled in ice, is the brain of a human being who was alive only a few hours earlier.
It is no ordinary brain — if any brain could be said to be ordinary — but one that has a deadly secret buried inside it. The individual who was until recently embodied within this mass of pink, gray and white tissue died of one of the neurodegenerative diseases that are increasingly a cause of death for the aging population.
Illustration: Yusha
Perhaps it was Alzheimer’s disease that gradually robbed them of their connection to reality, or frontotemporal dementia that transformed their personality, or Parkinson’s disease that shook their body and mind. Whatever claimed their life, this organ is on its way to the Sydney Brain Bank, housed within NeuRA.
“I really hope that this is the brain that will get us across the line,” said Affleck, a research associate at the Sydney Brain Bank.
The hope is that scientists will be able to glean some new and vital insight from the brain tissue. Maybe, one day, that insight will lead to a better understanding, a better treatment or even a cure.
“Every donation, bringing the tissue back into the laboratory, I say to myself, I really hope that this is the tipping point,” Affleck said. “That is really exciting, and gets you wanting to do the best you can; not only for science, but for the family themselves.”
The inside of the Sydney Brain Bank looks like a typical research facility: carpeted offices walled with glass and laboratories where every available space is filled with equipment, glassware and folders, but everything is scrupulously clean and tidy.
There are no brains in jars or any Hollywood-esque embellishments that might give a visitor any sense of the 600 or so brains — and some spinal cords — that have passed through the hands of the scientists there.
Several floors below the gleaming laboratories, in a basement that is normally accessed via a goods lift, is a room about the size of a typical boardroom. It is filled with mobile shelves that can be separated and moved with the touch of a button.
The shelves are lined with sealed white plastic buckets, each containing one half of a brain that has been preserved in formalin.
Sydney Brain Bank director Claire Shepherd is almost apologetic about it.
“The buckets don’t look very glamorous or scientific, but years of experience have told us that they’re the best vehicle to store the brains in,” she said.
The temperature-controlled room is comfortably warm and totally silent, apart from a few electronic beeps as the powered shelves are moved apart. It is a peaceful space; like being in a room full of deep sleepers.
The other halves of each of these preserved brains are stored upstairs in ultra-low freezers at minus-80°C.
The Sydney Brain Bank is one of many such facilities around Australia and around the world that collect brain and spinal cord tissue from people afflicted with a variety of diseases and conditions.
That tissue is made available to researchers searching for answers to the questions of why these diseases happen, how they progress and what can be done to treat, halt or prevent them.
The Sydney Brain Bank’s focus is neurodegenerative diseases; in particular, the dementias and the movement disorders, such as Parkinson’s disease, motor neurone disease, Huntington’s disease and progressive supranuclear palsy.
Brain donation is a different beast to organ donation, not the least because one is for transplant, while the other is for research.
“A lot of people just think that it’s on their organ donation card, and they ask me: ‘Can I donate my brain because I’m an organ donor?’” Shepherd said.
However, donating a brain is far more complex, because for scientists to get the most information from that donated tissue, they need to know about the donor’s life before they died.
The donors connected to the Sydney Brain Bank are recruited through a network of specialist neurologists and clinics around Sydney, who collect standardized data about their patients, such as their medical history and the unique history and features of their disease. These data include blood tests and regular imaging with technology such as magnetic resonance imaging.
“Then the value of the tissue is really enriched, because we not only have the tissue, but we have all this information about what the individual looked like in life, and it is standardized information on cohorts of individuals as well,” Shepherd said.
However, the donor’s personal identity and life are hidden from the staff and researchers who work with the tissue. It has to be that way, not just for privacy reasons, but also for the benefit of the staff who handle the donated brains.
Shepherd recalls the family member of a donor who had died, who sent the brain bank a homemade booklet about the donor’s life and who they were.
Seeing that snapshot of the donor’s life was an intensely emotional experience for Shepherd, and that emotion is still very close to the surface.
