Katrina Ford. Scientific Thought: In Context. Editor: K Lee Lerner & Brenda Wilmoth Lerner. Volume 1, Gale, 2009.
Introduction
Vaccines that provide protection against deadly diseases are one of the most significant developments in medical history. Many vaccines are substances derived from disease-causing microorganisms that have been weakened or killed, preventing them from causing disease. When the vaccine is introduced into the body, the immune system produces specific antibodies to fight that particular illness. This response protects the body if it is later attacked by a full-strength or virulent strain of the disease. This immunity may last a few months, a few years, or a lifetime.
When the first vaccine was developed at the end of the eighteenth century, little was known about how it worked. As the germ theory of disease became widely accepted, however, beginning in the late nineteenth century scientific advances proved that infectious diseases were caused by specific microbes, laying the foundations for the development of still more vaccines and the study of the immune system. Newer and better laboratory techniques in the mid-twentieth century gave further stimulus to vaccine development. Large-scale immunization programs were begun in many countries, reducing outbreaks of infectious diseases in the industrialized world to near zero.
In the 1980s, biotechnological advances opened up enormous possibilities for better, safer vaccines for a wider range of diseases. Yet new challenges also arose: Lethal new diseases emerged and old ones made a comeback. Issues relating to the inequitable development and distribution of vaccines around the world also needed to be faced. In many Western countries, resistance to vaccination increased from people who questioned the benefits and risks of vaccine use.
Historical Background and Scientific Foundations
Smallpox
The eighteenth century was a period of massive social change. Increasing trade and urbanization produced a mobile population, spreading diseases among communities that had not experienced them before. Overcrowded and unsanitary cities provided ideal breeding grounds for illnesses. Smallpox was endemic (constantly present) in many cities and large towns.
Regular epidemics occurred every few years. Contemporary accounts describe the disease as universal; there was not a person who was not affected by smallpox in some way. Mortality rates are difficult to establish with certainty, but in Europe at the end of the eighteenth century, as many as 400,000 people died of smallpox each year. In other parts of the world, the impact of smallpox was even worse. In the New World, sixteenth-century European explorers unleashed smallpox onto a population that had no natural immunity, causing massive mortality and terrible suffering. Smallpox is thought to have been partially responsible for the collapse of the Aztec and Inca civilizations as well as the success of the Spanish conquest of Central and South America. The disease wreaked havoc on a global scale.
However, there were some ways to protect against smallpox. People who survived the disease became immune; it is exceedingly rare for anyone to get smallpox twice. For hundreds of years, in China, India, and the Middle East, techniques existed that aimed to artificially produce milder cases of smallpox in people, to make them immune. A form of this practice was brought to England from Turkey in 1721 by Lady Mary Wortley Montagu (1689-1762), who observed it while in Constantinople, Turkey, where her husband served as the British Ambassador Extraordinary.
Smallpox inoculation, or variolation, involved making a cut in the patient’s arm, and inserting material from a smallpox pustule. This was intended to cause a mild and safe case of smallpox, while providing protection against the more virulent form of the disease. This outcome was not guaranteed, however. Instead of a mild case the patient could develop severe smallpox and die. People who had been inoculated with smallpox were also infectious. They could pass serious cases of smallpox to family and friends, causing an epidemic to break out. Despite these risks, inoculation spread throughout Europe and North America in the eighteenth century.
Cowpox
The dangers of variolation meant the discovery of another way to protect people from smallpox was significant. Cowpox was a disease that caused watery pustules to form on a cow’s udder. Occasionally, people milking infected cows got these pustules on their hands and arms. In the rural communities that were familiar with the disease, it had been observed that people who contracted cowpox were also protected against smallpox. In England and other parts of Europe, there were individual instances of people deliberately inoculating themselves and their families with cowpox to protect them from smallpox. Yet, because the disease was not widely known outside of these rural communities, the significance of this knowledge to the wider control of smallpox was not recognized.
Then in 1796 an English country doctor named Edward Jenner (1749-1823) conducted a series of experiments to test this country wisdom. He confirmed that cowpox did protect people from smallpox, and also showed that cowpox could be deliberately passed from one person to another, through inoculation with material from the cowpox pustules. As the symptoms of cowpox were a slight, mild fever and pustules at the site where the cowpox was inoculated, it was far preferable to the risk of variolation. Jenner named the cowpox matter he used to inoculate people “vaccine,” from the Latin vaccines, “from cows.”
Jenner’s experiments were very important. In showing that cowpox could be transmitted from person to person, he had indicated the possibility for wide-scale inoculation of the population without the risks associated with variolation. Jenner recognized these implications, and was willing to risk his reputation by publishing his observations in a pamphlet in 1798.
