Showing posts with label impact. Show all posts
Showing posts with label impact. Show all posts
Saturday, October 18, 2014
Tungsten filament
The invention:
Metal filament used in the incandescent light bulbs
that have long provided most of the world’s electrical lighting.
The people behind the invention:
William David Coolidge (1873-1975), an American electrical
engineer
Thomas Alva Edison (1847-1931), an American inventor
The Incandescent Light Bulb
The electric lamp developed along with an understanding of
electricity in the latter half of the nineteenth century. In 1841, the
first patent for an incandescent lamp was granted in Great Britain.A
patent is a legal claim that protects the patent holder for a period of
time from others who might try to copy the invention and make a
profit from it. Although others tried to improve upon the incandescent
lamp, it was not until 1877, when Thomas Alva Edison, the famous
inventor, became interested in developing a successful electric
lamp, that real progress was made. The Edison Electric Light
Company was founded in 1878, and in 1892, it merged with other
companies to form the General Electric Company.
Early electric lamps used platinum wire as a filament. Because
platinum is expensive, alternative filament materials were sought.
After testing many substances, Edison finally decided to use carbon
as a filament material. Although carbon is fragile, making it difficult
to manufacture filaments, it was the best choice available at the time.
The Manufacture of Ductile Tungsten
Edison and others had tested tungsten as a possible material for
lamp filaments but discarded it as unsuitable. Tungsten is a hard,
brittle metal that is difficult to shape and easy to break, but it possesses
properties that are needed for lamp filaments. It has the highest
melting point (3,410 degrees Celsius) of any known metal; therefore,
it can be heated to a very high temperature, giving off a
relatively large amount of radiation without melting (as platinum
does) or decomposing (as carbon does). The radiation it emits when
heated is primarily visible light. Its resistance to the passage of electricity
is relatively high, so it requires little electric current to reach
its operating voltage. It also has a high boiling point (about 5,900 degrees
Celsius) and therefore does not tend to boil away, or vaporize,
when heated. In addition, it is mechanically strong, resisting breaking
caused by mechanical shock.
William David Coolidge, an electrical engineer with the General
Electric Company, was assigned in 1906 the task of transforming
tungsten from its natural state into a form suitable for lamp filaments.
The accepted procedure for producing fine metal wires was
(and still is) to force a wire rod through successively smaller holes in
a hard metal block until a wire of the proper diameter is achieved.
The property that allows a metal to be drawn into a fine wire by
means of this procedure is called “ductility.” Tungsten is not naturally
ductile, and it was Coolidge’s assignment to make it into a ductile
form. Over a period of five years, and after many failures, Coolidge
and his workers achieved their goal. By 1911, General Electric
was selling lamps that contained tungsten filaments.
Originally, Coolidge attempted to mix powdered tungsten with a
suitable substance, form a paste, and squirt that paste through a die
to form the wire. The paste-wire was then sintered (heated at a temperature
slightly below its melting point) in an effort to fuse the
powder into a solid mass. Because of its higher boiling point, the
tungsten would remain after all the other components in the paste
boiled away. At about 300 degrees Celsius, tungsten softens sufficiently
to be hammered into an elongated form. Upon cooling, however,
tungsten again becomes brittle, which prevents it from being
shaped further into filaments. It was suggested that impurities in
the tungsten caused the brittleness, but specially purified tungsten
worked no better than the unpurified form.
Many metals can be reduced from rods to wires if the rods are
passed through a series of rollers that are successively closer together.
Some success was achieved with this method when the rollers
were heated along with the metal, but it was still not possible to
produce sufficiently fine wire. Next, Coolidge tried a procedure
called “swaging,” in which a thick wire is repeatedly and rapidly
struck by a series of rotating hammers as the wire is drawn past
them. After numerous failures, a fine wire was successfully produced
using this procedure. It was still too thick for lamp filaments,
but it was ductile at room temperature.
