Tag Archives: Proceedings of the National Academy of Sciences

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Must we stop and smell the flowers?

Apart from passive receptivity, I have had no more opportunity to experience perfumes than any other nose in the average crowd. And even in that chaos, the scents seem to be equally admixed with whatever else clings to us -not all of it encouraging. But I have to believe that the ability to notice different smells, let alone be repulsed or attracted to them, must serve more purpose than merely warning us off things that might be harmful. Why dedicate an entire organ just to avoid rotting carcasses or to pick pleasing flowers -as socially useful as that might be?

Indeed there may be an entire chemical vocabulary entrusted to smells, that enriches the umwelt of the otherwise utilitarian world of the animal kingdom. Given our common origins, why would we be any different?

Of course, except for their behaviour, animals are unable to communicate what they are reading in the odour, and until the very recent identification of olfactory receptor genes, even variations in humans were, by and large, a mystery. And yet, their importance is signalled by the finding that these genes appear to constitute the largest gene family in all the mammalian genomes.

The problem, perhaps, has always been in the attribution. As with animals, if we don’t know that odours are responsible for an action, we wouldn’t think to credit them. If a dog, for example, marks a spot after smelling it, we have no idea what that means. Does it merely suggest that the dog simply likes whatever it was it smelled, or something more? Is the dog leaving a message other than ‘I was here, too’?

You see the difficulty: an odour may engender an action, but neither the signal nor the response can be reliably categorized as anything other than a generic stimulus/response. And given the size of the olfactory receptor gene family, a purposeless, or motiveless reflexive response seems unlikely.

So, how have we made use of this prowess historically? Well, for one thing, we have used odours, to mask odours -a rather recursive, circular activity, it seems. The fact that bathing, at one time was frowned upon -or perhaps difficult to achieve with any regularity for other than the wealthy- usually demanded olfactory disguise amongst those not similarly handicapped. The need to remedy the resultant smell, in itself suggests a nascent awareness of a message, camouflaged as it might be in societal norms.

And, think of the now discredited Miasma theory: that many diseases -the Bubonic Plague springs to mind- were caused by ‘bad air’: smells, in other words. One can certainly understand the conflation of the odour of, say, rotting meat and sickness that might follow ignoring the message inherent in its telltale reek, with the idea that the smell itself might be the cause. Only when germs were identified, and -in the absence of germs- not the air around them, did the idea of smell become merely an indicator, not a cause of disease.

But there’s a hint of a more useful and atavistic function of odours in the discovery of its importance in the initial bonding and identification of human mothers with their newly born offspring. I suppose it should have been obvious for millennia, though: an orphan lamb is often rejected by an unrelated lactating mother unless the strange lamb is made to smell like her.

So, where am I going with this? Well, first of all, the findings of a recent study [lead author Casey Trimmer, PhD] published online in advance of print in the Proceedings of the National Academies of Sciences: https://www.sciencedaily.com/releases/2019/04/190430164208.htm

‘Humans have about 400 different types of specialized sensor proteins, known as olfactory receptors, in their noses. One odor molecule can activate several different olfactory receptors, while any given receptor can be activated by several different odor molecules. In a process that remains to be decrypted, the olfactory system somehow interprets these receptor activation patterns to recognize the presence, quality (does it smell like cherry or smoke?) and intensity of millions, maybe even trillions, of different smells… Small differences in olfactory receptor genes, which are extremely common in humans, can affect the way each receptor functions. These genetic differences mean that when two people smell the same molecule, one person may detect a floral odor while another smells nothing at all… Because most odors activate several receptors, many scientists thought that losing one receptor wouldn’t make a difference in how we perceive that odor. Instead, our work shows that is not the case…  A change in a single receptor was often sufficient to affect a person’s odor perception… olfactory receptors in the nose encode information about the properties of odors even before that information reaches the brain.’

Why the receptor complexity if odours are mainly simple social adjuncts? Or, is there more going on than meets the nose? Obviously we seem to have less appreciation of the panoply of chemicals around us than, say, the average dog, but because we do not ‘smell’ them with equal facility, does that mean they have less of an effect on us? As we have begun to appreciate in terms of mother/infant recognition, not all odours reach conscious awareness. Not all smells are nameable.

Some perfume manufacturers maintain that their products contain pheromones (chemical signals) which might activate aphrodisiac-like behaviour in humans, but so far the evidence is tenuous, to say the least. Given our common evolutionary history with animals who do produce and react to pheromones, and our own incredible biological investment in olfactory receptors, however, I suspect it is just a matter of time before similar chemicals and effects are identified and utilized in us.

What brought this whole subject to mind, though, was a titillating article in the Smithsonian Magazine about Cleopatra’s perfume: https://www.smithsonianmag.com/smart-news/may-be-what-cleopatra-smelled-180972854/

‘Back in 2012, the archaeologists uncovered what was believed to be the home of a perfume merchant, which included an area for manufacturing some sort of liquid as well as amphora and glass bottles with residue in them… The researchers took their findings to two experts on Egyptian perfume, Dora Goldsmith and Sean Coughlin, who helped to recreate the scents following formulas found in ancient Greek texts.’

And, no, there’s no proof that what was recreated was what Cleopatra used -in fact, ‘It’s believed she had her own perfume factory and created signature scents instead of wearing what would be the relative equivalent of putting on a store-bought brand.’ But still, it’s a smell that Cleopatra might have worn…

There’s a legend that she believed so fervently in her perfume’s allure that she soaked the sails of her royal ship in it – so much, in fact, that Marc Antony could smell her coming all the way from shore when she visited him at Tarsus.

