Martin Rodbell:Discovering How Cells Respond to Signals

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Rodbell's Inspiration:

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In the mid-1960s, Rodbell was studying enzymes. At that time, the only test medium available was crude chunks of fat tissue. To get more precise results, Rodbell developed a method for isolating single fat cells from the fat tissue. Because fat floats, Rodbell first put the minced tissue in a liquid and then treated the floating cells with a substance called collagenase to separate the fat cells from other cells.

"Great," he shouted, but are they viable cells?"
–Bernardo Houssay

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Photo of Martin Rodbell peering into a microscope
Martin Rodbell, 1966

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Courtesy of the Rodbell Family

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Fat cells isolated by Rodbell's method.

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Courtesy of Dr. May-Jan Zarnowski and Dr. Joseph Brzostawski, NIDDK

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image of Rodbell's commentary.
Rodbell's 1980 commentary on his 1964 paper, which became a "Citation Classic."

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Reproduced with Permission from ISI (R).
Original material published in Current Contents, Number 45, November 10, 1980

To confirm for the Nobel laureate Bernardo Houssay, who was visiting Rodbell's laboratory, that these cells were viable, Rodbell showed that the cells reacted normally to the hormone insulin. This was a turning point in his career—Rodbell's focus shifted from studying the metabolism of fat to examining the actions of hormones.

"Apparently, it often happens that a simple idea can engender consequences that are far beyond the intent."
–Martin Rodbell

The procedure for isolating fat cells was a boon to hormone research, because fat cells respond to a wide variety of hormones. No one before had been able to study hormones' effects on cells this way. Many researchers began using Rodbell's method, making his paper "The Metabolism of Isolated Fat Cells" one of the most widely cited in the field.

What causes that surge of energy you get when you are frightened?

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Martin Rodbell holding a pipe
Martin Rodbell, 1967

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Courtesy of Robert O. Scow, NIDDK

Before the work of Earl W. Sutherland, scientists knew that the adrenal gland produces a hormone called epinephrine, which travels to the body's cells and causes an increase in blood sugar. The sugar gives your body energy to react to stressful situations. But no one understood exactly how this hormone produced such an effect.

In the late 1950s, Sutherland investigated the effect of epinephrine on liver tissue. He and T.W. Rall discovered that the hormone—the "first" messenger—stimulates formation of a "second messenger" within cells. It is this second substance, cyclic adenosine monophosphate (cAMP), that stimulates the breakdown of stored carbohydrate into sugar. Sutherland suggested that the actions of many other hormones could be explained in the same way.

In 1965, Martin Rodbell was inspired when Sutherland spoke at the NIH. Rodbell realized that his isolated fat cells were the perfect medium for further investigation of the mechanism of hormone action.

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Illustration of hormone action at the cell membrane
Sutherland's model of hormone action
A receptor accepts a hormone and stimulates adenylyl cyclase (AC) to convert adenosine triphosphate (ATP) inside the cell to cyclic adenosine monophosphate (cAMP). The hormone is the first messenger; cAMP is the second. Sutherland won a Nobel Prize for this work in 1971

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Courtesy of NY Academy of Sciences - G.A. Robinson

Martin Rodbell:Discovering How Cells Respond to Signals

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Rodbell's Inspiration:

What causes that surge of energy you get when you are frightened?

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