A marvellous mind
Dr Nicolas Bazan of Louisiana State University Health New Orleans, School of Medicine (LSU) has spent a lifetime uncovering fundamental neurobiological processes, identifying early instructive signals as disease modifiers for neurodegenerative diseases and transforming academic medicine, becoming a household name to thousands of neuroscientists. However, like the great thinkers of history it doesn’t stop there, he has also found the time and talent to write books, make a film, mentor the next generation, patronise the arts and lead communities forward with his fresh ideas.
Dr Bazan has featured in so many magazine articles, from Forbes to his local New Orleans Living, that his background and upbringing is almost a matter of public knowledge. Born in Los Sarmientos, Tucuman province, Argentina, it was in Tucuman City that he studied medicine. Drawn to this subject after experiencing first-hand the chilling effects of neurological disease in his family, he completed his training at Harvard Medical School after a year’s stint in New York’s Columbia University College of Physicians and Surgeons.
Those who witnessed him achieve selection to the faculty of the University of Toronto at the age of twenty-six must have known he was destined for great things. From here he moved back to his home country of Argentina where he became the founder of the Instituto de Investigaciones Bioquimicas. He also set up a graduate programme in biochemistry and assembled a large group of students and fellows to work in his newly established lab. With exceedingly limited equipment and resources, he struck on two budgetarily feasible ideas: using early amphibian (toad) development as a model of cellular membrane biogenesis and using the retina to study the brain — a decision that would prove enormously beneficial to his work. This productive period was, however, cut short in the early 80s by the political turbulence in the country. In fear of his safety, Dr Bazan was forced to leave his successful institute and flee with his family back to the United States.
The move to LSU quickly followed, where a few years later he was asked to become the founding Director of the Neuroscience Center of Excellence. There he certainly found his scientific home, but it is as likely also that his long stay is due to the finding of a different satisfaction in the cultural melting pot of New Orleans. He credits his faith and family, along with the strong relationships he has built with many around him, as the grounding force that has helped him overcome the hurdle of sudden displacement and other setbacks, among them his triumphal bout against advanced inoperable cancer 14 years ago. Dr Bazan celebrates rather than laments the difficulties he has faced, saying ‘adversities bring strength and renewed perspective’.
His awards, honours and collaborations make for a very long list, so long that no one seems to have the time or space to publish it in full. From membership of editorial boards across Europe and the American continent, to chairs, elected to Academic Societies and fellowships of distinguished faculties in the United States (US) and further afield; Dr Nicolas Bazan is a name synonymous with first-class neuroscience research. As Michael Moskowitz, Professor of Neurology at Harvard Medical School/Massachusetts General Hospital puts it, he ‘is passionate about everything he does in life, especially his science, and this passion has driven a lifetime of discoveries that have inspired both his students and colleagues’.
The man of science
Dr Bazan focuses his attention not on the lucrative or straightforward cases, but on those neurodegenerative diseases for which there is no known cure. It is perhaps even more telling therefore, that he has made such inroads into the understanding of the underlying pathology. Considering the difficulty of establishing treatments for such diseases, it is no wonder that Dr Bazan himself believes that, ‘the only way to conquer them is by getting a new understanding of the cellular and molecular mechanisms engaged in the onset and early progression of brain and retina disease’. This has been his focus during a lifetime of research, a labour which he says he has been, ‘lucky to have been able to contribute to’.
Here again the list just goes on and on. There have been breakthroughs in the understanding of the response to the foremost causes of long-term disability in the US — cerebral ischemia (stroke) and seizures (as in epilepsy) — the mechanism of which is now known as the Bazan Effect (as Bengt Samuelsson, a Swedish researcher and Nobel Laureate at the Karolinska Institutet in Stockholm, defines it, ‘the Bazan effect is the release of polyunsaturated fatty acids during seizures and ischemia’). There is the identification of targets for novel therapeutics, and the uncovering of the novel compounds themselves, to combat the onset and progression of epilepsy; a condition which 30% of US patients do not have adequate control over. Or you can point to the identification of a novel protective molecule to hopefully slow the onset of Alzheimer’s disease. Dr Bazan has also targeted chronic pain by developing a novel generation of non-addictive, non-toxic analgesics (painkillers), which he is bringing to market via a new start-up company he co-founded specifically for this purpose, using the findings from his work on injury and inflammation of the brain.
