Gene Finding Reveals a Secret of Smell
By NATALIE ANGIER
Published: April 5, 1991
Humans and other mammals detect an exquisitely complex bouquet of smells by using at least a thousand different genes that are active exclusively in nose cells, scientists have found.
The discovery of the huge family of smell genes offers scientists their first insight into the fundamental mechanism of smell.
"This is a wonderful piece of work, and it's all the more exciting because the problem has been hanging out there for some time," said Dr. Eric Kandel, a neurobiologist at the Columbia University College of Physicians and Surgeons, who is familiar with the new study. "We had almost no knowledge of the olfactory system, and this really opens up the molecular study of smell in a very fascinating way."
The report of the novel family of genes, discovered by Dr. Richard Axel and Dr. Linda Buck of the Howard Hughes Medical Institute at Columbia, appears today in the journal Cell.
Each of the different genes seems designed to respond to a small group of different odors, and together the sensory genes can recognize all the 10,000 or so scents that mammals can smell.
The genes also serve as messengers, passing along the signals of the odors from the nerve cells in the nose onto a small region of the brain called the olfactory bulb.
Many scientists who specialize in neurobiology and smell research expressed great enthusiasm for the new results. "I'm really excited about this," said Dr. Cornelia Bargmann of the Massachusetts Institute of Technology, who works on the sense of smell in lower organisms like worms.
With the smell genes in hand, researchers can now ask fundamental questions about how odors are detected and how the brain interprets those signals. They can work with the genes, known as receptors, to determine how the nose and brain together discriminate between the astringency of lemon juice, the sweetness of a hyacinth and the sharp acidity of a skunk's spray.
"No odorant receptors have ever been identified before," said Dr. Axel.
The scientists were astonished to discover that so many different receptors seem necessary to allow animals to smell. By comparison, said Dr. Axel, the eye uses only three different types of receptors to recognize thousands or tens of thousands of colors. In the eye, he said, there are photoreceptors that respond to red, green and blue. When viewing an object, the three different types of photoreceptors pass along signals of varying intensity, and the brain then combines and interprets the signals to tell pink from violet from turquoise. Very Different From Vision
But the new work strongly suggests that the olfactory system is very different in structure. It relies on a great diversity of receptors in the nose cells to recognize a somewhat greater diversity of smells. Thus, scientists said, the brain does not need to combine and process as much information coming from the nose cells before concluding it has recognized a particular odor.
"The complexity of the system is at the early stage, when an odor is first detected," said Dr. Kandel. "That makes later processing of information, in the brain, much easier."
Researchers believe that the system makes sense from an evolutionary point of view. The sense of smell is quite primitive, they said, and early animals were probably far more reliant on smell than they were on vision. They also lacked a brain large enough to integrate a lot of input. Thus, they needed greater variety in their peripheral cells, especially their smell cells, to handle vital information from the outside world.
Apparently the system of using a huge number of odor receptors to avoid needing a bigger brain to understand those odors has been preserved even in big-brained humans, Dr. Axel said.
"We're very visual animals, so to us the sense of smell doesn't seem very important," Dr. Bargmann said. "But for animals, smell is very important. And even for humans, during the early stages of civilization, it was probably important to ascertain if your food is spoiled, or whether it's poisonous, and you do that through smell."
The scientists discovered the receptors through artful applications of molecular biological techniques. They worked on rats, isolating nerve cells from the tissue of the nasal canal and seeking evidence of genes exclusive to that cell type.
Reasoning that receptors for odors were likely to have a structure similar to that of photoreceptors and other known receptors, the scientists also hunted for genes with a peculiar snakelike shape that winds in and out of the cell surface seven different times. The intricate shape allows the receptor to respond to molecules from the outside world, like odor molecules. It further allows the signal from those molecules to be easily passed along from the nasal cell and eventually into the brain.
That search led them to discover a family of closely related receptors far bigger than they had expected. Dr. Axel said they had directly detected about 200 different smell genes in the rat's quotient of DNA, the basic genetic material in cells. "But we have good evidence that we haven't even begun to cover the entire array" of receptors, he said. They have found equivalent smell genes in human nasal cells.
Dr. Axel said the smell receptors could constitute the single largest family of genes in mammalian DNA.
Chart: "How the Nose Discriminates" Scientists have made a major discovery about the receptors in the nose that enable humans to distinguish between some 10,000 odors. The discovery is of a large family of genes that specify the receptor proteins embedded in the cell membranes of th nasal cavity. Each protein presumably recognises a different kind of odor molecule. Source: Dr. Linda Buck and Dr. Richard Axel