Science: Medical Advances

 

A Century of Breakthroughs in Medicine

Medical Milestones Since WWII

Cancer Advances

Drug Discoveries

Fighting Plagues

Polio

Emerging Plagues

Some Historically Significant Epidemics

BIOTECH FRONTIERS

Medical Inventions/Discoveries

What’s Next

 

 

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A Century of Breakthroughs in Medicine

 

A child born in 1900 could only expect to live to the age of 47, and faced a host of killer plagues from smallpox to polio. Today, these diseases have slipped into the annals of medical history, and 47 is considered middle aged. The Surgeon General’s office estimates that a third of Americans born this year will live to be 100. While the century has seen increases in diseases such as cancer and heart disease, as well as the emergence of AIDS, doctors and researchers have met these health challenges with newer and more efficient prevention and treatment strategies, including technology, drug breakthroughs, and painstaking research into the mechanisms and causes of disease.

 

As the country has become more affluent, growing financial resources have been mustered to wage war against disease. In 1901, Congress appropriated $35,000 for the construction of a Hygenic Laboratory in which scientists were to investigate “infectious and contagious diseases and matters pertaining to the public health.” This laboratory grew to become the National Institutes of Health, with 24 separate institutions under its aegis and a total budget exceeding $13 billion in 1998. This budget is expected to increase further in coming years, to keep up with ever expanding areas of medical research.

 

Medical Milestones Since WWII

 

1944 Willem Kolff (Dutch-American) develops first kidney dialysis machine

 

1947 First use of “broadspectrum” antibiotic: Eugene Payne (American) uses chloromycetin to treat typhus patients

 

1948 Philip S. Hench (American) and Edward C. Kendall synthesize cortisone and use it to treat arthritis victims

 

1953 John H. Gibbon, Jr. (American) uses heart-lung machine for first time in successful open-heart operation

 

1954 Surgeons led by Joseph Murray (American) perform the first successful kidney transplant

 

1954 E. Cuyler Hammond and Daniel Horn (both Americans) present dramatic evidence of the dangers of smoking 1955 Jonas Salk (American) announces that human trials of the first vaccine against polio are successful. Drug approved for use in U.S.

 

1958 Wilson Greatbatch (American) invents the implantable artificial pacemaker

 

1961 Scientists at Bell Laboratories (Americans) announce the first continuously operating laser, a tool having many surgical uses. Prototype Laser was invented by Gould (American) in 1957 1963 Thomas Starzl (American) performs the first human liver transplant operation

 

1964 James Hardy (American) performs the first human lung transplant

 

1965 Medicare and Medicaid are established, guaranteeing medical insurance coverage for the aged and the poor

 

1966 Paul Parkman and Harry Myer (both Americans) develop the vaccine for rubella (German measles)

 

1966 Insulin synthesized independently by Michael Katsoyannis (American) and scientists in the People’s Republic of China — the first hormone to be synthesized

 

1967 Christiaan Barnard (South African) performs the world’s first heart transplant

 

1967 Rene Favaloro (Argentinean) performs the first successful coronary bypass operation

 

1969 Denton Cooley (American) implants the first temporary artificial heart in a human being

 

1972 Computerized axial tomography (CAT scan) is introduced in Great Britain

 

1978 First “test tube baby” (person conceived outside the human body) is born, in England (Source: The New York Times 1998 Almanac)

 

1979 Smallpox eradication - World Health Organization (UN) (Source: The World Almanac, 1998)

 

1981 Scientists identify acquired immune deficiency syndrome (AIDS), a previously unknown disease

 

1981 Surgeons at University of California at San Francisco perform the first successful operation on a fetus

 

1982 William DeVries (American) performs the first complete replacement of a human heart with an artificial heart on Dr. Barney B. Clark at the University of Utah

 

1984 First baby produced from frozen embryo is born, in Melbourne, Australia

 

1984 Luc Montagnier (French) discovers the virus believed to cause AIDS

 

1990 First gene therapy used in a human: R. Michael Blaese, W. French Anderson, and Kenneth W. Culver (Americans) develop a procedure to infuse genetically engineered blood cells for treatment of immune system disorder

 

1993 The EPA concludes that environmental tobacco smoke (“secondhand smoke”) is a lung carcinogen and causes respiratory problems for infants and young children 1997 British scientists identify a gene for human obesity

 

(Source: The New York Times 1998 Almanac)

 

Cancer Advances

 

“I propose to speak of a monster that is more insatiable than the guillotine; more destructive to life and health than the mightiest army that ever marched to battle; more terrifying than any scourge that has ever threatened the existence of the human race,” proclaimed West Virginia Senator Matthew Neely in a 1928 speech. “The name of this loathsome, deadly, and insatiate monster is cancer.” Despite Neely’s apocalyptic tone, Congress scuttled a bill appropriating $50,000 to study this disease, and it would not enact legislation establishing the National Cancer Institute for another nine years.

 

Today, the National Cancer Institute has a budget of over $3 billion, and many more private dollars go toward researching this modern scourge. The investment seems to have paid off, both in new knowledge about the disease, and in measures to prevent and treat it. A child diagnosed with Leukemia today has a good chance of living to adulthood, and some cancers are treatable, even curable. In the last two years, the cancer rate has decreased significantly. And new cancer-fighting drugs are on the horizon. But a “cure” for the 200 or so cancer diseases is far off, experts say. Future efforts may focus on prevention, as well as treatments that transform the disease from a killer to a mere annoyance.

 

Key discoveries in the past 25 years leading to our current understanding of the link between gene alterations and cancer.

