Firsts at the Forefront
Dr. Oswald Robertson discovered a way to preserve blood and, during the first world war, established the first blood bank. Later, in Chicago (at Cook County Hospital), he established the first civilian blood bank.
In the 1930s, Dr. Dallas B. Phemister proved that most cases of surgical shock are caused by loss of blood. The widespread use of blood transfusion largely eliminated surgical shock as a cause of death.
In 1954, Eugene Goldwasser explained the basic principles behind the action of erythropoeitin, a hormone that stimulates the production of red blood cells. Goldwasser first isolated erythropoeitin in 1977. This hormone has since proved useful in treatment of several forms of anemia, and is undergoing trials for treatment of sickle cell anemia, AIDS, and other diseases. It may also prove to be a boon to the blood banking industry.
Until 1941, the cancer cell was thought to be a renegade, its growth unchecked by any of the body's normal control mechanisms. Then, Dr. Charles Huggins published the results of a series of experiments on the relationship of testosterone to prostate cancer. After completing a series of promising animal studies, Huggins treated 21 patients suffering from advanced prostate cancer by removing their testes, depriving these cancers of the hormone they needed to grow. The concept of hormonal treatment of cancer has since become a mainstay of care for several types of cancer, including breast and gynecological cancers. Huggins was awarded the Nobel Prize for physiology or medicine in 1966.
A similar hormonal approach, removal of the ovaries and the adrenal glands, produced substantial regression and some complete remissions in women with advanced breast cancer (reported by Huggins in 1951).
Huggins developed (1959-64) the standard experimental animal model of hormone-sensitive breast cancer. This animal model--which has been of tremendous value for the investigation of several types of tumors--was produced with a single injection of a polycyclic aromatic hydrocarbon, a chemical carcinogen that is still under intensive investigation at the University in the laboratory of Dr. Ronald Harvey.
A group of researchers in the Ben May Department for Cancer Research, led by Elwood Jensen and Dr. Eugene DeSombre, discovered in the late 1950s that hormones act through receptors on their target cells. They identified the estrogen-binding characteristic of breast cancers, developed monoclonal antibodies and immunoassays for estrogen receptors, and worked out the molecular basis of estrogen and anti-estrogen therapy in relation to these binding sites. They have also applied this approach to progesterone and testosterone binding sites.
Another group, led by Dr. Shutsung Liao, also of the Ben May Department for Cancer Research, has charted the pathway of testosterone production and worked out the molecular basis of male steroid activity and binding sites.
Steroid receptors may soon become the target sites for "magic bullet" cancer therapies. Several researchers at the University and elsewhere are attempting to attach radioactive markers or radioactive or chemical toxins to hormones that bind with these receptors and use them to deliver a lethal dose directly to hormone-dependent cancer cells.
In 1943, Dr. Leon Jacobson--the chief physician for the Metallurgical Laboratory, part of the Manhattan Project--was one of the first to test the effects of nitrogen mustard, the active agent in the mustard gas that was used as a weapon in World War I, as a treatment for terminally ill patients with lymphoma and leukemia. This is widely considered the beginning of chemotherapy. Many drugs still in use against cancer are derivatives of nitrogen mustard.
Chromosomes and Cancer
In 1972, Dr. Janet Rowley discovered the first consistent chromosome translocations associated with cancer, a finding that helped to demonstrate that cancer was a genetic disease. For her work, she was awarded the coveted Lasker Award and the National Medal of Science in 1998.
In 1962, Rowley began to study the chromosomes of patients with leukemia. For the next decade she labored over the microscope, looking for consistent chromosome abnormalities amid the seeming genetic chaos of leukemic cells.
The first such abnormality had just been reported by Peter Nowell and colleague David Hungerford, who found that patients with chronic myelogenous leukemia (CML) had an abnormally small chromosome 22 in their tumor cells, which they labelled the "Philadelphia" chromosome.
The next big step came in the early 1970s when geneticists perfected the art of chromosome "banding," a new way of visualizing segments of chromosomes with great precision. This improved resolution allowed Rowley to discover that chromosomes from leukemic cells not only lost genetic material, they sometimes exchanged it. Early in 1972, Rowley discovered the first such "translocation," an exchange of small pieces of DNA between chromosomes 8 and 21 in patients with acute myeloblastic leukemia.
Later that same year, she found that Nowell and Hungerford's "Philadelphia" chromosome was also the result of a translocation. In patients with CML, a crucial segment of chromosome 22 broke off and moved to chromosome 9, where it did not belong. At the same time, a tiny piece of chromosome 9, which included an important cancer-causing gene, had moved to the breakpoint on chromosome 22. Because of this transfer from one chromosome to another, important genes that regulated cell growth and division were no longer located in their normal position on the chromosome. This provided critical evidence that cancer was a genetic disorder.
