Clinical research milestones: 100 years of improving lives

The last century gave rise to a long list of medical breakthroughs – all of which played an important role in advancing the field of clinical research and, aven more importantly, improving the quality of life. Whether it was a drug compound, a research technique or a specific device, research scientists have helped make dreams of medical miracles a reality.

To pay tribute to these milestones, Pharmaceutical Representative asked medical and pharmaceutical experts to list some of the most influential clinical research discoveries of the last 100 years. The top ten responses, listed chronologically, follow:

Establishment of Lister's Aseptic Technique. Before the 19th century, little thought was given to the possibility of microbial contamination during surgery and its link to postoperative infection. Joseph Lister was concerned, however. Basing his beliefs on the scientific papers of Louis Pasteur that discussed the presence of microorganisms suspended in air, he hypothesized that similar microorganisms were responsible for decay inside an infected wound or incision. With that in mind, he devised a surgical protocol called antisepsis. He sprayed the air surrounding the surgical area with a mist of diluted phenol, washed the surgical instruments and surgeons' hands with diluted phenol and soaked dressings with the chemical. The protocol dramatically reduced postoperative infection and death. Lister's initial protocol was modified to omit the phenol mist and to have surgeons wash their hands well with cleaning solutions that were milder than phenol, but to retain the practice of sterilizing wound dressings and surgical instruments or treating them with disinfectants before use. This modified system, applied in every healthcare setting today, is now called asepsis.

Switch from prescription to OTC. Some of the simplest drugs to surface in the last century are also some of the most effective. Century-old aspirin, for example, has provided an inexpensive pain management solution to millions of people worldwide. Nearly five decades of research later, scientists are now linking aspirin to the prevention of stroke and heart attacks. As little as one half of a regular-strength aspirin administered as soon as a heart attack is suspected (and continued for 30 days) has been found to cut the risk of death from a heart attack by 23%. A few other over-the-counter "miracles" include Benadryl, immodium compounds and anti-arthritic medications. "Many times, people forget about the importance of over-the-counter drugs and the effect they have on the quality of life. They are often overlooked – until they are needed," said Mickey Smith, professor of Pharmacy Administration at the University of Mississippi. "Aspirin has transcended the century and is still being recognized for all its benefits. Benadryl was considered the [medicinal] cure for the common cold and the anti-diarrheal drugs are worth their weight in gold. Their accessibility makes them that much more valuable."

Detection of blood types. In the early 1900s, Austrian physician Karl Landsteiner observed for the first time that humans have distinctly different types of blood (A, B, AB and O). These blood types, marked by the presence of antigens on the surface of red blood cells, prompted the advent of safe, effective blood transfusions and have played a critical role in the success of organ transplants.

Discovery of insulin. Thanks to two young Canadians, Frederick Banting and Charles Best, January 23, 1922 marked the end of the death sentence for people suffering from diabetes mellitus. "While insulin still is not a cure, the researchers' discovery of insulin has given the hope of life and health to millions of diabetics," noted Philip Gerbino, president of the Philadelphia College of Pharmacy and Science.

Advent of antibiotic therapy. Few can argue that the discovery and development of antibiotic drugs marked the most important therapeutic advancement of the 20th century. Penicillin, discovered in 1929 by Alexander Fleming, was first introduced into clinical use in 1940. Since then, antibiotics have dramatically changed the course of many illnesses, making them little more than an inconvenience. "Antibiotics, although something many of us take for granted, have been the ultimate triumph for the medical field," noted William R. Jarvis, chief of the Investigation and Prevention Branch of the Centers for Disease Control and Prevention in Atlanta. "Without antibiotics, our fight against life-threatening infectious diseases would be a lost cause. And even though we are now battling antibiotic-resistant organisms, not having the drugs at all would be even more detrimental."

Vaccine development. Although the smallpox vaccine surfaced in the late 1700s, the development of most other vaccines didn't happen until much later. In 1952, researcher Jonas Salk became the first to develop a successful vaccine for the poliovirus, a discovery that ultimately led to eradication of the deadly disease. Today, vaccines are available for a broad range of viruses, including influenza, and are greatly responsible for increasing life expectancy. According to the CDC, the average life expectancy increased from 47 years in 1900 to 67 years in 1959. Today, most people can expect to live well into their 70s. "Thanks in large part to high immunization rates, we have seen a breathtaking decline in suffering and death from most vaccine-preventable diseases," said Donna Shalala, secretary of the U.S. Department of Health and Human Services.

Advancement of molecular genetics. Although genetic cloning has been making more headlines in recent years, its history goes back much further. In 1953, James Watson and Francis Crick were the first to report a three-chain structure representing DNA. Three years later, American biochemist Arthur Kornberg and his associates artificially produced a chemically exact, but inert, DNA molecule – a discovery that won them the 1959 Nobel Prize in physiology. At Stanford in 1967, Kornberg headed a team that took his previous achievement a step further by synthesizing DNA in a biologically active state. Kornberg's discovery has been the cornerstone of today's genetic milestones. The U.S. Human Genome Project, a 13-year-long study that began in 1990, was created in hopes of identifying all 100,000 genes in human DNA and the sequences of the 3 billion chemical base pairs that make up human DNA. In 1997, scientists used modern molecular genetic principles to successfully clone a sheep.

Creation of oral contraceptives. When Gregory Pincus and his colleagues discovered the birth control pill in 1950, they swiftly changed the face of women's health. Although the pill, first issued in 1960, was intended to prevent unplanned pregnancies, research now shows it can help prevent certain health problems, some of which are life-threatening. Not only have oral contraceptives been found to reduce a woman's chance of developing ovarian and endometrial cancers, but they can also prevent ovarian and breast cysts and reduce the likelihood of developing pelvic inflammatory disease. Research is currently being conducted to determine the pill's role in reducing osteoporosis risks.

Use of transdermal patches. For the millions who regularly swallowed and injected their medication, the development of the transdermal patch in 1981 was a dream come true. The patch, which delivers medication through the skin and into the bloodstream, is available to treat or manage a number of health conditions, including chronic pain, heart disease, high blood pressure, menopause, motion sickness and nicotine addiction. More uses for the patch are in development, including birth control and treatment of diabetes and asthma. Transdermal delivery offers several advantages over traditional methods: It can deliver medication at a more consistent level over an extended period of time, minimizing the need to take pills more frequently. And because the transdermally introduced medication bypasses the gastrointestinal tract, GI-related side effects may also be avoided. "Once-a-day dosing and improved dosage form deliveries such as the patch have made life much simpler for individuals who, in the past, were forced to take their medication several times a day," explained Smith.

Production of protease inhibitors. Treatment of the Human Immunodeficiency Virus has come a long way since the AIDS epidemic first reared its ugly head nearly two decades ago. On March 19, 1987, the Food and Drug Administration approved AZT, the first drug developed for the treatment of AIDS. Two years later, AZT-combination therapies were introduced, making treatment of early HIV disease even more effective. Today, the combination of new protease inhibitors and other antiretroviral agents are making it possible for HIV-infected individuals to live longer, more productive lives. Researchers, astonished by the advancements in HIV therapy over the last two decades, remain confident that a cure may be found in the not-so-distant future. PR