 

1969 Normal cells are found to have genes that suppress the growth of tumors. When a rat tumor cell line was fused with normal cells, the tumor cells were no longer Able to cause tumors in laboratory rats — showing that normal cells have genes that suppress the tumor cell genes.

 

1970 The first oncogene, now known as the src oncogene, is identified in a chicken tumor virus. The chicken virus, an RNA tumor virus discovered in 1911, was known to cause chicken tumors, but it was not known at the time that a specific gene in the virus caused the tumors.

 

1973 Cancer is linked to DNA exchanges between chromosomes. The chromosomes of patients with chronic myelogenous leukemia (CML) were found to have pieces of chromosome 9 and chromosome 22 exchanged.

 

1976 Oncogenes are discovered in normal DNA. The src oncogene (see 1970) was found in normal chicken DNA, showing that oncogenes do not have to come from outside the cell via a virus. This experiment suggested that a normal gene already present in the cell has the potential of becoming an oncogene.

 

1978 The src protein is found to be a member of the protein kinase family of enzymes. This was the first clue to the function of an oncogene. Although the exact function of the src protein was not known, this family of enzymes was known to be involved in cellular communications.

 

1979 The first human RNA tumor virus, HTLV-1, is discovered. The virus is associated with adult T-cell leukemia.

 

1981 Hepatitis B virus is associated with liver cancer.

 

1981 The first biologically active human tumor oncogene is identified from a human bladder carcinoma cell line.

 

1982 The 1981 human tumor oncogene is identified as Ha-Ras, similar to an oncogene previously found in rat RNA tumor virus. 1982 DNA analysis shows that the difference between the ras oncogene and ras proto-oncogene (the normal gene before it is altered to become an oncogene) lies in a change in a single base (a subunit of DNA).

 

1982 The myc oncogene is found to be activated in Burkitt’s lymphoma, a form of leukemia. This showed the association between cancer and an overproduced oncogene product. In the lymphoma, the oncogene becomes activated when it is transferred from chromosome 8 to chromosome 14.

 

1982 The Abl oncogene is found to be activated in leukemia patients. This showed the association between cancer and an overly active oncogene product. In CML, when the oncogene is transferred from chromosome 9 to chromosome 22, the mutated Abl protein was found to be a fusion product — part of Abl is fused with another protein, making it much more active in the cell (see 1973).

 

1982 Several copies of the myc oncogene are found in human leukemia cells. This is the first evidence that an oncogene can become activated by having an excessive number of gene copies in a cell.

 

1983 The sis oncogene product is found to be a mutant form of a known protein, the platelet-derived growth factor (PDGF). This discovery provided the first link between an oncogene and a protein with a known function in the cell.

 

1984 The erbB oncogene product is discovered to be a truncated version of a protein (the epidermal growth factor receptor) that sits on the surface of certain cells. This discovery showed how a mutation in an oncogene can disrupt the normal function of the protein product. (The mutated ErbB protein was found to lack the part of the receptor that normally binds to molecules outside the cell.)

 

1985 Researchers discover that proto-oncogenes can function as transcription factors (proteins in the cell nucleus that regulate gene activity). The erbA oncogene product was shown to be similar to thyroid hormone receptors that were known transcription factors.

 

1986: The first tumor suppressor gene, Rb-1, the retinoblastoma gene, is isolated. Genetic studies show that the development of retinoblastoma is due to inactivation of both copies of Rb-1.

 

1988 An oncogene is associated with apoptosis, or programmed cell death. The Bcl-2 oncogene product, isolated from B-cell lymphoma, is shown to block apoptosis in B cells.

 

1989 The p53 gene, originally discovered in 1979 and thought to be an oncogene, is recognized as a tumor suppressor gene. Both copies of p53 are inactivated in about 50 percent of cancers.

 

1990 A rare familial cancer, the Li-Fraumeni Syndrome, is linked to mutations in both copies of the p53 gene.

 

1991 The adenomatous polyposis coli (APC) tumor suppressor gene, associated with hereditary colorectal cancer, is isolated.

 

1993 Several tumor suppressor genes associated with familial cancers are isolated: NF2, associated with acoustic nerve and brain tumors; VHL, associated with benign and malignant tumors in the kidney, retina, central nervous system, pancreas and adrenal gland; and p16/MTS-1, a cell-cycle inhibitor associated with malignant melanoma and pancreatic cancer.

 

1993 & 1994 Additional tumor suppressor genes associated with familial cancers are isolated: MHS-2 and MLH-1, associated with hereditary nonpolyposis colon cancer (HNPCC), are known to function normally in DNA repair; their mutated forms disrupt DNA repair.

 

1994 & 1995 Additional genes associated with familial cancer syndromes are isolated, including two tumor suppressor genes: BRCA1, associated with breast and ovarian cancer, and BRCA2, associated with breast cancer. One oncogene, CDK4, associated with melanoma, was also isolated; this proto-oncogene is a regulator of the cell cycle.

 

Drug Discoveries

 

It’s hard to believe that the poison arsenic was ever used as a medication, but early in this century it was considered an effective treatment for syphilis. Then again, 19th century doctors would probably laugh at the idea that a common mold would prove to provide a miracle cure for many infections, as penicillin was found to do. Also in this century, anesthetics evolved out of the dark ages of whiskey and teeth-gritting into safer and more effective alternatives. Medications to ease common pain have become refined, while the new benefits of deceptively simple medications such as aspirin continue to be discovered. Then there’s the revolution in “lifestyle” drugs, from the debacle of diet pills to the promise of new medications that treat baldness (Propecia) and male impotence (Viagra).