Microscopic examination of the wire revealed a change in the
crystalline structure of tungsten as a result of the various treatments.
The individual crystals had elongated, taking on a fiber like
appearance. Now the wire could be drawn through a die to achieve
the appropriate thickness. Again, the wire had to be heated, and if
the temperature was too high, the tungsten reverted to a brittle
state. The dies themselves were heated, and the reduction progressed
in stages, each of which reduced the wire’s diameter by a
thousandth of an inch.
Finally, Coolidge had been successful.Pressed tungsten bars
measuring 1/4 x 3/8x6 inches were hammered and rolled into rods 1/8
inch , or 125/1000 inc, in diameter.
The unit 1/1000 inch is often called a “mil.”
These rods were then swaged to approximately 30 mil and
then passed through dies to achieve the filament size of 25 mil or
smaller, depending on the power output of the lamp in which the
filament was to be used. Tungsten wires of 1 mil or smaller are now
readily available.
Impact
Ductile tungsten wire filaments are superior in several respects
to platinum, carbon, or sintered tungsten filaments. Ductile filament
lamps can withstand more mechanical shock without breaking.
This means that they can be used in, for example, automobile
headlights, in which jarring frequently occurs. Ductile wire can also
be coiled into compact cylinders within the lamp bulb, which makes
for a more concentrated source of light and easier focusing. Ductile
tungsten filament lamps require less electricity than do carbon filament
lamps, and they also last longer. Because the size of the filament
wire can be carefully controlled, the light output from lamps
of the same power rating is more reproducible. One 60-watt bulb is
therefore exactly like another in terms of light production.
Improved production techniques have greatly reduced the cost
of manufacturing ductile tungsten filaments and of light-bulb man-
ufacturing in general. The modern world is heavily dependent
upon this reliable, inexpensive light source, which turns darkness
into daylight.
See also : Fluorescent lighting; Memory metal; Steelmaking process.
Thursday, September 25, 2014
Tuberculosis vaccine
The invention:
Vaccine that uses an avirulent (nondisease) strain
of bovine tuberculosis bacilli that is safer than earlier vaccines.
The people behind the invention:
Albert Calmette (1863-1933), a French microbiologist
Camille Guérin (1872-1961), a French veterinarian and
microbiologist
Robert Koch (1843-1910), a German physician and
microbiologist
Isolating Bacteria
Tuberculosis, once called “consumption,” is a deadly, contagious
disease caused by the bacterium Mycobacterium tuberculosis,
first identified by the eminent German physician Robert Koch in
1882. The bacterium can be transmitted from person to person by
physical contact or droplet infection (for example, sneezing). The
condition eventually inflames and damages the lungs, causing difficulty
in breathing and failure of the body to deliver sufficient oxygen
to various tissues. It can spread to other body tissues, where
further complications develop.Without treatment, the disease progresses,
disabling and eventually killing the victim. Tuberculosis
normally is treated with a combination of antibiotics and other
drugs.
Koch developed his approach for identifying bacterial pathogens
(disease producers) with simple equipment, primarily microscopy.
Having taken blood samples from diseased animals, he would
identify and isolate the bacteria he found in the blood. Each strain of
bacteria would be injected into a healthy animal. The latter would
then develop the disease caused by the particular strain.
In 1890, he discovered that a chemical released from tubercular
bacteria elicits a hypersensitive (allergic) reaction in individuals
previously exposed to or suffering from tuberculosis. This chemical,
called “tuberculin,” was isolated from culture extracts in which tubercular
bacteria were being grown.
When small amounts of tuberculin are injected into a person subcutaneously
(beneath the skin), a reddened, inflamed patch approximately
the size of a quarter develops if the person has been exposed
to or is suffering from tuberculosis. Injection of tuberculin into an
uninfected person yields a negative response (that is, no inflammation).
Tuberculin does not harm those being tested.
