BRIEF PROPOSALS A MOLECULAR THEORY FOR THE PHENOMENON OF SLEEP BEN SHEINER, M.D.* The ultimate end product ofall metabolism is a gaseous substance, CO2, which when inhaled in sufficient concentration is capable ofproducing narcosis. An increase in blood CO2 is the only significant biochemical change that has been measured during sleep orjust prior to falling asleep. All other physiological measurements parallel observations ofthe anesthetic state. Heart rate, temperature, blood pressure, and O, utilization decrease in sleep as in most anesthetic states. Like CO2, anesthetic agents are not only capable of producing unconsciousness but also multiple profound physiological changes. It may well be, therefore, that CO3 is responsible for the phenomenon ofsleep. Two moleculartheories have beenadvanced to explainthephenomenon ofanesthesia. One is the hydrate microcrystal theory ofPauling. The other is the "iceberg" theory of Miller. It is mycontentionthatCO2producessleep byfollowing apath combining aspeas of both molecular theories. The following is my theory ofsleep. During our waking hours carbon dioxide is continually being formed and enteringthe blood stream. There it uniteswith water molecules to form simple clathrate structures. As these clathrates are formed, they arecarried viathe circulationto the vast CO2 stores ofthe body. Here they remain in a state ofdynamic equilibrium—e.g., some clathrate s are formed while other CO2 molecules go back into simple solution. Some ofthe CO2 clathrates are carried to nerve endings where a negative heat ofimpulse transmission follows thepositivephase. At that exact instant and placethe clathrates meet an environment oftemperature and blood proteins opportune for the formation of the complex hydrate microcrystal as described by Pauling. These crystals accumulating at nerve endings and within neuronal structures impede an ever increasing number of impulses. Because of its multisynaptic configuration, the most vulnerable structure isthe reticular activating system. As continually fewer impulses penetrate to the cerebral cortex, the cortex interprets the paucity ofimpulses as a feeling oftiredness. Active inhibitory cortical signals are then sent to the reticular activating system as a result of autosuggestion. These inhibitory impulses create zones of inactivity conducive to the formation ofmore hydrate microcrystals. When a sufficient degree of impedance is created, sleep ensues. * Director ofAnesthesia, Pascack Valley Hospital, Westwood, NewJersey. 249 Cortical impulses may also set up electric oscillations conducive to crystal melting. Persons can thus actively will themselves to remain awake. Metabolism decreases during sleep. Only then are more crystals broken down than areformed. The CO2 clathrates areexcreted via skin, feces, lungs, and urine. As the crystals decrease, peripheral impulses via proprioceptors, sight, hearing, and smell are increasingly able to penetrate cortical levels. The initiation ofsufficient cortical impulses creates zones ofelectrical activity capable of melting the remaining microcrystals and brings about a state ofwakefulness. Whenanesthesia is viewed as apossibleextension ofsleep, circulatorychanges common to both states take on a new physiological significance—e.g., increase in peripheral blood flow. This may facilitate excretion ofthe CO2 or anesthetic clathrates. Increased muscular circulation (muscle being the greatest storehouse of CO2) may also facilitate increased excretion. Summary: During the course oflife metabolic processes take place which result ultimately in a release of CO2. It may well be that CO2 clathrate structures converted into the hydrate microcrystals ofPauling at nerve endings and within neuronal structures offer a sufficient degree ofimpulse impedance to bring about the physiological state ofsleep. references i. S. S. Kbty. Sleep and energy metabolism ofthe brain, the nature ofsleep. Boston: Little, Brown & Co., i960. 2.L. Pauling. Science, 134:3471, 1961. 3.S. L. Miller. Proc. Nat. Acad. Sei. U.S.A., 47: 1315 iofir. 4.D. Nachmansohn. J.A.M.A., 179:639, 1962. 25? BriefProposals Perspectives in Biology and Medicine · Winter 1964 ...