Teflon

The invention: 



Afluorocarbon polymer whose chemical inertness
and physical properties have made it useful for many applications,
from nonstick cookware coatings to suits for astronauts.


The person behind the invention:


Roy J. Plunkett (1910-1994), an American chemist










Nontoxic Refrigerant Sought


As the use of mechanical refrigeration increased in the late 1930’s,
manufacturers recognized the need for a material to replace sulfur
dioxide and ammonia, which, although they were the commonly
used refrigerants of the time, were less than ideal for the purpose.
The material sought had to be nontoxic, odorless, colorless, and not
flammable. Thomas Midgley, Jr., and Albert Henne of General Motors
Corporation’s Frigidaire Division concluded, from studying
published reports listing properties of a wide variety of chemicals,
that hydrocarbon-like materials with hydrogen atoms replaced by
chlorine and fluorine atoms would be appropriate.
Their conclusion led to the formation of a joint effort between the
General Motors Corporation’s Frigidaire Division and E. I. Du Pont
de Nemours to research and develop the chemistry of fluorocarbons.
In this research effort, a number of scientists began making
and studying the large number of individual chemicals in the general
class of compounds being investigated. It fell to Roy J. Plunkett
to do a detailed study of tetrafluoroethylene, a compound consisting
of two carbon atoms, each of which is attached to the other as
well as to two fluorine atoms.



The “Empty” Tank


Tetrafluoroethylene, at normal room temperature and pressure,
is a gas that is supplied to users in small pressurized cylinders. On
the morning of the day of the discovery, Plunkett attached such a
tank to his experimental apparatus and opened the tank’s valve. To

his great surprise, no gas flowed from the tank. Plunkett’s subsequent
actions transformed this event from an experiment gone
wrong into a historically significant discovery. Rather than replacing
the tank with another and going on with the work planned for
the day, Plunkett, who wanted to know what had happened, examined
the “empty” tank. When he weighed the tank, he discovered
that it was not empty; it did contain the chemical that was listed on
the label. Opening the valve and running a wire through the opening
proved that what had happened had not been caused by a malfunctioning
valve. Finally, Plunkett sawed the cylinder in half and
discovered what had happened. The chemical in the tank was no
longer a gas; instead, it was a waxy white powder.
Plunkett immediately recognized the meaning of the presence of
the solid. The six-atom molecules of the tetrafluoroethylene gas had
somehow linked with one another to form much larger molecules.
The gas had polymerized, becoming polytetrafluoroethylene, a solid
with a high molecular weight. Capitalizing on this occurrence,
Plunkett, along with other Du Pont chemists, performed a series of
experiments and soon learned to control the polymerization reaction
so that the product could be produced, its properties could be
studied, and applications for it could be developed.
The properties of the substance were remarkable indeed. It was
unaffected by strong acids and bases, withstood high temperatures
without reacting or melting, and was not dissolved by any solvent
that the scientists tried. In addition to this highly unusual behavior,
the polymer had surface properties that made it very slick. It was so
slippery that other materials placed on its surface slid off in much
the same way that beads of water slide off the surface of a newly
waxed automobile.

Although these properties were remarkable, no applications were
suggested immediately for the new material. The polymer might
have remained a laboratory curiosity if a conversation had not
taken place between Leslie R. Groves, the head of the Manhattan
Project (which engineered the construction of the first atomic bombs),
and a Du Pont chemist who described the polymer to him. The
Manhattan Project research team was hunting for an inert material
to use for gaskets to seal pumps and piping. The gaskets had to be
able to withstand the highly corrosive uranium hexafluoride with

which the team was working. This uranium compound is fundamental
to the process of upgrading uranium for use in explosive devices
and power reactors. Polytetrafluoroethylene proved to be just
the material that they needed, and Du Pont proceeded, throughout
World War II and after, to manufacture gaskets for use in uranium
enrichment plants.
The high level of secrecy of the Manhattan Project in particular
and atomic energy in general delayed the commercial introduction
of the polymer, which was called Teflon, until the late 1950’s. At that
time, the first Teflon-coated cooking utensils were introduced.



Impact


Plunkett’s thoroughness in following up a chance observation
gave the world a material that has found a wide variety of uses, ranging
from home kitchens to outer space. Some applications make use

of Teflon’s slipperiness, othersmake use of its inertness, and others take

advantage of both properties.
The best-known application of Teflon is as a nonstick coating for cookware.
Teflon’s very slippery surface initially was troublesome, when it proved to be
difficult to attach to other materials. Early versions of Teflon-coated cookware

shed their surface coatings easily, even when care was taken to avoid scraping it off.

A suitable bonding process was soon developed, however, and the present coated

surfaces are very rugged and provide a noncontaminating coating that can be cleaned
easily.
Teflon has proved to be a useful material in making devices that
are implanted in the human body. It is easily formed into various
shapes and is one of the few materials that the human body does not
reject. Teflon has been used to make heart valves, pacemakers, bone
and tendon substitutes, artificial corneas, and dentures.
Teflon’s space applications have included its use as the outer skin
of the suits worn by astronauts, as insulating coating on wires and
cables in spacecraft that must resist high-energy cosmic radiation,
and as heat-resistant nose cones and heat shields on spacecraft.

