The discovery of insulin
In May 1921, Banting and Best began to conduct experiments on dogs. They removed the pancreas of some dogs and tied off the pancreatic duct of others. The dogs whose pancreas had been removed altogether developed diabetes, as expected, while the dogs whose ducts had been tied did not. While the pancreatic cells that produced digestive secretions degenerated in the dogs whose pancreatic duct had been tied, the islets of Langerhans remained undamaged. Clearly, the islets of Langerhans produced the secretions that prevented diabetes occurring. Banting and Best wanted to extract and isolate these secretions, but it was difficult to keep the dogs alive long enough to carry out tests.
After numerous setbacks, resulting in the deaths of several dogs, they succeeded in keeping a severely diabetic dog alive with injections of an extract made from the tied-off pancreas. They called this extract isletin. Their next challenge was to find a way of producing enough extract to make it a practicable treatment for diabetes. Realizing that relying on a supply of dogs was going to hold back research, Banting and Best moved on to using the pancreas of cows, obtained from a local slaughterhouse. They managed to extract a substance that contained a greater amount of the active ingredient and injected it into one of the laboratory dogs that had had its pancreas removed. The dog’s blood sugar dropped significantly.
Human testing
At the end of 1921, Macleod invited James Collip, a skilled biochemist to help purify Banting and Best pancreatic extract for clinical testing in humans. On 11 January 1922, the extract was injected into 14-year-old Leonard Thompson a diabetic patient who was close to death, at the Toronto Gene Hospital. The first test proved disappointing, but it was repeated with a purer version of the extract around two weeks later, this time with much better results.
Thompson’s blood sugar returned to normal levels and his other symptoms abated. ’In May 1922, Macleod delivered a paper, “The Effects Produced on Diabetes by Extracts of Pancreas”, on behalf of the team at the annual conference of the Association of American Physicians. He received a standing ovation. The paper used the word “insulin”for the first time.
Monoclonal antibodies
Monoclonal antibodies (mAbs) are unlimited identical copies of the same antibody that are produced artificially. They were first made in 1975 by two immunologists, Cesar Milstein from Argentina and Georges Kohler from Germany, and although research is ongoing, they have already proved useful in many areas of medicine. They make up a high proportion of new drugs and diagnostic tests, from innovative treatments for cancers to identifying blood types. Antibodies are proteins the body uses to target alien cells such as germs. There are millions of kinds, each matching a different alien protein (or antigen), and they latch on to their specific antigen either to neutralize it or to identify it as a target for the body’s immune cells. Paul Ehrlich coined the term “antibodies”in 1891, and went on to describe how they interact with antigens like lock and key. By the 1960s, scientists knew they are made by white blood cells called B-cells, or Blymphocytes, each primed with its own antibody. When triggered by its matching antigen, a B-cell clones itself, producingmultiple copies of plasma cells, which release floods of antibodies.As plasma cells produce more than one kind of antibody, the process is described as “polyclonal”. Milstein and Kohler’s breakthrough was to create limitless copies of identical “monoclonal” antibodies using cells made in the lab called hybridomas. These are artificial fusions of plasma cells and myeloma cells (abnormal plasma cells that cause cancer) primed to produce the desired antibody. Plasma cells are short-lived, whereas myeloma cells reproduce indefinitely. By fusing them, Milstein and Kohler created an endlessly multiplying source of their chosen antibody. Milstein’s original intention was to find a way to make antibodies for research. But he and Kohler quickly realized that mAbs might also be a “magic bullet”, offering tailor-made antibodies to target any disease. Although monoclonal antibodies have not yet proved to be a magic cure-all, they are finding new uses all the time. They can even be used to detect biological weapons. In pregnancy tests, mAbs detect the hormone HCG, and in tissue typing, they help prevent a donor organ from being rejected by blocking the immune response. They can identify blood clots and rogue cells and are used in cancer treatment to carry drugs or radiation to targeted cells. Monoclonal antibodies are also used to fight autoimmune diseases including rheumatoid arthritis, and new mAb drugs are in the pipeline for malaria, influenza, and HIV. In 2020, scientists found several mAbs that appear to neutralize the COVID-19 virus in cell cultures.
Medical systems
Each of the ancient civilizations developed medical practices, many of them linked to religious rituals. In Egypt, in the 4th millennium BCE, serious disease was regarded as the work of the gods — probably as a punishment for a misdemeanour in the current or past life. Temple priests administered herbal medications, carried out healing rituals, and placated the gods with offerings. By the 2nd millennium BCE, there were Egyptian doctors who specialized in disorders of the eyes, digestion, joints, and teeth, and in surgery that was informed by many centuries of experience in mummification and embalming. In China, the Huangdi Neijing (The Yellow Emperor’s Classic of Internal Medicine) sets out the principles and methods of traditional Chinese medicine. In India, Ayurvedic medicine developed from around 800 ВСЕ. Still practised by some physicians today, its central premise is that illness is caused by an imbalance between the body’s three elemental doshas: vata (wind), pitta (bile), and kapha (phlegm). The task of the vaidya, the Ayurvedic physician, is to detect imbalances and correct them using herbal and mineral remedies, bloodletting, laxatives, enemas, emetics, and massage. Ancient China developed a theory of health based on balance within the body between the oppositions of yin and yang, the five elements of fire, water, earth, wood, and metal, and the life sustaining energy of qi flowing along the body’s many meridians (channels). Chinese medicine included some remedies that were common to other ancient civilizations, such as herbs, diets, and massage, but it also developed its own practices. It placed great emphasis on the pulse for diagnosis, and on acupuncture — the insertion of needles along the meridians – to correct imbalances in the body.
MRI
In 1974,Mansfieldmade the first MRI scan of a human body part – cross-sectional images of a student’s finger. However, the scans took up to 23 minutes to create. To speed up the process, he developed the echo-planar imaging technique, which produced multiple nuclear NMR echoes from a single excitation of the protons. This meant that an entire MR image could be obtained in a fraction of a second. The advantage of echo-planar imaging is that it can image rapid physiological processes, such as respiration and cardiac rhythm. Mansfield used echo-planar imaging in his prototype scanner, which went into experimental use in 1978. In the US, Damadian unveiled the first whole-body MRI scanner in May 1977. The US Food and Drug Administration (FDA) approved it for use in 1984. The big advantage of MRI is that it provides extremely detailed images. It is used for non-invasive examination of the brain and spinal cord, bones and joints, breasts, blood vessels, the heart, and other organs. One disadvantage is the cost of an MRI scanner —as high as £1.5 million (US$2 million). The other disadvantage of MRI is that it cannot be used on patients with metallic implants. Despite this, there were more than 50,000 MRI scanners in service in 2018, with the highest concentration — 55 per 1 million people — in Japan. Scanners with powerful 3T (tesla) magnets produce very high-quality images of the minute details of the musculoskeletal and nervous systems. Engineers are building increasingly powerful scanners that will provide even more detailed images of the body faster. British electrical engineer Godfrey Hounsfield and American physicist Allan MacLeod Cormack developed CT (computed tomography) — also known as CAT (computerized axial tomography)—scanning formedical diagnosis.Hounsfield’s first scanner, in 1968, took nine days to capture a full three-dimensional (3D) image of a dead pig’s brain. He later used X-rays and reduced the scanning time to nine hours. It worked by firing gamma rays as it rotated around the brain, one degree at a time, creating thousands of cross-sectional images. A computer programme then assembled these “slices”(the word tomography derives from tomei, the Greek word for slice) to produce the 3D image.