Tizón temprano (Alternaria sp.)

Because his school had no money for this sort of research, Banting went to see Dr. John Macleod, the head of the physiology department at the University of Toronto and an expert on diabetes. Initially, Macleod was not interested in giving Banting the space, equipment, and money he needed to conduct the experiment. Banting persisted, though, and Macleod eventually agreed, giving Banting a small labora-tory to use during the summer of 1921 and some money to buy a few experimental dogs. Macleod also put Banting in touch with Charles Best, a 21-year-old ex-soldier who was going to enter medical school in the fall, who agreed to work as Banting’s research assistant.

Working together, Banting and Best performed the tie-off proce-dure on two dogs, which were always treated like favorite pets. During the day, they roamed free in the lab. When Banting operated, the dogs were under anesthetic, and they received the kind of care any human patient would receive while they recovered. Their first attempt to tie off a dog’s pancreas failed: the catgut Banting used to close the duct disintegrated before the gland dried up. Switching to silk thread, the researchers tied off the duct of a dog named Marjorie, which developed diabetes within a few weeks. They removed the pancreas and dissolved it in a salt solution, coming up with a compound they called iletin.

Dr. Frederick Banting and Charles Best with Marjorie, the subject of the 1921 experiment that proved the existence of insulin. (Courtesy Eli Lilly and Company)

When they gave Marjorie an injection of iletin, her symptoms cleared up within a few hours. Her blood sugar was normal, and there was no sugar in her urine.

Banting and Best had found a treatment for diabetes. But how long could they keep diabetic animals alive? More important, how long could they keep diabetic humans alive? How large an injection did someone need at a time, and how often did they need it? What would happen if someone overdosed? The two men kept running out of the drug, and they needed more in order to answer these questions. Then Banting had another idea. He had grown up on a farm, and he remem-bered that his father and other cattle ranchers bred their beef cattle shortly before they went to the slaughterhouse, because pregnant cows ate more and put on weight. Banting wanted the pancreas glands from the fetal (unborn) calves. It seems gruesome, but there was a practical reason for taking these pancreases: They do not secrete digestive juice until after the fourth month of development, but they do produce insulin. Going to area slaughterhouses, Banting and Best collected the fetal pancreases that would otherwise have been thrown away and used them in their work.

Eventually, the two researchers injected each other with iletin to see if the drug was safe for humans. By this time, Macleod returned from a summer vacation and was astounded at what the two had accomplished. However, he insisted on changing the name of the hor-mone extract to insulin, as the word was easier to say and other researchers had used it. He also added two biochemists, E. C. Noble and James Collip, to the team to work on purifying and standardizing the hormone. In November 1921, just six months after the project began, Banting and Best presented their discovery at a scientific meet-ing in Toronto. The next month, Bantmeet-ing read a paper about insulin to the American Physiological Society in Connecticut. News of insulin’s magic spread quickly, but it also created problems for the researchers.

Banting had added Macleod’s name to the team’s work in order to pres-ent the paper to the physiological society: Macleod was a member, and adding his name was the only way Banting was able to present the paper. That addition, as well as news reports on speeches Macleod gave about insulin, created the impression that Macleod made the discovery.

Despite this problem of publicity, and Banting’s fury when he and Macleod won a Nobel Prize in medicine and physiology in 1923 that ignored Charles Best, insulin joined the ranks of miracle drugs that would include sulfa drugs and penicillin. Doctors everywhere wanted a supply of insulin to treat their patients. The Connaught Laboratories in Canada, near the University of Toronto, and the Eli Lilly Company in the United

States began making the drug, setting up entire production lines devoted solely to producing insulin. Banting and Best did not get rich from their discovery, though. Refusing to patent the drug in their names, they turned over the rights to insulin to the University of Toronto, which used the funds from licensing production rights to pay for more research.