Roy J. Plunkett






Roy J. Plunkett was born in 1910 in New Carlisle, Ohio. In
1932 he received a bachelor’s degree in chemistry from Manchester
College and transferred to Ohio State University for
graduate school, earning a master’s degree in 1933 and a doctorate
in 1936. The same year he went to work for E. I. Du Pont
de Nemours and Company as a research chemist at the Jackson
Laboratory in Deepwater, New Jersey. Less then two years later,
when he was only twenty-seven years old, he found the strange
polymer tetrafluoroethylene, whose trade name became Teflon.
It would turn out to be among Du Pont’s most famous products.
In 1938 Du Pont appointed Plunkett the chemical supervisor
at its largest plant, the Chamber Works in Deepwater, which
produced tetraethyl lead. He held the position until 1952 and
afterward directed the company’s Freon Products Division. He
retired in 1975. In 1985 he was inducted into the Inventor’s Hall
of Fame, and after his death in 1994, Du Pont created the
Plunkett Award, presented to inventors who find new uses for
Teflon and Tefzel, a related fluoropolymer, in



See also :



Buna rubber; Neoprene; Nylon; Plastic; Polystyrene;

Talking motion pictures

The invention:



The first practical system for linking sound with

moving pictures.



The people behind the invention:



Harry Warner (1881-1958), the brother who used sound to

fashion a major filmmaking company

Albert Warner (1884-1967), the brother who persuaded theater

owners to show Warner films

Samuel Warner (1887-1927), the brother who adapted soundrecording

technology to filmmaking

Jack Warner (1892-1978), the brother who supervised the

making of Warner films











Taking the Lead



The silent films of the early twentieth century had live sound accompaniment

featuring music and sound effects. Neighborhood

theaters made do with a piano and violin; larger “picture palaces”

in major cities maintained resident orchestras of more than seventy

members. During the late 1920’s, Warner Bros. led the American

film industry in producing motion pictures with their own soundtracks,

which were first recorded on synchronized records and later

added on to the film beside the images.

The ideas that led to the addition of sound to film came from corporate-

sponsored research by American Telephone and Telegraph

Company (AT&T) and the Radio Corporation of America (RCA).

Both companies worked to improve sound recording and playback,

AT&T to help in the design of long-distance telephone equipment

and RCAas part of the creation of better radio sets. Yet neither company

could, or would, enter filmmaking. AT&T was willing to contract

its equipment out to Paramount or one of the other major Hollywood

studios of the day; such studios, however, did not want to

risk their sizable profit positions by junking silent films. The giants

of the film industry were doing fine with what they had and did not

want to switch to something that had not been proved.

In 1924,Warner Bros. was a prosperous, though small, corporation

that produced films with the help of outside financial backing. That

year, HarryWarner approached the importantWall Street investment

banking house of Goldman, Sachs and secured the help he needed.

As part of this initial wave of expansion,Warner Bros. acquired a

Los Angeles radio station in order to publicize its films. Through

this deal, the four Warner brothers learned of the new technology

that the radio and telephone industries had developed to record

sound, and they succeeded in securing the necessary equipment

from AT&T. During the spring of 1925, the brothers devised a plan

by which they could record the most popular musical artists on film

and then offer these “shorts” as added attractions to theaters that

booked its features. As a bonus, Warner Bros. could add recorded

orchestral music to its feature films and offer this music to theaters

that relied on small musical ensembles.





“Vitaphone”



On August 6, 1926,Warner Bros. premiered its new “Vitaphone”

technology. The first package consisted of a traditional silent film

(Don Juan) with a recorded musical accompaniment, plus six recordings

of musical talent highlighted by a performance from Giovanni

Martineli, the most famous opera tenor of the day.

The first Vitaphone feature was The Jazz Singer, which premiered

in October, 1927. The film was silent during much of the movie, but

as soon as Al Jolson, the star, broke into song, the new technology

would be implemented. The film was an immediate hit. The Jazz

Singer package, which included accompanying shorts with sound,

forced theaters in cities that rarely held films over for more than a

single week to ask to have the package stay for two, three, and

sometimes four straight weeks.

The Jazz Singer did well at the box office, but skeptics questioned

the staying power of talkies. If sound was so important, they wondered,

why hadn’t The Jazz Singer moved to the top of the all-time

box-office list? Such success, though, would come a year later with

The Singing Fool, also starring Jolson. From its opening day (September

20, 1928), it was the financial success of its time; produced for an

estimated $200,000, it took in $5 million. In New York City, The

Singing Fool registered the heaviest business in Broadway history,

with an advance sale that exceeded more than $100,000 (equivalent

to more than half a million dollars in 1990’s currency).





Impact



The coming of sound transformed filmmaking, ushering in what

became known as the golden age of Hollywood. By 1930, there were

more reporters stationed in the filmmaking capital of the world

than in any capital of Europe or Asia.

As a result of its foresight,Warner Bros. was the sole small competitor

of the early 1920’s to succeed in the Hollywood elite, producing

successful films for consumption throughout the world.

After Warner Bros.’ innovation, the soundtrack became one of

the features that filmmakers controlled when making a film. Indeed,

sound became a vital part of the filmmaker’s art; music, in

particular, could make or break a film.