There’s got to be something in that: where there’s smoke there’s fire, eh?

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Breast and Ovarian Cancer Screening

I am sometimes troubled by the concept of risk. I mean how can we possibly decide whether or not a risk is acceptable? No matter the statistics, if the issue under consideration doesn’t happen, then the risk assumed was acceptable. So far, so good. But of course the converse is also true: no matter how low the risk, if it does occur, well…

Ours is a culture of prediction. Statistics. Guessing. I rationalize buying a lottery ticket by convincing myself that if I don’t buy it, I won’t win -no matter how low the odds, no matter how unreasonable it would be to assume that I would be the one in –what?- ten million who wins the jackpot. Or anything, for that matter…  And no matter that without a year of such profligate spending, I could treat myself to a sumptuous dinner at a good restaurant.

Of course, we all live in hope, and if the lottery ticket funds some worthwhile government project, then it is an almost enjoyable form of indirect taxation. Assimilable because it is freely chosen. Optional.

It is a different proposition entirely if the risk is one to which we do not wish to subscribe but have no choice: genetic defects in a developing pregnancy, cancers, diseases, to name but a few. It is likely to our advantage to interrogate these, if possible. Of course, the question then becomes who should undergo the screening. Only those at the highest risk –those with a family member with the condition, say- or everybody? Just in case.

Screening always seems to be bathed in a soft, warm glow. If you can test, then why not? Just pop in to your local lab and get that PSA; find out if your prostate is betraying you. Demand yearly mammograms as soon as you feel concerned. As soon as a friend or even a friend-once-removed has a cancer scare. And at any age, because you never know…

If only screening was that good; if only all negative tests were reliable –and, for that matter, didn’t have to be repeated at intervals to keep pace with the ravages of Time wreaking its not so subtle havoc on our aging bodies.

Screening for specific inherited genetic mutations for breast and ovarian cancers are the relatively new species of Wunderkind: BRCA1 and BRCA2. These are tumour suppressor genes broadly speaking; we all have them, and they are located on chromosomes 17 (BRCA1) and 13 (BRCA2). But if they contain defects -mutations- they may no longer function efficiently and so be unable to winnow out mistakes such as tumours from proliferating. The mutations are inherited in an autosomal dominant manner and women with these particular mutated genes have a lifetime breast cancer risk of 50-85%. .

So why not screen all women for these genes? Indeed, a recent study published in the Proceedings of the National Academy of Sciences (USA) suggested just that: http://www.pnas.org/content/111/39/14205.abstract

On first reading, it sounds like a reasonable approach. But I’m not so sure. First of all let’s put the whole issue into context. Less than 10% of breast cancers (and <15% of ovarian cancers) seem to be associated with BRCA1 or BRCA2 mutations. And, although even less common, there are hereditary breast cancers associated with other genes, so there might be a false sense of security from testing only the BRCAs.

And then there’s the uncomfortable fact that there have been over a thousand different mutations in BRCA1 and 2 discovered so far. You’d have to know which one to look for. Of course, some populations have more prevalent mutations –so called Founder effects– which might simplify the search. Two per cent of Ashkenazi Jews, for example, carry specific mutations of BRCA1 or BRCA2. And there are other populations carrying unusual founder mutations that might facilitate searches in them as well: people from the Netherlands, Quebec, Iceland, to name a few. Or in still other groups -some families, for example- if the particular mutation resulting in their tumours has been identified, then the process is obviously easier.

The most successful screening is in people with identifiable risks, however. With breast cancer, such things as family history -especially a young age of developing the breast or ovarian cancers (the younger, the more chance there is a risk that can be  inherited), or a family history of so-called triple negative breast cancers –progesterone, estrogen and HER2 receptor negative. Males with breast cancer (yes it happens) are another, albeit infrequent clue to increased risk.

But screening everybody? Let’s get back to risk assimilability. Just what risk is acceptable? Less than 50%? Less than 25%? No risk at all..? Sometimes the answer is easy: a 50-85% lifetime risk of breast cancer if specific BRCA1 or 2 mutations are present is likely not tolerable. But what about the odds if only 2% of the population had that risk, as is the case for BRCA1 and 2 mutations in the Ashkenazim? Or if the chances of those mutations are even lower: 1/800-1/1000 as it is in the general population?

And what if you are not a member of a high risk population, or if there are no cases of breast or ovarian cancer in the family? Should you still be screened? And if so, with what? Remember there are many different mutations possible on the BRCAs -not all of which may result in an increased cancer risk. And there are other genes than BRCA that may play a similar role sometimes. So if you are just concerned that you might be at some risk, or worse, merely curious… Well, its best to remember that we are all exposed to dangers each day that we don’t even think about -and there’s no avoiding them: everything from tripping and falling down the stairs, to slipping on some ice; from having a heart attack, to getting hit by a car crossing the street to shop. We have to put things in perspective: life is a risk, and we are fragile creatures. Remember Shakespeare’s Hotspur in Henry IV:

‘Tis dangerous to take a
cold, to sleep, to drink; but I tell you, my lord fool, out of
this nettle, danger, we pluck this flower, safety.

So, if there is reason to believe there is a risk on the horizon, then it’s best to mitigate it. But don’t go looking for it in places it doesn’t exist.