At the ages of 50, 60, 65, I felt an intense joy in living, such as I described in my _Studies on Human Nature_ and _Optimistic Essays_. In the last few years it has lessened markedly. Scientific work still provokes in me an invincible enthusiasm, but I am becoming more indifferent to many of the pleasures of life. And indeed he no longer had the joyous soul of former days; into his life a funereal note had crept, low but continuous and obstinate. He gave all the more energy to the study of those questions the solution of which was to bring about the reign of orthobiosis. He spent the whole winter in researches on the intestinal flora and on the completion of his studies on infantile cholera. In the spring, on the occasion of his anniversary, he wrote the following: SÈVRES, _16th May 1914_. I have to-day entered my 70th year; it is a great event for me. As I analyse my feelings, I realise more and more the _weakening_ of my "life-instinct." In order to verify my impressions, I wished to hear again the musical compositions which formerly used to make me shed tears of enthusiasm (for instance, Beethoven's 7th Symphony or Bach's aria for the violin). Well, my impressionability towards music has very much lessened. In spite of the facility with which old people weep, I hardly shed a single tear, save with rare exceptions. I observe the same change in other circumstances. This spring, the blossoming of flowers, buds, bushes, and trees, all this renascence of nature, has not excited in me a shadow of the emotion of preceding years. Rather I felt a melancholy, not on account of my coming end, but because of the consciousness of the burden of existence. There is no question for me now of the old joy of living; my predominant feeling is _infinite anxiety_ for the health and happiness of those I love. I now so well understand Pettenkoffer, who committed suicide at 84 after losing all his family. Their death had evidently been precocious because of the impotence of medicine. At every step, one comes across cases where neither hygiene nor therapeutics can do anything. How many are infected with tuberculosis, no one knows how or where. What is to be done to avoid it? And the consequences of measles, of scarlet fever, perhaps of a simple sore throat, followed sometimes by tuberculosis or nephritis! What is the use of being able to foretell, by means of the proportion of urea in the blood, the precise moment of the death of an "azotemic" patient when you cannot prevent it or cure him? This imperfection of medical science prevents many from reaching true _orthobiosis_, and it is understandable that, seeing the present state of medicine, the feeling of the "burden of existence" may be precocious, as in my case.