Artificial blood

The invention: Aperfluorocarbon emulsion that serves as a blood plasma substitute in the treatment of human patients. The person behind the invention: Ryoichi Naito (1906-1982), a Japanese physician. Blood Substitutes The use of blood and blood products in humans is a very complicated issue. Substances present in blood serve no specific purpose and can be dangerous or deadly, especially when blood or blood products are taken from one person and given to another. This fact, combined with the necessity for long-term blood storage, a shortage of donors, and some patients’ refusal to use blood for religious reasons, brought about an intense search for a universal bloodlike substance. The life-sustaining properties of blood (for example, oxygen transport) can be entirely replaced by a synthetic mixture of known chemicals. Fluorocarbons are compounds that consist of molecules containing only fluorine and carbon atoms. These compounds are interesting to physiologists because they are chemically and pharmacologically inert and because they dissolve oxygen and other gases. Studies of fluorocarbons as blood substitutes began in 1966, when it was shown that a mouse breathing a fluorocarbon liquid treated with oxygen could survive. Subsequent research involved the use of fluorocarbons to play the role of red blood cells in transporting oxygen. Encouraging results led to the total replacement of blood in a rat, and the success of this experiment led in turn to trials in other mammals, culminating in 1979 with the use of fluorocarbons in humans. Clinical Studies The chemical selected for the clinical studies was Fluosol-DA, produced by the Japanese Green Cross Corporation. Fluosol-DA consists of a 20 percent emulsion of two perfluorocarbons (perfluorodecalin and perfluorotripopylamine), emulsifiers, and salts that are included to give the chemical some of the properties of blood plasma. Fluosol-DA had been tested in monkeys, and it had shown a rapid reversible uptake and release of oxygen, a reasonably rapid excretion, no carcinogenicity or irreversible changes in the animals’ systems, and the recovery of blood components to normal ranges within three weeks of administration. The clinical studies were divided into three phases. The first phase consisted of the administration of Fluosol-DA to normal human volunteers. Twelve healthy volunteers were administered the chemical, and the emulsion’s effects on blood pressure and composition and on heart, liver, and kidney functions were monitored. No adverse effects were found in any case. The first phase ended in March, 1979, and based on its positive results, the second and third phases were begun in April, 1979. Twenty-four Japanese medical institutions were involved in the next two phases. The reasons for the use of Fluosol-DA instead of blood in the patients involved were various, and they included refusal of transfusion for religious reasons, lack of compatible blood, “bloodless” surgery for protection from risk of hepatitis, and treatment of carbon monoxide intoxication. Among the effects noticed by the patients were the following: a small increase in blood pressure, with no corresponding effects on respiration and body temperature; an increase in blood oxygen content; bodily elimination of half the chemical within six to nineteen hours, depending on the initial dose administered; no change in red-cell count or hemoglobin content of blood; no change in wholeblood coagulation time; and no significant blood-chemistry changes. These results made the clinical trials a success and opened the door for other, more extensive ones. IMPACT Perfluorocarbon emulsions were initially proposed as oxygencarrying resuscitation fluids, or blood substitutes, and the results of the pioneering studies show their success as such. Their success in this area, however, led to advanced studies and expanded use of these compounds in many areas of clinical medicine and biomedical research. Perfluorocarbon emulsions are useful in cancer therapy, because they increase the oxygenation of tumor cells and therefore sensitize them to the effects of radiation or chemotherapy. Perfluorocarbons can also be used as “contrasting agents” to facilitate magnetic resonance imaging studies of various tissues; for example, the uptake of particles of the emulsion by the cells of malignant tissues makes it possible to locate tumors. Perfluorocarbons also have a high nitrogen solubility and therefore can be used to alleviate the potentially fatal effects of decompression sickness by “mopping up” nitrogen gas bubbles from the circulation system. They can also be used to preserve isolated organs and amputated extremities until they can be reimplanted or reattached. In addition, the emulsions are used in cell cultures to regulate gas supply and to improve cell growth and productivity. The biomedical applications of perfluorocarbon emulsions are multidisciplinary, involving areas as diverse as tissue imaging, organ preservation, cancer therapy, and cell culture. The successful clinical trials opened the door for new applications of these compounds, which rank among the most versatile compounds exploited by humankind.

