04 January 2015
Asuper-high-velocity centrifuge designed to separate
colloidal or submicroscopic substances, the ultracentrifuge
was used to measure the molecular weight of proteins and
proved that proteins are large molecules.
The people behind the invention:
Theodor Svedberg (1884-1971), a Swedish physical chemist and
1926 Nobel laureate in chemistry
Jesse W. Beams (1898-1977), an American physicist
Arne Tiselius (1902-1971), a Swedish physical biochemist and
1948 Nobel laureate in chemistry
Svedberg Studies Colloids
Theodor “The” Svedberg became the principal founder of molecular
biology when he invented the ultracentrifuge and used it to
examine proteins in the mid-1920’s. He began to study materials
called “colloids” as a Swedish chemistry student at the University
of Uppsala and continued to conduct experiments with colloidal
systems when he joined the faculty in 1907. A colloid is a kind of
mixture in which very tiny particles of one substance are mixed
uniformly with a dispersing medium (often water) and remain
suspended indefinitely. These colloidal dispersions play an important
role in many chemical and biological systems.
The size of the colloid particles must fall within a certain
range. The force of gravity will cause them to settle if they are too
large. If they are too small, the properties of the mixture change,
and a solution is formed. Some examples of colloidal systems include
mayonnaise, soap foam, marshmallows, the mineral opal,
fog, India ink, jelly, whipped cream, butter, paint, and milk.
Svedberg wondered what such different materials could have in
common. His early work helped to explain why colloids remain
in suspension. Later, he developed the ultracentrifuge to measure
the weight of colloid particles by causing them to settle in a controlled
Svedberg Builds an Ultracentrifuge
Svedberg was a successful chemistry professor at the University
of Uppsala in Sweden when he had the idea that colloids could be
made to separate from suspension by means of centrifugal force.
Centrifugal force is caused by circular motion and acts on matter
much as gravity does. Aperson can feel this force by tying a ball to a
rope and whirling it rapidly in a circle. The pull on the rope becomes
stronger as the ball moves faster in its circular orbit. A centrifuge
works the same way: It is a device that spins balanced containers of
substances very rapidly.
Svedberg figured that it would take a centrifugal force thousands
of times the force of gravity to cause colloid particles to settle. How
fast they settle depends on their size and weight, so the ultracentrifuge
can also provide a measure of these properties. Centrifuges were
already used to separate cream from whole milk and blood corpuscles
from plasma, but these centrifuges were too slow to cause the
separation of colloids. An ultracentrifuge—one that could spin samples
much faster—was needed, and Svedberg made plans to build one.
The opportunity came in 1923, when Svedberg spent eight months
as visiting professor in the chemistry department of the University
ofWisconsin at Madison and worked with J. Burton Nichols, one of
the six graduate students assigned to assist him. Here, Svedberg announced
encouraging results with an electrically driven centrifuge—
not yet an ultracentrifuge—which attained a rotation equal
to about 150 times the force of gravity. Svedberg returned to Sweden
and, within a year, built a centrifuge capable of generating 7,000
times the force of gravity. He used it with Herman Rinde, a colleague
at the University of Uppsala, to separate the suspended particles
of colloidal gold. This was in 1924, which is generally accepted
as the date of the first use of a true ultracentrifuge. From 1925 to
1926, Svedberg raised the funds to build an even more powerful ultracentrifuge.
It would be driven by an oil turbine, a machine capable
of producing more than 40,000 revolutions per minute to generate
a force 100,000 times that of gravity.
Svedberg and Robin Fahraeus used the new ultracentrifuge to
separate the protein hemoglobin from its colloidal suspension. Together
with fats and carbohydrates, proteins are one of the most
abundant organic constituents of living organisms. No protein had
been isolated in pure form before Svedberg began this study, and it
was uncertain whether proteins consisted of molecules of a single
compound or mixtures of different substances working together in
biological systems. The colloid particles of Svedberg’s previous
studies separated at different rates, some settling faster than others,
showing that they had different sizes and weights. Colloid particles
of the protein, however, separated together. The uniform separation
observed for proteins, such as hemoglobin, demonstrated for the
first time that each protein consists of identical well-defined molecules.
More than one hundred proteins were studied by Svedberg
and his coworkers, who extended their technique to carbohydrate
polymers such as cellulose and starch.
Svedberg built more and more powerful centrifuges so that smaller
and smaller molecules could be studied. In 1936, he built an ultracentrifuge
that produced a centrifugal force of more than a halfmillion
times the force of gravity. JesseW. Beams was an American
pioneer in ultracentrifuge design. He reduced the friction of an airdriven
rotor by first housing it in a vacuum, in 1934, and later by
supporting it with a magnetic field.
The ultracentrifuge was a central tool for providing a modern understanding
of the molecular basis of living systems, and it is employed
in thousands of laboratories for a variety of purposes. It is
used to analyze the purity and the molecular properties of substances
containing large molecules, from the natural products of the biosciences
to the synthetic polymers of chemistry. The ultracentrifuge is
also employed in medicine to analyze body fluids, and it is used in biology
to isolate viruses and the components of fractured cells.
Svedberg, while at Wisconsin in 1923, invented a second, very
different method to separate proteins in suspension using electric
currents. It is called “electrophoresis,” and it was later improved by
his student, Arne Tiselius, for use in his famous study of the proteins
in blood serum. The technique of electrophoresis is as widespread
and important as is the ultracentrifuge.