“I am the custodian of the brain tissue,” she said. “That doesn’t mean I’m insensitive to who that person is, obviously, but I don’t have that close relationship and it would be dangerous if I did I think, because it would affect me on this level every day.”
Time is the enemy of organ donation. The longer an organ — whether heart, kidney or brain — remains inside a body that is no longer supplying it with life-giving oxygen, the more the tissue breaks down and the poorer the quality of the information can be gleaned from it.
Sydney Brain Bank staff carry pagers with them 24 hours a day, seven days a week, 365 days a year. When a donor dies, one of the first calls made by the family, carers or medical staff is to that paging service.
Things have to happen quickly. Whoever is on call then liaises with the mortuary where the body is to be taken, and with the funeral service.
“One of the main things that we aim to do is to really not disrupt the funeral arrangements for the family … as best we can, we try and expedite the donation for them so that there is no delay,” Affleck said.
The removal of the brain — and spinal cord if that is also being donated — takes place at one of the few remaining operational mortuaries in Sydney. It is a relatively quick process, a couple of hours at most, then Affleck or whoever is on call takes the tissue back to the brain bank.
Once it arrives, the brain is divided into two hemispheres. One half is frozen, along with tissue samples that are dissected from brain regions that are of particular interest to researchers. The frozen tissue can later be studied under a microscope, but more importantly, the freezing preserves the DNA, proteins and biochemistry of the tissue.
The other half of the brain is immersed in formalin for two weeks, which allows the liquid preservative to fully penetrate the brain. Once that process is complete, that hemisphere is stored in 3mm sections, layered on fine sheets of acetate, in the white buckets that line the basement shelves.
At this point the brain bank staff also take smaller samples, or “blocks,” from different parts of the brain that are of interest for further study.
“Maybe there’s softening or there’s tissue discoloration or there’s something that really does need further investigation under the microscope,” Affleck said.
These smaller sections are also treated with a variety of stains that highlight the presence — or absence — of proteins and structures.
The final step is a complete, standardized report that ties together what the brain bank has observed about the tissue with what was known about the donor’s life and disease. That information is the starting point for researchers interested in studying the tissue.
Perhaps, somewhere in these folders, boxes of slides, samples of tissue and pages of data, is the answer they are seeking.
What about the donors and their families? What are they seeking when they tick that box and consent to their or their loved one’s most personal organ being removed after death?
Lucille Bloch had never heard of brain donation until she attended a lecture by Professor John Hodges, who heads up a research group at NeuRA.
“He said dementia is growing in numbers, we have to think about creating a cure for dementia, and what we need are people with dementia, once they have passed away, we need their brains,” she said.
Lucille’s husband Keith had been diagnosed with frontotemporal dementia. After the lecture, she sat down with him and told him what she had learned.
“He said, ‘Well, dear, we’ve got four children at the moment and two grandchildren, I’m going to give my brain, because I want to help, if our children get it and other people [get it],” Lucille said.
Keith died 10 years ago, but Lucille still occasionally visits NeuRA. “I’m part of it,” she said. The experience has made her an advocate for brain donation, and for a greater awareness and understanding of dementia.
When her time comes, she said she will also donate her brain.
Lisa Webb’s husband Bob died about two years ago of what was diagnosed as primary progressive aphasia — a gradual loss of language abilities. However, this was actually a symptom of Parkinson’s disease, a diagnosis that was not revealed until after his death.
Fairly soon after Bob’s diagnosis, the subject of brain donation came up during a visit to NeuRA for tests.
“For him, the brain was just part of the body; he was always happy to donate organs and the brain was just another organ,” Lisa said. “I guess I have the same view; I looked at it and thought: If there’s anything we can do to help other people not have to go through this, then let’s do it.”
The thought that Bob’s tissue resides somewhere in the Sydney Brain Bank and is helping researchers gives her a sense of comfort.
“There’s that little bit of me that’s out there going, actually, he’s not really gone; like he’s still doing good, and that’s a really nice thing to hold on to,” Lisa said.
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