 

The Food and Drug Administration, founded in 1930, has come to symbolize the power government has over the medicine cabinets of America. It was not until 1938 that drug manufacturers had to demonstrate that their drugs were safe before marketing them to the public. Early criticism of this approval system focused on its bureaucratic slowness. In recent years, the FDA has adopted new procedures to speed the approval of drugs for patients with serious illnesses such as AIDS, cancer and Alzheimer’s disease. However, in the last year, several FDA-approved drugs were found to be unsafe, and questions have arisen as to whether the FDA’s approval process might be too speedy. This issue will likely continue to be debated as the ever-growing pharmaceutical industry offers more and more drugs for FDA approval.

 

Some major pharmaceutical breakthroughs of the 20th century

 

1898 Discovery of radium announced; potentialities for treating cancer realized.

 

1910 Paul Erlich & Sahachiro Hata find that arsphenamine, a synthetic preparation containing arsenic, is lethal to the microorganism responsible for syphilis.

 

1913 Behring introduces toxin-antitoxin mixture used to immunize children against diptheria.

 

1921 Insulin discovered by Frederick Banting, Charles H. Best and J.J.R. Macleod. Found to be effective in treating diabetes.

 

1928 Alexander Fleming discovers penicillin by noticing inhibitory action of stray penicillium mold on plate culture of staphylococcus bacteria in his laboratory at St. Mary’s Hospital in London. Late

 

1930s Yellow fever vaccine developed by microbiologist Max Theiler.

 

1930s Preparation of tetanus toxins found to be efficient toxoid (vaccine) against tetanus when injected in humans.

 

1936 English physician Leonard Colebrook and colleagues show that red dye Prontosil, containing antibacterial sulfanilamide, is effective against streptococcal septicemia (bloodstream infection), ushering in the sulfonamide era.

 

1938 Howard Florey, Ernst Chain and colleagues at Oxford University isolate penicillin in relatively pure form and demonstrate its potency and relative lack of toxicity.

 

1940s A group of drugs known as the sulfones appeared for treatment of leprosy.

 

1944 Selman A. Waksman and colleagues announce finding that streptomycin, produced from cultures of a soil organism, Streptomyces griseus, is active against tuberculosis. Although tuburcule bacillus tends to become resistant to it, the disease is brought well under control with supplementary drugs such as para-aminosalicylic acid (PAS) and isoniazid.

 

1945 First relatively effective vaccine produced for influenza.

 

1949 Philip S. Hench and colleagues announce that cortisone, a substance isolated from the cortex of the adrenal gland, has dramatic effect upon rheumatoid arthritis.

 

1954 Jonas E. Salk introduces vaccine for poliomyelitis (polio).

 

1960s Effective measles and rubella (German measles) vaccines come into use. (Source: Encyclopedia Britannica) March 9, 1961 First female oral contraceptive, Enovoid-10, gets FDA approval. (Source: Food and Drug Administration)

 

1987 Prozac (fluoxetine), new antidepressant that inhibits re-uptake of the brain chemical serotonin, approved by FDA, ushering in new era of treatment for depression and related mental illness.

 

1987 AZT (Zidovudine), first major anti-AIDS drug, approved for use in United States.

 

1996 Sequinavir, first in a class of anti-AIDS drugs called protease inhibitors, offers hope that AIDS will no longer be a terminal illness.

 

March 27, 1998 Viagra, first male oral impotence treatment approved by FDA, spurs unprecedented sales of over $1 billion in first month it is available.

 

Fighting Plagues

 

Imagine a presidential candidate revealing that he or she has battled a crippling, stigmatizing viral plague. Such a person might not be elected today, but Franklin Delano Roosevelt, who was partially paralyzed by the polio virus in childhood, was re-elected to a fourth term. Perhaps this difference illustrates how far we have come in this century toward eliminating infectious diseases.

 

In 1900, people not only had to worry about epidemics of polio, but also viral and bacterial plagues of influenza, smallpox, tuberculosis, typhus, yellow fever, diphtheria, measles, and, in the South, dengue fever. With the development of vaccines and antitoxins, as well as improvements in sanitation, these threats have all but disappeared in the second half of the century — at least in the developed world.

 

However, with the increasing globalization of commerce and travel, as well as a growing homeless population that receives little health care, those threats may be on their way back. Tuberculosis, for example, has re-emerged, though with early detection the bacteria can be wiped out before it causes any damage.

 

One deadly plague remains a threat at the end of the century. The Acquired Immune Deficiency Syndrome (AIDS), which first appeared as a public health threat in 1981, had already killed more than 360,000 Americans as of December 1996. Although promising new treatments known as protease inhibitors have reduced the death rate in the last two years, there is still no cure.

 

Polio

 

POLIO HISTORY

 

1000 B.C. First description of paralytic polio engraved on an Egyptian monument.

 

1916 First major polio epidemic in the United States in New York City area.

 

1921 Franklin Delano Roosevelt struck by paralytic polio.

 

1938 President Roosevelt establishes the National Foundation for Infantile Paralysis, which later became known as the March of Dimes from a term coined by comedian Eddie Cantor. July 6, 1938 First March of Dimes research grant awarded to Yale University’s Poliomyelitis Unit. March 12,

 

1939 First March of Dimes chapter established in Coshocton, Ohio.

 

1941 First iron lung provided to assist polio victims with paralyzed respiratory muscles.

 

1949 March of Dimes begins project to determine number of different polio virus types against which a vaccine should provide protection. Dr. Jonas Salk heads participating laboratory.

