January 16, 2024 | Jerry Bergman

The Sense of Smell Seems Almost Magical

Smell is far more
complex than believed,
new research shows

 

by Jerry Bergman, PhD

Of the five human senses, the most neglected is the sense of smell. One reason is that loss of smell is usually a minor inconvenience. In contrast, the loss of eyesight and hearing produce major handicaps. This is why enormous levels of research have been expended to determine the causes of blindness and deafness and to ameliorate them. When sight or hearing are abruptly lost, one immediately becomes aware of the loss. The same is not true of smell. Its loss is often at first noticed only when one encounters a familiar smell, such as when cooking a meal, and notes the expected smell sensation does not result.

The complete loss of smell (anosmia) and taste (ageusia) is rare. That’s another reason for less focus on this sense. Smell and taste are often discussed as a pair that work together. The inability to smell foods and drinks greatly affects their taste. These combined senses allow distinguishing the difference between coffee and tea, or blueberries and raspberries.

In an effort to understand how humans can distinguish trillions of different smells, a research team has uncovered a previously undetected mechanism involving RNA “that could explain how each sensory cell, or neuron, in mammalian noses becomes tailored to detect a specific odor chemical” such as that emanating from coffee or tea.[1]

“sensory magic emerges from an intricate developmental mechanism that tailors each of the nose’s sensory cells.”

The Biology of Smell and Taste

Smelling results, the study at Columbia University says, when “sensory magic emerges from an intricate developmental mechanism that tailors each of the nose’s sensory cells.”[2] When molecules in the air enter your nose and mouth, the sense of smell, technically called olfaction, is activated. These molecules bond to receptor cells located in the nasal mucus membranes. The bond to the receptors results in sending information to your brain that determines, among other traits, if something has a neutral, pleasant, or foul aroma.

The taste sense, called gustation, likewise works when molecules dissolved in liquids activate the taste buds. These taste buds located on the tongue contain receptors that respond to dissolved compounds. To magnify the taste sensation, humans have taste receptors on the roof of their mouth and in the back of their throat. These receptors send messages to the brain that determine sweet, salty, sour, bitter or savory (umami) taste. The messages obtained from smell and taste are combined, allowing the brain to effectively determine the difference between similar molecules. Scientists are still attempting to understand in detail how the brain determines these differences.

As is the trend in most other areas of anatomy and physiology, research has caused us to realize the smell sensory system is much more complex than previously believed.  Consequently, it is even less likely to have evolved.

Results of the Columbia University Research

Specifically, Pourmorady et al. found that there exists sensory neurons in our noses connected to receptors uniquely designed to detect an estimated one-trillion distinct scents.[3] One example is that some receptors can detect ethyl vanillin, the main odorant in the vanilla flavor, and other cells can detect limonene, lemon’s signature odorant.[4] Specifically, how and why the ability to detect vanilla and limonene were learned has never been explained; thus the Pourmorady et al. research attempted to explain this process. It was once thought that the first time vanillin or lime pie was tasted, the taster could respond to the taste. Pourmorady‘s team has challenged this view.

Their new research has determined that detecting specific tastes

is exceedingly complex and involves a dizzying cast of molecular characters… that either dial up or down each gene’s ability to produce olfactory receptors …[requiring]  a variety of gene-regulating molecules. By ….  various alliances within the genome, these molecular players help turn specific [smell] genes on or off.[5]

As evolutionists, they attempt to explain smell, but they describe it as a miracle. The use of flowery words do not explain anything, such as in the following:

The mammalian nose is a work of evolutionary art. Its millions of nerve cells, each tailored with just one of thousands of specific odor-chemical receptors encoded in the genome, can collectively distinguish a trillion distinct scents. Those sensations, in turn, inform many behaviors, from assessing food options to discerning friends from foes to sparking memories.”[6]

The Putative Role of RNA

The leading researchers in the area of smell admit their theories are tentative. Evidence for this conclusion includes adding words that support this tentative admission, such as “may” and “likely,” 5 times in one short paragraph quoted below, and 15 times in the entire article, most of which consists of diagrams.

Although we favor an RNA-mediated symmetry-breaking process, we cannot ignore other explanations of our data. Transcription-enabled chromatin remodeling of the OR locus, which may facilitate transcription factor binding on P2 DNA and GI hub assembly, may also contribute to biased P2 choice upon tTA induction. Similarly, tTA may synergize with endogenous transcription factors on the P2 promoter, facilitating GI hub recruitment to the P2 locus. However, in both scenarios, the competing OR–GI hub interactions dissipate only when P2 RNA levels reach a threshold, supporting a direct role of the OR mRNA in symmetry breaking. We also acknowledge that tTA-induced P2 transcription at the polygenic state (INPs, iOSNs) is stronger than the transcription of competing endogenous ORs, which may artificially bias P2 choice. However, tTA-driven P2 transcription in mOSNs is not as high as the transcription of the already chosen OR, yet it also hijacks the OR choice apparatus. Thus, it is likely that the transcriptional advantage that tTA induction confers on P2 mimics the advantage that different endogenous ORs have along the dorsoventral axis of the MOE, breaking symmetry in a biased, positionally informed fashion. [7]

