1. Sledge, George W. Jr. MD

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My wife and I were walking down the street recently when we came upon an old black Ford, lovingly kept up by its owner. I recognized it immediately as an early 1950s model of the sort my parents owned when I was a child. The Antique Automobile Club of America defines "antique" as a car over 25 years of age, so I guess this was an antique, but for a moment I was transported back to when it was new. And I was new, and not the antique I am now.

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George W. Sledge, Jr... - Click to enlarge in new windowGeorge W. Sledge, Jr., MD. GEORGE W. SLEDGE, JR., MD, is Professor of Medicine and Chief of the Division of Oncology at Stanford University. He also is

My first conscious memory was of waking up in the back seat of our black family Ford. I remember the car as having a high ceiling, though that memory may only reflect my own short stature. Cars in those days had no seatbelts, and there were no car seats for children, so I must have been sleeping on the back seat. I remember waking up with my mother and father talking to each other up front, and I remember the car stopping and getting out, and I remember literally nothing else happening before that experience. Even at the time, I remembered remembering nothing before that moment.


When was your first conscious memory? I must have been about 3 years old. Studies of first memory give ranges between 1 and 4 years old, with a plurality occurring at age 3, so I was distinctly average. The folks who study consciousness for a living say that "first conscious memory" is not the same thing as "first evidence of consciousness." That boundary has been pushed back to 2 months of age through the use of functional MRI studies. Still, I like to think that waking up in the back seat of a black Ford sedan as the moment that my consciousness, my own sense of myself as an independent individual, blinked on.


There are numerous-too numerous-definitions of consciousness, though I like the one used by Wikipedia: "the state or quality of awareness, or, of being aware of an external object or something within oneself." Consciousness is an exceptionally contentious subject, argued over endlessly by philosophers, biologists, neurologists, physicists (quantum theory-don't even ask), and just about everyone else at some time or other.


The philosophers have been thinking about this the longest and have the most interesting arguments. Descartes based his theory of philosophy on what he viewed as the solid rock of consciousness: cogito ergo sum, I think therefore I am. At the other end of the spectrum, a modern philosopher, the ever-entertaining Daniel Dennett, belittles what he calls the "Cartesian theater" of consciousness, viewing it as little more than an epiphenomenon, a largely irrelevant by-product of complex neural wiring in higher organisms.


As has happened so often in science, philosophy has given way to measurement. Whereas 20 years ago the science of consciousness was essentially nonexistent, at least in the sense understood by working scientists, today it is a robust field of discovery, propelled by novel technologies such as functional MRI scans, electro- and magnetoencephalography, combined with imaginative experimental designs. Several theories of consciousness have emerged from this work, the premier among which-as far as I can tell-is something called the global neuronal workspace theory.


The global neuronal workspace theory emerges from studies of visual inputs. Flash an image for a brief period-50 microseconds or less-and the visual cortex will light up on an fMRI, but nothing else happens. Longer exposures to the image light up not just the visual cortex but multiple areas of the brain. The image is now being shared across the global neuronal workspace, and multiple areas of the brain now have access to the input. This, in simple (overly simple-I'm not a neuroscientist) is the basis of consciousness. Anyone wishing a deeper understanding of consciousness should read Stanislas Dehaene's wonderful book on the subject. A competing theory, the integrated information theory, is also championed by many neuroscientists.


The parts of the brain involved in consciousness are quite specific, and particularly involve the cerebral cortex in the posterior portions of the brain: the parietal, occipital, and temporal lobes. You can lose your entire cerebellum and not have it affect consciousness.


Early philosophers and biologists separated humans from "lower" animals based upon their ability to form conscious thought. Current neuroscience isn't so sure, extending consciousness to many vertebrate species. Anesthetize a chimpanzee, paint a red spot on part of its anatomy it usually doesn't see, and when the animal wakes up in a room with a mirror, it will touch the spot, even moving the mirror to get a better view. This mirror self-recognition test is not a perfect marker of self-awareness, but the animals that pass it tend to be clustered at the upper end of the animal kingdom, neural capacity-wise: bottlenose dolphins and killer whales, bonobos, orangutans, Asian elephants, and Eurasian magpies; perhaps dogs. Human children typically pass the test at around 18 months of age.


And then there is the octopus. The octopus doesn't pass the mirror self-recognition test, though they do freak out when they see themselves in a mirror. But the octopus seems really smart to me. Peter Godfrey-Smith in his wonderful book, Other Minds, calls the octopus "the closest thing we'll ever see to an alien intelligence." The octopus has the brain capacity of a small dog, with around 500 million neurons (we have a bunch more). Weirdly, three-fifths of the neurons in an octopus are found, not in the brain, but in the arms.


Octopuses do not live very long: an elderly octopus is 3 or 4 years old at most. But in their prime they seem self-aware, and quite aware of their environment. They can identify, remember, and target individual humans in an aquarium environment. They are escape artists. They participate in play behavior. They are tool-users. They communicate with each other, in part, through chromatophores located in their skin. Think of having a conversation conducted in changing patterns and colors of skin pigment. And they are invertebrates, a half-billion years separate from our common evolutionary ancestor. They've evolved consciousness independently of us and our higher vertebrate relatives. They are deeply weird, and ineffably cool.


But back to us. We lose consciousness every day. We call it sleep, that pre-programmed disappearance-aside from those vivid dreams that sometimes intrude on the next morning's memory-of that conscious state that normally defines us. We think nothing of it, yet it is really quite wonderful and mysterious. One minute I am snoring, the next my alarm clock or a pager goes off and within seconds (OK, maybe a minute) I am conscious. We also induce loss of consciousness with regularity. Indeed, it's pretty much the definition of what it means to be a general anesthetic. Nothing wrong with that. The brain is good at re-initializing its consciousness programming.