Tuberculosis’s Weaker Grandchildren
The first vaccine to prevent tuberculosis was developed in 1921
by two French microbiologists, Albert Calmette and Camille Guérin.
Calmette was a student of the eminent French microbiologist Louis
Pasteur at Pasteur’s Institute in Paris. Guérin was a veterinarian
who joined Calmette’s laboratory in 1897. At Lille, Calmette and
Guérin focused their research upon the microbiology of infectious
diseases, especially tuberculosis.
In 1906, they discovered that individuals who had been exposed to
tuberculosis or who had mild infections were developing resistance to
the disease. They found that resistance to tuberculosis was initiated by
the body’s immune system. They also discovered that tubercular bacteria
grown in culture over many generations become progressively
weaker and avirulent, losing their ability to cause disease.
From 1906 through 1921, Calmette and Guérin cultured tubercle
bacilli from cattle. With proper nutrients and temperature, bacteria
can reproduce by fission (that is, one bacterium splits into two bacteria)
in as little time as thirty minutes. Calmette and Guérin cultivated
these bacteria in a bile-derived food medium for thousands of
generations over fifteen years, periodically testing the bacteria for
virulence by injecting them into cattle. After many generations, the
bacteria lost their virulence, their ability to cause disease. Nevertheless,
these weaker, or “avirulent” bacteria still stimulated the animals’
immune systems to produce antibodies. Calmette and Guérin
had successfully bred a strain of avirulent bacteria that could not
cause tuberculosis in cows but could also stimulate immunity against
the disease.
There was considerable concern over whether the avirulent strain
was harmless to humans. Calmette and Guérin continued cultivating
weaker versions of the avirulent strain that retained antibody-
stimulating capacity. By 1921, they had isolated an avirulent antibody-
stimulating strain that was harmless to humans, a strain they
called “Bacillus Calmette-Guérin” (BCG).
In 1922, they began BCG-vaccinating newborn children against
tuberculosis at the Charité Hospital in Paris. The immunized children
exhibited no ill effects from the BCG vaccination. Calmette and
Guérin’s vaccine was so successful in controlling the spread of tuberculosis
in France that it attained widespread use in Europe and
Asia beginning in the 1930’s.
Impact
Most bacterial vaccines involve the use of antitoxin or heat- or
chemical-treated bacteria. BCG is one of the few vaccines that use
specially bred live bacteria. Its use sparked some controversy in
the United States and England, where the medical community
questioned its effectiveness and postponed BCG immunization
until the late 1950’s. Extensive testing of the vaccine was performed
at the University of Illinois before it was adopted in the
United States. Its effectiveness is questioned by some physicians to
this day.
Some of the controversy stems from the fact that the avirulent,
antibody-stimulating BCG vaccine conflicts with the tuberculin
skin test. The tuberculin skin test is designed to identify people
suffering from tuberculosis so that they can be treated. A BCGvaccinated
person will have a positive tuberculin skin test similar
to that of a tuberculosis sufferer. If a physician does not know that
a patient has had a BCG vaccination, it will be presumed (incorrectly)
that the patient has tuberculosis. Nevertheless, the BCG
vaccine has been invaluable in curbing the worldwide spread of
tuberculosis, although it has not eradicated the disease.
See also:
Antibacterial drugs; Birth control pill; Penicillin; Polio vaccine (Sabin);
Polio vaccine (Salk)
Wednesday, July 16, 2014
Transistor
The invention:
A miniature electronic device, comprising a tiny
semiconductor and multiple electrical contacts, used in circuits
as an amplifier, detector, or switch, that revolutionized electronics
in the mid-twentieth century.
The people behind the invention:
William B. Shockley (1910-1989), an American physicist who led
the Bell Laboratories team that produced the first transistors
Akio Morita (1921-1999), a Japanese physicist and engineer who
was the cofounder of the Sony electronics company
Masaru Ibuka (1908-1997), a Japanese electrical engineer and
businessman who cofounded Sony with Morita
The Birth of Sony
In 1952, a Japanese engineer visiting the United States learned
that the Western Electric company was granting licenses to use its
transistor technology. He was aware of the development of this device
and thought that it might have some commercial applications.
