Pheromones

Zoologist Tristram D Wyatt on moth traps, alarm pheromones, and the Erox Corporation

faq | May 19, 2017

Pheromones are invisible chemical signals between members of the same species and they are important because they are possibly some of the most universal ways of communication across the animal kingdom.

History of term

Biologist Catherine Dulac on triggers of social behavior, the genetic breakthrough, and pheromones
We have known that they must exist for a very long time. The ancient Greeks knew that there were invisible signals that female dogs gave off when they wanted to mate (“in heat”). Male dogs could sense the signals and if the secretion from the female dogs were put on a towel, male dogs would follow the towel. So it was not a sound given off by female dogs, it was a smell. The problem was that the quantities were tiny and for the most part, as humans we cannot smell the signals between other animals. Only in the 1950s, after about 20 years of work by a team of chemists led by Adolf Butenandt, who had won a Nobel Prize for his work on human steroid molecules,was the chemical identification of the first pheromone published. This was for bombykol, the female sex pheromone in silk moths.

How do pheromones function

Pheromones are chemical signals that travel between the emitting animal and the receiver, usually carried either in air or water. When they reach the receiver, the receiving animal, they are almost always detected through the sense of smell. In the case of mammals that is through the nose, in insects, and crustaceans like lobsters, it is the antenna. Specialized nerve cells in the nose or in the antenna that have a particular kind of receptor that binds with a pheromone molecule are responsible for detecting the pheromone. When the pheromone molecule binds to the receptor it excites the nerve which sends a message to the brain that pheromone has been detected. What happens next depends on the signal and the animal. If it is a male moth that has detected a female sex pheromone, he takes off and by series of responses to the pheromone he eventually finds the female. But pheromones are used in all sorts of contexts. Another pheromone is one given off by mother rabbits, in their milk. This mammary pheromone stimulates the rabbit pup to find the nipple. This is a very specific response and it enables the rabbit pup to find the nipple very quickly: baby rabbits need to do this because they only have three or four minutes a day to take milk from their mother.

Adult silkworm moth // Wikipedia.org

Pheromone signals work in much the same way as any other kind of signal except that a molecule has to travel from the signaler to the receiver. That makes them very good to use at night but it does mean that you have to be in reasonably close proximity. So it is different from a sound or a visual signal, which potentially can work from much greater distances.

Many types of pheromones exist in animals

Pheromones have actions in connection with all life stages and all kinds of situations. It depends on the species. So it was mentioned that sex pheromones in moths and in dogs, and the mammary pheromone in rabbits. In social insects including bees, wasps, ants and termites there are an enormous number of different kinds of pheromones that are involved in a wide variety of different kinds of behaviors. For example, alarm pheromones are found in many social insect species. A honeybees’ nest is a very rich resource, which attracts bears (and humans) which want to steal the honey. Bees have a collective defense and when a bee stings a bear, the sting remains in the skin of the bear and continues to release an alarm pheromone. This acts as a beacon that attracts other bees to attack the bear. Ants’ alarm pheromones are important when colonies are fighting: the pheromone draws more soldiers into the battle. Of course, ants also have trail pheromones which is how they are recruited in large numbers by scouts to a source of food like a picnic.

Zoologist and entomologist Sean O'Donnell on Army Ants, chemical weapons, and invasive species
There also other kinds of pheromones which have an effect not on behavior directly but via changes in the physiology of the receiving animal. For example, there are pheromones in mice, which seem to either slow down or speed up sexual maturity. They slow down puberty, for example. There are other pheromones which, unlike most pheromones, bypass the olfactory system. For example, in honeybees, the food fed to honey bee larvae, royal jelly, contains pheromones including a protein called royalactin. If the honeybee larvae are fed exclusively with royal jelly they will become queens. If they are also fed with pollen instead they become workers. Pheromones in the royal jelly act by changing gene expression, switching development into a queen.

Applications of pheromones

Some 80 years before the first pheromone was identified, the first state entomologist, in New York State, Joseph Lintner, had some female silk moths in his window in his office. Through the open window their pheromone attracted large male moths that were fluttering over the sidewalk, attractinga crowd of people who gathered down below. Lintner speculated that the strong attraction must surely be to some kind of chemical given off the female moths. If this attractive chemical could be synthesized and produced in large quantities then perhaps it could be a way to control pest moths. The adult moths don’t cause any problem; it’s the caterpillars that do the damage to apples or other crops. So if you can disrupt mating, to prevent the adults from finding each other and fertilizing the eggs, then you could stop the caterpillars. In the 1960s the first experiments were made to test this idea in orchards and in corn and cotton fields. In the decades since, it has turned out to be a very successful technique. It often provides a solution when pesticides have stopped working because the pest moths have become resistant to the pesticide. Pheromones provide an environmentally friendly and cost-effective way of pest control, not killing the moths but by preventing adults meeting, so we have none of the pest larvae. Mating disruption, pest control using pheromones, is used on at least 10 million hectares around the world: on cotton in the USA, on tomatoes in Mexico, on aubergine(eggplant) in Pakistan, and on peaches in South Africa. Unlike pesticides, synthetic pheromones do not kill predatory insects and other natural enemies so these can help keep pest insect populations in check. However, one challenge for pheromones for pest control is that their species-specificity means that each species’ pheromone has to be investigated and its delivery optimized for effective pest control.