 

1950 March of Dimes establishes regional respiratory centers to care for polio patients — one of which is in a wing of Jefferson Davis Hospital. September

 

1951 Using March of Dimes grants, scientists identify the three major polio viruses. March 1953 Salk publishes the first report confirming the feasibility of a killed-virus vaccine.

 

1954 Drs. John Enders, Thomas Weller and Frederick Robbins receive the Nobel Prize for developing a tissue culture method for growing polio virus.

 

March of Dimes begins field trials of Salk vaccine with 1,830,000 schoolchildren participating. April 12, 1955 Results of field trials prove the Salk vaccine is “safe, potent and effective.”

 

1962 Oral polio vaccine, developed by Dr. Albert Sabin with support from the March of Dimes, is licensed.

 

1979 Last cases of wild-type polio identified in the United States. Late

 

1970s-1980s First cases of post-polio syndrome recognized in people who had polio 30 to 40 years previously. Doctors theorize that muscles and nerves that had taken the place of those destroyed by the diseases were wearing out from overuse.

 

1985 Rotary International and the Pan American Health Organization vow to eradicate polio from the world. The disease remains a problem in the Third World.

 

1988 World Health Organization makes polio eradication one of its major goals.

 

1991 Last case of polio in the Western Hemisphere is identified in Peruvian toddler Fermin Tenorio Cortez.

 

1994 Western Hemisphere declared free of polio.

 

January 1997 The Advisory Committee on Immunization Practice releases new guidelines for polio immunization in the United States, giving parents a choice of giving their children oral polio vaccine, injected polio vaccine or a combination of the two. The move was taken to reduce the risk of vaccine-associated paralytic polio. Eight to 10 people in the United States get vaccine-associated paralytic polio each year.

 

2005 Rotarians and WHO hope to declare the world polio-free. [source: The Houston Chronicle, 1998]

 

Emerging Plagues

 

Ebola Named after a river in northern Zaire, Ebola kills up to eight out of 10 people who contract it, according to the World Health Organization. Epidemics were reported in Zaire in 1976 and Sudan in 1979, killing hundreds.

 

Other strains have been reported. Marburg broke out in Germany and Serbia in 1967, carried, doctors suspected, by infected monkeys from the Philippines. The Reston strain emerged in a U.S. laboratory in 1989. Pneumonic Plague Swept parts of India in September 1994, with the Indian government reporting more than 6,000 cases and 50 deaths. The WHO was able to confirm only 272 cases and some doctors have disputed whether the disease was actually plague. Whatever it was, the epidemic caused a worldwide health scare, with some governments warning citizens not to visit India and some imposing restrictions on flights from New Delhi. Necrotising Fasciitis Known in the popular media as the “flesh-eating bug,” this streptococcus A bacterium infection destroys human flesh, killing some of its victims within hours. Media reports about how the infection literally melts muscle and fat touched off a global scare. The WHO said U.S. officials estimated up to 450 Americans may have died from it each year from 1989 to 1991. Hantavirus One form of this rodent virus swept through the southwestern United States in

 

1992, killing 44 of the 80 people diagnosed as infected. It has also occurred on Long Island. It infects humans who touch or inhale rodent feces or urine. Symptoms include muscle cramping, high fever, nausea and coughing. Cholera An age-old disease, an outbreak of a new variant known as cholerae 0139 started spreading through India, Pakistan and southwest China in 1992. In one hospital in Calcutta, 434 people died of the disease in a 15-week period. Cholera mutates quickly into drug-resistant forms, making vaccines marginally useful at best. It kills by dehydrating its victims, who suffer diarrhea and vomiting. AIDS (Acquired Immune Deficiency Syndrome) was first reported in 1981 among gay men in the United States. The Human Immunodeficiency Virus (HIV) that causes AIDS was identified by 1983. By the year 2000 WHO conservatively projects that there will be up to 40 million HIV infections. There is as yet no cure for the illness, which always kills once full AIDS develops. It is not particularly virulent, being passed through bodily fluids such as blood and semen. Morbilli Virus A distant relation of the measles virus, morbilli killed 14 horses and their trainer in Australia in 1994. A stablehand fought for his life for nearly two months before recovering. Australian health authorities imposed a “category III” alert, the highest there is to deal with an outbreak of an exotic infectious disease, quarantining the stables while they investigated. Tuberculosis Another age-old killer, it is on the rise again after developing resistance to 20th-century antibiotics. Health officials report it is increasingly common among the homeless and the unemployed in big cities as well as in developing nations. Influenza Flu kills thousands each year. Very contagious, it kills the weak and elderly, merely inconveniencing more healthy people. An outbreak killed an estimated 20 million people in the winter of 1918-19. [source: Reuters]

 

Some Historically Significant Epidemics

 

480 B.C. The Plague of Xerxes, probably an outbreak of dysentery, hit the Persian army, facilitating its defeat by the Greeks. The Greek historian Herodotus probably exaggerated its impact, but it is nonetheless significant as one of the first epidemics recorded in a lengthy written account.

 

451 B.C. A severe outbreak of an unidentified disease struck Rome, and was recorded by the historians Livy and Dionysius of Halicarnasus.

 

430 B.C. The Great Plague of Athens was described by Thucydides, who survived an attack himself. The symptoms described have been variously interpreted as smallpox, typhus, bubonic plague, or most recently, Ebola virus. The outbreak seriously impaired the Athenian army, and prolonged the Peloponnesian War.

 

410 B.C. The first recorded epidemic of mumps was described by Hippocrates, who was probably present on the Island of Thasos where the epidemic struck.