Masaru Ibuka told his business partner in Japan about the opportunity,
and they decided to raise the $25,000 required to obtain a license.
The following year, his partner, Akio Morita, traveled to New
York City and concluded negotiations with Western Electric. This
was a turning point in the history of the Sony company and in the
electronics industry, for transistor technology was to open profitable
new fields in home entertainment.
The origins of the Sony corporation were in the ruins of postwar
Japan. The Tokyo Telecommunications Company was incorporated
in 1946 and manufactured a wide range of electrical equipment
based on the existing vacuum tube technology. Morita and Ibuka
were involved in research and development of this technology during
the war and intended to put it to use in the peacetime economy.
In the United States and Europe, electrical engineers who had done
the same sort of research founded companies to build advanced
audio products such as high-performance amplifiers, but Morita
and Ibuka did not have the resources to make such sophisticated
products and concentrated on simple items such as electric water
heaters and small electric motors for record players.
In addition to their experience as electrical engineers, both men
were avid music lovers, as a result of their exposure to Americanbuilt
phonographs and gramophones exported to Japan in the early
twentieth century. They decided to combine their twin interests by
devising innovative audio products and looked to the new field of
magnetic recording as a likely area for exploitation. They had learned
about tape recorders from technical journals and had seen them in
use by the American occupation force.
They developed a reel-to-reel tape recorder and introduced it in
1950. It was a large machine with vacuum tube amplifiers, so heavy
that they transported it by truck. Although it worked well, they had
a hard job selling it. Ibuka went to the United States in 1952 partly
on a fact-finding mission and partly to get some ideas about marketing
the tape recorder to schools and businesses. It was not seen as a
consumer product.
Ibuka and Morita had read about the invention of the transistor
inWestern Electric’s laboratories shortly after the war. John Bardeen
andWalter H. Brattain had discovered that a semiconducting material
could be used to amplify or control electric current. Their point
contact transistor of 1948 was a crude laboratory apparatus that
served as the basis for further research. The project was taken over
byWilliam B. Shockley, who had suggested the theory of the transistor
effect. A new generation of transistors was devised; they were
simpler and more efficient than the original. The junction transistors
were the first to go into production.
Ongoing Research
Bell Laboratories had begun transistor research becauseWestern
Electric, one of its parent companies along with American Telephone
and Telegraph, was interested in electronic amplification.
This was seen as a means to increase the strength of telephone signals
traveling over long distances, a job carried out by vacuum
tubes. The junction transistor was developed as an amplifier.Western
Electric thought that the hearing aid was the only consumer
product that could be based on it and saw the transistor solely as a
telecommunications technology. The Japanese purchased the license
with only the slightest understanding of the workings of
semiconductors and despite the belief that transistors could not be
used at the high frequencies associated with radio.
The first task of Ibuka and Morita was to develop a highfrequency
transistor. Once this was accomplished, in 1954, a method
had to be found to manufacture it cheaply. Transistors were made
from crystals, which had to be grown and doped with impurities to
form different layers of conductivity. This was not an exact science,
and Sony engineers found that the failure rate for high-frequency
transistors was very high. This increased costs and put the entire
project into doubt, because the adoption of transistors was based on
simplicity, reliability, and low cost.
The introduction of the first Sony transistor radio, the TR-55, in
1955 was the result of basic research combined with extensive industrial
engineering. Morita admitted that its sound was poor, but
because it was the only transistor radio in Japan, it sold well. These
were not cheap products, nor were they particularly compact. The
selling point was that they consumed much less battery power than
the old portable radios.
The TR-55 carried the brand name Sony, a relative of the Soni
magnetic tape made by the company and a name influenced by the
founders’ interest in sound. Morita and Ibuka had already decided
that the future of their company would be in international trade and
wanted its name to be recognized all over the world. In 1957, they
changed the company’s name from Tokyo Telecomunications Engineering
to Sony.