Human pheromones

Human pheromones have been speculated about for a long time. It is an attractive idea and certainly in terms of traditional folk knowledge it goes back a long way. There are stories about a central European village men keeping a handkerchief in their armpit and waving it in a village dance to the woman of their desires, who instantly, of course, falls in love. The real stories in some ways are a bit more disappointing. If you search on the web for human pheromones an enormous number of commercial sites will try to sell you what they claim is the real thing. And if you look at the scientific literature there are also many studies, which claim to show the effects of what they usually call “putative human pheromones”. A few years ago I was intrigued by the claims and looked for the source of the ideas in the scientific literature. What I found really surprised me: it turned out that most of the published studies could be traced back to one paper in 1991. This was a study of two molecules androstadienone and estratetraenol which were proposed as the human pheromones for males and females respectively. However, there is no evidence provided in the paper, which was in a conference proceedings. The methods section of the paper describing the molecules simply said that they were supplied by the Erox Corporation. So I wondered what are the Erox Corporation had done. And there all I found was a patent, in fact series of patents, which described in detail the synthesis of the molecules, but provided almost no evidence that these were human pheromones. What kind of evidence would actually really show they were pheromones? For that you can go back to the silk moth work in 1959. In his pioneering study, Butenandt laid down what has become the gold standard for discovering and demonstrating a real pheromone.

First, you have to carefully isolate the molecules and then you have to test if the molecules in your extract have the same effect as the natural secretion. You then identify the molecules, synthesize them and show that your synthesized molecules reproduce the original effect which you had observed. When it comes to humans, it turns out that those crucial steps that have never been done. These two molecules appeared almost to have been plucked out of the air and deemed to be “pheromones”. It was simply said that there pheromones, but there was no evidence from proper testing, no evidence that they have a particular behavior or physiological response when applied. Basically there was no evidence. What’s happened is a literature has grown up taking as a matter of faith that these molecules really are pheromones. And what I did in my review in 2015 was show there are lots of reasons for thinking that these molecules are probably not pheromones. The molecule claimed to be a female pheromone has only ever been found in the urine of women in their third semester of pregnancy, which would make it a very unlikely sex pheromone for attracting a mate. The purported male “pheromone” has been found in human armpits. But so have hundreds and hundreds of other molecules. So there is simply no reason to choose these molecules. I am afraid that that is where we are, so far as the sex pheromones are concerned.

Current research

The first human pheromone to be robustly identified probably won’t be a sex pheromone, though that has attracted most interest in the past.Instead the likely pheromone is one that may be involved in communication between mothers and babies. To identify a pheromone, you need a simple experiment that you can repeat reliably when you going through the stages of identifying the molecules. We have such a potentially smell-driven behavior and a bioassay in the interactions between human mothers and their babies. This is work done in France by Professor Benoist Schaal. His team has shown that there are secretions produced around the nipple of lactating mothers that seem to cause any baby, not just their own, to start to suckle. The researchers have developed a simple bioassay, recording the suckling responses of newborn babies to secretions, which may allow them to track down and identify the molecules in the pheromone, should one exist. It may be that there is a human pheromone equivalent to the rabbit mammary pheromone.

In terms of exciting things that are going on in the world of pheromones generally, it’s turned out that this is a very exciting way to study both animal behavior and neuroscience. What we have in the moth is an identified pheromone given off by the female moth and in the male highly specialized structures, antennae,for detecting the pheromone signal. There are specific pheromone receptors on the many thousands of olfactory sensory neurons going into particular parts of the antennal lobe in the male’s brain. Researchers in many parts of the world have been looking at how the signal is received by the olfactory sensory neurons and how the signal is processed in the various levels of the brain, ultimately leading to a signal to the wings to start flight. Every stage can be investigated at the level of physiology but also genetics. So we can look at the genetics and evolution of the enzymes producing the pheromone signal by the female. Similarly, researchers are also investigating the evolution of the receptors in the antenna and neural circuits in the brains of the males. There are similar studies of mammals and other vertebrates, but these are at a much earlier stage because of the challenges of studying mammalian neural circuits. Among the pheromones so far identified in mice are darcin and ESP1 (exocrine gland-secreted peptide 1).

Open questions

In many ways the whole area of chemosensory research has been a late starter compared with the other senses. That’s reflected in the dates of the Nobel Prizes. Those for the discovery of the mechanisms of hearing and vision go back to 1961 and 1967 respectively. For smell (olfaction) it was only in 2004 that the Nobel Prize went to Richard Axel and Linda B. Buck for their 1991 discovery of the family of 1000 olfactory receptors in mice. Each receptor is tuned to particular kinds of odor molecules and a given odor molecule may stimulate more than one kind of receptor. The brain can tell which molecule has been sniffed by the combination of receptors (and their neurons) that are stimulated. This is facilitated by the convergence of all neurons carrying a particular receptor converging on a glomerus in the olfactory bulb. There are therefore as many glomeruli as there are receptor types.

We have known about the mechanisms of smell for a very short time and the advances have been exceedingly rapid, but there is still so much more to learn. Even in some of the commonest species we’re still working out what their pheromones are. To give a final example: I mentioned the domestic dog at the start. While we know that the male dogs can detect the pheromones of a female in heat at quite a great distance, we do not know conclusively what all those molecules are, so there is still very much to discover.

Senior Research Associate, Department of Zoology, University of Oxford; Emeritus Fellow, Kellogg College, University of Oxford
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