It is the disappearance or alteration of consciousness during daytime and with disease that bothers us. Drugs and disease both disrupt consciousness. Indeed, while the average doctor would have trouble defining consciousness, we are pretty good at gauging its loss: the Glasgow Coma Scale, with its measures of eye, verbal, and motor responses, is widely used by neurologists.


There are so many ways that the body can go wrong. Cancer doctors regularly deal with altered consciousness. Sometimes it's a brain metastasis causing an epileptic fit, the electric spasm spreading through the brain, shutting off consciousness, the brain then re-booting like some errant computer. Sometimes it has been a drug effect: too much of this sedative or that chemotherapeutic. All too often it has been the end result of liver failure, the body's metabolites reaching toxic levels, the patient slipping off into that final sleep from which none awake.


I remember (I am conscious of) standing by my father's bed as he died. In his case it was hypoxia that eliminated consciousness, aided by morphine sulfate.


He had metastatic prostate cancer, his bones riddled with castrate-resistant, taxane-resistant, agony-inducing disease. He had been fading for some time, the cancer gradually robbing him of independence, of energy, and of any realistic hope. I had visited 2 weeks before for his wedding anniversary, then gone back home to see to my patients. It had been a sad visit. My brother asked me how long I thought dad had to live. Two weeks, I said. Probably not more. Sometimes we know too much.


The proximate cause of his dying was by a pulmonary embolus. He had a deep venous thrombosis in his left leg nearly a year before, abetted by a long drive from Madison, Wis., to Bonita Springs, Fla. My dad was ever an impatient driver, keen to get from point A to point B in the shortest time possible. He had not stopped a second longer than necessary, had not gotten out of the car to walk around, and the result was that he spent the last 10 months of his life on warfarin. So, the call from my brother, announcing that dad had a pulmonary embolus and was in the hospital dying came as no particular surprise.


I was in Indiana at the time, my parents in Wisconsin. I got the message in the middle of my Tuesday outpatient clinic. I called a colleague for coverage (thanks, Kathy, I still appreciate it), left work, got in my car, and drove straight to Madison.


My father was a religious man, far more so than his son, and not afraid of death. But he fought for life. He was not impatient to see what was on the other side. The day he died, he asked his oncologist whether there were any clinical trials he might enter. This was the late '90s, and anti-angiogenic therapy was all the rage, and the University of Wisconsin was scheduled to be one of the first sites for a phase I trial of endostatin, the drug a certain Nobel Laureate famously said was going to cure cancer within 2 years. My dad had told me, more than once, that if only he could hang on long enough he might yet beat the disease that inexorably consumed him.


I know, optimism bias. His performance status was such that no clinical trial in the land would have had him, and both I and his oncologist told him so, months before he lay on his deathbed. But he was a fighter, and though things were hopeless he never gave up.


When I got to the hospital, dad was severely short of breath, hyperventilating and clearly dying, and his oncologist did what kind oncologists do in such a setting: he turned up the oxygen and turned up the morphine. My dad had drifted in and out of an opiate haze for weeks, one minute drowsy, the next alert. But now he was mostly awake, conscious almost to the end.


In the last few minutes, something odd happened. At least it seemed odd to me then, and still does now. He opened his eyes, and they darted around the room, never resting for more than a second or two on any spot. It was disconcerting. Every now and then they would touch on my face, pause briefly, and move on. I had the feeling he was looking for something, something unobtainable, something... not there.


Was that the last flicker of consciousness, or just a dying brain's random electrical impulses? I'll never know. But then it was over, his consciousness utterly gone.


We speak of the soul fleeing the body, and perhaps that happened too, though that is a matter of belief rather than of science. But consciousness, at least to the extent we understand it, involves massive parallel processing of information via widely dispersed neural networks, a thoroughly natural electrochemical process, but also a highly fragile, easily disrupted one. Turn off the lights and the signaling goes away, and with it consciousness.


Are gliomas conscious? A very strange thought: could brain tumors take part in the conscious process, act as part of the global neuronal workspace? It sounds like something out of a horror story. Brain metastases certainly affect conscious function all the time. My Uncle John's smoking-induced lung cancer, upon spreading to his brain, turned that calm, church-going Baptist into an irritable spewer of obscenities. But that was loss of function, disinhibition due to frontal lobe damage. I don't think small cell lung cancer is capable of demonic possession.


The breast cancer doctor in me thinks of a well-differentiated tubular adenocarcinoma of the breast, where the cancer does its best to act like a milk duct. Could a well-differentiated brain tumor have analogous functionality, pretending conscious connectivity? Unsurprisingly, the medical literature contains no hint of such capability, and frankly I'm happy for that: it is a creepy thought, a brain hijacked by something malignant, with malignant consequences.


Charles Whitman, the 1966 Texas Tower shooter who killed 17 people and wounded 96 in America's first mass shooting-back when such events were rare-knew that something was wrong. He was, he wrote in his suicide note, the "victim of many unusual and irrational thoughts. These thoughts constantly recur, and it requires a tremendous mental effort to concentrate on useful and progressive tasks."


He requested that an autopsy be performed after his death. A pecan-sized mass, later ruled to be a glioblastoma multiforme, was discovered. Neurologists argued then, and ever since, whether it was a contributing factor in the massacre. Hard to say. But I doubt the glioma was consciously altering Whitman's consciousness.


Great evil doesn't require a physiologic explanation, though that might give us some comfort, some belief that we can explain and therefore control. We're quite good at hijacking consciousness: addictive drugs, paranoid politics, and fanatical religion being prominent examples. So leave glioma mind control to science fiction, please.


I'll stick with that old black Ford, and the comforting voices of my parents sitting in the front seat. It's a pleasant memory.