The Noble Prize: Legacy
by Olivia Parks & Erin Cullen
Part I: The Merchant of Death and the History of the Nobel Prize
St. Petersburg, Russia, Summer 1862
Swedish chemist and engineer, Alfred Bernhard Nobel, returns from a two-year study abroad trip to find that his father’s business has collapsed. In the absence of a steady job, Nobel begins experimenting with a chemical known as nitroglycerine. He sets fire to the compound and witnesses an explosion.
A year later Nobel receives a patent for what he calls the Nobel Lighter. Nobel believes his invention is a harbinger of peace. He believes the Nobel lighter, commonly called dynamite, will end war and global violence.
Nobel and his father build factories to manufacture nitroglycerine. In 1864, the factory blows up. Several of Nobel’s employees are killed. Nobel’s brother, Emil, is also among the dead. A local newspaper accidentally publishes Nobel’s obituary instead of Emil’s. In the obituary, Nobel is called the Merchant of Death.
St. Petersburg, Russia, Winter 1896
After building several other nitroglycerine factories, Alfred Nobel passes away. In the unique position of having already seen his will years earlier, Nobel leaves behind instructions for his 31-million dollar worth to be appropriated annually to scientists and inventors making exceptional contributions in their fields.
Four years later, the Nobel Foundation is established to manage Nobel’s finances and administer what are now called the Nobel Prizes in physics, chemistry, peace, physiology or medicine, and literature. The first Nobel prizes are awarded in December 1901.
Stockholm, Sweden, September 2013
Nominations for the 2014 Nobel Prizes are being decided upon. The Nobel committee begins with 3,000 individuals and, through an extensive process of research, discussion, and voting, chooses 300 potential recipients. Experts from each field are called in. After months of deliberation, the Nobel Prize winners are chosen; up to three laureates can receive a Nobel Prize in each category.
Norway, December 2014
During Nobel Week, prize recipients travel from all over the world to be honored by their peers and the public. Prize laureates arrive in Norway to hold press conferences, attend dinners at the iconic Grand Hotel, and receive their awards during the highly publicized Nobel Concert.
Part II: The Cells of Cognitive Mapping
The 2014 Nobel Prize in Physiology or Medicine was awarded to Dr. John O’Keefe, Professor and Director of the Sainsbury Neural Circuits & Behavior Centre at the University College London; Dr. May-Britt Moser, Professor and Director of the Centre for Neural Computation at the Norwegian University of Science & Technology; and Dr. Edvard I. Moser, Professor and Director of the Kavli Institute for Systems Neuroscience at the Norwegian University in Trondheim. These three neuroscientists contributed to the discovery of two types of cells in the hippocampus, a part of the brain located in the medial temporal lobe and primarily responsible for memory. The two types of cells are named place cells and grid cells.
In 1971, O’Keefe, with the help of his student Jonathan Dostrovsky, discovered place cells, pyramidal-shaped cells that aid in cognitive map formation. These cells were discovered by attaching electrodes to a rat’s brain while the rat moved around in its environment. O’Keefe and Dostrovsky found that certain neurons would fire signals collecting information about the rat’s spatial location. This information helped create spatial cognitive maps, a type of memory that tracks location.
Think about the first day of college when you walked around campus, hopelessly lost, trying to find the Chevron Science Center. You may have used a physical map to help you get there, but as weeks went on and you advanced from general chemistry to organic chemistry, walking to Chevron seemed like second nature. Now, you can easily picture how to get from wherever you are to Chevron, even if you take a slightly different route because your brain formed a cognitive map of the areas around Chevron.
When you enter a new environment that is completely unfamiliar, the place cells in the hippocampus create a new place field that is a cognitive map of the environment. An astonishing feature of these place cells is that, in order to create a new place field for an unfamiliar environment, only 40-50 percent of the hippocampal place cells need to be activated. The wide coverage of place cells around the hippocampus enables them to respond immediately when the animal enters a new environment.
Figure 1 shows an illustration of the firing pattern of seven hippocampal place cells as a rat runs on an elevated, triangular track. Over time, place cells update the place field as the animal interacts with the unfamiliar location. They also further interact with various other neurons in the hippocampus that aid in the brain’s spatial processing. However, little was known about these other related neurons that help the place cells create their place fields.
Several years after O’Keefe’s discovery, no further progress had been made in the study of place cells. Many scientists repeated O’Keefe’s original experiments, but all hit dead ends in their research.
It was not until 2005 that a married couple—Drs. May-Britt Moser and Edvard I. Moser—made a contribution to further O’Keefe’s findings. They discovered another type of cell, grid cells, that functioned independently but also interacting with place cells.
The Mosers studied grid cells in a similar way to O’Keefe’s. They conducted experiments by implanting electrodes in a rat brain and measured activity levels by placing the subject in various environments. The grid cells were given their name due to the hexagonal grid-like pattern created by the firing of signals in the brain. This electrical pattern of stimulation progression was discovered to be independent of the animal’s spatial location in its environment, leading the Moser couple to conclude that this type of cell was separate in function from O’Keefe’s place cells.
With further investigation, the Mosers found other differences between grid cells and place cells. For instance, the grid cells work in layers of varying density within the hippocampus whereas place cells are dispersed throughout.