Finally, the coming of sound helped make films a dominant medium

of mass culture, both in the United States and throughout the

world. Innumerable fashions, expressions, and designs were soon created

or popularized by filmmakers. Many observers had not viewed

the silent cinema as especially significant; with the coming of the talkies,

however, there was no longer any question about the social and

cultural importance of films. As one clear consequence of the new

power of the movie industry, within a few years of the coming of

sound, the notorious Hays Code mandating prior restraint of film content

went into effect. The pairing of images and sound caused talking

films to be deemed simply too powerful for uncensored presentation

to audiences; although the Hays Code was gradually weakened and

eventually abandoned, less onerous “rating systems” would continue

to be imposed on filmmakers by various regulatory bodies.





The Warner Brothers


Businessmen rather than inventors, the four Warner brothers
were hustlers who knew a good thing when they saw it.
They started out running theaters in 1903, evolved into film distributors,
and began making their own films in 1909, in defiance
of the Patents Company, a trust established by Thomas A. Edison
to eliminate competition from independent filmmakers.
HarryWarner was the president of the company, Sam and Jack
were vice presidents in charge of production, and Abe (or Albert)
was the treasurer.
Theirs was a small concern. Their silent films and serials attracted
few audiences, and during World War I they made
training films for the government. In fact, their film about syphilis,
Open Your Eyes, was their first real success. In 1918, however,
they released My Four Years in Germany, a dramatized
documentary, and it was their first blockbuster. Although considered
gauche upstarts, they were suddenly taken seriously by
the movie industry.
When Sam first heard an actor talk on screen in an experimental
film at the Bell lab in New York in 1925, he recognized a
revolutionary opportunity. He soon convinced Jack that talking
movies would be a gold mine. However, Harry and Abe were
against the idea because of its costs—and because earlier attempts
at “talkies” had been dismal failures. Sam and Jack
tricked Harry into a seeing a experimental film of an orchestra,
however, and he grew enthusiastic despite his misgivings.Within
a year, the brothers released the all-music Don Juan. The rave
notices from critics astounded Harry and Abe.
Still, they thought sound in movies was simply a novelty.
When Sam pointed out that they could make movies in which
the actors talked, as on stage, Harry, who detested actors, snorted,
“Who the hell wants to hear actors talk?” Sam and Jack pressed
for dramatic talkies, nonetheless, and prevailed upon Harry to
finance them. The silver screen has seldom been silent since.





See also :



Autochrome plate; Dolby noise reduction; Electronicsynthesizer;



Further Reading :

Syphilis test

The invention: 



The first simple test for detecting the presence of

the venereal disease syphilis led to better syphilis control and

other advances in immunology.



The people behind the invention:



Reuben Leon Kahn (1887-1974), a Soviet-born American

serologist and immunologist



August von Wassermann (1866-1925), a German physician and

bacteriologist









Columbus’s Discoveries



Syphilis is one of the chief venereal diseases, a group of diseases

whose name derives from Venus, the Roman goddess of love. The

term “venereal” arose from the idea that the diseases were transmitted

solely by sexual contact with an infected individual. Although

syphilis is almost always passed from one person to another in this

way, it occasionally arises after contact with objects used by infected

people in highly unclean surroundings, particularly in the underdeveloped

countries of the world.

It is believed by many that syphilis was introduced to Europe by

the members of Spanish explorer Christopher Columbus’s crew—

supposedly after they were infected by sexual contact withWest Indian

women—during their voyages of exploration. Columbus is reported

to have died of heart and brain problems very similar to

symptoms produced by advanced syphilis. At that time, according

to many historians, syphilis spread rapidly over sixteenth century

Europe. The name “syphilis” was coined by the Italian physician

Girolamo Fracastoro in 1530 in an epic poem he wrote.

Modern syphilis is much milder than the original disease and relatively

uncommon. Yet, if it is not identified and treated appropriately,

syphilis can be devastating and even fatal. It can also be passed from

pregnant mothers to their unborn children. In these cases, the afflicted

children will develop serious health problems that can include

paralysis, insanity, and heart disease. Therefore, the understanding,

detection, and cure of syphilis are important worldwide.

Syphilis is caused by a spiral-shaped germ called a “spirochete.”

Spirochetes enter the body through breaks in the skin or through the

mucous membranes, regardless of how they are transmitted. Once

spirochetes enter the body, they spread rapidly. During the first four

to six weeks after infection, syphilis—said to be in its primary

phase—is very contagious. During this time, it is identified by the

appearance of a sore, or chancre, at the entry site of the infecting spirochetes.

The chancre disappears quickly, and within six to twenty-four

weeks, the disease shows itself as a skin rash, feelings of malaise,

and other flulike symptoms (secondary-phase syphilis). These problems

also disappear quickly in most cases, and here is where the real

trouble—latent syphilis—begins. In latent syphilis, now totally without

symptoms, spirochetes that have spread through the body may

lodge in the brain or the heart. When this happens, paralysis, mental

incapacitation, and death may follow.





Testing Before Marriage







Because of the danger to unborn children, Americans wishing to

marry must be certified as being free of the disease before a marriage

license is issued. The cure for syphilis is easily accomplished

through the use of penicillin or other types of antibiotics, though no

vaccine is yet available to prevent the disease. It is for this reason

that syphilis detection is particularly important.