Aqualung

The invention: A device that allows divers to descend hundreds of meters below the surface of the ocean by enabling them to carry the oxygen they breathe with them. The people behind the invention: Jacques-Yves Cousteau (1910-1997), a French navy officer, undersea explorer, inventor, and author. Émile Gagnan, a French engineer who invented an automatic air-regulating device. The Limitations of Early Diving Undersea dives have been made since ancient times for the purposes of spying, recovering lost treasures from wrecks, and obtaining natural treasures (such as pearls). Many attempts have been made since then to prolong the amount of time divers could remain underwater. The first device, described by the Greek philosopher Aristotle in 335 b.c.e., was probably the ancestor of the modern snorkel. It was a bent reed placed in the mouth, with one end above the water. In addition to depth limitations set by the length of the reed, pressure considerations also presented a problem. The pressure on a diver’s body increases by about one-half pound per square centimeter for every meter ventured below the surface. After descending about 0.9 meter, inhaling surface air through a snorkel becomes difficult because the human chest muscles are no longer strong enough to inflate the chest. In order to breathe at or below this depth, a diver must breathe air that has been pressurized; moreover, that pressure must be able to vary as the diver descends or ascends. Few changes were possible in the technology of diving until air compressors were invented during the early nineteenth century. Fresh, pressurized air could then be supplied to divers. At first, the divers who used this method had to wear diving suits, complete with fishbowl-like helmets. This “tethered” diving made divers relatively immobile but allowed them to search for sunken treasure or do other complex jobs at great depths. The Development of Scuba Diving The invention of scuba gear gave divers more freedom to move about and made them less dependent on heavy equipment. (“Scuba” stands for self-contained underwater breathing apparatus.) Its development occurred in several stages. In 1880, Henry Fleuss of England developed an outfit that used a belt containing pure oxygen. Belt and diver were connected, and the diver breathed the oxygen over and over. Aversion of this system was used by the U.S. Navy in World War II spying efforts. Nevertheless, it had serious drawbacks: Pure oxygen was toxic to divers at depths greater than 9 meters, and divers could carry only enough oxygen for relatively short dives. It did have an advantage for spies, namely, that the oxygen—breathed over and over in a closed system—did not reach the surface in the form of telltale bubbles. The next stage of scuba development occurred with the design of metal tanks that were able to hold highly compressed air. This enabled divers to use air rather than the potentially toxic pure oxygen. More important, being hooked up to a greater supply of air meant that divers could stay under water longer. Initially, the main problem with the system was that the air flowed continuously through a mask that covered the diver’s entire face. This process wasted air, and the scuba divers expelled a continual stream of air bubbles that made spying difficult. The solution, according to Axel Madsen’s Cousteau (1986), was “a valve that would allow inhaling and exhaling through the same mouthpiece.” Jacques-Yves Cousteau’s father was an executive for Air Liquide— France’s main producer of industrial gases. He was able to direct Cousteau to Émile Gagnan, an engineer at thecompany’s Paris laboratory who had been developing an automatic gas shutoff valve for Air Liquide. This valve became the Cousteau-Gagnan regulator, a breathing device that fed air to the diver at just the right pressure whenever he or she inhaled.With this valve—and funding from Air Liquide—Cousteau and Gagnan set out to design what would become the Aqualung. The first Aqualungs could be used at depths of up to 68.5 meters. During testing, however, the dangers of Aqualung diving became apparent. For example, unless divers ascended and descended in slow stages, it was likely that they would get “the bends” (decompression sickness), the feared disease of earlier, tethered deep-sea divers. Another problem was that, below 42.6 meters, divers encountered nitrogen narcosis. (This can lead to impaired judgment that may cause fatal actions, including removing a mouthpiece or developing an overpowering desire to continue diving downward, to dangerous depths.)Cousteau believed that the Aqualung had tremendous military potential. DuringWorldWar II, he traveled to London soon after the Normandy invasion, hoping to persuade the Allied Powers of its usefulness. He was not successful. So Cousteau returned to Paris and convinced France’s new government to use Aqualungs to locate and neutralize underwater mines laid along the French coast by the German navy. Cousteau was commissioned to combine minesweeping with the study of the physiology of scuba diving. Further research revealed that the use of helium-oxygen mixtures increased to 76 meters the depth to which a scuba diver could go without suffering nitrogen narcosis. Impact One way to describe the effects of the development of the Aqualung is to summarize Cousteau’s continued efforts to the present. In 1946, he and Philippe Tailliez established the Undersea Research Group of Toulon to study diving techniques and various aspects of life in the oceans. They studied marine life in the Red Sea from 1951 to 1952. From 1952 to 1956, they engaged in an expedition supported by the National Geographic Society. By that time, the Research Group had developed many techniques that enabled them to identify life-forms and conditions at great depths. Throughout their undersea studies, Cousteau and his coworkers continued to develop better techniques for scuba diving, for recording observations by means of still and television photography, and for collecting plant and animal specimens. In addition, Cousteau participated (with Swiss physicist Auguste Piccard) in the construction of the deep-submergence research vehicle, or bathyscaphe. In the 1960’s, he directed a program called Conshelf, which tested a human’s ability to live in a specially built underwater habitat. He also wrote and produced films on underwater exploration that attracted, entertained, and educated millions of people. Cousteau has won numerous medals and scientific distinctions. These include the Gold Medal of the National Geographic Society (1963), the United Nations International Environment Prize (1977), membership in the American and Indian academies of science (1968 and 1978, respectively), and honorary doctor of science degrees from the University of California, Berkeley (1970), Harvard University (1979), and Rensselaer Polytechnical Institute (1979).