The first product intended for the export market was a small
transistor radio. Ibuka was disappointed at the large size of the TR-
55 because one of the advantages of the transistor over the vacuum
tube was supposed to be smaller size. He saw a miniature radio as a
promising consumer product and gave his engineers the task of designing
one small enough to fit into his shirt pocket.
All elements of the radio had to be reduced in size: amplifier,
transformer, capacitor, and loudspeaker. Like many other Japanese
manufacturers, Sony bought many of the component parts of its
products from small manufacturers, all of which had to be cajoled
into decreasing the size of their parts. Morita and Ibuka stated that
the hardest task in developing this new product was negotiating
with the subcontractors. Finally, the Type 63 pocket transistor radio
the “Transistor Six”—was introduced in 1957.
Impact
When the transistor radio was introduced, the market for radios
was considered to be saturated. People had rushed to buy them
when they were introduced in the 1920’s, and by the time of the
Great Depression, the majority of American households had one.
Improvements had been made to the receiver and more attractive
radio/phonograph console sets had been introduced, but these developments
did not add many new customers. The most manufacturers
could hope for was the replacement market with a few sales
as children moved out of their parents’ homes and established new
households.
The pocket radio created a new market. It could be taken anywhere
and used at any time. Its portability was its major asset, and it
became an indispensable part of youth-oriented popular culture of
the 1950’s and 1960’s. It provided an outlet for the crowded airwaves
of commercialAMradio and was the means to bring the new
music of rock and roll to a mass audience.
As soon as Sony introduced the Transistor Six, it began to redesign
it to reduce manufacturing cost. Subsequent transistor radios
were smaller and cheaper. Sony sold them by the millions, and millions
more were made by other companies under brand names such
as “Somy” and “Sonny.” By 1960, more than twelve million transistor
radios had been sold.
The transistor radio was the product that established Sony as an
international audio concern. Morita had resisted the temptation to
make radios for other companies to sell under their names. Exports
of Sony radios increased name recognition and established a bridgehead
in the United States, the biggest market for electronic consumer
products. Morita planned to follow the radio with other transistorized
products.
The television had challenged radio’s position as the mechanical
entertainer in the home. Like the radio, it stood in nearly every
American living room and used the same vacuum tube amplification
unit. The transistorized portable television set did for images
what the transistor radio did for sound. Sony was the first to develop
an all-transistor television, in 1959. At a time when the trend
in television receivers was toward larger screens, Sony produced
extremely small models with eight-inch screens. Ignoring the marketing
experts who said that Americans would never buy such a
product, Sony introduced these models into the United States in
1960 and found that there was a huge demand for them.
As in radio, the number of television stations on the air and
broadcasts for the viewer to choose from grew.Apersonal television
or radio gave the audience more choices. Instead of one machine in
the family room, there were now several around the house. The
transistorization of mechanical entertainers allowed each family
member to choose his or her own entertainment. Sony learned several
important lessons from the success of the transistor radio and
television. The first was that small size and low price could create
new markets for electronic consumer products. The second was that
constant innovation and cost reduction were essential to keep ahead
of the numerous companies that produced cheaper copies of original
Sony products.
In 1962, Sony introduced a tiny television receiver with a fiveinch
screen. In the 1970’s and 1980’s, it produced even smaller models,
until it had a TV set that could sit in the palm of the hand—the
Video Walkman. Sony’s scientists had developed an entirely new
television screen that worked on a new principle and gave better
color resolution; the company was again able to blend the fruits of
basic scientific research with innovative industrial engineering.
The transistorized amplifier unit used in radio and television sets
was applied to other products, including amplifiers for record players
and tape recorders. Japanese manufacturers were slow to take
part in the boom in high-fidelity audio equipment that began in the
United States in the 1950’s. The leading manufacturers of highquality
audio components were small American companies based
on the talents of one engineer, such as Avery Fisher or Henry Koss.