Vaccination Takes on the World
Dubbed “vaccination” by a friend of Jenner’s, the practice of inoculating people with cowpox quickly spread around the world. Vaccine was sent in the post to physicians, dried on threads, quills, or ivory tips. The first vaccinations in North America took place in 1798, after Jenner sent vaccine to a friend in Newfoundland. In the United States, physician Benjamin Waterhouse (1754-1846) received vaccine in 1800 and began vaccinating, eventually enlisting the help of the American President Thomas Jefferson (1743-1826) in distributing vaccine. Governments recognized the benefits of vaccination, because it prevented the economic, social, and political disruption that smallpox epidemics caused. Many tried to compel their citizens to become vaccinated. Legislation to this effect began to appear in various countries from 1807, although the systems to enforce this were not always in place. In England, legislation making infant vaccination compulsory was passed in 1853, with fines imposed on parents who refused to have their babies vaccinated.
Opposition to Vaccination
Almost as soon as vaccination became widely publicized, it met with opposition. Some of this was nothing more than misguided superstitions, such as those who attacked it for fear that putting material from cows into the body would cause people to acquire cow-like attributes. But opposition was also often learned, informed, and came from medical and public experts on the control and prevention of disease. Many people questioned a practice that put an unclean foreign substance directly into the body, pointing to the risks of infection from other diseases.
Such concerns were not entirely unfounded. With arm-to-arm vaccination, when matter was taken from the pustules of one person and placed directly into cuts on another, it was possible that diseases such as tuberculosis and syphilis could also be transmitted. Even if the vaccine were pure, there could be complications. In the unhygienic conditions of nineteenth-century urban life, with open sewers and no running water, it was difficult to prevent the vaccination wound from becoming
infected. Among the urban working classes in particular, compulsory vaccination was regarded as an aggressive measure by a hostile and callous state intent upon injecting their children with filthy pus. Some public health experts and urban reformers opposed vaccination on the grounds that it approached the problems of disease from the wrong angle. Instead of vaccinating against disease, they argued, governments should work to remove the true causes of disease: the overcrowding, bad nutrition, inadequate drainage and sewerage systems that created such lethal environments in cities and towns.
Problems were also caused by lack of knowledge about the vaccine. Often, vaccination was blamed for smallpox epidemics. It is likely that mild cases of smallpox may have been mistaken for cowpox, and inadvertently inoculated into other people, giving them smallpox. Opponents also claimed that vaccination did not work. Difficulties with transporting the vaccine meant that people could be vaccinated with weak vaccines that provided no protection. There were also questions about long the protection the vaccine gave lasted.
A case of smallpox in most cases provided lifelong protection and Edward Jenner made similar claims for his vaccine at first. But it became clear as time went on that this was not the case. Some people who had been vaccinated as children caught smallpox as adults, and the need for revaccination became apparent. There were myriad questions surrounding many aspects of vaccination that could not be answered and these gaps in knowledge were exploited by vaccination’s opponents. However, as more knowledge was accumulated, some of these issues were addressed. Techniques were developed to produce large quantities of uncontaminated vaccine material on the flanks of calves bred specially for the purpose, eliminating the chance of cross-infection. Proponents of vaccination amassed statistics to show that vaccination decreased smallpox mortality.
Smallpox Eradication
In the twentieth century, smallpox gradually disappeared from most Western countries. Yet it remained a terrible problem in many poorer and developing nations, particularly in parts of South America, Africa, and the Indian subcontinent, as well as Southeast Asia. With the global migration of peoples in the twentieth century, wealthy developed nations could not ignore the continued threat of smallpox, and billions continued to be spent on vaccination programs and control.
In an increasingly interconnected world, the epidemics of the Third World were an economic cost for the First. In the middle decades of the twentieth century, the World Health Organization (WHO) proposed a campaign for the eradication of smallpox, a massive project that overcame incredible hurdles of logistics, geography, culture, and religious beliefs. The last case of smallpox in the wild occurred in Somalia in 1977, and its global eradication was declared in 1979. Vaccination programs were ended around the world, saving billions of dollars. However, the possible threat of a bioterrorist attack using the smallpox virus means the disease is not forgotten, and in 2002 the British and American governments reinstituted limited vaccination plans for military personnel and health workers.
Bacteriology and Vaccines
For most of the nineteenth century, there was little understanding of how vaccination worked to protect people from smallpox. This changed in the late nineteenth century when new theories suggested that microorganisms, or germs, were responsible for infectious diseases.
Given the widespread concerns about the massive public health problems that existed in the world’s large cities, germ theory seemed to offer medical science the potential to understand and control infectious diseases for the first time. In 1876 the German physician and researcher Robert Koch (1843-1910) proved that a specific microorganism, the Bacillus anthracis, was the specific agent responsible for causing cases of anthrax in animals. The identification of specific pathological agents for a whole series of infectious diseases followed over the next few decades.