 

400 B.C. Hippocrates also recorded an outbreak of a cough followed by pneumonia and other symptoms, at Perinthus in northern Greece (now part of Turkey). Several possible identifications have been suggested, including influenza, whooping cough and diphtheria.

 

212 B.C. The Roman army was struck by an infectious disease, perhaps influenza, described by the historian Livy.

 

1st century A.D. The earliest unequivocal epidemic of bubonic plague in the Mediterranean occurred in Libya, Egypt and Syria.

 

165-80 The Antonine Plague, or Plague of Galen, was probably smallpox or measles, or both, and was brought back to the Roman Empire by troops returning from the Middle East. The Roman emperors Lucius Verus and Marcus Aurelius Antoninus both died from it, in 169 and 180 respectively.

 

251-270 The Plague of Cyprian takes its name from Saint Cyprian, bishop of Carthage, who described symptoms that suggest measles or smallpox rather than bubonic plague. This epidemic killed the Roman emperor Claudius in 270, and is credited with encouraging mass conversions to Christianity. It has also been suggested as the time that Christians first began wearing black as the color of mourning.

 

542 The Plague of Justinian was the first pandemic of bubonic plague, beginning in Egypt and Ethiopia and sweeping through the Mediterranean. About 300,000 people died in Constantinople alone during the first year. The Byzantine emperor Justinian was stricken, but recovered; however the disease crushed his ambitions to recover the full extent of the old Roman empire under his rule. Merchant ships carried the disease into the rest of the Mediterranean, and it flared up repeatedly in Europe for the next 50 years.

 

569 A smallpox epidemic struck Arabia and forced the Ethiopian army to retreat, thus ending their rule there. This was known as the Elephant War epidemic, for the white elephant on which the Christian prince Abraha rode into Mecca before his defeat, and is described in the Koran. It was one of the earliest recorded epidemics of smallpox.

 

590 A.D. Bubonic plague killed Pope Pelagius II, who was succeeded by the reformer Gregory the Great.

 

680 A.D. Plague again struck Rome and Italy, and is credited with the origin of the cult of St. Sebastian, a third century martyr who was regarded as a protector against disease, because the epidemic abated after his bones were moved from Rome to the church of San Pietro in Vincoli in Pavia.

 

700s-800s Japan suffered repeated epidemics of smallpox. The one in 735-736 killed several members of the ruling Fujiwara family, and led to a religious fervor that facilitated the spread of Buddhism.

 

746-748 A.D. Constantinople was struck again by plague.

 

10th century Japan was struck again by smallpox epidemics, and also by measles.

 

1081 The army of the Holy Roman Emperor Henry IV was defeated by disease in his attempt to conquer Rome, probably typhoid fever and dysentery, and perhaps also malaria.

 

1098 The First Crusade was delayed and made more difficult by disease, in particular by an epidemic probably of typhoid fever that struck in Syria in 1098 after the siege of Antioch.

 

1148. An epidemic at Adalia on the coast of Anatolia wiped out soldiers and pilgrims of the Second Crusade and facilitated their defeat by the Turks.

 

1167 The army of Frederick Barbarossa was nearly destroyed after his conquest of Rome in 1167 by an epidemic disease. Whether this was typhus, malaria, or something else has not been decided.

 

14th century The Black Death, an outbreak of bubonic plague, was the most devastating single epidemic of all time, killing probably a third or more of the population of Europe and Asia. It originated in central Asia and had already killed an estimated 25 million people before it reached Constantinople in 1347. From there it was spread around the Mediterranean by merchant ships and by crusaders returning from the Middle East. By 1350 it had spread throughout Europe, and at least another 25 million people had died. The social upheaval that ensued is generally regarded as the end of the Middle Ages. Outbreaks of bubonic plague continued sporadically in various European locations throughout the 15th and 16th centuries.

 

1494-95 Syphilis first appeared in Europe, beginning among Spanish soldiers in Naples. Historians differ on whether it was brought back by explorers returning from America. Smallpox, which had existed previously in Europe, also got its modern name at this time, to distinguish it from syphilis which was also known as “the pox”.

 

1499 Plague struck London, causing thousands of deaths, the first of a number of outbreaks in that city.

 

1507-1551 England was struck several times during this period by a mysterious disease characterized by profuse sweating. After the last outbreak in 1551, it disappeared permanently, and has never been identified unequivocally with a modern disease.

 

1512 Syphilis struck Japan for the first time, and was attributed to Chinese traders coming to Nagasaki.

 

1507 and 1518 Two epidemics of smallpox killed from a third to more than half of the native populations of Cuba, Haiti, and Puerto Rico.

 

1520 Smallpox followed by starvation killed millions of the native inhabitants of Mexico. Introduced at Veracruz with the arrival of Panfilo de Narvaez on April 23,

 

1520, it rapidly spread inland, and was credited with the victory of Cortes over the Aztec empire at Tenochtitlan (present-day Mexico City) in 1521. From Mexico it spread south into Central and South America, exterminating huge numbers of natives in those areas as well.

 

1525-27 Smallpox in Peru killed the Inca ruler, Huayna Capac, and some 200,000 others, and destroyed the Inca Empire.

 

1528 Typhus attacked French troops besieging Naples, killing well over half the army. The remaining soldiers retreated and were then destroyed by forces of the Holy Roman Empire. The troops of Charles V later suffered their own defeat to typhus at the French city of Metz in 1552, however.