Rowley and her colleagues subsequently identified several other chromosome translocations that were characteristic of specific malignancies, such as the 14;18 translocation seen in follicular lymphoma, and the 15;17 translocation that causes acute promyelocytic leukemia (APL). Quickly picking up on her lead that specific translocations defined specific forms of cancer, scientists around the world joined the search for chromosomes that either exchanged genetic material or in some cases lost it altogether in a process known as a "deletion." Others used the translocations as road maps to narrow the search for specific genes that were disrupted by chromosome damage, thus opening up the current era of cancer genetics.
Isolation of Beta Cells
In a series of investigations beginning in 1906, Robert R. Bensley demonstrated that the islets of Langerhans were specialized elements of the pancreas. He developed staining methods that distinguished between alpha cells and the beta cells that produce insulin. Bensley's work was fundamental to the discovery of insulin. Bensley later developed techniques to disassemble cells and isolate cellular components by spinning them in a centrifuge, a technique he used in 1934 to isolate mitochondria and analyze them.
Blood Glucose Measurement
In 1914, Dr. Franklin McLean was the first to measure the level of glucose in the blood.
Insulin Production--Proinsulin: The First Pro-Hormone
Dr. Donald Steiner discovered, in 1965, how the double-chain hormone insulin is made in the pancreas as proinsulin, a single chain that doubles back on itself. He discovered that the body cleaves off the segment connecting the two chains to produce insulin. Proinsulin was the first "pro-hormone" to be discovered, and it has served as a model of how other proteins are manufactured in the body. Steiner has also worked with a biotechnology firm to produce human insulin for diabetics. Steiner's work on insulin production has been called the most important finding in diabetes since the discovery of insulin.
Knowledge of how insulin is made permitted Dr. Arthur Rubenstein and Steiner to develop the first accurate method to measure insulin secretion in diabetics taking animal insulin (by measuring C peptide, the piece that is removed from proinsulin). It also was key to the commercial production of human insulin for diabetics.
Steiner, working with Rubenstein and Howard Tager at the University of Chicago, discovered the first case of diabetes caused by an abnormal insulin (which they labeled "insulin Chicago") and the first instance of an abnormal insulin receptor.
Dr. Graeme Bell, a researcher in the University of Chicago's Howard Hughes Medical Institute, was part of the team that first cloned the insulin gene. He has since cloned the gene for the insulin receptor. Bell also discovered and characterized a family of similar proteins that control transport of glucose out of the bloodstream and into cells.
Genetics of Diabetes
Dr. Graeme Bell has dominated genetic studies of type 2 diabetes. In a 1991 landmark paper, the Bell lab mapped MODY1, the gene responsible for an unusual form of early-onset diabetes, to a small region on chromosome 20. This was the first time genetic techniques had been used to determine the chromosomal location of a gene that could cause diabetes. Thus allowing researchers to successfully predict which children from the family would eventually develop diabetes.
In 1992, they found MODY2. Bell and colleagues discovered that mutations of the gene for the enzyme glucokinase caused early-onset type 2 diabetes in a different family.
In 1995, they mapped MODY3 to a specific region on chromosome 12. And, in 1996, Bell and colleagues mapped NIDDM1, the gene responsible for a significant proportion of diabetes in Mexican-Americans, to one end of chromosome 2.
In 1997, the Bell lab found that patients from MODY3 families had one of several different mutations in the gene for hepatocyte nuclear factor 1a (HNF-1a) but healthy subjects had normal copies of the gene. Finding MODY3 led to the rapid discovery of MODY1, a functionally related gene known as HNF-4a.
In 2000, in a finding that provided an enormous boost for scientists interested in either diabetes or genetics, a team led by Bell and Nancy Cox identified the major susceptibility gene for type 2 or non-insulin-dependent diabetes mellitus (NIDDM) in Mexican-Americans. The gene pinpointed a new and unexpected biochemical pathway leading to diabetes and suggests novel approaches to prevention, diagnosis, and treatment. This was the first time that a genome-wide approach has successfully led to the identification of a susceptibility gene responsible for a common, genetically complex disorder.
Ecology and Evolution
At the turn of the 20th century, botanist Henry Chandler Cowles introduced the concept of ecological succession with his famous studies of the changing plant communities on the dunes of the Lake Michigan shore. A decade later, zoologist Warder Clyde Allee pioneered the study of animal social interactions.
While doing field research in Papua New Guinea in the early 1990s, graduate student John Dumbacher discovered the first known poisonous bird, the hooded pitohui, a brilliant orange-and-black songbird that contains a potent neurotoxin in its skin and feathers to discourage predators.