The Nature article did not speculate exactly how this ability to sense an estimated trillion distinct scents came about. A post by Columbia University admitted that “How sensory cells in the nose make their receptor choices has been one of the most vexing mysteries about olfaction.”[8] And the results by the research of Pourmorady et al. published in Nature make it even more vexing. The process of producing the specific receptor, they speculated,

unfolds entirely within the minuscule confines of each olfactory neuron’s nucleus, where the cell’s chromosomes and genes reside. There, in a ….  winner-takes-all competition, a developing cell’s myriad olfactory receptor genes vie with each other in a process that winnow them down, in stages, first to a handful of finalists and then to a single winner. The prevailing gene is the one that determines the cell’s odorant sensitivity. In their study, Dr. Lomvardas and his team uncover details of the final stage of this process when the winner emerges from the finalist genes. “It’s basically a battle between 1000 contenders.”[9]

According to their research. given a trillion different distinct scents, and a battle between 1,000 contenders, one quadrillion or 1,000,000,000,000,000 steps would be required to produce these receptors.

Discussion

Many conditions affect the mammal olfactory senses. It is well documented that a wide variance in smelling capabilities exists from person to person. These include hyposmia, a partial loss of smell compared to when one was younger, and anosmia, the complete loss or absence of smell. In humans, the ability to smell often weakens after age 50 because nasal membranes become thinner and drier, and nerves function less effectively.

Conversely, it is uncommon to lose the sense of taste. Most often, the cause is a loss of smell that causes foods to lose their taste, producing a bland taste. Complete inability to taste, which is very rare, is called ageusia. Hypogeusia, the loss of taste ability, occurs with age and certain diseases such as COVID-19. One result is that non-bitter foods now taste bitter and one may have a harder time determining sweet or salty foods. Exploration of these factors can help us to better understand the anatomy and physiology of smell.

Conclusions

The Pourmorady research has provided evidence that smell develops due to the cell’s RNA. This RNA alters the “genome’s architecture in ways that bolster the expression of one olfactory receptor gene while also shutting down all the others.” But “Big gaps in this genome-controlling story remain.”[10] Another problem is, one person cannot describe new smells to someone if they have never smelled something similar. This problem is similar to trying to describe a color to a person who was born blind. Furthermore, there are not enough words to describe the estimated over one-trillion different smells, and, as far as is known, no one has ever smelled most of these one-trillion existing smells. No one person can smell, describe, and remember this many smells. The following conclusion made in 2010 is still accurate:

Human sensory processes are well understood: hearing, seeing, perhaps even tasting and touch—but we do not understand smell—the elusive sense. That is, for the others we know what stimuli causes what response, and why and how. These fundamental questions are not answered within the sphere of smell science; we do not know what it is about a molecule that … smells.[11]

References

[1] Columbia University. “A trillion scents, one nose.” Science Daily; https://www.sciencedaily.com/releases/2023/12/231221012741.htm, 21 December 2023.

[2] Columbia: Zuckerman Institute. “A Trillion Scents. One Nose;” https://zuckermaninstitute.columbia.edu/trillion-scents-one-nose, 20 December 2023.

[3] Pourmorady, Areal D., and 14 other authors. “RNA-mediated symmetry breaking enables singular olfactory receptor choice.” Nature 625:181-188, p. 188, 4 January 2024.

[4] Columbia: Zuckerman Institute, 2023.

[5] Columbia: Zuckerman Institute, 2023.

[6] Columbia: Zuckerman Institute, 2023.

[7] Pourmorady, et al., 2024, p. 188. Emphases added.

[8] Columbia: Zuckerman Institute, 2023.

[9] Pourmorady, et al., 2024.

[10] Columbia University, 2023.

[11] Brookes, Jennifer. “Science is perception: What can our sense of smell tell us about ourselves and the world around us?” Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences. 368(1924): 3491–3502. doi: 10.1098/rsta.2010.0117, 13 August 2010.


Dr. Jerry Bergman has taught biology, genetics, chemistry, biochemistry, anthropology, geology, and microbiology for over 40 years at several colleges and universities including Bowling Green State University, Medical College of Ohio where he was a research associate in experimental pathology, and The University of Toledo. He is a graduate of the Medical College of Ohio, Wayne State University in Detroit, the University of Toledo, and Bowling Green State University. He has over 1,300 publications in 12 languages and 40 books and monographs. His books and textbooks that include chapters that he authored are in over 1,800 college libraries in 27 countries. So far over 80,000 copies of the 60 books and monographs that he has authored or co-authored are in print. For more articles by Dr Bergman, see his Author Profile.

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