 

1555 Smallpox struck Brazil for the first time, killing vast numbers of natives.

 

1560s Bubonic plague struck London again in 1563, probably in its worst outbreak ever, which killed an estimated quarter to a third of the population. Subsequent outbreaks occurred in 1578, 1593, 1603, 1625, 1636, and 1665, each time killing thousands. In terms of proportion of the total population destroyed, the

 

1563 and 1665 epidemics were the worst.

 

1576 Mexico’s first epidemic of typhus killed many natives. This was another of the lethal diseases introduced by Europeans.

 

1576 Paris and several other European cities suffered from diphtheria. This epidemic marks the first accurate description of this disease, by the physician Guillaume de Baillou. Two years later he described whooping cough in its first confirmed outbreak, although the disease probably had existed prior to this time.

 

1591 Smallpox struck the Philippines for the first time, arriving on a Spanish ship from Mexico and spreading through the country with high mortality rates.

 

1590-1610 Plague swept many European cities again.

 

1592-96 One of the earliest outbreaks of measles among Native Americans in North America struck the Seneca Indians in central New York state, and caused hundreds or maybe thousands of deaths.

 

1617-1619 A smallpox outbreak killed 90 percent of the Massachusetts Bay Indians, probably introduced from fishing boats that visited the coast before there was a permanent English settlement there. The few remaining natives were weakened, and were unable to resist the landing of the Mayflower settlers at Plymouth in 1620.

 

1618 Italy was swept by outbreaks of diphtheria.

 

1618-48 The period of the Thirty Years War in Germany was marked by repeated epidemics, including typhus, plague and dysentery that spread to other European countries.

 

1625-40 Bubonic plague spread through France. Probably the worst single outbreak was in Lyon in 1628.

 

1633 Smallpox again struck the Indians in Massachusetts, probably brought on arriving ships of settlers. At least 15 children died on incoming ships, as well as about 20 colonists already resident.

 

1634 A catastrophic smallpox epidemic was introduced to Connecticut by Dutch traders, and killed 95 percent of the Indians along the Connecticut River, then spread north into Canada. The English settlers were mostly immune, having had the disease as children themselves, but attributed their escape, and the Indians’ death, to God’s will. The elimination of the natives in the Connecticut valley opened up that area to settlement.

 

1647 Yellow fever killed more than 5,000 people in Barbados, and spread from there to Mexico, Cuba, and elsewhere. A second outbreak in 1691 killed many of the British settlers in Barbados, who had arrived since the earlier outbreak, whereas older natives were by this time immune.

 

1648-49 Another smallpox outbreak spread to many towns in the Massachusetts colony. By this time there had been many children born in the colony who were susceptible. A simultaneous epidemic of whooping cough added to the severity of the epidemic, and to the overall death toll.

 

1662 Smallpox killed more than a thousand Iroquois in central New York state.

 

1665 The Great Plague of London killed at least 20 percent of the city’s population, perhaps as many as 100,000 people.

 

1666 A smallpox outbreak struck Boston, but was relatively mild, and only about 40 people died.

 

1668 Probably the earliest recorded epidemic of yellow fever in non-tropical America struck New York in late summer and early fall of 1668, and was described as an “autumnal bilious fever in infectious form”. The contemporary accounts leave some possibility open that it could have been some other disease, but yellow fever seems the most likely suspect.

 

1677-78 Another smallpox epidemic in Boston was much worse than the 1666 epidemic, and killed several of the town leaders.

 

1679 Plague spread from the Ottoman Empire into Austria, killing thousands of people especially in Vienna.

 

1699 Charleston S.C. had a yellow fever epidemic, the first there to be positively identified as such; about 160-190 probably died.

 

1702 Yellow fever struck New York, killing more than 500 people over a three-month period, which was probably about 10 percent of the population at the time.

 

1702-1703 Smallpox hit Boston again. This time about 300 died, but a simultaneous outbreak of scarlet fever makes it hard to assess who died from what.

 

1706 Charleston S.C. was struck with yellow fever again. About 5 percent of the population died.

 

1720 Another outbreak of plague occurred in France, centering on Marseilles and probably killing a third to half the population there.

 

1721-22 Smallpox struck Boston again, with about 6,000 people affected in a total population of 11,000, of whom 844 died. This epidemic prompted the first use of inoculation against smallpox in the New World.

 

1728,1732 Charleston S.C. was hit by yellow fever twice in a four year period. The cause (mosquitoes) was not understood, and treatment wasn’t very effective.

 

1735-40 Epidemics of diphtheria and scarlet fever spread through various parts of New England. Both diseases were referred to as “throat distemper” and weren’t distinguished. Hundreds of people died, most of them children.

 

1743-1745 Yellow fever struck New York again. A correlation with the dockyard areas was noticed, but mosquitoes were still not recognized as the vector.

 

1763-64 Smallpox hit Boston once again, with about 170 deaths. This epidemic was less serious than previous ones, probably because of inoculation.

 

1789 A widespread epidemic of influenza hit New England, New York and Nova Scotia in fall 1789. Most deaths appear to have been from secondary pneumonia.

 

1792-99 Yellow fever ravaged cities all along the East Coast, including Charleston, Philadelphia, New Haven, New York, and Baltimore. The outbreak in Philadelphia in the summer of 1793 was the most severe, and most memorable. The disease was probably introduced from ships carrying French refugees who were fleeing turmoil in Santo Domingo, and then spread by mosquitoes that bred in stagnant water, which had been waterways and canals in years with more rain. Ten percent of the population in that city died, about 5,000 people altogether. The new city of Washington D.C. was under construction at the time, and Philadelphia was the interim capital. Most of the government officials fled the city, including George Washington and the members of his cabinet. Various treatments were tried, none of them very effective, and controversy raged over the best way to prevent and treat the disease. Cold weather finally brought an end to the outbreak, in late October.