Sewall Wright, in a career spanning 76 years, laid the groundwork of mammalian genetics. His study of guinea pigs established a model system for understanding the nature of gene action and interaction. In the theoretical realm, he mathematically reconciled Mendelian heredity with Darwinian evolutionary theory, a key step in the development of modern biology.
Michael Wade provided the first experimental support for one of Wright's most controversial theories. Wright's 1931 "shifting balance" theory postulated that a well-adapted species can evolve to a stronger state, even if it must pass through a less-fit intermediate stage along the way--if improvements arise in partially isolated subpopulations. Sixty years later, Wade simulated the process in a laboratory colony of flour beetles by demonstrating that increased overall production of offspring arose from a few prolific subgroups.
In the 1970s, population geneticist Brian Charlesworth developed a mathematical model of the evolutionary biology of aging, demonstrating the declining impact of the forces of natural selection with age. Charlesworth showed, in fruit flies, that longevity was tied to age of reproduction, that animals with a longer life span had reduced early reproductive output. This idea of a trade-off between adult survival and reproduction is one of the centerpieces of evolutionary ecology.
First Specialized Section
Dr. Walter L. Palmer of the University of Chicago established the first full-time academic gastroenterology section in the United States in 1927.
First Use of Gastroscope
In 1934, Dr. Rudolph Schindler, fleeing Nazi Germany, brought the first gastroscope to the United States for use at the University of Chicago. For gastroenterology, the gastroscope is considered the most important research tool since the discovery of the X-ray.
Dr. Walter Palmer demonstrated that the mechanism of pain in peptic ulcers is related to the presence of acid, not to contractions of the stomach.
Dr. Lester G. Dragstedt demonstrated that ulcers are caused by excess secretion of normal gastric juice and developed the vagotomy operation for the treatment of ulcers in 1943. This operation, still used today, severs the vagus nerve where it connects to the stomach, decreasing gastric secretion.
Inflammatory Bowel Disease (IBD)
A research team led by Dr. Joseph Kirsner has dominated the investigation of new treatments for inflammatory bowel disease--ulcerative colitis and Crohn's disease--since the 1930s. Working with Kirsner, Dr. George Block developed operations to avoid the need for an ileostomy when removing the colon.
In the 1940s, Paul R. Cannon developed the "rat depletion model," which he used to determine the minimum daily requirements for the essential amino acids--the building blocks of proteins--as well as for calories and potassium. Cannon also discovered the relationship between a shortage of dietary protein and decreased immune function.
Cardiologist and biochemist Dr. Angelo Scanu was the first researcher to separate the fat and protein components of a human serum lipoprotein, a fatty substance in the bloodstream, and to characterize the protein. In 1958, he and a colleague from the Cleveland Clinic described the biochemical makeup of HDL, the "good" cholesterol. His pioneering studies in the biochemistry of these important molecules have led to an understanding of how fats are transported through the bloodstream.
Dr. Scanu is also a leader in the investigation of lipoprotein (a), commonly referred to as Lp(a), an abnormal version of a lipoprotein that occurs in about 20 percent of the population. Lp(a) has been shown to contribute to both atherosclerosis and thrombosis, playing a major role in the development of early heart disease.
In 1906, Dr. Howard Taylor Ricketts, a University of Chicago pathologist, demonstrated that Rocky Mountain spotted fever is spread by cattle ticks and caused by a blood-borne "bipolar bacillus." Four years later, he showed that typhus is caused by a similar organism carried by lice; Ricketts was investigating the disease in Mexico City that year when he was stricken and died. The two organisms Ricketts discovered were the first of what were later shown to be an unusual genus of virus-like bacteria--the Rickettsiae.
Dr. Alexander A. Maximow provided a new understanding of tuberculosis in the 1920s when he reproduced the disease in lung tissue isolated from rabbits and traced the entire progress of the disease under the microscope.
During World War II, Drs. Lowell Coggeshall and Alf Alving began testing chloroquine, generally considered too toxic for use, as a remedy for malaria. They established a safe and effective dosage schedule and chloroquine became the standard treatment to suppress acute attacks of the disease. Alving went on to lead tests of primaquine in combination with chloroquine which again became the standard treatment.
James W. Moulder pioneered the biology of the large viruses which infect humans and animals. He was the first to discover drug resistance in large viruses.
Bernard Roizman is currently studying the genetics of herpes simplex viruses--including the factors that control viral growth, reproduction, latency, or virulence--and searching for ways to create a vaccine against the virus. Roizman has developed tools to manipulate individual genes within the viral genome to determine the function of each gene. He has made significant progess in understanding the genes involved in viral latency and virulence. A vaccine he designed is currently undergoing clinical trials in Europe.