The first viable test for syphilis was originated by August von

Wassermann in 1906. In this test, blood samples are taken and

treated in a medical laboratory. The treatment of the samples is

based on the fact that the blood of infected persons has formed antibodies

to fight the syphilis spirochete, and that these antibodies will

react with certain body chemicals to cause the blood sample to clot.

This indicates the person has the disease. After the syphilis has been

cured, the antibodies disappear, as does the clotting.

Although the Wassermann test was effective in 95 percent of all

infected persons, it was very time-consuming (requiring a two-day

incubation period) and complex. In 1923, Reuben Leon Kahn developed

a modified syphilis test, “the standard Kahn test,” that was

simpler and faster: The test was complete after only a few minutes.

By 1925, Kahn’s test had become the standard syphilis test of the

United States Navy and later became a worldwide test for the detection

of the disease.

Kahn soon realized that his test was not perfect and that in some

cases, the results were incorrect. This led him to a broader study of

the immune reactions at the center of the Kahn test. He investigated

the role of various tissues in immunity, as compared to the role of

white blood antibodies and white blood cells. Kahn showed, for example,

that different tissues of immunized or nonimmunized animals

possessed differing immunologic capabilities. Furthermore,

the immunologic capabilities of test animals varied with their

age, being very limited in newborns and increasing as they matured.

This effort led, by 1951, to Kahn’s “universal serological reaction,”

a precipitation reaction in which blood serum was tested

against a reagent composed of tissue lipids. Kahn viewed it as a potentially

helpful chemical indicator of how healthy or ill an individual

was. This effort is viewed as an important landmark in the development

of the science of immunology.



Impact



At the time that Kahn developed his standard Kahn test for syphilis,

theWassermann test was used all over the world for the diagnosis

of syphilis. As has been noted, one of the great advantages of the

standard Kahn test was its speed, minutes versus days. For example,

in October, 1923, Kahn is reported to have tested forty serum

samples in fifteen minutes.

Kahn’s efforts have been important to immunology and to medicine.

Among the consequences of his endeavors was the stimulation

of other developments in the field, including the VDRL test (originated

by the Venereal Disease Research Laboratory), which has replaced

the Kahn test as one of the most often used screening tests for

syphilis. Even more specific syphilis tests developed later include a

fluorescent antibody test to detect the presence of the antibody to

the syphilis spirochete.





See also: Abortion pill;Antibacterial drugs; Birth control pill;

Mammography; Pap test; Penicillin;







Further Reading :

Synthetic RNA

 





The invention: 



A method for synthesizing the biological molecule
RNA established that this process can occur outside the living
cell.


The people behind the invention:


Severo Ochoa (1905-1993), a Spanish biochemist who shared
the 1959 Nobel Prize in Physiology or Medicine
Marianne Grunberg-Manago (1921- ), a French biochemist
Marshall W. Nirenberg (1927- ), an American biochemist
who won the 1968 Nobel Prize in Physiology or Medicine
Peter Lengyel (1929- ), a Hungarian American biochemist











RNA Outside the Cells


In the early decades of the twentieth century, genetics had not
been experimentally united with biochemistry. This merging soon
occurred, however, with work involving the mold Neurospora crassa.
This Nobel award-winning work by biochemist Edward Lawrie
Tatum and geneticist George Wells Beadle showed that genes control
production of proteins, which are major functional molecules in
cells. Yet no one knew the chemical composition of genes and chromosomes,
or, rather, the molecules of heredity.
The American bacteriologist Oswald T. Avery and his colleagues
at New York’s Rockefeller Institute determined experimentally that
the molecular basis of heredity was a large polymer known as deoxyribonucleic
acid (DNA). Avery’s discovery triggered a furious
worldwide search for the particular structural characteristics of
DNA, which allow for the known biological characteristics of genes.
One of the most famous studies in the history of science solved
this problem in 1953. Scientists James D.Watson, Francis Crick, and
Maurice H. F.Wilkins postulated that DNAexists as a double helix.
That is, two long strands twist about each other in a predictable pattern,
with each single strand held to the other by weak, reversible
linkages known as “hydrogen bonds.” About this time, researchers
recognized also that a molecule closely related to DNA, ribonucleic

acid (RNA), plays an important role in transcribing the genetic information
as well as in other biological functions.
Severo Ochoa was born in Spain as the science of genetics was
developing. In 1942, he moved to New York University, where he
studied the bacterium Azobacter vinelandii. Specifically, Ochoa was
focusing on the question of how cells process energy in the form of
organic molecules such as the sugar glucose to provide usable biological
energy in the form of adenosine triphosphate (ATP). With
postdoctoral fellow Marianne Grunberg-Manago, he studied enzymatic
reactions capable of incorporating inorganic phosphate (a
compound consisting of one atom of phosphorus and four atoms of
oxygen) into adenosine diphosphate (ADP) to form ATP.
One particularly interesting reaction was followed by monitoring
the amount of radioactive phosphate reacting with ADP. Following
separation of the reaction products, it was discovered that
the main product was not ATP, but a much larger molecule. Chemical
characterization demonstrated that this product was a polymer
of adenosine monophosphate. When other nucleocide diphosphates,
such as inosine diphosphate, were used in the reaction, the
corresponding polymer of inosine monophosphate was formed.
Thus, in each case, a polymer (a long string of building-block
units) was formed. The polymers formed were synthetic RNAs, and
the enzyme responsible for the conversion became known as “polynucleotide
phosphorylase.” This finding, once the early skepticism
was resolved, was received by biochemists with great enthusiasm
because no technique outside the cell had ever been discovered
previously in which a nucleic acid similar to RNA could be
synthesized.







