I was lucky enough to grow up all over the world – Thailand, Hong Kong, Germany, Romania and Greece. Some of my fondest memories are around food. My mom was a fabulous cook, which was a vital part of my father’s work as a cultural affairs officer in the US Foreign Service.
Vanilla bean plant
One of my earliest memories was of making a landing in Anchorage Alaska on a return trip from Bangkok to my parents’ home town of Biloxi, Mississippi. I remember the large stuffed polar bear in the lobby, and more importantly, my first taste of vanilla ice cream. Having come from the heat of Bangkok, with my daily food rich in hot peppers and ginger, this cooling fragrant treat was nectar from the gods.
When I started to learn to cook standing over my mom’s pot of gumbo she stressed the importance of simmer with the last ingredients – two bay leaves. They looked so simple – small dried plant material – but an hour later, the aroma of my Nannie’s gumbo was bigger than just the file and seafood, with the bay leaves providing a vibrant top note. Years later, deep into a career researching active molecules in medicinal plants, I realized that the food culture I grew up in was full of medicinal plants in the spices added to our evening meals.
Bay Leaf
Spices both sense of taste and smell. Our sense of smell, in particular, is influenced by the characteristics of the molecules responsible for odor. How quickly do they volatilize (how easily molecules vaporize)? How soluble are they in water or oil? How acidic is the food (a tomato based food or something with lemon)? Even our genes can influence the sense of smell.
A molecule that we can sense through smell is called a fragrance or odorant. Those molecules need to reach the olfactory system in the upper part of our nose. To do so, generally the molecular weight of these molecules needs to be equal to or less than 300 g/mol (a scientific designation for the mass of a substance divided by the amount of the substance). Ultimately, our sense of smell comes down to a pattern of activity of neurons in the brain responding to the stimulus of odor molecules binding to receptors (Malnic et al., 1999).
We have receptors (a protein in a cell membrane that responds to molecule attaching to it) in our nasal passages that are triggered by these molecules. Each olfactory receptor recognizes more than one odorant, and each odorant can be detected by several different olfactory receptors. This reflects a combinatorial process common to biological systems. Several factors influence the resulting signal sent from the receptor site.
We know that the shape of a molecule is important (Saberi and Seyed-Allaei, 2016), and that as the molecule binds (or sticks to) a receptor, the receptor changes shape, which leads to neural signals reaching the brain. Several theories exist to help us understand how to map the process of detecting odors, based largely on chemical qualities of the odorants.
Mori et al. (1994) suggested that the odor signal are more complex than a single receptor binding event, rather the signal is a product of a series of receptor excitations from numerous receptor sub sites (odotypes). This became known as the Odotope Theory. This theory also explains odor-less molecules as the presence sub sites more numerous than the limit of potential binding sites.
A second important theory, Dyson (1938) originated the Vibrational Theory that Wright (1982) later refined. This theory posits that olfactory receptors might really sense vibrational energy on a quantum level rather than structural shapes of the molecule when detecting odors. Quantum mechanics describes nature at the smallest scales of energy levels of atoms or substances.
Combining the two theories, Turin and Yoshi suggest that the tightness of receptor binding, based on both the physical and charge shape (polarity) of an odorant molecule may influence the intensity of the odor, while the character of the odor is effected by vibrational characteristics of the molecule.
To help visualize the theories, we can take a series of molecules found in medicinal plants that have a common base structure, and explore how their odor characteristics may be influenced by chemical features such as solubility, volatility, molecular shape and size (see Table 1).
Starting with the basic structure, vanillin give vanilla its signature sweet, perfumed, woody aroma. The molecular weight is relatively low, and it volatilizes easily, filling a room with the odor when cooked. The oxygen R-groups (groups that “hang” from the ring) on the benzene ring of vanillin make it highly solubility in water.
Built from the same basic structure, eugenol has a short hydro-carbon tail that gives it a stronger odor than vanillin, the familiar aroma found in bay leaf or allspice. This hydro-carbon tail also makes it more fat soluble and may influence the intensity of receptor binding. The odor threshold of eugenol is also lower than that of vanillin. The less polar binding site on the molecule may influence the strength of binding in this example, and explain why the vanillin odor is not as persistent as that of bay leaf or allspice.
Table 1: Vanillin Based Molecular Structures with Odor Thresholds
Zingerone has an even longer hydro-carbon tail connected to the basic vanillin shape, making it insoluble in water. Found in ginger and mustard oil, it gives a rich, sweet, warm and woody fragrance. However, the presence of the carbonyl group (C=O) in the tail means that the zingerone molecules tend to attract each other, limiting how easily it volatilizes. Thus, ginger is less likely to fill a room as quickly with its aroma than vanilla.
