effective vaccination of the whole population, which are accentuated by the active opposition of people who are ignorant and wilfully remain so.  There exists in every state a number of people unprotected by vaccination, and among these single cases of smallpox appear.  The unprotected individuals gradually increase in number, forming an inflammable material awaiting the spark or infection which produces a conflagration in the one case and an epidemic in the other.

Cerebro-spinal meningitis is another example of a disease which exists in sporadic and epidemic form.  This disease is caused by a small micrococcus, the organisms joined in pairs.  The seat of the disease is in the meninges or membranes around the brain and spinal cord.  The micrococci enter the body from the throat and nose, and either pass directly from here into the meninges, or they enter into the blood and are carried by this into the meninges.  The organisms are easily destroyed and cannot long survive the conditions outside the body, so that for infection to take place the transmission must be very direct.  Carriers who have the organisms in the throat, but who do not have the disease, are the principal agents in dissemination.  The mortality is high, and even in recovery permanent damage is often done to the brain or to the organs of special sense.  Sporadic cases constantly occur in small numbers, and it is difficult or impossible to trace any connection between these cases.  At varying intervals, often twenty years intervening, an epidemic appears which sometimes remains local in a city or state, sometimes extends to adjoining cities or states, and may even extend over a very large area.  In the epidemics the mortality is much higher than in the sporadic cases.  The same explanation given for smallpox cannot apply here, for there is not a similar accumulation of susceptible material.  We know there is a great deal of variation in the virulence of the different pathogenic organisms, and the virulence can be artificially increased and diminished.  In epidemics of meningitis the virulence of the organisms is increased, as is shown by the greater mortality.  It is highly probable that such epidemics are due to changes which arise in the organisms from causes we do not know and which increase their capacity for harm.  It is possible that such a change would convert a carrier into a case of disease, the organism acquiring greater powers of invasion.  Such a strain of organisms arising in one place and producing an epidemic could be transported to another locality and exert the same action, or similar changes in the organisms could arise simultaneously in a number of places.  Analogies to such conditions are given in plants.  In certain plants it has been shown that from unknown causes there appears a tendency to the production of variations.  A very beautiful herbaceous peony known as “Bridesmaid” after having grown for a number of years in single form, in one year wherever grown suddenly became double.  The peculiar thing with the lower unicellular organisms is that the changes which so arise do not tend to become permanent, the organism reverts to its usual character, the disease to its sporadic type.