Learning the Language








Ochoa, Peter Lengyel, and MarshallW. Nirenberg at the National
Institute of Health took advantage of this breakthrough to synthesize
different RNAs useful in cracking the genetic code. Crick had
postulated that the flow of information in biological systems is from
DNA to RNA to protein. In other words, genetic information contained
in the DNA structure is transcribed into complementary
RNAstructures, which, in turn, are translated into the protein. Pro-

tein synthesis, an extremely complex process, involves bringing a
type of RNA, known as messenger RNA, together with amino acids
and huge cellular organelles known as ribosomes.
Yet investigators did not know the nature of the nucleic acid alphabet—
for example, how many single units of the RNA polymer
code were needed for each amino acid, and the order that the units
must be in to stand for a “word” in the nucleic acid language. In
1961, Nirenberg demonstrated that the polymer of synthetic RNA
with multiple units of uracil (poly U) would “code” only for a protein
containing the amino acid phenylalanine. Each three units (U’s)
gave one phenylalanine. Therefore, genetic words each contain
three letters. UUU translates into phenylalanine. Poly A, the first
polymer discovered with polynucleotide phosphorylase, was coded
for a protein containing multiple lysines. That is, AAA translates
into the amino acid lysine.
The words, containing combinations of letters, such as AUG, were
not as easily studied, but Nirenberg, Ochoa, and Gobind Khorana of
the University of Wisconsin eventually uncovered the exact translation
for each amino acid. In RNA, there are four possible letters (A, U,
G, and C) and three letters in each word. Accordingly, there are sixtyfour
possible words. With only twenty amino acids, it became clear
that more than one RNAword can translate into a given amino acid.
Yet, no given word stands for any more than one amino acid. A few
words do not translate into any amino acid; they are stop signals, telling
the ribosome to cease translating RNA.
The question of which direction an RNA is translated is critical.
For example, CAA codes for the amino acid glutamine, but the reverse,
AAC, translates to the amino acid asparagine. Such a difference
is critical because the exact sequence of a protein determines its
activity—that is, what it will do in the body and therefore what genetic
trait it will express.





Consequences








Synthetic RNAs provided the key to understanding the genetic
code. The genetic code is universal; it operates in all organisms, simple
or complex. It is used by viruses, which are nearly life but are not
alive. Spelling out the genetic code was one of the top discoveries of

the twentieth century. Nearly all work in molecular biology depends
on this knowledge.
The availability of synthetic RNAs has provided hybridization
tools for molecular geneticists. Hybridization is a technique in which
an RNA is allowed to bind in a complementary fashion to DNA under
investigation. The greater the similarity between RNAand DNA,
the greater the amount of binding. The differential binding allows for
seeking, finding, and ultimately isolating a target DNAfrom a large,
diverse pool of DNA—in short, finding a needle in a haystack. Hybridization
has become an indispensable aid in experimental molecular
genetics as well as in applied sciences, such as forensics.



 See also :



 Artificial hormone; Cloning; Genetic“fingerprinting”;

Genetically engineered insulin; In vitro plantculture;

Synthetic amino acid ; Synthetic DNA , Small interfering RNA



 Further Reading :

Synthetic DNA

The invention: 



A method for replicating viral deoxyribonucleic

acid (DNA) in a test tube that paved the way for genetic engineering.



The people behind the invention:



Arthur Kornberg (1918- ), an American physician and

biochemist

Robert L. Sinsheimer (1920- ), an American biophysicist

Mehran Goulian (1929- ), a physician and biochemist









The Role of DNA



Until the mid-1940’s, it was believed that proteins were the

carriers of genetic information, the source of heredity. Proteins

appeared to be the only biological molecules that had the complexity

necessary to encode the enormous amount of genetic information

required to reproduce even the simplest organism.

Nevertheless, proteins could not be shown to have genetic properties,

and by 1944, it was demonstrated conclusively that deoxyribonucleic

acid (DNA) was the material that transmitted hereditary

information. It was discovered that DNA isolated from a

strain of infective bacteria that can cause pneumonia was able to

transform a strain of noninfective bacteria into an infective strain;

in addition, the infectivity trait was transmitted to future generations.

Subsequently, it was established that DNA is the genetic material

in virtually all forms of life.

Once DNA was known to be the transmitter of genetic information,

scientists sought to discover how it performs its role. DNA is a

polymeric molecule composed of four different units, called “deoxynucleotides.”

The units consist of a sugar, a phosphate group, and a

base; they differ only in the nature of the base, which is always one of

four related compounds: adenine, guanine, cytosine, or thymine. The

way in which such a polymer could transmit genetic information,

however, was difficult to discern. In 1953, biophysicists James D.Watson

and Francis Crick brilliantly determined the three-dimensional

structure of DNAby analyzing X-ray diffraction photographs of DNA

fibers. From their analysis of the structure of DNA,Watson and Crick

inferredDNA’s mechanism of replication. Their work led to an understanding

of gene function in molecular terms.