Drug makers went through huge amounts of pancreases to make insulin in those early years. For each ounce, a laboratory processed the glands of 6,000 cattle or 24,000 hogs (which later research revealed also could provide human-compatible insulin). Today, though some insulin still comes from cattle or hog pancreases, much more comes from genetically engineered bacteria. DNA is deoxyribonucleic acid, the material that contains the genetic information in the chromosomes of all living things. It holds the chemical blueprint that determines what each cell of an organism will become, how it will work, and what it will look like. In a technique called recombining, scientists remove a piece of DNA from one organism and place it in the DNA of another.

When the recombined DNA molecule reproduces, it passes along the genetic information in the DNA of both organisms.

In harnessing this technique of recombinant DNA to insulin pro-duction, drug makers splice a human insulin-making gene into a com-mon, one-celled bacterium called Escherichia coli. They grow the

Workers packaging insulin for Eli Lilly and Company in the 1920s (Courtesy Eli Lilly and Company)

These days, manufactured insulin comes from recombinant DNA technology.

(Courtesy Eli Lilly and Company)

This is the first drop of insulin manufactured by Eli Lilly and Company. (Courtesy Eli Lilly and Company)

engineered bacterium in huge vats, where they double their number every 20 minutes, multiplying by the millions and making insulin as the spliced gene directs. Producing insulin in this way is much faster and less expensive than getting it from animal pancreases. Better still, the insulin is always the same, never varying in quality and potency.

Banting and Best’s success seemed to usher in a period of remark-able growth in the discovery of human hormones. Some researchers pursued the sex hormones, isolating estrone and progesterone, two of the female sex hormones, in 1929 and 1934, respectively. The discov-ery of testosterone, the main male hormone, came in 1935. At the same time, researchers became a little too eager to find hormone drugs that would be equal to insulin in treating once-untreatable maladies. A derivative of female hormones called diethylstilbestrol, or DES, appeared in 1938 as an easily produced antimiscarriage drug. Doctors around the world eagerly began prescribing the drug. However, taking DES turned out to have an unforeseen consequence: the drug caused an increase in some types of cancer and other problems in women’s reproductive organs, as well as in their children’s.

On the other hand, a hormone-based contraceptive—norethin-drone, a progestin drug—successfully and more or less safely inter-rupted the monthly reproductive cycle. It and a later drug, a combination of progestin and estrogen that became known as the Pill, gave women a level of control over their reproductive system they had never had before. In turn, the Pill became a central feature of the women’s liberation movement of the 1960s and 1970s and led to a rad-ical shift in the social fabric of modern society.

In the 80 years after Banting and Best ground up dog and cattle pancreases for insulin, scientists have developed easier and more effi-cient means of producing needed hormones. For instance, the endocrine system in some children and young adults—roughly 10,000 in the United States alone—fails to produce enough hormones to pro-duce normal growth. Not too many years ago, the only way to get human growth hormone was to take it from the pituitary glands in the brains of dead human bodies—the fresher, the better. It was so expen-sive and difficult to harvest this chemical that every bit of it went right to children whose bodies did not make enough of their own. Even so, there was barely enough. These days, though, the hormone is plentiful because the gene for making it was spliced into a number of cells, including E. coli and mouse cells, which reproduced and made the hor-mone. A Swiss company, Aries-Serono, that was seeking a safer method of making the hormone, developed the mouse-cell method. E. coli is a bacterium, and the insulin it produced carried the risk of triggering the

body’s immune system to reject it. Because mice, like humans, are mammals, the Swiss company’s researchers reasoned that insulin from mouse cells would be less likely to cause that reaction.

Similar techniques have gone into producing estrogen and proges-terone supplements for women who have gone through menopause, the point at which the reproductive system naturally ceases to work.

This process is one of intense hormonal swings that cause hot flashes, irritability, and other reactions; it also leaves women vulnerable to health problems later in their lives. Once derived from animal sources, female hormones now come from synthetic production lines that—like those which produce insulin, growth hormones, and other types of these regulatory chemicals—ensure consistent quality and prevent such problems as allergic reaction.