The spots on this girl's tongue are an early sign of vitamin C deficiency, which is also called scurvy. This disorder, which may be fatal, is uncommon today because foods high in vitamin C are relatively available. They include tomatoes, peppers, and citrus fruits such as oranges, lemons, and limes. However, scurvy was a well known problem on navy ships in the 1700s. It was said that scurvy caused more deaths in the British fleet than did French and Spanish arms. At that time, the cause of scurvy was unknown and vitamins had not yet been discovered. Anecdotal evidence suggested that eating citrus fruits might cure scurvy. However, no one knew for certain until 1747, when a Scottish naval physician named John Lind did an experiment to test the idea. Lind's experiment was one of the first clinical experiments in the history of medicine.
What Is an Experiment?
An experiment is a special type of scientific investigation that is performed under controlled conditions. Like all investigations, an experiment generates evidence to test a hypothesis. But unlike some other types of investigations, an experiment involves manipulating some factor in a system in order to see how it affects the outcome. Ideally, experiments also involve controlling as many other factors as possible in order to isolate the cause of the experimental results.
An experiment generally tests how one particular variable is affected by some other specific variable. The affected variable is called the dependent variable, or outcome variable. The variable that affects the dependent variable is called theindependent variable. It is also called the manipulated variable because this is the variable that is manipulated by the researcher. Any other variables (control variable) that might also affect the dependent variable are held constant, so the effects of the independent variable alone are measured.
Lind's Scurvy Experiment
Lind began his scurvy experiment on board a British ship after it had been at sea for two months and sailors had started showing signs of scurvy. He chose a group of 12 sailors with scurvy and divided the group into 6 pairs. All 12 sailors received the same diet, but each pair also received a different daily supplement to the diet, as shown in the table below.
|Pair of Subjects||
Daily Supplement to the Diet Received by this Pair
|1||1 quart of cider|
|2||5 drops of sulfuric acid|
|3||6 spoons of vinegar|
|4||1 cup of seawater|
|5||2 oranges and 1 lemon|
|6||spicy paste and a drink of barley water|
Lind's experiment ended after just five days when the fresh citrus fruits ran out for pair 5. However, the two sailors in this pair had already fully recovered or greatly improved. The sailors in pair 1 (receiving the quart of cider) also showed some improvement, but sailors in the other pairs showed none.
Can you identify the independent and dependent variables in Lind's experiment? The independent variable is the daily supplement received by the pairs. The dependent variable is the improvement/nonimprovement in scurvy symptoms. Lind's results supported the citrus fruit cure for scurvy, and it was soon adopted by the British navy with good results. However, the fact that scurvy is caused by a vitamin C deficiency was not discovered until almost 200 years later.
Lind's scurvy experiment included just 12 subjects. This is a very small sample by modern scientific standards. The sample in an experiment or other investigation consists of the individuals or events that are actually studied. It rarely includes the entire population because doing so would likely be impractical or even impossible.
There are two types of errors that may occur by studying a sample instead of the entire population: chance error and bias.
- Chance error occurs if the sample is too small. The smaller the sample is, the greater the chance that it does not fairly represent the whole population. Chance error is mitigated by using a larger sample.
- Bias occurs if the sample is not selected randomly with respect to a variable in the study. This problem is mitigated by taking care to choose a randomized sample.
A reliable experiment must be designed to minimize both of these potential sources of error. You can see how the sources of error were addressed in another landmark experiment: Jonas Salk's famous 1953 trial of his newly developed polio vaccine. Salk's massive experiment has been called the "greatest public health experiment in history."
Salk's Polio Vaccine Experiment
Imagine a nation-wide epidemic of a contagious flu-like illness that attacks mainly children and often causes paralysis. That's exactly what happened in the U.S. during the first half of the 20th century. Starting in the early 1900s, there were repeated cycles of polio epidemics, and each seemed to be stronger that the one before. Many children ended up on life support in so-called "iron lungs" (see photo below) because their breathing muscles were paralyzed by the disease.
This photo shows the iron lung ward in a California hospital in 1953, the same year that Salk undertook his nationwide vaccine experiment.
Polio is caused by a virus, and there is still no cure for this potentially devastating illness. Fortunately, it can now be prevented with vaccines. The first polio vaccine was discovered by Jonas Salk in 1952. After testing the vaccine on himself and his family members to assess its safety, Salk undertook a nationwide experiment to test the effectiveness of the vaccine using more than a million school children as subjects. It's hard to imagine a nationwide trial of an experimental vaccine using children as "guinea pigs." It would never happen today. However, in 1953, polio struck such fear in the hearts of parents that they accepted Salk's word that the vaccine was safe and gladly permitted their children to participate in the study.
Salk's experiment was very well designed. First, it included two very large, random samples of children — 600,000 in the treatment group, called experimental group, and 600,000 in the nontreatment group, called control group. Using very large and randomized samples reduced the potential for chance error and bias in the experiment. Children in the experimental group were injected with the experimental polio vaccine. Children in the control group were injected with a harmless saline (salt water) solution. The saline injection was a placebo. A placebo is a "fake" treatment that actually has no effect on health. It is included in trials of vaccines and other medical treatments so subjects will not know in which group (control or experimental) they have been placed. Use of a placebo helps researchers control for the placebo effect. This is a psychologically based reaction to a treatment that occurs just because the subject is treated, even if the treatment has no real effect.
Experiments in which a placebo is used are generally blind experiments, because the subjects are "blind" to their experimental group. This helps prevent bias in the experiment. Often, even the researchers do not know which subjects are in each group. This type of experiment is called a double-blind experiment, because both subjects and researchers are "blind" to which subjects are in each group. Salk's vaccine trial was a double-blind experiment, and double-blind experiments are now the considered the gold standard of clinical trials of vaccines, therapeutic drugs, and other medical treatments.