They sold expensive amplifiers and loudspeakers to audiophiles.
The transistor reduced the size, complexity, and price of these components.
The Japanese took the lead devising complete audio units based on transistorized
integrated circuits, thus developing the basic home stereo.
In the 1960’s, companies such as Sony and Matsushita dominated
the market for inexpensive home stereos. These were the basic
radio/phonograph combination, with two detached speakers.
The finely crafted wooden consoles that had been the standard for
the home phonograph were replaced by small plastic boxes. The
Japanese were also quick to exploit the opportunities of the tape cassette.
The Philips compact cassette was enthusiastically adopted by
Japanese manufacturers and incorporated into portable tape recorders.
This was another product with its ancestry in the transistor
radio. As more of them were sold, the price dropped, encouraging
more consumers to buy. The cassette player became as commonplace
in American society in the 1970’s as the transistor radio had
been in the 1960’s.
The Walkman
The transistor took another step in miniaturization in the Sony
Walkman, a personal stereo sound system consisting of a cassette
player and headphones. It was based on the same principles as the
transistor radio and television. Sony again confounded marketing
experts by creating a new market for a personal electronic entertainer.
In the ten years following the introduction of theWalkman in
1979, Sony sold fifty million units worldwide, half of those in the
United States. Millions of imitation products were sold by other
companies.
Sony’s acquisition of the Western Electric transistor technology
was a turning point in the fortunes of that company and of Japanese
manufacturers in general. Less than ten years after suffering defeat
in a disastrous war, Japanese industry served notice that it had lost
none of its engineering capabilities and innovative skills. The production
of the transistor radio was a testament to the excellence of
Japanese research and development. Subsequent products proved
that the Japanese had an uncanny sense of the potential market for
consumer products based on transistor technology. The ability to incorporate
solid-state electronics into innovative home entertainment
products allowed Japanese manufacturers to dominate the
world market for electronic consumer products and to eliminate
most of their American competitors.
The little transistor radio was the vanguard of an invasion of new
products unparalleled in economic history. Japanese companies
such as Sony and Panasonic later established themselves at the leading
edge of digital technology, the basis of a new generation of entertainment
products. Instead of Japanese engineers scraping together
the money to buy a license for an American technology, the
great American companies went to Japan to license compact disc
and other digital technologies.
William Shockley
William Shockley’s reputation contains extremes. He helped
invent one of the basic devices supporting modern technological
society, the transistor. He also tried to revive one of the most
infamous social theories, eugenics.
His parents, mining engineer William Hillman Shockley,
and surveyor May Bradford Shockley, were on assignment in
England in 1910 when he was born. The family returned to
Northern California when the younger William was three, and
they schooled him at home until he was eight. He acquired an
early interest in physics from a neighbor who taught at Stanford
University. Shockley pursed that interest at the California Institute
of Technology and the Massachusetts Institute of Technology,
which awarded him a doctorate in 1936.
Shockley went to work for Bell Telephone Laboratories in
the same year. While trying to design a vacuum tube that could
amplify current, it occurred to him that solid state components
might work better than the fragile tubes. He experimented with
the semiconductors germanium and silicon, but the materials
available were too impure for his purpose. World War II interrupted
the experiments, and he worked instead to improve radar
and anti-submarine devices for the military. Back at Bell
Labs in 1945, Shockley teamed with theorist John Bardeen and
experimentalistWalter Brattain. Two years later they succeeded
in making the first amplifier out of semiconductor materials
and called it a transistor (short for transfer resistor). Its effect on
the electronics industry was revolutionary, and the three shared
the 1956 Nobel Prize in Physics for their achievement.
