Tripping on the Edge of Consciousness: A Life’s Work

I've been lucky in my scientific life; I’ve chosen great scientific problems to work on and made many discoveries.  I have marveled at the commentaries about the scientific method and how science is supposed to progress; so formal, so structured, guaranteed not to go wrong; so logical, that human frailties could not influence scientific outcome; so comfortable, a safe secure way to earn a living. Or so I thought at the onset of my career. I have discovered that science is far more rewarding than I ever dreamed, an intense human endeavor, and a complete joy.  Moreover, I found that science could steer the radical rebellious thoughts of my youth (and now old age) into productive endeavors.   

My research has been in neuroscience and it is an unusual scientific field.  We have no idea of what we are talking about in terms of how the brain produces perception, thought, consciousness, i.e. its most important products.  Yet, neuroscience is a most sophisticated field with some of the smartest people in the world devoting their every waking minute to it.  We use some of the most advanced, expensive equipment available.  Our knowledge of molecules and cells is massive, beyond the grasp of any one individual.  We can predict pathological outcome in response to specific brain injury including loss of small numbers of specific brain cells.  We are superb at manipulating aggregate behavior as evidenced by marketing successes, e.g. Muzak Corporation, subliminal advertising, and political campaigns.  Yet, no one can explain how even the simplest percept emerges from the dazzling complexity of the molecular and cellular milieu so extensively characterized in our literature and textbooks.  To use a vernacular metaphor, we've described the detailed features of the trees yet remain unaware of how the forest got there.  For the young inquisitive reader this is an open invitation for a life's-work; challenging, interesting, meaningful, helpful, and full of opportunity to address some of the questions puzzling mankind for eternity.  For the older reader more interested in posterity, mankind is up against the wall, with anthropogenic heat being our, and every living creature’s, executioner.  Consciousness must understand itself to enable solutions to this most ominous threat, or be forever lost.

Sleep, my specific area of neuroscience research, fits snugly into neuroscience; we don't know its function.  This is preposterous, we spend a third of our lives asleep, yes about 27 years in total - all of us will sleep more than Rip Van Winkle!  We intuitively recognize the importance of sleep to our physical and mental performance and our health and well-being.  We likely know someone with a sleep disorder and most of us have transiently experienced sleep disturbance.  Within regulatory agencies, scientific groups and economists, the economic and safety impacts of disturbed sleep are well-known and very large.  Deadly mistakes are made, in the hospital, on the road, in the air, operating nuclear reactors (Chernobyl), and elsewhere by the sleepy.  Our sleep scientists have ferreted out many discoveries relating molecules, cells, neuronal networks and behavior to sleep.  Yet we cannot verify our grandmother's advice to get plenty of sleep to prevent and recuperate from infection and injury and for a fulfilling life.  Nevertheless, within the last 35 years sleep research has brought neuroscience to the cusp of explanation of many of these unknowns and to practical application of such knowledge to medicine, the work place, regulatory agencies, and to everyday life.  This essay is an effort to bring the reader to the forefront of one of these issues through description of a personal discovery.

The personal side of a discovery:

I began doing neuroscience in 1968, a time when authority was questioned and radicalism an acceptable moral form of expression.  I soon discovered this is exactly what science embraces although different vocabulary is used, e.g. by testing theory authority is challenged, paradigm shifts begin as radical out-of-the-box ideas.  Those of you who knew me in the early 1960’s know my personality and world outlook was thus a perfect fit for science.  I began, quietly at first, to question the dominant paradigm of sleep research; that sleep is a whole brain phenomena imposed upon the brain by brain sleep centers.  I kept asking questions seldom addressed by sleep researchers, such as:  What is the smallest bit of brain capable of sleeping?  When did sleep start in evolution?  Why do we sleep?  Is there a connection between sleep mechanisms (the molecules and cells causing sleep) and sleep function?   In the 1980’s, Ferenc Obal Jr. (from Hungary – a communist state at the time) and I met in San Juan, Puerto Rico, and began collaborating soon after.  We entered into discussions about these issues and compiled a list of evidence that was eating away at the dominant paradigm in sleep research.  For instance, Russian scientists had showed that dolphins sleep only on one side of the brain at a time.  Countless brain lesion studies and post-stroke patients led us to the simple conclusion that no matter what area of brain was damaged, if the animal or person survived, it slept.  There is not a single exception to this statement in the scientific literature.  This strongly indicates that no circuit in brain is necessary for sleep.  Further, it suggests that sleep is a self-organizing phenomena of any neuronal circuit, whether found in worms, man or even of neurons grown in a dish.  In a nutshell, this is revolution at its finest.  

Obal and I also began to think hard about the popular theories of sleep function at the time.  None of them seemed sound to us (including my own that sleep served an immune function) because all of the proposed functions could be achieved without an animal losing consciousness.  For example, it   made no sense to us that sleep serves to remove one from “harm’s way” since to us it seemed to do the opposite.  These discussions took place over a two year period; this was a slow, hard process.  It required much academic discipline because we knew we were heading for new theories of brain organization of sleep and of sleep function.  These theories would challenge the powers that be with the sleep research world.  We came up with many ideas, several of them written, only to reject them or reformulate them because thought experiments led to logical contradictions.  I clearly remember a long luncheon conversation with Ferenc at a typical European sidewalk café during which we discussed the weaknesses of our theory thoughts.  I was so engrossed in our discussion that I cannot remember today what city we were in.  Finally in 1993, we agreed to publish the first version of our theory.  Its main tenets were that sleep was a fundamental property of small groups of highly interconnected neurons.  Second, waking, sleep, and sleepiness were viewed as emergent properties consequent of synchronization of populations of small neuronal/glial circuits in different states.  A third major aspect of the theory was that sleep was targeted to areas in brain depending upon neuronal use during wakefulness.  Fourth, we posited that sleep served to preserve brain plasticity, something necessary to maintain our ability to learn.  These were radical ideas at the time. They were threatening to our friends and colleagues.  These ideas provided an entirely new way to look a sleep mechanisms and function.  At first the ostrich factor was strong; we were ignored.  Within the year, however, Lee Kavanau at UCLA, came to similar conclusions using completely independent reasoning.  Second, Alex Borbely, at the University of Zurich, tested our theory.  He showed we were on the right track; sleep is targeted to areas of brain depending upon the cellular activity of those areas during wakefulness.

Within the past few years, our view of brain organization of sleep has become socially and scientifically acceptable.  Modern brain imaging studies show that there is differential activation of various brain areas during sleep that is dependent upon what part of the brain is used during wakefulness.  Electrophysiological studies of small circuits, even neuronal circuits grown in a dish, show that the electrophysiological characteristics used to define whole animal or human sleep are fundamental emergent properties of small networks.  In fact, we have already identified one gene that controls the emergence of neuronal network properties during development that are used to define sleep.  It is only a matter of time to link that finding to the emergence of consciousness!  Our biochemical studies show that sleep affects expression of molecules associated with synaptic plasticity differentially, depending upon the dynamics of the neuronal circuit’s synaptic organization.  Strong evidence that sleep affects the synaptic plasticity associated with cell activity has also provided support for our theory.  Our view has thus replaced the old paradigm.  This has been very rewarding and I guess it has made me an establishment member, much to my chagrin.  But, you know, I can’t get the other radical thoughts of my youth out of my head.  More later!

James M. Krueger,
Regents Professor-Washington State University


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