I am grateful to each of the authors for their interest in my article and for their thought-provoking reflections on theories of evolution. Of the questions they raise in their letters, the most perplexing concerns the basic unit of evolution.

Dr. Schwam maintains that the basic unit of evolution is the gene. Genes certainly play a fundamental role in the process; however, the proposition that "genes making copies of themselves" is the essence of evolution, although provocative in its simplicity, does nothing to enhance our understanding of why some genetic traits survive and others disappear during evolution. It also does not explain why fever, a biological process controlled by many genes, protects the host in certain situations and harms it in others. Similarly, if survival of the individual is the essence of evolution, why would a physiologic response (fever), maintained for more than 400 million years of the evolutionary process, accelerate the demise of individuals with sepsis? Perhaps, as Dr. Ubel suggests, the occasional pernicious effects of fever simply reflect the fact that evolution is an imperfect process. I cannot disprove this hypothesis but find it intellectually unsatisfying.

I am nevertheless grateful to Dr. Ubel for his discussion of group selection and to Dr. Fischer for sharing "Hamilton's key insight ... that an individual's genes can be passed on to the next generation, not only in the offspring of that individual but also in that individual's siblings and cousins." I believe that such group selection is precisely the means by which the febrile response might have established itself within the gene pool of primitive life forms.

Phylogenetic data suggests that the febrile response first emerged in the common ancestor of annelids and arthropods. Thus, the evolutionary struggle that ultimately established fever as an almost universal response of higher animals occurred hundreds of millions of years before humans emerged. If closely related subpopulations of this early life form derived some survival advantage from the genetic trait, then, according to our current understanding of evolution, the trait itself would probably have been preserved from one generation of the organism to the next.

I believe that the detrimental effects of fever during sepsis could only have been advantageous—and therefore likely to have been preserved during evolution—if the welfare of the group rather than of the individual were the primary determinant in the evolutionary process. If so, hastening the death of an individual with sepsis during an epidemic might have been a means by which a subpopulation of the early life form limited the spread of epidemic diseases among its members. If it was effective in this regard and if the epidemic disease was particularly virulent, the capacity of fever for accelerating the elimination of individuals with sepsis might have enabled a closely related subpopulation (that is, siblings and cousins) possessing the trait to survive the epidemic, whereas other unrelated subpopulations not possessing the trait died.

I agree with Dr. Schiller that his proposal is "far-fetched." I do not believe, nor am I proposing, that the primary function of the febrile response is to weed crippled persons from the species. Its primary function is to accelerate recovery from infection. Nevertheless, considerable experimental evidence indicates that the febrile response increases mortality in patients with gram-negative sepsis, a condition that, contrary to Dr. Johnson's contention, can be highly contagious and extremely lethal if the gram-negative bacillus happens to be a bacterium such as Pasteurella pestis. Fortunately, such epidemic infections are rare in humans, although they had a devastating influence earlier in our history. If similar epidemics plagued the primitive precursor of annelids and anthropods, the darker side of fever might have evolved and established itself widely within the gene pool as a result of the process of group selection so succinctly described by Dr. Ubel.