But what made the seemingly independent discoveries of O’Keefe and the Mosers so impactful was how these cells work together to create a comprehensive map in the brain about an animal’s location and environment. Place cells indicate where an organism is in space and keep track of sensory information that the organism collects about a particular surrounding. Meanwhile, grid cells work in the brain by using the information gathered by place cells about an organism’s location in order to determine how the organism will behave in that particular environment.
In essence, place cells and grid cells work together to create a complex physical and cognitive plan that the organism can use to navigate and problem solve in its environment. Little was known about how a rat could “magically” work its way through a maze, but the discovery of these two cells helped illuminate the neural pathway of cognitive map formation.
Research conducted using fMRIs of the human brain has indicated that the hippocampus is extremely important for spatial navigation. However, until this research in hippocampal cells, no one really knew how the hippocampus helped us function spatially on a specific cellular level. Furthermore, this discovery has implicated a tremendous breakthrough in understanding a part of the brain that is often the first to be affected by Alzheimer’s disease. Further research in this fast-evolving field could even lead to similar breakthroughs and possible cures for conditions such as Parkinson’s disease and Lou Gehrig’s disease.
Part III: Single-Molecule Imaging
Have you ever seen a molecule? If I were to ask you this question right now, your answer would undoubtedly be “Yes! Everything that we see and touch is entirely made up of molecules. The world wouldn’t exist without them.”
But have you ever seen a molecule isolated from the others around it?
Despite the publication of a list of known molecules in the 1800’s—a list known as the Periodic Table—the first lone molecule was not actually seen until 1989, a year marked by a slew of inventions and improvements in the field of microscopy. Until a few years ago, seeing how individual molecules moved and interacted was a tedious process that was inaccessible to most scientists.
However, the collective work of Drs. Stefan Hell, Eric Betzig, and Steven Moerner changed this perception forever. This cohort of geniuses developed the technique of super-resolved fluorescence microscopy, making it feasible to view tissue samples and the molecules within them with unparalleled clarity. Although their work began in the 1990’s, the three scientists are just now being recognized for their amazing work as recipients of the 2014 Nobel Prize in Chemistry.
Super-resolved fluorescence microscopy—also known as nanoscopy—is made possible by the existence of fluorescent molecules. When targeted by a certain wavelength of light, molecules absorb energy and are induced to emit fluorescence. The awardees came up with two different ways to utilize this concept. The first technique, called STED (simulated electron depletion) microscopy was discovered when Hell created a microscope that utilizes two laser beams. One beam causes molecules to fluoresce and another cancels out the effects of the initial fluorescence, leaving only a tiny segment of about 1 nanometer illuminated. The tiny illuminated patch makes it possible to view a group of molecules without interference from the fluorescence around them. Taking a picture of one illuminated nanometer at a time and then putting the images together yielded a clearer picture of living tissue than had ever been produced in the past.
Betzig and Moerner, who work on opposite coasts of the United States at Howard Hughes Medical Institute and Stanford University, respectively, built on Hell’s technique. They discovered a method that could be used to illuminate single molecules using a process that would switch the fluorescence of a molecule on or off. This particular discovery is what allows scientists to track the movements of individual molecules in a living cell today. By building off of Hell’s technique of fluorescence microscopy, Betzig and Moerner made it possible to view lone molecules through microscopes for the first time in the history of science.
"Prior to W.E. [Moerner]'s work, we all believed in molecules, but no one had ever seen one. He was the first one to allow us to actually visualize a molecule. It opened up all sorts of new experiments in which you can see how cells divide, how the ribosomes can make proteins, and how the cells work,” said one of Moerner’s colleagues.
Since the development of nanoscopy, scientists all around the world have used it to study topics in fields ranging from physics to neurology. Moerner himself has spent a large part of his career studying the proteins involved in Huntington’s disease. His work focuses on tracking individual proteins through living cells, which was an impossible task prior to the development of nanoscopy. Various other scientists have likewise used this novel technique to further their work and provide stronger support for their findings with the backing of more advanced and accurate results. In the 20 years since its invention, nanoscopy has opened up many possibilities in a wide range of scientific fields.
This year’s Physiology or Medicine and Chemistry laureates aptly demonstrate that understanding diverse aspects of science is crucial for making any significant discovery. The laureates’ interdisciplinary interests are evident in their backgrounds: all three of the awardees in Chemistry are PhD physicists, and May-Britt and Moser both received bachelor’s degrees in psychology prior to their careers in neurophysiology.
The intersection between fields is especially apparent when one considers the application of the prize-winning discoveries in Physiology or Medicine and Chemistry to one narrow field—the neurobiology of disease. The discovery of place cells may have a significant impact on research related to Alzheimer’s disease, and nanoscopy has made it possible to physically track the proteins involved in Huntington’s disease throughout the brain
The Nobel prizes this year follow a long tradition of Nobel-worthy discoveries with staying power and interdisciplinary applications. Though the awards are categorized by scientific field, the discoveries that warrant such accolades are projects that embrace the fundamental connections between scientific disciplines. Even today Alfred Nobel’s legacy brings together members of the scientific community in order to celebrate the scope and diversity of academic accomplishments made around the world.