of AIDS occurred because a relatively small concentration of urban commercial sex workers acted as the source of infection of working men living apart from their families. The periodic travel by men to their isolated village homes resulted in the virus being found with increasing frequency in isolated family units. Further spread resulted from infected women leaving brothels and prostitution to return to their villages to take up family life.
Another important factor in the spread of AIDS is technology. HIV could not have spread and posed the threat it now does in the world of a century ago. Generally lower population densities and lower concentrations of individuals at risk at that time would have precluded HIV from gaining a foothold in the population. Slower rates of communication and much more restricted travel and migration would have precluded rapid spread; also, the transmission of blood and blood products as therapeutic tools was unknown a century ago.
Of course, this dynamic interaction between pathogen and host is not confined to viruses; any pathogen exhibits it. The study and characterization of the genetic accommodations that viruses make, both to natural resistance generated in a population of susceptible hosts and to human‐directed efforts at controlling the spread of viral disease, provide much insight into evolutionary processes and population dynamics. Indeed, many of the methodologies developed for the study of interactions between organisms and their environment can be applied to the interaction between pathogen and host.
The history of virology
The historic reason for the discovery and characterization of viruses, and a continuing major reason for their detailed study, involve the desire to understand and control the diseases and attending degrees of economic and individual distress caused by them. As studies progressed, it became clear that there were many other important reasons for the study of viruses and their replication.
Since viruses are parasitic on the molecular processes of gene expression and its regulation in the host cell, an understanding of viral genomes and virus replication provides basic information concerning cellular processes in general.
The whole development of molecular biology and molecular genetics is largely based on the deliberate choice of some insightful pioneers of “pure” biological research to study the replication and genetics of viruses that replicate in bacteria: the bacteriophages. (Such researchers include Max Delbrück, Salvadore Luria, Joshua Lederberg, Gunther Stent, Seymour Benzer, André Lwoff, François Jacob, Jacques Monod, and many others.)
The bacterial viruses (bacteriophages) were discovered through their ability to destroy human enteric bacteria such as Escherichia coli, but they had no clear relevance to human disease. It is only in retrospect that the grand unity of biological processes, from the simplest to the most complex, can be seen as mirrored in replication of viruses and the cells they infect.
The biological insights offered by the study of viruses have led to important developments in biomedical technology and promise to lead to even more dramatic developments and tools. For example, when infecting an individual, viruses target specific tissues. The resulting specific signs and symptoms, as already noted, define their pathogenicity. The normal human, like all vertebrates, can mount a defined and profound response to virus infections. This response often leads to partial or complete immunity to reinfection. The study of these processes was instrumental to gaining an increasingly clear understanding of the immune response and the precise molecular nature of cell–cell signaling pathways. It also provided therapeutic and preventive strategies against specific virus‐caused disease. The study of virology has and will continue to provide strategies for the palliative treatment of metabolic and genetic diseases not only in humans, but also in other economically and aesthetically important animal and plant populations.
Examples of the impact of viral disease on human history
There is archeological evidence in Egyptian mummies and medical texts of readily identifiable viral infections, including genital papillomas (warts) and poliomyelitis. There are also somewhat imperfect historical records of viral disease affecting human populations in classical and medieval times. While the recent campaign to eradicate smallpox has been successful and the virus no longer exists in the human population (owing to the effectiveness of vaccines against it, the genetic stability of the virus, and a well‐orchestrated political and social effort to carry out the eradication), the disease periodically wreaked havoc and had profound effects on human history over thousands of years. Smallpox epidemics during the Middle Ages and later in Europe resulted in significant population losses as well as major changes in the economic, religious, political, and social life of individuals. Although the effectiveness of vaccination strategies gradually led to decline of the disease in Europe and North America, smallpox continued to cause massive mortality and disruption in other parts of the world until after World War II. Despite smallpox being eradicated from the environment, the attack of September 11, 2001, on the World Trade Center in New York has led some government officials to be concerned that the high virulence of the virus and its mode of spread might make it an attractive agent for bioterrorism.
Other virus‐mediated epidemics had equally major roles in human history. Much of the social, economic, and political chaos in native populations resulting from European conquests and expansion from the fifteenth through nineteenth centuries was mediated by introduction of infectious viral diseases such as measles. Significant fractions of the indigenous population of the Western Hemisphere died as a result of these diseases.
Potential for major social and political disruption of everyday life continues to this day. As discussed in later chapters of this book, the “Spanish” influenza (H1N1) of 1918–1919 killed tens of millions worldwide and, in conjunction with the effects of World War I, came very close to causing a major disruption of world civilization. Remarkable medical detective work using virus isolated from cadavers of victims of this disease frozen in Alaskan permafrost has led to recovery of the complete genomic sequence of the virus and reconstruction of the virus itself (some of the methods used will be outlined in Part V). While we may never know all the factors that caused it to be so deadly, it is clear that the virus was derived from birds and passed directly to humans. Further, a number of viral proteins have a role in its virulence. Ominously, there is no reason why another strain of influenza could not arise with a similar or more devastating aftermath or sequela – indeed, in the spring/summer of 2005, there was legitimate cause for concern because a new strain of avian influenza (H5N1) had been transmitted to humans. At the present time, human transmission of H5N1 influenza has not been confirmed, but further adaptation of this new virus to humans could lead to it establishing itself as a major killer in the near future.
In April 2009, a new version of H1N1 influenza (now called the 2009 H1N1 flu by the Centers for Disease Control and Prevention [CDC]) was identified in Veracruz, Mexico. Initially H1N1 became epidemic in Mexico, and, as the virus spread rapidly, on June 11, 2009, the World Health Organization declared a pandemic. Because this virus has the same surface markers (H1 and N1) as the infamous “Spanish flu” of nearly 100 years before, there were fears of the same kinds of morbidity and mortality as seen in the early years of the twentieth century. However, this virus turned out to be of no greater lethality than the other seasonal influenza strains currently circulating in the human population. We will discuss more details about this later in this book.
A number of infectious diseases could become established in the general population as a consequence of their becoming drug resistant or introduced as weapons of bioterrorism, or because of human disruption of natural ecosystems. As will be discussed in later chapters, a number of different viruses exhibiting different details of replication and spread could, potentially, be causative agents of such diseases.
Animal and plant pathogens are other potential sources of disruptive