Apple II computer

The invention:
The first commercially available, preassembled
personal computer, the Apple II helped move computers out of
the workplace and into the home.

The people behind the invention:

Stephen Wozniak (1950- ), cofounder of Apple and designer
of the Apple II computer
Steven Jobs (1955-2011 ), cofounder of Apple
Regis McKenna (1939- ), owner of the Silicon Valley public
relations and advertising company that handled the Apple
account
Chris Espinosa (1961- ), the high school student who wrote
the BASIC program shipped with the Apple II
Randy Wigginton (1960- ), a high school student and Apple
software programmer

Antibacterial drugs

Mechanisms of genetic resistance to antimicrobial agents: Bacteria have developed, or will develop, genetic resistance to all known antimicrobial agents that are now in the marketplace. The five main mechanisms that bacteria use to resist antibacterial drugs are shown in the figure. a | The site of action (enzyme, ribosome or cell-wall precursor) can be altered. For example, acquiring a plasmid or transposon that codes for a resistant dihydrofolate reductase confers trimethoprim resistance to bacteria52. b | The inhibited steps can be by-passed. c | Bacteria can reduce the intracellular concentration of the antimicrobial agent, either by reducing membrane permeability, for example, as shown by Pseudomonas aeruginosa53, or by active efflux of the agent54. d | They can inactivate the drug. For example, some bacteria produce beta-lactamase, which destroys the penicillin beta-lactam ring50, 51 . e | The target enzyme can be overproduced by the bacteria. The invention: Sulfonamides and other drugs that have proved effective in combating many previously untreatable bacterial diseases. The people behind the invention: Gerhard Domagk (1895-1964), a German physician who was awarded the 1939 Nobel Prize in Physiology or Medicine Paul Ehrlich (1854-1915), a German chemist and bacteriologist who was the cowinner of the 1908 Nobel Prize in Physiology or Medicine. The Search for Magic Bullets Although quinine had been used to treat malaria long before the twentieth century, Paul Ehrlich, who discovered a large number of useful drugs, is usually considered the father of modern chemotherapy. Ehrlich was familiar with the technique of using dyes to stain microorganisms in order to make them visible under a microscope, and he suspected that some of these dyes might be used to poison the microorganisms responsible for certain diseases without hurting the patient. Ehrlich thus began to search for dyes that could act as “magic bullets” that would destroy microorganisms and cure diseases. From 1906 to 1910, Ehrlich tested numerous compounds that had been developed by the German dye industry. He eventually found that a number of complex trypan dyes would inhibit the protozoans that caused African sleeping sickness. Ehrlich and his coworkers also synthesized hundreds of organic compounds that contained arsenic. In 1910, he found that one of these compounds, salvarsan, was useful in curing syphilis, a sexually transmitted disease caused by the bacterium Treponema. This was an important discovery, because syphilis killed thousands of people each year. Salvarsan, however, was often toxic to patients, because it had to be taken in large doses for as long as two years to effect a cure. Ehrlich thus searched for and found a less toxic arsenic compound, neosalvarsan, which replaced salvarsan in 1912. In 1915, tartar emetic (a compound containing the metal antimony) was found to be useful in treating kala-azar, which was caused by a protozoan. Kala-azar affected millions of people in Africa, India, and Asia, causing much suffering and many deaths each year. Two years later, it was discovered that injection of tartar emetic into the blood of persons suffering from bilharziasis killed the flatworms infecting the bladder, liver, and spleen. In 1920, suramin, a colorless compound developed from trypan red, was introduced to treat African sleeping sickness. It was much less toxic to the patient than any of the drugs Ehrlich had developed, and a single dose would give protection for more than a month. From the dye methylene blue, chemists made mepacrine, a drug that was effective against the protozoans that cause malaria. This chemical was introduced in 1933 and used duringWorldWar II; its principal drawback was that it could cause a patient’s skin to become yellow. Well Worth the Effort Gerhard Domagk had been trained in medicine, but he turned to research in an attempt to discover chemicals that would inhibit or kill microorganisms. In 1927, he became director of experimental pathology and bacteriology at the Elberfeld laboratories of the German chemical firm I. G. Farbenindustrie. Ehrlich’s discovery that trypan dyes selectively poisoned microorganisms suggested to Domagk that he look for antimicrobials in a new group of chemicals known as azo dyes. A number of these dyes were synthesized from sulfonamides and purified by Fritz Mietzsch and Josef Klarer. Domagk found that many of these dyes protected mice infected with the bacteria Streptococcus pyogenes. In 1932, he discovered that one of these dyes was much more effective than any tested previously. This red azo dye containing a sulfonamide was named prontosil rubrum. From 1932 to 1935, Domagk began a rigorous testing program to determine the effectiveness and dangers of prontosil use at different doses in animals. Since all chemicals injected into animals or humans are potentially dangerous, Domagk determined the doses that harmed or killed. In addition, he worked out the lowest doses that would eliminate the pathogen. The firm supplied samples of the drug to physicians to carry out clinical trials on humans. (Animal experimentation can give only an indication of which chemicals might be useful in humans and which doses are required.) Domagk thus learned which doses were effective and safe. This knowledge saved his daughter’s life. One day while knitting, Domagk’s daughter punctured her finger with a needle and was infected with a virulent bacteria, which quickly multiplied and spread from the wound into neighboring tissues. In an attempt to alleviate the swelling, the infected area was lanced and allowed to drain, but this did not stop the infection from spreading. The child became critically ill with developing septicemia, or blood poisoning. In those days, more than 75 percent of those who acquired blood infections died. Domagk realized that the chances for his daughter’s survival were poor. In desperation, he obtained some of the powdered prontosil that had worked so well on infected animals. He extrapolated from his animal experiments how much to give his daughter so that the bacteria would be killed but his daughter would not be poisoned. Within hours of the first treatment, her fever dropped, and she recovered completely after repeated doses of prontosil. Impact Directly and indirectly, Ehrlich’s and Domagk’s work served to usher in a new medical age. Prior to the discovery that prontosil could be use to treat bacterial infection and the subsequent development of a series of sulfonamides, or “sulfa drugs,” there was no chemical defense against this type of disease; as a result, illnesses such as streptococcal infection, gonorrhea, and pneumonia held terrors of which they have largely been shorn.Asmall injury could easily lead to death. By following the clues presented by the synthetic sulfa drugs and how they worked to destroy bacteria, other scientists were able to develop an even more powerful type of drug, the antibiotic. When the American bacteriologist Rene Dubos discovered that natural organisms could also be used to fight bacteria, interest was renewed in an earlier discovery by the Scottish bacteriologist Sir Alexander: the development of penicillin. Antibiotics such as penicillin and streptomycin have become some of the most important tools in fighting disease. Antibiotics have replaced sulfa drugs for most uses, in part because they cause fewer side effects, but sulfa drugs are still used for a handful of purposes. Together, sulfonamides and antibiotics have offered the possibility of a cure to millions of people who previously would have had little chance of survival.