Watson and Crick showed that DNA has a very long doublestranded

(duplex) helical structure. DNAhas a duplex structure because

each base forms a link to a specific base on the opposite

strand. The discovery of this complementary pairing of bases provided

a model to explain the two essential functions of a hereditary

molecule: It must preserve the genetic code from one generation to

the next, and it must direct the development of the cell.

Watson and Crick also proposed that DNA is able to serve as a

mold (or template) for its own reproduction because the two strands

ofDNApolymer can separate. Upon separation, each strand acts as a

template for the formation of a new complementary strand. An adenine

base in the existing strand gives rise to cytosine, and so on. In

this manner, a new double-stranded DNAis generated that is identical

to the parent DNA.





DNA in a Test Tube



Watson and Crick’s theory provided a valuable model for the reproduction

of DNA, but it did not explain the biological mechanism

by which the process occurs. The biochemical pathway of DNA reproduction

and the role of the enzymes required for catalyzing the

reproduction process were discovered by Arthur Kornberg and his

coworkers. For his success in achievingDNAsynthesis in a test tube

and for discovering and isolating an enzyme—DNA polymerase—

that catalyzed DNA synthesis, Kornberg won the 1959 Nobel Prize

in Physiology or Medicine.

To achieve DNAreplication in a test tube, Kornberg found that a

small amount of preformed DNA must be present, in addition to

DNApolymerase enzyme and all four of the deoxynucleotides that

occur in DNA. Kornberg discovered that the base composition of

the newly made DNAwas determined solely by the base composition

of the preformed DNA, which had been used as a template in

the test-tube synthesis. This result showed that DNA polymerase

obeys instructions dictated by the template DNA. It is thus said to

be “template-directed.” DNA polymerase was the first templatedirected

enzyme to be discovered.

Although test-tube synthesis was a most significant achievement,

important questions about the precise character of the newly

made DNAwere still unanswered. Methods of analyzing the order,

or sequence, of the bases in DNA were not available, and hence it

could not be shown directly whetherDNAmade in the test tube was

an exact copy of the template of DNA or merely an approximate

copy. In addition, some DNAs prepared by DNA polymerase appeared

to be branched structures. Since chromosomes in living cells

contain long, linear, unbranched strands of DNA, this branching

might have indicated that DNA synthesized in a test tube was not

equivalent to DNA synthesized in the living cell.

Kornberg realized that the best way to demonstrate that newly

synthesizedDNAis an exact copy of the original was to test the new

DNAfor biological activity in a suitable system. Kornberg reasoned

that a demonstration of infectivity in viral DNA produced in a test

tube would prove that polymerase-catalyzed synthesis was virtually

error-free and equivalent to natural, biological synthesis. The

experiment, carried out by Kornberg, Mehran Goulian at Stanford

University, and Robert L. Sinsheimer at the California Institute of

Technology, was a complete success. The viral DNAs produced in a

test tube by the DNA polymerase enzyme, using a viral DNA template,

were fully infective. This synthesis showed that DNA polymerase

could copy not merely a single gene but also an entire chromosome

of a small virus without error.





Consequences











The purification of DNApolymerase and the preparation of biologically

active DNA were major achievements that influenced

biological research on DNA for decades. Kornberg’s methodology

proved to be invaluable in the discovery of other enzymes that synthesize

DNA. These enzymes have been isolated from Escherichia

coli bacteria and fromother bacteria, viruses, and higher organisms.

The test-tube preparation of viral DNA also had significance in

the studies of genes and chromosomes. In the mid-1960’s, it had not

been established that a chromosome contains a continuous strand of

DNA. Kornberg and Sinsheimer’s synthesis of a viral chromosome

proved that it was, indeed, a very long strand of uninterrupted

DNA.

Kornberg and Sinsheimer’s work laid the foundation for subsequent

recombinant DNAresearch and for genetic engineering technology.

This technology promises to revolutionize both medicine

and agriculture. The enhancement of food production and the generation

of new drugs and therapies are only a few of the subsequent

benefits that may be expected.





See also : Artificial hormone; Cloning; Genetic“fingerprinting”;

Genetically engineered insulin; In vitro plant culture;

Synthetic amino acid;Artificial gene synthesis.





Further Reading

Synthetic amino acid

 The invention :



Amethod for synthesizing amino acids by combining
water, hydrogen, methane, and ammonia and exposing the
mixture to an electric spark.



The people behind the invention : 



Stanley Lloyd Miller (1930- ), an American professor of
chemistry

Harold Clayton Urey (1893-1981), an American chemist who
won the 1934 Nobel Prize in Chemistry



Aleksandr Ivanovich Oparin (1894-1980), a Russian biochemist

John Burdon Sanderson Haldane (1892-1964), a British scientist







Prebiological Evolution



The origin of life on Earth has long been a tough problem for scientists

to solve. While most scientists can envision the development

of life through geologic time from simple single-cell bacteria

to complex mammals by the processes of mutation and natural selection,

they have found it difficult to develop a theory to define

how organic materials were first formed and organized into lifeforms.

This stage in the development of life before biologic systems

arose, which is called “chemical evolution,” occurred between

4.5 and 3.5 billion years ago. Although great advances in

genetics and biochemistry have shown the intricate workings of

the cell, relatively little light has been shed on the origins of this intricate

machinery of the cell. Some experiments, however, have

provided important data from which to build a scientific theory of

the origin of life. The first of these experiments was the classic

work of Stanley Lloyd Miller.

