In Excellence: The Nobel Prize in Physiology or Medicine for 2013

By: Erica Lee

Albert Nobel and the Nobel Prize

Albert Nobel was dynamite.

As a child, he inhaled languages and absorbed every scientific text he could find.  He later became the sole chemist among a family of engineers.  When the Crimean War ended in 1856, the state no longer had any use for the Nobel family’s factory for war material.  Nobel, who was still a young man at the time, began working to stabilize nitroglycerine into a safe and effective explosive, a compound he refined into dynamite.

With his new invention, Nobel morphed into an entrepreneur, rolling when his factories exploded and investing wisely when sales jumped.  He patented his invention in 1867, and the next year, he and his father were awarded the Letterstedt Prize by the Royal Swedish Academy of Sciences for “important discoveries of practical value to humanity.”

However, his work came at a grave price.

Nobel’s obsessive, often dangerous overwork wracked his body with indigestion, headaches and depression.  He had few friends and rarely allowed himself to spend time with them.  He was always working, always worrying. Later in life, his chronic stress manifested in severe angina pectoris, or chest pain due to restricted vessels.  His physicians found that the compound he created, nitroglycerin, would help his condition. He was amused at this coincidence but declined treatment and died of a stroke in 1896.

He left behind a massive estate and a revolutionary will.  It stated that every year, the interest on his estate would be split into five prizes which would mark excellence in physics, chemistry, physiology or medicine, literature and peace.

It wasn’t a smooth transition.  His family vehemently opposed the establishment of a prize, and the prize awarders he had named refused to follow his will.  Five years passed before they reconsidered and moved to honor his wishes.  The first Nobel Prize was awarded in 1901.

Influential Discoveries Awarded the Nobel Prize in Physiology or Medicine

1901- The first Nobel Prize was awarded to Emil von Behring for his work in serum therapy.  Behring focused on the eradication of diphtheria, a bacterial upper respiratory tract infection.  Diphtheria was one of the major epidemics in history, and Behring’s antitoxin saved countless lives.

1930– Karl Landsteiner discovered human blood groups.

1945– Alexander Fleming, Ernst Boris Chain and Sir Howard Walter Florey discovered penicillin and its wide range of medicinal uses.

1953– Hans Adolf Krebs and Fritz Albert Lipan discovered the citric acid cycle and co-enzyme A and their roles in cellular metabolism.

1962– Francis Harry Compton Crick, James Dewey Watson and Maurice Hugh Frederick Wilkins discovered DNA and its use in cellular reproduction.

1988– Sir James W. Black, Gertrude B. Elion and George H. Hitchings discovered important principles for drug treatment, including the discovery of receptor-blocking drugs.

2009– Elizabeth H. Blackburn, Carol W. Greider and Jack W. Szostak discovered how telomeres and telomerase protect chromosomes during replication.

The Nobel Prize in Physiology or Medicine for 2013

Cells are the basic building block of all living organisms.  They were first discovered by Robert Hooke in 1665. In the three-and-a-half centuries since, scientists have unveiled an entirely new world in these microscopic structures.  For a cell to function as a part of a whole organism like the human body, it must organize its nutrients and production centers efficiently.  Sometimes the cell needs to transport structures to another part of the cell or outside of it, and the cell does this through vesicles.

Vesicles are an important part of the cell’s endomembrane system, the membranes that occur inside the cells themselves and are not the outer protective membrane. They often have different chemical characteristics than the cytosol of the cell to attract different solutes to transport.  When scientists viewed animal cells under a microscope, it was very clear that they used these little bubble-like structures to transport various structures. However, scientists knew little about how cells moved these vesicles.

Until 2013, James E. Rothman, Randy W. Schekman and Thomas c. Südhof  were jointly awarded the Nobel prize for their discoveries of the cellular mechanisms in vesicle traffic and cellular transport.

James E. Rothman is a professor of Biomedical Sciences at Yale University, the Chairman of the Department of Cell Biology at the Yale School of Medicine and the Director of the Nanobiology Institute at the Yale West Campus.

Rothman studied vesicle transport in the 1980s and 1990s.  When studying mammalian cells, he discovered a certain protein structure that allows transport vesicles to “dock” onto their target membranes and release their contents inside those membranes.  Many proteins on both the vesicle membrane and the target membrane bind to each other like a zipper. This happens both inside the cell itself and when travelling vesicles attach onto the outside of the entire cell membrane.

Randy W. Schekman is a cell biologist at the University of California and serves as the editor for eLife, a scientific journal published by the Howard Hughes Medical Institute.

He began his study of the cell’s transport systems in the 1970s using yeast as a model system to understand the genetic code behind vesicle transport.  In his studies, he observed that sometimes the vesicles in the yeast cells piled up in certain parts of the cell like a bottlenecked road.  He went to find the reason for this in the genetic code and found a mutated gene.  He later identified three genes that control the cell’s transport system in both these yeast cells and in mammalian cells

Thomas C. Südhof is a biochemist specializing in synaptic transmission. He is a professor in the School of Medicine in the Department of Molecular and Cellular Physiology and Psychiatry and Behavioral Sciences at Stanford University.

Südhof investigated how neurotransmitters in the brain communicated with each other.  Neurons in the brain use neurotransmitters to communicate with each other.  These neurotransmitters are released from vesicles from the first neuron and attach to the second neuron in the chain and release their contents there.  What makes neurotransmitters unique is their specificity.  Hormones, for example, are delivered to the entire body, but neurotransmitters only arrive at certain neurons.  Südhof found that molecular machinery in these nerve cells responds to calcium ions which direct nearby proteins to bind these vesicles to the outer membrane of the second nerve cell.  Then, like in Rothman’s discovery, the “zipper” opens up the cell and joins the vesicle with its membrane.

The Impact of this Discovery

This new information about cell physiology and how cells transport their cargo might shine a new light on diseases caused by imperfect mutations to the genes involved in cellular transport.  Since cells use vesicle transport in almost every aspect of their function, it is crucial to continue to unveil its exact process.  Imperfect or mutated genes result in many kinds of diseases, including neurological and immunological disorders.  It also plays a factor in diabetes.  A greater understanding of vesicle transport will allow scientists and physicians to better treat these diseases.