Even though Capsaicin also has a long, hyrdo-carbon rich tail, the polar amide group (-NHCO-) makes it slightly more soluble in water than zingerone. The size of the tail also limits the molecule’s volatility. Capsaicin has no odor, and given the numerous sites along that long tail with the potential of binding to a receptor sub sites, this may be an example of a molecule with too many binding sites, as the Odotope theory suggests.
Chili peppers
So the next time in you are in the kitchen and the aromas are filling your senses, see if you can think about the shapes and characteristics of the molecules influencing that wonderful moment.
References:
Malnic B, Hirono J, Sato T, Buck LB. (1999) Combinatorial receptor codes for odors. 96(5), 713.
Mori, K. and Shepherd, GM. (1994). Emerging principles of molecular signal processing by mitral/tufted cells in the olfactory bulb. Semin Cell Biol 5-1:65-74.
Dyson, G.M. The scientific basis of odour . Chem Ind 57: 647-651.
Wright, R.H. (1982) The sense of smell CRCpress, Boca Raton, Florida, USA.
Turin, L, and Yoshi, F. (2003) Structure-Odor Relations: a modern perspective in Handbook of Olfaction and Gustation Second Edition. Doty RL, Ed. New York Marcel Dekker.
Although I’ve met and friended folks who claim they’ve seen it, I’ve never witnessed a plant that could run. Instead, they engage in chemical warfare or communication. The chemicals are the result of multi-step metabolic networks that provide the chemical apparatus to change the staring material into a bioactive substance. Such a chain of chemical reactions is controlled by a series of proteins, called enzymes. Each protein is coded for by a gene.
This research identified a large cluster of 15 genes that encode enzymes in the metabolic pathway with morphine as an endpoint. Approximately 50 alkaloids are found in Opium poppy (Papaver somniferum), with morphine the largest in concentration.
According to the study, the pathway for the painkilling drugs evolved around 7.8 million years ago (mya). Primates are presumed to have appeared 63 mya, Hominidae (precursors to modern humans) 15 mya, and humans 1.3-1.8 mya. First recorded humans use appears in 5000 BCE in the Neolithic age. The PBS show Frontline provides a timeline of human use. It’s history shows that Morphine has been a “wonder” drug for pain, and a bane for those addicted to it and it’s derivatives
The mechanism responsible for euphoria also kills. Morphine binds to receptors in the brain, inhibiting neurotransmitter release and resulting in among other physiological changes, pain relief, but also slowed breathing. Overdose victims often stop breathing.
Since the plant has been around for quite some time, I wondered if there were any histories to show animals consuming this or other plants to reduce pain or to give pleasure? A brief review showed the following:
Researchers discovered it was chili peppers. Next, they studied tree shrews in the wild and discovered they ate one particular pepper, the Piper boehmeriaefolium, and actually preferred to eat it over other plants and vegetation.
Scientific Reportsprovides evidence that Borneo based apes chew leaves of the Dracaena cantleyi plant to create a white lather, which they then rub onto to their bodies
A study of chimps found that they roll Aspilia leaves for a period of time (they are very bitter to chew). This plant material contain thiarubine A , which kills harmful bacteria, and fungi because they contain thiarubine A, a powerful antibiotic. Research also suggests these leaves act as a stimulant, since chimps ingest them first thing in the morning.
What’s more compelling is the rich association of the opium poppy with war. with a few examples below. One aftermath of each – the trail of addiction that followed either the imposition of trade or the use of morphine on the battlefield to reduce pain from horrible damage.
During the 18th century, forcibly exported opium to China, even while it was banned in Britain because the government and industry knew it was not good for the populace in general. It took two opium wars, eventually disrupting the country and leading to the collapse of the Qing Dynasty.
After World War I in remembrance of the fallen soldiers, the living commemorate the sight of thousands of blood-red poppies appearing on the battle-scarred fields of Flanders, in Northern France.
US wars in Vietnam and Afghanistan have been greatly affected by opium production supporting the opposing militaries ability to pay for the fighting.
Now America is facing a public health crisis of opioid addiction. In an interesting turn, last November, President Donald Trump asked Chinese President Xi Jinping to help stop the “flood of cheap and deadly” fentanyl from China into the United States. Fentanyl is a synthetic opioid, 50 to 100 times stronger than morphine.
For better or worse, this is an example of co-evolution – humans identifying and applying a plant to alleviate the pain they, themselves create.
