In Focus: A Brilliant Brainstorm

The launch of Brain Bank Singapore by the Lee Kong Chian School of Medicine, the National Neuroscience Institute and the National Healthcare Group is set to be a gamechanger for neuroscientists and brain researchers in the city state and beyond.

Think about it: the human brain was not accorded its place of importance, as the seat of intellect, reason, emotion and function until 6th century BC when Alcmaeon, a Greek medical writer and student at the school of natural philosophy set up by Pythagoras in what is today, Crotone, Italy, studied animal structure, described arteries and veins, and discovered the optic nerve.

Before that, the Ancient Egyptians considered the heart to be the all-important organ in the human body and the seat of intelligence – they didn't even have a name for the brain. During mummification, the heart was kept in place, while other organs were removed and stored separately; the brain was extracted via a hook through the nose carefully – so as not to disfigure the face – and disposed of.    

By the time of Hippocrates, in the 1st century BC, he had written much on brain surgery and was aware of the many clinical aspects of head injuries. The study of the brain gathered pace until it hit a dark patch in the 17th century, which lasted until the 19th century.

"Looking" into the physical brain perhaps began in earnest with the invention of the electroencephalograph (EEG) in 1929 by German neuropsychiatrist Hans Berger, which today is still being used to diagnose serious brain injuries, brain tumours and other degenerative diseases of the brain.

Today, there are many brain tissue banks around the world – in the US, UK and Europe – even one for sportspeople in Australia called the Australian Sports Brain Bank. There are also brain banks in China, India and Japan.

Brain Bank Singapore, launched on 27 November at the Lee Kong Chian School of Medicine (LKCMedicine) Novena campus by Guest-of-Honour, Director of Medical Services at the Ministry of Health Singapore (MOH), Associate Professor Benjamin Ong, is the only one in Southeast Asia right now.

In a tripartite partnership between LKCMedicine, the National Neuroscience Institute (NNI) and the National Healthcare Group (NHG), Brain Bank Singapore as a donor-based ethical research depository for post-mortem brain and spinal cord tissues is a vision shared by many researchers and clinicians in Singapore, having been on their wish list for years.

The dream has become reality.

"Today marks a milestone for the neuroscience community in Singapore, with the launch of Brain Bank Singapore. While recent technological developments in science have enhanced our understanding about the structure and function of the human brain; advances in neuroimaging in human studies, in optogenetics in animal studies have been hugely important. However, many intricacies of the human brain remain a mystery," said LKCMedicine Dean Professor James Best in his welcome address at the launch. "We need to study human brain tissue directly, hence the need for a brain bank. By bringing NNI and NHG together as initial partners, we're also bringing together two different disciplines – neurology and psychiatry – both interested in the diseases of the same organ, the human brain."

He stressed that brain research will kick into a higher gear now, "Together with our partners, we are already conducting robust research on dementia, as well as collecting baseline population health data from a large cohort of the population. Brain Bank Singapore is an elevated platform on which neuroscientists and clinician-scientists can work together to find solutions that will address debilitating brain diseases in Singapore."

In front of an audience packed with members of the healthcare community, A/Prof Ong said in his speech, "The establishment of Brain Bank Singapore is in alignment with MOH's efforts to encourage research on neurological disorders."

He went on to say that under the Research, Innovation and Enterprise 2020 Plan, MOH has identified neurological and sense disorders as a priority area for research. "In August, the National Medical Research Council awarded a $25 million Open Fund – Large Cooperative Grant to a multi-institutional team led by the National Neuroscience Institute (NNI) for the research proposal 'Singapore's Parkinson's Disease Translational Clinical Programme' to identify new drugs to improve health outcomes in Parkinson's disease as well as identify rish and protective factors to slow disease progression."

A theme investigator on this programme, otherwise known as 'SPARK, Phase II' is the recently appointed LKCMedicine Vice-Dean of Research Professor Lim Kah Leong, who is a renowned neuroscientist with particular interest in the field of Parkinson's Disease.

 
Playing the genetic card

The founding Director of Brain Bank Singapore, LKCMedicine Professor Richard Reynolds, who is also Professor of Cellular Neurobiology at Imperial College London, said, "We now know that genetic background is very important in determining the onset and course of neurodegenerative and neuropsychiatric disorders. It is essential that neuroscientists in Singapore have access to brains from patients with the appropriate genetic and ethnic background."

Prof Reynolds was also the founding director of the Multiple Sclerosis and Parkinson's Tissue Bank, an international brain tissue bank based in London, UK, that he has led for the last two decades.