Pasteur and Attenuated Organisms
While identifying the specific microbes that cause various diseases was enormously significant, not every disease-causing agent was so easily identified. No one was able to isolate the microorganism that caused smallpox or cowpox, however, because these diseases are caused by viruses, which are much smaller than bacteria. Although viruses could not be seen until the development of the electron microscope in the 1930s, so powerful was the germ theory that many people were certain that smallpox was caused by a specific microbe. Discussion in French medical circles about the relationship between cowpox and smallpox led French chemist Louis Pasteur (1822-1895) to consider how this relationship might be artificially produced in the laboratory in the case of other infectious diseases.
He was able to achieve this in 1880 with fowl cholera, a disease that affected chickens. But rather than finding a related disease that protected against this disease, as Jenner had done in the case of cowpox and smallpox, Pasteur was able to modify fowl cholera in the laboratory. By weakening, or attenuating the bacteria, Pasteur produced a strain of fowl cholera that didn’t cause the disease, but protected chickens against the full strength or virulent strain of the disease.
Pasteur applied these principles to other infectious disease agents. He next attenuated the anthrax bacillus by exposing it to heat. In a very famous series of experiments in May-June 1881, he demonstrated the success of this weakened form of anthrax in protecting animals inoculated with virulent strains. Pasteur, indicating his understanding of the relationship between his work and the principles behind the cowpox vaccine, also named his attenuated strains “vaccines,” widening the application of the term to any substance that provided protection against disease.
Pasteur went on to develop a vaccine for rabies using this same principle of attenuation. Controversially he began to use the vaccine on people in 1885, to prevent those who had been bitten by rabid dogs from developing rabies. Many people, including some of his closest colleagues, felt that he was taking an unwarranted risk, when the results of trials of the vaccine were far from conclusive. Issues surrounding testing, proving the efficacy and safety of vaccines, and the ethics of human trials would become contentious themes in vaccine development.
New Vaccine Era
For a time, it seemed that man’s triumph over all infectious diseases was at hand. However, it was not to be so straightforward. Not all diseases lent themselves to modification through the methods that Pasteur developed, and researchers turned to other ways to produce vaccines that would provide protection against disease. In 1886, veterinary pathologist Daniel Salmon (1850-1914) and epidemiologist Theobald Smith (1859-1934) in the United States published the results of their use of a killed virus vaccine for hog cholera, also known as swine flu. Instead of using a live but weakened vaccine, as Pasteur had done, they killed the virus using heat. They found that when this killed virus was injected into pigeons, it still provided protection from the living strain.
By the beginning of the twentieth century, five vaccines existed against human infectious diseases; smallpox, rabies, typhoid, plague, and cholera. The groundbreaking discoveries of the late-nineteenth century continued to be the basis for continued work into vaccine development for the next few decades. In France, Albert Calmette (1863-1933) and Camille Guérin (1872-1961) developed the BCG (Bacillus Calmette-Guérin) vaccine against tuberculosis, which was first used in the 1920s. That decade also saw the development of a vaccine against diphtheria, a disease caused by a toxin excreted by the diphtheria bacillus. An antitoxin was developed in 1891, which could counter the effects of the toxin in those who were already infected. But it was not until 1923 that a vaccine was developed, a deactivated form of toxin known as a toxoid, which could produce active immunity in the recipient. A toxoid vaccine was also developed for tetanus in 1927. In 1943 the two were combined with the pertussis or whooping cough vaccine to produce DPT, a combination vaccine used in widespread childhood immunization campaigns in many countries from 1948.
The Golden Age
Since viruses can only be grown within living cells, at first research into virus vaccines required extensive use of costly and time-consuming animal testing. In 1931-1933 a major advance in the study of viruses was made with the development of techniques using chicken embryos to grow viruses. This provided the basis for the first influenza and yellow fever vaccines. However, an even more crucial advance was the development of tissue cell cultures in 1949, which enabled researchers to grow viruses without living hosts, which was easier, less expensive, and had less potential for cross-contamination. The period from 1950 onward has been described as the “Golden Age” of vaccine development. The next two decades saw vaccines developed for a variety of viral diseases, including polio, measles, mumps, and rubella. MMR, a combination vaccine for these last three diseases was licensed in 1971, and is one of the most widely used vaccines in the world.
Changing Vaccine Technologies
Other important developments occurred in the methods used to create vaccines. Subunit or purified vaccines are comprised of antigens, the chemical components within the disease organism that stimulate the production of specific antibodies. As researchers were better able to understand and identify these chemical components, vaccines could be developed that were composed of just these parts. These vaccines cannot cause cases of the actual disease, and are less likely to stimulate adverse reactions.