 

1802 Smallpox killed about two thirds of the Omaha Indians in what is now northeast Nebraska.

 

1805-07 Typhus outbreaks occurred during the occupation of Vienna by the French army in 1805, and spread throughout central Europe with Napoleon’s army, affecting both soldiers and civilians.

 

1812-1813 Napoleon’s army was attacked again by typhus and dysentery during his invasion of Russia, both on the march eastward and again on the return, where disease was exacerbated by severe cold and starvation. It is estimated that only about 30,000 survived of the nearly 600,000 troops that began the campaign.

 

1817-1823 The first great cholera pandemic of the

 

19th century swept Asia, probably originating near Calcutta and spreading from there throughout southeast Asia, Japan and China. Although it spread as far as southern Russia and the Middle East, an exceptionally cold winter in

 

1823-24 kept it from reaching western Europe.

 

1826-28 Dengue fever spread from Savannah, Georgia, to other cities along the southeastern coast, and through the Caribbean.

 

1829-33 In the Pacific northwest, malaria killed an estimated 150,000 native Americans. Other diseases may have contributed to the death toll, but contemporary writing describes symptoms that closely correspond to those of malaria. The disease was probably introduced in February 1829 by a ship reaching Oregon after coming from Chile, carrying infected mosquitoes in water tanks onboard ship. The Columbia River was flooded at the time, creating stagnant water in which the mosquitoes could breed.

 

1830-31 An influenza epidemic began in Asia, probably China, late in 1829, and spread from there to the Philippines in September 1830, to Indonesia in January 1831, through the Malay peninsula and into Asia in 1832. The disease also broke out in Moscow and St. Petersburg in the winter of 1830-31 and spread westward overland through the summer of 1831. By November it had reached the U.S., and continued to spread there in 1832. Another outbreak of influenza spread through Asia and Europe during 1836-37 but except for a single Canadian focus, did not reach North America.

 

1826-37 The second cholera pandemic of the 19th century, and the most devastating one, began in Bengal and spread through India in 1826. It reached Afghanistan in 1827, and spread further into central Asia and the Middle East. By late 1830 it had reached Moscow, and from there spread westward into Europe in 1831. It reached England on a ship from Hamburg in October 1831 and spread throughout the British Isles. It reached New York in 1832, and spread from there throughout most of the U.S.

 

1837 Smallpox started with a Sioux tribe in Missouri in June 1837, then spread to Blackfoot and other tribes in Montana and Saskatchewan. The last previous outbreak among the Blackfoot had been in 1781, so by 1837 most of the population was susceptible.

 

1847 Hundreds of Cayuse Indians in the Pacific northwest were killed by measles. This tribe had never been exposed to measles previously, and missionaries were blamed for introducing it. One missionary near present-day Walla Walla, Washington tried to provide them with food and medicine, but the Indians thought he was making it worse, and killed him, his wife and twelve others at the mission, and took a number of others hostage. Several years of conflict followed.

 

1849 The third major worldwide pandemic of cholera, again starting in Bengal, reached Europe and the U.S. in

 

1848-49. The English physician John Snow demonstrated in 1854 that it was spread by contaminated water.

 

1850-51 An extensive epidemic of dengue fever began in Charleston S.C., then spread to Savannah, Augusta, New Orleans, Mobile, Galveston, and other southern coastal cities.

 

1853 Smallpox was introduced to Hawaii by a ship arriving from San Francisco. At least 2500 people died, possibly as many as 5,000.

 

1861-65 The U.S. Civil War brought epidemics of dysentery, typhoid fever, hepatitis, malaria, smallpox, measles, and venereal diseases. More than three times as many soldiers died of infectious disease than of battle wounds.

 

1863-66 The fourth cholera pandemic of the 19th century began in India in 1863, spread first to the Middle East, and then into the Mediterranean. It arrived in New York on a ship coming from France in October 1865, and spread rapidly. Public health reform kept the death toll lower than in previous epidemics, but there were tens of thousands of deaths nonetheless. Another wave swept through the south and midwest in 1873, hitting particularly hard in the Mississippi and Ohio valleys.

 

1868-75 Smallpox outbreaks hit New York, Philadelphia and other cities, and it was discovered that many children had not been vaccinated. The New York City Board of Health recommended that all residents be vaccinated in 1870, but there was widespread public resistance, since the vaccine itself was not without risk, and people perceived the campaign as creating a panic situation and allowing doctors to profit from it.

 

1875-76 A particularly bad epidemic of scarlet fever swept Australia, with high mortality rates.

 

1878-79 Yellow fever again swept through New Orleans, Memphis, and the Mississippi and Ohio River valleys.

 

1881-1896 A fifth cholera pandemic was notable for the discovery of its cause, by the German physician Robert Koch. Like its predecessors, this epidemic began in India, and spread both east and west from there. By this time improvements in sanitation kept it from affecting many European cities, and improved diagnosis and quarantine measures kept it out of the U.S. A sixth pandemic began in

 

1899, and continued to spread through Asia over the next ten years. The U.S. was not affected, nor were most western European cities.

 

1887 Paralytic polio was first described in an epidemic in Sweden.

 

1889-90 A worldwide epidemic of influenza, the most devastating to that time, began in central Asia in the summer of 1889, spread north into Russia, east to China and west to Europe. By December it had struck the major U.S. cities, and continued to spread through North America the following year. Parts of Africa and the Middle East were infected early in 1890; and India, southeast Asia, Australia and New Zealand were reached between February and May. Completing the circle, eastern China had the last major outbreak of this pandemic, in September and October of 1890.