Prof Lim added that according to a study conducted by NNI, there is a similar risk of developing Parkinson's Disease among the three races: Chinese, Malay and Indian. 

"We need Brain Bank Singapore to help understand Parkinson's Disease. We can't be reliant on data from the West. We have to find out what is the issue with our local population. Singapore is in a privileged position because our population comprises three major races that represent huge continents in Asia. So whatever you discover, it is applicable and relevant to a huge Asian population. With this resource, we now finally have a chance to take a deeper dive to understand the mechanisms underlying neurodegenerative conditions," said Prof Lim.

The Singapore challenge

Therein lies the urgency for Brain Bank Singapore, as it will open up new research possibilities that will generate new knowledge about the expected growing prevalence of neurological disorders.

By 2030, the number of Singaporeans 65 years and older will have doubled, making up a quarter of the population. Age does play a part in certain chronic neurological disorders which affect the brain and nervous system.

The 2017 Burden of Disease study revealed a stark picture of the incoming healthcare challenge: stroke, dementia (including Alzheimer's disease), epilepsy and Parkinson's disease are the most common neurological disorders affecting the Singapore population, with stroke being the fourth leading cause of death and third leading cause of disease burden.

Irene Tan Liang Kheng Chair Professor of Neuroscience and LKCMedicine Professor of Neuroscience and Mental Health George Augustine said that Brain Bank Singapore will be a valuable addition to the Singapore research landscape, "It will provide unique access to brain tissue from the local population. We need to get Asian samples to learn about how similar or different we are in regard to brain properties and brain disorders."

Prof Augustine has been using mouse models for his dementia research thus far and is not involved in the Brain Bank Singapore; he nonetheless said, "Brain Bank Singapore is another step forward for the neuroscience research communities of LKCMedicine, and for Singapore, more generally."

Living long, living well

A/Prof Ong said in his speech, "Biomedical research should not be done in isolation as it requires clinical input from the healthcare sector to gain relevance in the translation of healthcare outcomes." With the Brain Bank Singapore platform for collaboration across clinical and research lines, the best neuroscientists and clinician-scientists will be able to address the most pressing neurological and neurodegenerative issues affecting the Singapore population.

NNI and NHG both fit naturally as partners with LKCMedicine for the setting up of Brain Bank Singapore as both organisations have not only been treating patients with neurological and neuropsychiatric disorders respectively, but have also completed impactful research studies in these fields. The Institute of Mental Health and Tan Tock Seng Hospital under NHG, treat patients with both disorders.

Group CEO of NHG, Professor Philip Choo said, "It is our hope that establishing a robust data bank and conducting safe brain tissue research will expand our understanding of the underlying disease mechanisms of neurological disorders, so that we can seek better and more effective treatment strategies."

NNI Medical Director Associate Professor Ng Wai Hoe pointed out the long-term effects and impact of neurological diseases after their diagnosis, "Ultimately, we aim to improve care outcomes, safeguard the quality of life for our patients, and help Singaporeans live long, live well."

Representatives of the three collaborators of Brain Bank Singapore joined A/Prof Ong on stage for the launch. Prof Best, CEO of IMH Professor Chua Hong Choon and A/Prof Ng Wai Hoe first stepped forward in turn to place the three parts of the Brain Bank Singapore logo in their corporate colours of purple, teal and orange before A/Prof Ong, NTU President and Distinguished University Professor Subra Suresh, Prof Choo and SingHealth Group CEO Professor Ivy Ng, stepped forward to press the logo downwards which launched a hologram of the logos of the Brain Bank and its three collaborating institutions.

The game plan

The recruitment of brain donors has begun after approval by the SingHealth and NTU Institutional Review Boards. A number of donors have already signed up but Prof Reynolds said more work needs to be done to raise awareness and educate the public about this "ultimate and selfless gift" for research. "We will be talking to people in hospitals, clinics, community organisations about the importance of brain donation, not only those that have neurological conditions. It is equally important that we have brain donors who do not have such conditions."

In fact, one of the first brain donors to sign up went public at the launch of Brain Bank Singapore with her decision, which she said took some time to gain understanding from her family members.  Lovely Fernandez, who was diagnosed with multiple sclerosis 10 years ago, said, "There is no cure for my illness. Since I'm already an organ donor, I wanted to also donate my brain for research so that it can be used to study this illness and maybe something can be done for others."

Prof Reynolds hopes to have about 1,000 donors signed up over the next 3-4 years.