Professor Tipu Aziz (1956–2024)

Abstract

Tipu Zahed Aziz, Professor of Neurosurgery at Oxford University (UK) was a wondrous amalgam of striking contrasts, complexities, clinical acumen, charisma, and bad luck. It is with great sadness that we report his death from esophageal cancer after a 3-year period confined to a wheelchair following a head injury.

Tipu was born in Dhaka (aka Dacca) in 1956, moving with his family to the United States in 1957, where he grew up until 1963, when his father took a position at the Medical Research Center, Lahore in Pakistan. It was in Lahore in 1965 that Tipu witnessed the war between India and Pakistan, taking shelter at a hospital when things came too close for comfort—otherwise, for entertainment with his siblings, watching dogfights between fighter planes. Soon after the conflict ended, Tipu moved back to Dhaka, then in East Pakistan, with his mother, two sisters, and younger brother, only to find himself in the midst of the horrors of civil war in the days after Liberation. It is likely that the atrocities that Tipu had witnessed led to his evolving, paradoxically, an almost saintly calm and resilient approach to violence and evil as sad facts of life. He found that he simply had to accept and assimilate them, as he said, “as a little brown person with no particular importance in life.” He adored his mother, whose strong social conscience he had inherited, and this added to his personality a powerful determination to somehow do some good in this world of sorrows.

In 1971, in the newly created country of Bangladesh, the educational system was in turmoil. Tipu's mother was advised by his teachers to take her children abroad for a proper education. In light of this advice and the traumatic experiences of her children, in 1973 she once again moved with the four children—this time to Oxford, UK, for a fresh start.

Tipu was very proud of his father, Dr. Mohammed Abdul Aziz, who carried out the first clinical trials that demonstrated that the drug ivermectin could cure river blindness (onchocerciasis). He would probably have been awarded the Nobel Prize for that discovery, which was awarded in 2015, had he not died young in 1987. Tipu particularly admired his father's devotion to properly organized scientific method. Generations of Tipu's students will have good reason to be thankful for Tipu's adoption of that principle.

In Oxford, Tipu devoted himself to science A-levels and then progressed to study Physiology at University College London, graduating with First Class Honors in 1978. Under the strong influence of Nobel Prize winners Bernard Katz and Andrew Huxley, both of whom he met personally, he decided that he wanted to be an electrophysiologist. He thus carried out a prizewinning dissertation on the neuromuscular junction of the barnacle. Characteristic of Tipu, he ever after sought out restaurants all over the world that served barnacles! But Tipu always had a wide range of interests, and he found the time, during the same period, to take War Studies classes and also to study the history of neuroscience, and of smoking.

Dissatisfied with the limited lifestyle of the barnacle, Tipu then decided he needed to study medicine en route to his now-chosen career of neurosurgery. He won a place at King's College medical school and then carried out house and registrar jobs all over the country. In the early 1980s, Tipu was working as a Senior Registrar in Bristol. He contacted Prof. Alan Crossman, out of the blue, saying that he wished to pursue a career in functional neurosurgery, and he was interested by the work that Alan was doing in Manchester on movement disorders, including Parkinson's disease (PD). Tipu asked to come and work with him. Alan replied that, although he was very flattered to be asked, currently he had no funding for an extra position. Characteristically, Tipu replied, “Never mind. I will come and work with you for free!” And this he did. Fortunately, the work of the group was well regarded and that, together with Tipu's excellent CV, meant that he soon did gain a salary, as a Research Associate funded under the group's Medical Research Council Programme Grant.

It had recently been demonstrated in Alan's laboratory that, in animal models of PD, there was overactivity of the internal segment of the globus pallidus (GPi). They had also demonstrated that this was due to concomitant overactivity of the subthalamic nucleus (STN) through its excitatory, glutamatergic projection to the GPi. In 1990, they showed that pharmacological blockade of this projection, by injection of a glutamate antagonist into the GPi, alleviated the motor symptoms of parkinsonism.¹ In the same year, the group of Mahlon DeLong in Atlanta demonstrated the antiparkinson effect of injection of the excitotoxin ibotenic acid into the STN.² Neither of these crucial proof-of-concept studies used a method with direct applicability to the clinic.

As a consequence, Tipu became the first person in the world to show that lesioning the STN, using a technique routinely available in clinical neurosurgical facilities, immediately, completely, and permanently abolished all motor symptoms of parkinsonism.³ This pivotal work formed the basis of Tipu's MD thesis, the degree being awarded in Manchester in 1992. Tipu's work in Manchester convinced him that he should champion the use of animals in research, taking great personal risk, but determinedly pursuing what he felt was best for patients who needed help.