An example of a subunit vaccine is the pneumococcal polysaccharide vaccine, which first became available in 1977. Pneumococcal infections are a major cause of pneumonia and the vaccine is composed of the polysaccharides on the surface of the Streptococcus pneumoniae organism. Because subunit vaccines can often produce only a weak immune response, they have been tied to a carrier protein, increasing the vaccine’s ability to stimulate the immune system. These are called conjugate vaccines; the first came into use in 1987 against the Haemophilus influenzae type B (Hib) virus, a major cause of bacterial meningitis.
Still other biotechnological developments in the late 1970s and 1980s seemed to hold enormous potential for vaccine development. The hepatitis B vaccine, licensed for use in the United States in 1986, was developed using a form of genetic engineering; the gene that produces its antigen is inserted into yeast cells, which then reproduce the hepatitis B antigens that are harvested to be made into a vaccine. Recombinant technology has also been applied to the development of live viral vaccines, in which the vaccine is tied to a harmless virus, which spreads through the body. The immune system responds to both the carrier and the vaccine, and as the reaction is more like that of a natural infection, the immune response is much stronger and provides better and longer lasting protection from the disease.
Modern Cultural Connections
Many of the issues raised by the opponents of vaccination in the nineteenth century continue to be relevant today. Some publicize the risks and dangers associated with particular vaccines, while others reject the entire principle of vaccination, as well as the understanding of health and disease on which it is based. Many antivaccination groups and activists campaign to stop national immunization programs, as with the cessation of the use of the OPV in the United States. Such campaigns have had some success in undermining public confidence in vaccination.
Suspicions about the claims of doctors and governments regarding the benefits of vaccination are linked to increasingly skeptical attitudes towards the medical industry as a whole. This has meant some adults have little faith in assurances from governments and researchers that certain vaccines are safe. The debates over the safety of the widely used MMR vaccine indicated some of these attitudes. In 1998 an article in a leading British medical journal suggested a link between the vaccine and the development of autism and Crohn’s disease in children. Subsequent studies failed to find any link between the vaccine and these illnesses, yet the claim received widespread media coverage, leading to a 10% drop in MMR vaccination coverage in some parts of Britain, and similar decreases in areas of the United States.
Future Directions
The future scope of vaccine development seems enormous and wide-ranging, utilizing developments in a broad field of scientific disciplines, such as molecular biology, and biochemistry. The traditional methods of producing vaccines have been joined by an array of new techniques. For example, the practical application of genomic technology to vaccine development, following the mapping of the human genome in 2001, offers vast potential to study the genome sequences of viral and bacterial pathogens, and use this information to identify and produce antigens for diseases for which no current vaccine exists.
Research in this direction may prove especially effective against the human immunodeficiency virus (HIV), the virus that causes AIDS. The social and economic caused by this disease is enormous. The 2006 Joint United Nations Programme on HIV/AIDs (UNAIDS) estimated that approximately 38 million people worldwide are living with the disease. The burden of this falls disproportionately on the poorer countries in the world, with more than 95% of HIV infections occurring in developing countries. A vaccine is desperately needed in these parts of the world, especially since antiretroviral drugs, which have been used to effectively treat HIV/AIDS in developed countries, remain out of reach for most victims. The development of a vaccine remains a significant challenge, but researchers are optimistic that with the current pace of technological change, an effective vaccine is possible in the near future.
Vaccines have traditionally been used to prevent infectious diseases. But vaccines may also be able to prevent noninfectious diseases. Greater understanding of the relationship between certain types of cancer and infectious diseases has led to the utilization of vaccines to reduce cancer rates. For instance, the development of a vaccine against human papillomavirus infections in women, a significant factor in cervical cancer, has the potential to decrease the incidence of this cancer. Another major area of development is the use of vaccines to treat diseases, rather than just prevent them. Increasing understanding of how the immune system works has led to advances in cancer immunotherapy, where the patient is injected with substances to increase the body’s immune response, enabling it to recognize and attack the cancer cells. Vaccine research in the treatment of autoimmune diseases, multiple sclerosis, and diabetes has also produced promising results. Such research is therefore redefining the very meaning of the word “vaccine.”
Over two centuries have passed since Edward Jenner first publicized the results of his experiments with cowpox. In that time, vaccines have developed into one of humanity’s most potent weapons against disease. There is little doubt that safe and effective vaccines have saved millions of lives, and made many terrible diseases a thing of the past in some countries. Yet despite this, vaccination still excites a great deal of controversy.
At the heart of the debate lie many issues integral to the relationship between medicine and modern society. These include the conflict between individual freedom and public health imperatives; the ethics of medical research; the importance of ensuring public access to reliable sources of information; the role and influence of commercial interests in medicine; the imbalance between the richest and poorest nations in the world; and the value of human life itself. None of these problems have simple answers, and the use and development of vaccines will continue to be hotly contested.