The Birth of Nuclear Medicine
The Argonne Cancer Research Hospital, which opened in 1953 with support from the Atomic Energy Commission, was the first facility dedicated to the use of radioactive isotopes from high-energy sources for the diagnosis and treatment of disease.
Dr. Paul Harper, Robert Beck, and Donald Charleston originated technetium scanning, a widely used technique in diagnostic nuclear imaging.
Dr. Joseph Bolivar DeLee, called the father of modern obstetrical care, established his maternity facility, the Chicago Lying-in Hospital, at the University of Chicago in 1931. Under his direction, Chicago Lying-in opened one of the nation's first premature infant nurseries, produced the first medical motion pictures and pioneered the study of toxemia in pregnancy.
A series of deaths caused by one of the early "sulfa" drugs in 1937 was investigated by pharmacologist Dr. Eugene M.K. Geiling and pathologist Dr. Paul R. Cannon. They found that the toxicity was caused by the solvent, diethyleneglycol, and not the antibacterial agent. Their report on the investigation, their use of rabbits and dogs to assess the toxicity of new drugs, and their recommended safeguards for preclinical testing formed the basis of the Pure Food and Drug Act of 1938, which gave power to the Food and Drug Administration to regulate testing of drugs destined for human use.
Fluoridation of Water
Dr. J. Roy Blayney, founding director of the University's Zoller Dental Clinic, conducted a 15-year experiment (1946-61) in the Chicago suburbs of Oak Park and Evanston that demonstrated the cavity-fighting ability of fluoride in drinking water and led to the widespread flouridation of municipal water supplies.
Sleep research began at the University of Chicago when Professor Nathaniel Kleitman established the world's first sleep laboratory in the late 1920s. He was the first scientist to concentrate entirely on sleep. In 1939, he published the first major textbook on sleep, Sleep and Wakefulness, which rapidly became the gold standard of sleep researchers everywhere.
REM (Dream) Sleep
Dr. Nathaniel Kleitman and doctoral student Eugene Aserinsky revolutionized sleep research in 1953 when they announced the discovery of rapid eye movement (REM) sleep and its association with dreaming. This finding is usually considered the birth of modern scientific interest in sleep.
Dr. Nathaniel Kleitman and one of his students, Dr. William Dement, developed the techniques of all-night sleep recording, using measurements of eye motion and EEGs of brain activity. They used these measurements to chart the sequence of sleep patterns over the course of a night. This changed the established notion that sleep was a single state.
University of Chicago researchers Dr. Alan Rechtschaffen and Gerry Vogel, working with colleagues (including Dr. William Dement) at New York's Mt. Sinai Hospital, described narcolepsy--the first true sleep disorder--in a landmark paper in 1963. Patients with narcolepsy, a disorder of the neural mechanisms that regulate sleep and waking, often suffer from extreme sleepiness that can overwhelm them without warning.
A research group led by Dr. Alan Rechtschaffen performed a series of experiments in rats that demonstrated the lethal consequences of long-term (two weeks or more) sleep deprivation. A follow-up study demonstrated the lethal consequences of deprivation of only the REM sleep phase. The precise mechanism behind the damage caused by sleep deprivation remains unclear.
Organ transplantation began at the University of Chicago. Dr. Alexis Carrel, a pioneer in cardiac surgery, developed the technique for joining severed ends of blood vessels together making organ transplantation possible. He performed the first heart transplant, on a dog, at the University of Chicago in 1904. The dog survived for two hours. Carrel received a Nobel Prize for his transplant work in 1912, the first awarded in physiology or medicine for work done in America.
Bone Marrow Transplantation
The first bone marrow transplant was performed at the University of Chicago in the late 1940s. Dr. Leon Jacobson discovered that he could save a mouse, whose bone marrow and spleen had been destroyed with radiation, by transplanting donated spleen tissue into the mouse. Cells from the spleen would repopulate the marrow and restore the production of blood cells.
Dr. Christoph Broelsch performed the first liver transplant using a segment of a cadaver liver while at the University of Hannover in 1984. At the University of Chicago, he performed the first segmental transplant in the United States (1985), the first split-liver transplant (one donor, two recipients) in the United States (1988), and developed the technique for transplantation from a living donor. Broelsch's team performed the first living-donor liver transplant in the United States in November 1989 (which turned out to be the first successful living-donor liver transplant in the world). The University of Chicago was until recently the only center in the country using living liver donors.
In 1993, the University of Chicago performed the first liver transplant from an unrelated living donor, a close family friend of a 9-year-old boy with cystic fibrosis whose relatives were medically ineligible to donate.