Miller worked with Harold Clayton Urey, a Nobel laureate, on the

environments of the early earth. John Burdon Sanderson Haldane, a

British biochemist, had suggested in 1929 that the earth’s early atmosphere

was a reducing one—that it contained no free oxygen. In

1952, Urey published a seminal work in planetology, The Planets, in

which he elaborated on Haldane’s suggestion, and he postulated

that the earth had formed from a cold stellar dust cloud. Urey

thought that the earth’s primordial atmosphere probably contained

elements in the approximate relative abundances found in the solar

system and the universe.

It had been discovered in 1929 that the Sun is approximately 87

percent hydrogen, and by 1935 it was known that hydrogen encompassed

the vast majority (92.8 percent) of atoms in the universe.

Urey reasoned that the earth’s early atmosphere contained mostly

hydrogen, with the oxygen, nitrogen, and carbon atoms chemically

bonded to hydrogen to form water, ammonia, and methane. Most

important, free oxygen could not exist in the presence of such an

abundance of hydrogen.

As early as the mid-1920’s, Aleksandr Ivanovich Oparin, a Russian

biochemist, had argued that the organic compounds necessary

for life had been built up on the early earth by chemical combinations

in a reducing atmosphere. The energy from the Sun would

have been sufficient to drive the reactions to produce life. Haldane

later proposed that the organic compounds would accumulate in

the oceans to produce a “dilute organic soup” and that life might

have arisen by some unknown process from that mixture of organic

compounds.





Primordial Soup in a Bottle



Miller combined the ideas of Oparin and Urey and designed a

simple, but elegant, experiment. He decided to mix the gases presumed

to exist in the early atmosphere (water vapor, hydrogen, ammonia,

and methane) and expose them to an electrical spark to determine

which, if any, organic compounds were formed. To do this,

he constructed a relatively simple system, essentially consisting of

two Pyrex flasks connected by tubing in a roughly circular pattern.

The water and gases in the smaller flask were boiled and the resulting

gas forced through the tubing into a larger flask that contained

tungsten electrodes. As the gases passed the electrodes, an electrical

spark was generated, and from this larger flask the gases and any

other compounds were condensed. The gases were recycled through

the system, whereas the organic compounds were trapped in the

bottom of the system.

Miller was trying to simulate conditions that had prevailed on

the early earth. During the one week of operation, Miller extracted

and analyzed the residue of compounds at the bottom of the system.

The results were truly astounding. He found that numerous organic

compounds had, indeed, been formed in only that one week. As

much as 15 percent of the carbon (originally in the gas methane) had

been combined into organic compounds, and at least 5 percent of

the carbon was incorporated into biochemically important compounds.

The most important compounds produced were some of

the twenty amino acids essential to life on Earth.

The formation of amino acids is significant because they are the

building blocks of proteins. Proteins consist of a specific sequence of

amino acids assembled into a well-defined pattern. Proteins are necessary

for life for two reasons. First, they are important structural

materials used to build the cells of the body. Second, the enzymes

that increase the rate of the multitude of biochemical reactions of life

are also proteins. Miller not only had produced proteins in the laboratory

but also had shown clearly that the precursors of proteins—

the amino acids—were easily formed in a reducing environment

with the appropriate energy.

Perhaps the most important aspect of the experiment was the

ease with which the amino acids were formed. Of all the thousands

of organic compounds that are known to chemists, amino acids

were among those that were formed by this simple experiment. This

strongly implied that one of the first steps in chemical evolution was

not only possible but also highly probable. All that was necessary

for the synthesis of amino acids were the common gases of the solar

system, a reducing environment, and an appropriate energy source,

all of which were present on early Earth.



Consequences



Miller opened an entirely new field of research with his pioneering

experiments. His results showed that much about chemical

evolution could be learned by experimentation in the laboratory.

As a result, Miller and many others soon tried variations on

his original experiment by altering the combination of gases, using

other gases, and trying other types of energy sources. Almost all

the essential amino acids have been produced in these laboratory

experiments.

Miller’s work was based on the presumed composition of the

primordial atmosphere of Earth. The composition of this atmosphere

was calculated on the basis of the abundance of elements

in the universe. If this reasoning is correct, then it is highly likely

that there are many other bodies in the universe that have similar

atmospheres and are near energy sources similar to the Sun.

Moreover, Miller’s experiment strongly suggests that amino acids,

and perhaps life as well, should have formed on other planets.



See also : Artificial hormone; Artificial kidney .



Further Reading :

Synchrocyclotron

The invention: 



A powerful particle accelerator that performed

better than its predecessor, the cyclotron.



The people behind the invention:



Edwin Mattison McMillan (1907-1991), an American physicist

who won the Nobel Prize in Chemistry in 1951

Vladimir Iosifovich Veksler (1907-1966), a Soviet physicist

Ernest Orlando Lawrence (1901-1958), an American physicist

Hans Albrecht Bethe (1906- ), a German American physicist









The First Cyclotron



The synchrocyclotron is a large electromagnetic apparatus designed

to accelerate atomic and subatomic particles at high energies.