In the mid-1950’s Shockley left Bell Labs to start Shockley
Transistor, then switched to academia in 1963, becoming Stanford
University’s Alexander M. Poniatoff Professor of Engineering
and Applied Science. He grew interested in the relation
between race and intellectual ability. Teaching himself psychology
and genetics, he conceived the theory that Caucasians were
inherently more intelligent than other races because of their genetic
make-up. When he lectured on his brand of eugenics, he
was denounced by the public as a racist and by scientists for
shoddy thinking. Shockley retired in 1975 and died in 1989.
See also :
Cassette recording; Color television; FM radio; Radio;Television;
Further Reading :
Lyons, Nick. The Sony Vision. New York: Crown Publishers, 1976.
Marshall, David V. Akio Morita and Sony. Watford: Exley, 1995.
Morita, Akio, with Edwin M. Reingold, and Mitsuko Shimomura.
Made in Japan: Akio Morita and Sony. London: HarperCollins,
1994.
Reid, T. R. The Chip: How Two Americans Invented the Microchip and
Launched a Revolution. New York: Simon and Schuster, 1984.
Riordan, Michael. Crystal Fire: The Invention of the Transistor and the
Birth of the Information Age. New York: Norton, 1998.
Scott, Otto. The Creative Ordeal: The Story of Raytheon. New York:
Atheneum, 1974.
Labels:
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Masaru Ibuka,
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William B. Shockley
Wednesday, December 3, 2008
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).
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Thursday, November 27, 2008
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.
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Friday, November 14, 2008
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
Developing and Testing
In 1980, Alain Bélanger, a research chemist, was working with
Georges Teutsch at Roussel Uclaf, a French pharmaceutical company.
Teutsch and Bélanger were interested in understanding how
changes in steroids affect the chemicals’ ability to bind to their steroid
receptors. (Receptors are molecules on cells that can bind with
certain chemical substances such as hormones. Receptors therefore
act as connecting links to promote or prevent specific bodily activities
or processes.) Bélanger synthesized several steroids that bonded
to steroid receptors. Among these steroids was a compound that
came to be called “RU-486.”
Another member of the research project, Daniel Philibert, found
that RU-486 blocked the activities of progesterone by binding tightly
to the progesterone receptor. Progesterone is a naturally occurring
steroid hormone that prepares the wall of the uterus to accept a fertilized
egg. Once this is done, the egg can become implanted and
can begin to develop. The hormone also prevents the muscles of the
uterus from contracting, which might cause the uterus to reject the
egg. Therefore RU-486, by acting as a kind of shield between hormone
and receptor, essentially stopped the progesterone from doing
its job.
At the time, Teutsch’s group did not consider that RU-486 might
be useful for deliberately interrupting human pregnancy. It was
Étienne-Émile Baulieu, a biochemist and endocrinologist and a consultant
for Roussel Uclaf, who made this connection. He persuaded
the company to test RU-486 for its effects on fertility control.
Many tests were performed on rabbits, rats, and monkeys; they
showed that, even in the presence of progesterone, RU-486 could
prevent secretory tissue from forming in the uterus, could change
the timing of the menstrual cycle, and could terminate a pregnancy—
that is, cause an abortion. The compound also seemed to be
nontoxic, even in high doses.
In October of 1981, Baulieu began testing the drug with human
volunteers. By 1985, major tests of RU-486 were being done in
France, Great Britain, The Netherlands, Sweden, and China. When a
relatively low dose of RU-486 was given orally, there was an 85 percent
success rate in ending pregnancy; the woman’s body expelled
the embryo and all the endometrial surface. Researchers found that
if a low dose of a prostaglandin (a hormonelike substance that
causes the smooth muscles of the uterus to contract, thereby expelling
the embryo) was given two days later, the success rate rose to 96
percent. There were few side effects, and the low doses of RU-486
did not interfere with the actions of other steroid hormones that are
necessary to keep the body working.