His work has been recognised by distinguished colleagues around the world. Dr George Carman, Chief Scientific Officer at the New Jersey Institute for Food, Nutrition, & Health, Rutgers University, says Dr Bazan, ‘has dedicated his career to conducting the highest level of science to the underpinnings of brain function and diseases’. His work has also included a related and equally challenging area, blindness caused by retinal degeneration, and once again he is bringing his experience and intellect to bear with stunning effect.
A man can be known by his eyes
The focus of Dr Bazan’s work from its discovery at the earliest stage in his career is the brain release of arachidonic acid and docosahexaenoic acid (DHA) upon stimulation. DHA is an omega-3 fatty acid, the precursor of which is only available from dietary sources, and is retained in higher levels in the brain and retina than any other body tissue. DHA is a key component of membranes engaged in brain and retinal function, acting at the junction between brain cells known as the synapse, and in retina photoreceptors. This molecule has been the subject of intense study by Dr Bazan and his colleagues.
Dr Bazan celebrates rather than laments the difficulties he has faced, saying ‘adversities bring strength and renewed perspective’
The systems employed by the team have been many and varied, but it was during their use of the retina (the light-sensing part of the eye directly linked to the brain) as a model for research on neurones that DHA’s role, particularly that of bioactive derivatives, in retinal function and disease was established. Using this approach, they uncovered the mechanism by which DHA is accumulated in the differentiated neurones, the photoreceptor cells, having been absorbed from the diet. Dr Bazan postulated and then demonstrated both the ‘long loop’ of transport from the liver to the brain and retina, as well as a ‘short loop’ by which this fatty acid is recovered back to replenish the cells of the retina. This process assured the Bazan team of DHA’s status as a key molecule in normal neural function.
They then went on to further elucidate the fate of this molecule as it is first cleaved and then modified by a range of enzymes to produce bioactive docosanoids, molecules which are now known to promote homeostasis and neurorestoration (maintenance and repair respectively). One such of these was named Neuroprotectin D1 (NPD1) because of its role in fostering homeostasis, inhibiting uncompensated inflammatory signals and preventing apoptosis (programmed cell death) as well as other forms of cell death. The discovery that the availability of this potent molecule is decreased, along with its precursor DHA and the enzyme that makes one from the other, in the brain memory areas from early stage Alzheimer’s Disease (AD) patients in particular, convinced Dr Bazan and his colleagues that its presence is likely essential in preventing the onset of neurodegeneration.
Dr Bazan focuses on those neurodegenerative diseases for which there is no known cure
As the retina photoreceptors which provide the stimuli for sight are a type of differentiated neurone, it seems logical that a substance that prevents the death of neurones in AD could also be involved in age-related macular degeneration (AMD), the loss of sight associated with retinal cell death, as well as other inherited retina degenerations. Dr Bazan has led the way in describing the complex interplay of molecules involved in the management of homeostasis in retinal cells, particularly the retinal pigment epithelium (RPE) which is the layer of cells nourishing and sustaining the retinal visual cells. His work is so important it has been described by Prof Joan Miller, Professor and Chair of Ophthalmology at Harvard Medical School, as, ‘a lasting contribution to our understanding of the role of lipids in the retina, especially their function as modulators of neuroinflammation, which is the basis of so many ocular diseases’.
The renaissance man
Dr Bazan’s most recent research is just the latest in a lifetime of discovery. Bengt Samuelsson describes him as, ‘a leading neuroscientist and eye researcher’ and points to his work on the Bazan effect, showing that his influence is truly international. However, all his colleagues attest to knowing someone whose intellect is not constrained to a single subject, who has made as much of a mark in the other aspects of his varied life as he has in the scientific community. Prof Edmond Fischer, Nobel Laureate and Professor Emeritus of Biochemistry at the University of Washington says, ‘What impresses me most about Nicolas is his enduring enthusiasm and passion, not only for science, but for all of the wonderful things life has to offer. He is the epitome of the renaissance scholar.’