Therefore, it falls under the broad class of scientific devices

known as “particle accelerators.” By the early 1920’s, the experimental

work of physicists such as Ernest Rutherford and George

Gamow demanded that an artificial means be developed to generate

streams of atomic and subatomic particles at energies much

greater than those occurring naturally. This requirement led Ernest

Orlando Lawrence to develop the cyclotron, the prototype for most

modern accelerators. The synchrocyclotron was developed in response

to the limitations of the early cyclotron.

In September, 1930, Lawrence announced the basic principles behind

the cyclotron. Ionized—that is, electrically charged—particles

are admitted into the central section of a circular metal drum. Once

inside the drum, the particles are exposed to an electric field alternating

within a constant magnetic field. The combined action of the

electric and magnetic fields accelerates the particles into a circular

path, or orbit. This increases the particles’ energy and orbital radii.

This process continues until the particles reach the desired energy

and velocity and are extracted from the machine for use in experiments

ranging from particle-to-particle collisions to the synthesis of

radioactive elements.

Although Lawrence was interested in the practical applications

of his invention in medicine and biology, the cyclotron also was applied

to a variety of experiments in a subfield of physics called

“high-energy physics.” Among the earliest applications were studies

of the subatomic, or nuclear, structure of matter. The energetic

particles generated by the cyclotron made possible the very type of

experiment that Rutherford and Gamow had attempted earlier.

These experiments, which bombarded lithium targets with streams

of highly energetic accelerated protons, attempted to probe the inner

structure of matter.

Although funding for scientific research on a large scale was

scarce beforeWorldWar II (1939-1945), Lawrence nevertheless conceived

of a 467-centimeter cyclotron that would generate particles

with energies approaching 100 million electronvolts. By the end of

the war, increases in the public and private funding of scientific research

and a demand for higher-energy particles created a situation

in which this plan looked as if it would become reality, were it not

for an inherent limit in the physics of cyclotron operation.





Overcoming the Problem of Mass





In 1937, Hans Albrecht Bethe discovered a severe theoretical limitation

to the energies that could be produced in a cyclotron. Physicist

Albert Einstein’s special theory of relativity had demonstrated

that as any mass particle gains velocity relative to the speed of light,

its mass increases. Bethe showed that this increase in mass would

eventually slow the rotation of each particle. Therefore, as the rotation

of each particle slows and the frequency of the alternating electric

field remains constant, particle velocity will decrease eventually.

This factor set an upper limit on the energies that any cyclotron

could produce.

Edwin Mattison McMillan, a colleague of Lawrence at Berkeley,

proposed a solution to Bethe’s problem in 1945. Simultaneously and

independently, Vladimir Iosifovich Veksler of the Soviet Union proposed

the same solution. They suggested that the frequency of the

alternating electric field be slowed to meet the decreasing rotational

frequencies of the accelerating particles—in essence, “synchroniz-

ing” the electric field with the moving particles. The result was the

synchrocyclotron.

Prior toWorldWar II, Lawrence and his colleagues had obtained

the massive electromagnet for the new 100-million-electronvolt cyclotron.

This 467-centimeter magnet would become the heart of the

new Berkeley synchrocyclotron. After initial tests proved successful,

the Berkeley team decided that it would be reasonable to convert

the cyclotron magnet for use in a new synchrocyclotron. The

apparatus was operational in November of 1946.

These high energies combined with economic factors to make the

synchrocyclotron a major achievement for the Berkeley Radiation

Laboratory. The synchrocyclotron required less voltage to produce

higher energies than the cyclotron because the obstacles cited by

Bethe were virtually nonexistent. In essence, the energies produced

by synchrocyclotrons are limited only by the economics of building

them. These factors led to the planning and construction of other

synchrocyclotrons in the United States and Europe. In 1957, the

Berkeley apparatus was redesigned in order to achieve energies of

720 million electronvolts, at that time the record for cyclotrons of

any kind.





Impact



Previously, scientists had had to rely on natural sources for highly

energetic subatomic and atomic particles with which to experiment.

In the mid-1920’s, the American physicist Robert Andrews Millikan

began his experimental work in cosmic rays, which are one natural

source of energetic particles called “mesons.” Mesons are charged

particles that have a mass more than two hundred times that of the

electron and are therefore of great benefit in high-energy physics experiments.

In February of 1949, McMillan announced the first synthetically

produced mesons using the synchrocyclotron.

McMillan’s theoretical development led not only to the development

of the synchrocyclotron but also to the development of the

electron synchrotron, the proton synchrotron, the microtron, and

the linear accelerator. Both proton and electron synchrotrons have

been used successfully to produce precise beams of muons and pimesons,

or pions (a type of meson).

The increased use of accelerator apparatus ushered in a new era

of physics research, which has become dominated increasingly by

large accelerators and, subsequently, larger teams of scientists and

engineers required to run individual experiments. More sophisticated

machines have generated energies in excess of 2 trillion

electronvolts at the United States’ Fermi National Accelerator Laboratory,

or Fermilab, in Illinois. Part of the huge Tevatron apparatus

at Fermilab, which generates these particles, is a proton synchrotron,

a direct descendant of McMillan and Lawrence’s early

efforts.



See also: Atomic bomb; Cyclotron; Electron microscope;

Field ionmicroscope; Geiger counter; Hydrogen bomb;

Mass spectrograph;Neutrino detector; Scanning tunneling microscope;

Synchrocyclotron



Further Reading :