Salk's polio vaccine proved to be highly successful. Analysis of data from his study revealed that the vaccine was 80 to 90 percent effective in preventing polio. Almost overnight, Salk was hailed as a national hero. He appeared on the cover of Time magazine and was invited to the White House. Within a few years, millions of children had received the polio vaccine. By 1961, the incidence of polio in the U.S. had been reduced by 96 percent.
Limits on Experimentation
Well-done experiments are generally the most rigorous and reliable scientific investigations. However, their hallmark feature of manipulating variables to test outcomes is not possible, practical, or ethical in all investigations. As a result, many ideas cannot be tested by experimentation. For example, experiments cannot be used to test ideas about what our ancestors ate millions of years ago or how long-term cigarette smoking contributes to lung cancer. In the case of our ancestors, it is impossible to study them directly. Researchers must rely instead on indirect evidence, such as detailed observations of their fossilized teeth. In the case of smoking, it is unethical to expose human subjects to harmful cigarette smoke. Instead, researchers may use large observational studies of people who are already smokers, with nonsmokers as controls, to look for correlations between smoking habits and lung cancer.
Feature: Human Biology in the News
Lind undertook his experiment to test the effects of citrus fruits on scurvy at a time when seamen were dying by the thousands from this nutritional disease as they explored the world. Today's explorers are astronauts in space, and their nutrition is also crucial to the success of their missions. However, maintaining good nutrition in astronauts in space can be challenging. One problem is that astronauts tend to eat less while in space. Not only are they very busy on their missions, but they may also get tired of the space food rations. The environment of space is another problem. Factors such as microgravity and higher radiation exposure can have major effects on human health and require nutritional adjustments to help counteract them. A novel way of studying astronaut nutrition and health is provided by identical twin astronauts Scott and Mark Kelly, pictured below.
homozygote twin brothers astronauts Mark and Scott Kelly at the Johnson Space Center.
The Kelly brothers are the first identical twin astronauts, but twin studies are nothing new. Scientists have used identical (homozygotic) twins as research subjects for many decades. Identical twins have the same genes, so any differences between them generally can be attributed to environmental influences rather than genetic causes. Mark Kelly spent almost a full year on the International Space Station (ISS) between 2015 and 2016, while his twin brother Scott Kelly stayed on the ground, serving as a control in the experiment. You may have noticed a lot of media coverage of Mark Kelly's return to Earth in March 2016, because his continuous sojourn in space was the longest of any American astronaut at that time. NASA is learning a great deal about the effects of long-term space travel on the human body by measuring and comparing nutritional indicators and other health data in the twins. Watch this NASA video to learn more about NASA's nutritional experiments involving the Kelly twins.
Identical twins who were reared apart from birth make especially good subjects for studying the effects of genes vs. the environment on human health, development, and behavior. Watch the news report below to learn more. In the video, a researcher who specializes in studying twin pairs explains why they are so important as research subjects. She also shares some of her amazing findings.
- In 1747, John Lind undertook one of the first clinical experiments with his experiment to test citrus fruits as a cure for scurvy.
- An experiment is a special type of scientific investigation that is performed under controlled conditions. It involves manipulating some factor (the independent, or manipulated, variable) in order to see how it affects some other factor (the dependent, or outcome, variable). This is only possible when other variables (control variables) are kept content between control and experimental groups.
- The sample in an experiment consists of the individuals or events that are actually studied. A reliable experiment must be designed to minimize two potential sources of sampling error: chance error, which may occur if the sample is too small; and bias, which may occur if the sample is not selected randomly.
- Jonas Salk's landmark public health experiment, in which he tested his new polio vaccine, addressed both potential sampling errors by using very large random samples and a double-blind experimental design that included a placebo.
- Well-done experiments are generally the most rigorous and reliable scientific investigations, but many ideas cannot be tested by experimentation. The hallmark feature of experiments of manipulating variables to test outcomes is not possible, practical, or ethical in all investigations.
- How do experiments differ from other types of scientific investigations?
- Identify the independent and dependent variables in Salk's nationwide polio vaccine trial.
- Compare and contrast chance error and bias in sampling. How can each type of error be minimized?
- What is the placebo effect? Explain how Salk's experimental design controlled for it.
- Fill in the blanks. The _____________ variable is manipulated to see the effects on the ___________ variable.
- True or False. In studies of identical twins, the independent variable is their genetics.
- True or False. Experiments cannot be done on humans.
- True or False. Larger sample sizes are generally better than smaller ones in scientific experiments.
- Answer the following questions about Lind’s scurvy experiment.
a. Why do you think it was important that the sailors’ diets were all kept the same, other than the daily supplement?
b. Can you think of some factors other than diet that could have potentially been different between the sailors that might have affected the outcome of the experiment?
c. Why do you think the sailors who drank cider had some improvement in their scurvy symptoms?
Explain why double-blind experiments are considered to be more rigorous than regular blind experiments.
Why are studies using identical twins so useful?
Do you think it is necessary to include a placebo (such as an injection with saline in a drug testing experiment) in experiments that use animals? Why or why not?
Watch this entertaining TED talk, in which biochemist Kary Mullis talks about the experiment as the basis of modern science.
Check out this video to learn more about conducting scientific experiments:
Credit: By CDC (Public Health Image Library, ID#:6239) [Public domain], via Wikimedia Commons;
License: CC BY-NC 3.0
Credit: By Food and Drug Administration (http://www.fda.gov/cber/summaries/cent092302pp.htm) [Public domain], via Wikimedia Commons;
License: CC BY-NC 3.0
Credit: By NASA/Robert Markowitz [Public domain], via Wikimedia Commons;
License: CC BY-NC 3.0