Dirac Medal winner, John J. Hopfield, has brought his skills in physics to the world of neurobiology as part of a larger effort to better understand how the brain thinks.

Making Things Compute

John J. Hopfield

Most scientists count themselves fortunate to acquire international status in just a single field during their careers. John J. Hopfield, leader of computational neurobiology and computing networks at Princeton University, USA, and winner of the ICTP Dirac Medal in 2001, has had the rare good fortune to distinguish himself in two fields.
In 1969, just nine years after earning a doctorate in physics from Cornell University, Hopfield received the Oliver E. Buckley Prize for his research on the emission and absorption of light by semiconductors, a topic of central importance for understanding how light-emitting diodes function. At the time he was honoured, the prize had been awarded to no less than nine scientists who had received (or subsequently would receive) the Nobel prize. At the age of 36, Hopfield seemed well on his way to an illustrious career in his chosen field.
But over the course of the next two years, Hopfield would switch his research focus from physics to biology, earning an international reputation for his pioneering applications of physics-related computational techniques to the emerging field of neurobiology.
It's the bifocal quality of Hopfield's career--his uncanny ability to envision and then apply techniques learned in his study of physics to problems in neurobiology--that led the committee members of the Dirac Medal to speak of Hopfield's "special and rare giftto cross inter-disciplinary boundaries to discover new questions and propose answers that uncover the conceptual structure behind experimental facts."
"My mother and father were both physicists," explains Hopfield. "In fact, in the year I was born--1933--my father was helping to design a physics exhibition at the Century of Progress World's Fair in Chicago. I can't say I remember the exhibit, but my father's job at the Chicago world's fair shows that I was not the first person in my family to use training in physics in unusual ways." Hopfield made these remarks during a visit to Trieste this May to receive the Dirac Medal and present the Dirac Lecture.
"As a child in a household filled with physics," Hopfield notes, "it should come as no surprise to learn that I was fascinated by the physical world around me. But since the time that I knew enough to pursue 'new' science, I have always been more interested in trying to understand things that were not understood at all rather than in exploring established areas of knowledge where unanswered questions, by definition, focus on higher level problems."
Although Hopfield's switch from condensed matter physics to biology may appear to be a radical new career path to some, for him it represented a logical extension of the methodologies that he had been using in condensed matter physics.
"While I was intensely involved in my physics research," he says, "I noticed that many biologists were turning to quantitative measurements common in the study of physical structures. Put another way, biologists were trying to understand properties on the basis of structure-an approach that had long characterised the work of physicists."
Hopfield's breakthrough contribution to neurobiology is based upon his model of neural processing that offers keen insights into the vastly different mechanisms that the human brain and the digital computer use to compute information and make decisions. The Hopfield model, in fact, demonstrates how qualitatively different computation in our brain and in a computer can be.
"The secret behind these differences," Hopfield notes, "lies in connectivity. In the human brain, each neuron makes 'synaptic' connections to thousands of other neurons in a vast and intricate network. In a computer, despite its complexity, each transistor is usually connected to only two or three other transistors. The human/computer 'connectivity divide' represents not just a quantitative difference but a fundamentally qualitative difference that affects the way in which decisions are made."
Hopfield is particularly interested in the way in which the human brain understands the world through its senses. "Every sensory system," he observes, "senses--or, put another way, makes sense of--the world by dividing it into objects. Our visual system does it, our auditory system does it, and our olfactory system does it. Working in tandem with our sensory systems, the brain's ability to separate and objectify the world is what makes the world coherent."
"All of our sensory brain interactions involve complex physical structures and correlations," Hopfield notes, "but the visual system is particularly specialised and complicated."
Except for deciphering colours, the retina functions through a large number of identical receptor cells. "When the retina is exposed to light," he continues, "the pattern of excitation of the retinal cells is configured only when a given object is present (for example, a face). The pattern, however, also depends on the exact direction in which we are looking."
Consequently, the activity of a retinal cell is not only determined by what we are looking at but how we are looking at it--a situation that presents enormous complications for the study of visual pattern recognition.
By contrast, our sense of smell is based on having about 1000 different types of receptor cells, each harbouring a different response to any given odorant. As a result, in most circumstances, the most strongly driven receptor cells are determined solely by the object being smelled.
"Olfaction, "Hopfield observes," is one of the oldest and simplest senses. That has made it a logical place to pursue my neurobiology research and it explains why so much of my work has been based on studies of the olfactory system."
"The research challenge," he adds, "is particularly interesting in animals that use olfaction for remote sensing--for example, such carnivores as hyenas and bears that apply their sense of smell not only to identify and locate objects right in front of them but also objects that are not near-at-hand. Such remote sensing involves an assessment of the direction and force of the wind as well as an ability to distinguish the odour of the 'targeted' object from the background odours that are also present."
It's the nasal equivalent of being able to identify a distant sound by filtering out all of the noise in between. The ability of pigeons to find their way home over vast distances and the capacity of slugs to pinpoint their favourite food while sliming along in your garden provide excellent examples of such remote sensing capacities.
Hopfield recently discovered another organising factor in olfaction and, in the process, demonstrated a new principle explaining how the neural function takes advantage of the 'spiking' phenomenon (characteristic of interneural communication) in carrying out its computations. "My current research," he says, "focusses on how the brain's neural circuits produce such powerful and complex computations."
Hopfield acknowledges that understanding the biophysics of neurons is an enormously complicated task. How can we visualise--let alone begin to understand--the intricate web of biological and physical factors that is responsible for the way in which sensory information is presented to and then deciphered by the brain?
"Light and chemo-reception," he notes, "generate currents across a cell membrane by means of a cascade of physical and chemical events within a receptor cell. When information leaves the eye, nose or ear, it is represented as a sequence of action-potentials. Greater understanding of what turns action-potentials into objectified realities would shed enormous light on how the brain transforms sensory inputs into coherent information."
Hopfield believes that the 21st century will be the century of neurobiology much like the middle half of the 20th century was the century of the atom. "Researchers have been developing increasingly sophisticated techniques for understanding the basic mechanisms by which the brain computes, a process that has largely involved understanding the brain in computational terms."
"One of the most intriguing aspects of recent research," Hopfield notes, "has been the interaction--the intellectual back and forth--between trying to comprehend the workings of the brain and trying to develop brain-like computer programmes for useful application."
"As I mentioned before, the brain's intricate circuitry, driven by neurons linked together with huge synaptic connectivity, means that a brain functions differently than a computer. Nevertheless much of what the brain does can be described in terms of computation: associative memory, logic, inference, generating an appropriate sequence of locomotive commands, recognising a distinctive odour or judging the precise location of an object. All of these functions, at a fundamental level, require computation."
And that's where the application of computational tools, previously associated with physics to address unanswered questions in neurobiology, holds great promise. Such cross-disciplinary investigations, which serve as the centrepiece of Hopfield's current research, may offer an ideal strategy for better understanding how the human brain thinks.

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