Amniocentesis

The invention:

A technique for removing amniotic fluid from
pregnant women, amniocentesis became a life-saving tool for diagnosing
fetal maturity, health, and genetic defects.

The people behind the invention:

Douglas Bevis, an English physician
Aubrey Milunsky (1936- ), an American pediatrician

Ammonia

The invention:

The first successful method for converting nitrogen
from the atmosphere and combining it with hydrogen to synthesize
ammonia, a valuable compound used as a fertilizer.

The person behind the invention:

Fritz Haber (1868-1934), a German chemist who won the 1918
Nobel Prize in Chemistry

Alkaline storage battery

The invention:

The nickel-iron alkaline battery was a lightweight,
inexpensive portable power source for vehicles with electric motors.

The people behind the invention:

Thomas Alva Edison (1847-1931), American chemist, inventor,
and industrialist
Henry Ford (1863-1947), American inventor and industrialist
Charles F. Kettering (1876-1958), American engineer and
inventor

Airplane

 The invention:

The first heavier-than-air craft to fly, the airplane
revolutionized transportation and symbolized the technological
advances of the twentieth century.

The people behind the invention:

Wilbur Wright (1867-1912), an American inventor
Orville Wright (1871-1948), an American inventor
Octave Chanute (1832-1910), a French-born American civil
engineer

Abortion pill

The invention:
RU-486 was the first commercially available drug that prevented fertilized eggs from implanting themselves in the walls of women’s uteruses.
The people behind the invention:
Étienne-Émile Baulieu (1926- ), a French biochemist and endocrinologist Georges Teutsch, a French chemist
Alain Bélanger a French chemist
Daniel Philibert, a French physicist and pharmacologist