During the twentieth century, Austin Bradford Hill researched diseases and their causes in England and developed the Bradford Hill criteria, which comprise the minimal requirements that must be met for a causal relationship to be established between a factor and a disease. Hill also suggested that researchers should randomize clinical trials to evaluate the effects of a drug or treatment by monitoring large groups of people. In addition, Hill advocated for case-control studies, in which researchers compare a group of people with a medical condition to a group without that condition to investigate the condition's possible causes. Hill's own work with clinical trials and case-control studies helped him prove that smoking caused lung cancer. The Bradford Hill criteria have also been used to establish causal links between factors and cancer, including reproductive cancers such as human papillomavirus that causes cervical cancer.
In 1965, Austin Bradford Hill published the article “The Environment and Disease: Association or Causation?” in the Proceedings of the Royal Society of Medicine. In the article, Hill describes nine criteria to determine if an environmental factor, especially a condition or hazard in a work environment, causes an illness. The article arose from an inaugural presidential address Hill gave at the 1965 meeting of the Section of Occupational Medicine of the Royal Society of Medicine in London, England. The criteria he established in the article became known as the Bradford Hill criteria and the medical community refers to them when determining whether an environmental condition causes an illness. The criteria outlined in “The Environment and Disease: Association or Causation?” help identify the causes of many diseases, including cancers of the reproductive system.
Richard Woltereck first described the concept of Reaktionsnorm (norm of reaction) in his 1909 paper 'Weitere experimentelle Untersuchungen uber Art-veranderung, speziell uber das Wesen quantitativer Artunterschiede bei Daphniden' ('Further investigations of type variation, specifically concerning the nature of quantitative differences between varieties of Daphnia'). This concept refers to the ways in which the environment can alter the development of an organism, and its adult characteristics. Woltereck conceived of the Reaktionsnorm as the full range of potentialities latent in a single genotype, evocable by the environmental circumstances of a developing organism. Biologists used variants of Woltereck's concept of Reaktionsnorm, often called the reaction norm or norm of reaction, throughout the twentieth century in attempts to explain how developmental responses to the environment can evolve, and even alter the tempo and direction of evolutionary change.
In "Behavioral Thermoregulation by Turtle Embryos," published in Proceedings of the National Academy of Sciences in April, 2011, Wei-Guo Du, Bo Zhao, Ye Chen, and Richard Shine report that turtle embryos can move towards warmer temperatures within the egg when presented with a small, 0.8 degrees Celsius gradient. This behavioral thermoregulation may benefit the embryo's fitness by accelerating the rate of development enough to decrease the incubation period by up to four and a half days. Embryos are generally thought to have little control over their surroundings. This study revealed that embryos may be able to control their developmental environment by modifying their behavior.