In the March, 1990, issue of The New England Journal of Medicine,
Baulieu and his coworkers reported that with one dose of RU-486,
followed in thirty-six to forty-eight hours with a low dose of prostaglandin,
96 percent of the 2,040 women they studied had a complete
abortion with few side effects. The women were monitored after receiving
the prostaglandin to watch for side effects, which included
nausea, vomiting, abdominal pain, and diarrhea. When they returned
for a later checkup, fewer than 2 percent of the women complained
of side effects. The researchers used two different prostaglandins;
they found that one caused a quicker abortion but also
brought about more pain and a longer period of bleeding.
Using the Drug
In September, 1988, the French government approved the distribution
of RU-486 for use in government-controlled clinics. The next
month, however, Roussel Uclaf stopped selling the drug because
people opposed to abortion did not want RU-486 to be available and
were threatening to boycott the company.
Then, however, there were threats and pressure from the other
side. For example, members of the World Congress of Obstetrics
and Gynecology announced that they might boycott Roussel Uclaf
if it did not make RU-486 available. The French government, which
controlled a 36 percent interest in Roussel Uclaf, ordered the company
to start distributing the drug once more.
By the fall of 1989, more than one-fourth of all early abortions in
France were being done with RU-486 and a prostaglandin. The French
government began helping to pay the cost of using RU-486 in 1990.
Testing for approval of RU-486 was completed in Great Britain
and The Netherlands, but Roussel Uclaf’s parent company, Hoechst
AG, did not try to market the drug there or in any other country outside
France. (In the United States, government regulations did not
allow RU-486 to be tested using government funds.)
Medical researchers believe that RU-486 may be useful not only
for abortions but also in other ways. For example, it may help in
treating certain breast cancers and other tumors. RU-486 is also being
investigated as a possible treatment for glaucoma—to lower
pressure in the eye that may be caused by a high level of steroid hormone.
It may be useful in promoting the healing of skin wounds
and softening the cervix at birth, easing delivery. Researchers hope
as well that some form of RU-486 may prove useful as a contraceptive—
that is, not to prevent a fertilized egg from implanting itself in
the mother’s uterus but to prevent ovulation in the first place.
Impact
Groups opposed to abortion rights have spoken out against RU-
486, while those who favor the right to abortion have urged its acceptance.
The drug has been approved for use in China as well as in
France. In the United States, however, the government has avoided
giving its approval to the drug. Officials of theWorld Health Organization
(WHO) have argued that RU-486 could prevent the deaths
of women who undergo botched abortions. Under international
law,WHOhas the right to take control of the drug and make it available
in poor countries at low cost. Because of the controversy surrounding
the drug, however,WHOcalled for more testing to ensure
that RU-486 is quite safe for women.
Étienne-Emile Baulieu
Étienne-Émile Baulieu was born in Strasbourg, France, in
1926. He moved to Paris for his advanced studies at the Faculty
of Medicine and Faculty of Science of Pasteur College. He was
an Intern of Paris from 1951 until he received a medical degree
in 1955. He passed examinations qualifying him to become a
teacher at state schools in 1958 and during the 1961-1962 academic
year was a visiting scientist in Columbia University’s
Department of Biochemistry.
In 1963 Baulieu was made a Doctor of Science and appointed
director of a research unit at France’s National Institute of
Health and Medical Science, a position he held until he retired
in 1997. He also served as Head of Service of Hormonal Biochemistry
of the Hospital of Bicêtre (1970-1997), professor of
biochemistry at University of Paris-South (1970-1993), and consultant
for Roussel Uclaf (1963-1997).
Among his many honors are the Gregory Pincus Memorial
Award (1978), awards from the National Academy of Medicine,
the Christopher Columbus Discovery Award in Biomedical Research
(1992), the Joseph Bolivar DeLee Humanitarian Award
(1994), and Commander of the Legion of Honor (1990). Although
busy with research and teaching duties, Baulieu was on
the editorial board of several French and international newspapers,
a member of scientific councils, and a participant in the
Special Program in Human Reproduction of the World Health
Organization.
See also here !
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