 

1893-94 The first large recorded outbreak of polio in the U.S. began in Boston, and spread into New England, particularly Vermont. Of 132 cases documented in Vermont, there were 18 deaths and 30 victims left with permanent paralysis.

 

1890s The third plague pandemic began in China in the 1850s and spread slowly until it reached the seaports in the

 

1880s, then spread more rapidly around the world, striking particularly hard in India, Egypt, north Africa, and South America. The continental U.S. was largely spared, but Hawaii suffered a severe outbreak in 1899, and San Francisco was affected in 1900-1904, and again in 1907-1909. The second outbreak there was exacerbated by unsanitary conditions following the earthquake of 1906. Sporadic outbreaks continued worldwide for years, and officially this pandemic was not considered over until 1959.

 

1901-03 Smallpox had its last major outbreak in the urban northeast U.S., beginning in New York and spreading through other major cities.

 

1907-1916 Polio turned into a major problem in the U.S., with about a thousand cases in New York in 1907, and another outbreak in 1911. The disease was recognized as contagious, but there was no understanding yet of exactly how it was spread. The first widespread outbreak, seriously affecting 26 states, occurred in 1916. About 7,000 deaths were recorded.

 

1917-1919 The most lethal influenza pandemic in history killed half a million people worldwide. Its spread was facilitated by troop movements in the closing months of World War I. Mortality rates were unusually high for flu, especially among young, otherwise healthy adults. Deaths occurred both from the flu itself and from secondary pneumonia.

 

1931 Another outbreak of polio swept the U.S. during the summer of 1931, killing more than 4,000 people, about 12 percent of the reported cases.

 

1942-53 Polio continued to ravage the U.S., peaking in 1952 with about 60,000 cases. Introduction of the Salk vaccine in 1955 brought an end to the epidemic.

 

1957-58 The “Asian flu” started in southwest China in February 1957, possibly having originated in 1956 in Vladivostok. Globally it affected 10-35 percent of the population but overall mortality was much lower than in the 1918 epidemic, about 0.25 percent. The flu spread to Hong Kong and Singapore in April 1957, Japan in May, elsewhere in the Pacific in June, the Middle East and Africa in July, Europe in August-October, and the U.S. in October of 1957. This list was compiled largely from Encyclopedia of Plague and Pestilence, edited by George C. Kohn, and published by Facts On File, Inc., 1995.

 

BIOTECH FRONTIERS

 

The word “biotech” sounds futuristic, but the actual practice of biotechnology — human manipulation of biologically occurring agents — has existed for more than a century. In the late 1800s, for example, doctors used horse serum to create an antitoxin for the bacterial disease diphtheria. In 1902, after 13 children died from contaminated horse serum, Congress passed its first piece of biotechnology legislation, the Biologics Control Act, to regulate the production of horse serum antitoxins and other biological technologies, including antitoxins for tetanus and vaccines for smallpox and rabies. Since then, a number of important vaccines have been invented to stem the tide of disease, most importantly measles and polio vaccines developed in the 1950s, which put an end to potentially fatal childhood diseases.

 

In the latter part of the 20th century, biotechnology has expanded far beyond its early focus on curing disease, to inventions — some quite controversial — intended to improve the quality of life. The first of these breakthroughs was the oral contraceptive, popularly known as the birth control pill, which was developed in the 1950s. Just over 25 years later, biotechnology was not only preventing conception, but actually facilitating conception outside of the womb, when the first human egg was fertilized “in vitro,” in a test tube, and the embryo was successfully carried to term. Now, in vitro fertilization is commonplace, and the frontiers have moved to the ethically complex realm of genetically improving human embryos, and even cloning.

 

Medical Inventions/Discoveries

 

1954 First measles vaccine invented by Enders and Peebles (Americans)

 

1954 Birth control pill invented by Pincus and Rock (Americans)

 

1955 First polio vaccine invented by Salk (American)

 

1955 First oral polio vaccine invented by Sabin (American)

 

1957 Laser (light amplification by stimulated emission of radiation) invented by Gould (American) (Source: The World Almanac, 1998)

 

1958 First heart pacemaker implanted into the chest of a Stockholm cardiac patient by Senning (Swedish)

 

1972 First CAT (computer axial tomography) scanner, used to diagnose a brain tumor in a female patient, invented by Hounsfield (English) (Source: The 20th Century, Little Brown, 1995)

 

1974 First varicella (chicken pox) vaccine invented by Takahashi (Japan)

 

1978 First child conceived through in vitro fertilization, born in Oldham, England, conducted by Edwards and Steptoe (English) (Source: The Biotech Century, Tarcher/Putnam, 1998)

 

1996 First mammal cloned by Wilmut et al. (Scottish)

 

What’s Next

 

The 21st century is nearly upon us, and although today’s medical technology is more sophisticated than the rockets that took astronauts to the moon, we still haven’t cured cancer, heart disease, or AIDS. And we face other looming public health challenges: teenage smoking, continually high rates of substance abuse, and violent crime. In the coming decades, the medical establishment, government, and the private sector will have to find innovative ways to grapple with these nagging problems, most of which have proved resistant to simple solutions such as vaccines or pills.

 

Meanwhile, new developments in biotechnology will challenge our ethics as well as our ability to adapt to change. With mammalian cloning already a reality, leading scientists say that human cloning is technologically feasible within the next five to 10 years. But the question, which we will undoubtedly be asking of many new technologies that come along, is: Do we want it? If we don’t address these issues soon, the answer may be decided for us.

 

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