In 1992, Tipu was appointed as Senior Registrar in Neurosurgery at Oxford. During the interview, he impressed lead consultant Chris Adams by not only his academic and clinical prowess but also knowing the name of the artist who had drawn the sketches of neurosurgical anatomy displayed on the walls of the Cairns Suite at the John Radcliffe Hospital! This little anecdote is illustrative of Tipu's depth of knowledge of art and history, which few appreciated, seeing him, as they did, as a committed surgeon and researcher. Chris Adams was interested in deep brain surgery and invited Tipu to set up a service in Oxford. In those early years, workaholic Tipu found himself simultaneously setting up the Service in Oxford, creating a similar one in the Charing Cross Hospital in London, running a primate laboratory in Oxford, and contributing to the routine on call neurosurgery demand for the Oxford area.

Tipu had the drive and imagination to see how his pivotal experimental work in Manchester should be translated into the development of deep brain stimulation (DBS) of the STN for the treatment of PD, the first successful procedure being performed by Benabid and Pollak in 1993. In the region of 150,000 PD patients have now undergone this procedure, and Tipu performed a significant number of them himself. One of his star patients was Mike Robbins. Mike had a most disabling and incapacitating tremor, which was completely relieved when he switched on his STN DBS. You can see the dramatic result online (video is available at: https://www.youtube.com/watch?v=KDjWdtDyz5I).

Mike was a remarkable man in that he appeared on television and at lecture events, turning off his stimulator and then on again, explaining, “Without Tipu's research performed on animal models of Parkinson's disease, this is what I would be like.” This, and similar presentations, convinced the celebrated animal rights campaigner Peter Singer that Tipu's experiments on monkeys were justifiable because the results improved so many people's lives. This was at the peak of animal rights groups’ attacks on Tipu.

Tipu was appointed as Professor of Neurosurgery in 1995. He was renowned for his calm and competence when clipping circle of Willis aneurysms. When they leaked during surgery, his technique was to apply a swab to it, leave the table, smoke a cigarette, and then return to the table. Most times the bleeding was now under control! Despite these skills, he later collaborated enthusiastically with Andy Molyneux to render them redundant by relegating to history books the technique of clipping most aneurysms.

Tipu's research in Oxford centered on improving the targeting of sites in the basal ganglia for alleviating the symptoms of PD and also for cerebellar tremors and multiple sclerosis. He speedily discovered that this could be done best by recording the field potentials from the tip of the stimulating electrode, rather than attempting to record from single basal ganglia neurons with microelectrodes, a procedure that adds several hours to the operation. Tipu regularly amazed visiting surgeons by performing it in under half an hour. More recently, he showed that careful planning of the proposed electrode track on the basis of diffusion tensor imaging (DTI) tractography of each individual patient's basal ganglia connectivity reaped even better results.

Tipu then went on to show how clever use of individualized DTI could also improve outcomes for the treatment of dystonia, together with another of his interests—DBS of the brainstem pain matrix for chronic pain, particularly in end-stage cancer. Serendipitously, this work also led him into studying the brainstem pedunculopontine nucleus, because stimulating in this area not only helps to control pain but also can relieve freezing in PD. Tipu was planning further studies of possible DBS in anorexia and depression before his untimely accident. He was so remarkably imaginative and forward thinking in all his work.

Tipu published almost 500 peer-reviewed articles and won a large number of awards, including the Society of British Neurological Surgeons’ lifetime achievement award. His proudest achievement was his chapter in Gray's Anatomy on the basal ganglia. But Tipu was not at all pretentious, lofty, or distant. He was a modest man, loved by everyone from his senior clinical colleagues to his theater staff, his ward nurses, his patients, even the hospital porters. He would greet them all by name each morning, know their children's names, even their birthdays. He was not only a true patient advocate but a strong believer in the importance of social support in his community. He was sincerely loved by all for his dedication, down-to-earth manner, humor, and enthusiasm for making them comfortable. He mentored many hundreds of graduate and undergraduate students, clinical fellows, and post-docs whom he supported over three decades, and there are few functional neurosurgery units that he did not influence. He helped to set up units all over the world: in the United Kingdom, Europe, Ukraine, United States, China, Australia, India, and Bangladesh.

We will all miss this humble, affable, eccentric, and so generous character; his all-welcoming attitude; and his treasure trove of colorful stories relayed to us over a glass of his favorite Pinot Grigio in the Royal Oak.