Scientists now know what no nose knows vs. what the nose knows but no nose knows that noses know

 

A minireview

 

I don’t know how closely you’ve been following recent research into the nose – that didn’t come out quite the way I intended – but things are flowing right along. A big paper came out this week, just two years after the last one, which is impressive when you consider that entire decades can go by without a major finding in the nose. Individuals find something in there all the time, of course, but they don’t usually get scientific papers out of it.

Why hasn’t the nose achieved the prominence in science that it has on our faces? Noses don’t have the sex factor – a major disease to lobby for them. You don’t see stories that begin, “Every year three million Europeans die of infections due to the magenta nose virus, which causes the nose to turn a deep shade of magenta and then fall off. Patients who survive experience a decrease in quality of life due to the discomfort of wearing a prosthesis. Transplants offer an alternative, but they are often rejected, by both the person’s immune system and everyone who looks at the foreign nose, creating an important social burden.”

Cases of magenta nose virus are rare – in fact, nonexistent – so scientists are forced to start their stories with leads like, “The central position of the nose makes it a natural focal point for scientific inquiry.” Or, “Here we address an issue that has long puzzled a number of scientists, although not that big a number, and not that long, although it seems like it to those who work in the nose lab.”

The current paper answers the question: How many genes does it take to build a human nose? Previous estimates ranged anywhere from 1 to 23,500. The new study says 4 genes are required. That sounds about right: one for length, one for width, and one for each nostril. To know how they solved this you’d have to read the methods section, which is usually about as interesting as reading the instruction manual for your toaster. One approach would be to knock down 23,496 genes until the embryo developed only a nose.

The conclusion of the paper was somewhat modest, which is disappointing, because it’s the place where authors are usually willing to make wild speculations. Instead I’ll repeat what one of the authors said in an interview, anonymously: “This represents such a dramatic step forward in nose science that we believe it would not be entirely unreasonable to expect that it will open an avenue, a car-pool lane, or at least a mule path toward an entirely new discipline. We propose the following name: Systems Biology for the Regeneration of Personalized Noses, or SyBiRePeNos, although we may change the acronym because when people say it out loud it sounds like ‘cyber-penis.'”

I found this statement a bit grandiose, but at least the author didn’t claim they’d found the Holy Grail of the Nose. Maybe they wanted to but couldn’t – the Holy Grail of the Nose had already been found – just two years ago, in the study mentioned earlier.

* * * *

Every scientific field has a Holy Grail – which is good, because otherwise, why would people waste years of their lives looking for it? Holy Grails are so common in research, in fact, that if you pick up a rock you’re liable to find one. It happens every couple of weeks in one part of science or another, and the scientists who found it get free champagne and a parade. A single lab can find more than one Holy Grail, but only after the previous one passes its expiration date, which is more than two years.

To qualify as a Holy Grail, your work has to meet four criteria, and the Holy Grail of the Nose found in May 2014 met them all. The work has to involve 1) a group of experts (in this case, plastic surgeons); 2) the use of a high-throughput technology (questionnaires); 3) an appropriate model system (people’s faces); and 4) the thing you actually find.

What the lab discovered was a nose, of course, but not just any nose: they found the Perfect Nose. And if that doesn’t raise your pulse rate, notice where it was found: on the head of actress Scarlett Johansson. More specifically, on the ventral side of the head, running in a line along the anterior-posterior axis that divided the face almost perfectly symmetrically, slightly below the midline of the face.

This is the kind of study that sounds like it started in a bar at a convention of plastic surgeons; unusually, somebody remembered upon emerging from the next morning’s hangover, collected data, ran it through analytical and statistical programs, and voilà!  Scarlett Johansson had the “perfect nose.” Hey, if it passes through the peer review system, it qualifies as science, right?

How fortunate it was that the perfect nose was found on someone who was already a celebrity. It gave noses an instant spokesperson who could raise international awareness of the issue (the political issue, not the fluid), start funding drives for the nose-impaired, attract money for research, and lobby for an International Nose day.

It was also a nice experience for Scarlett’s individual nose; in 2014 other parts of her body had just been awarded the title “Sexiest Woman Alive.” Her nose was invited to that ceremony, of course, as a guest, so that it would appear the red carpet pictures. But it hadn’t received a single mention in the press – or any appreciation for the thankless, essential role it had played in her success. I doubt very much that Scarlett would have received all those film roles or been crowned “Sexiest Woman Alive” without a nose.

Scarlett’s nose quickly became the focus of intense media attention, got invited to all the best parties, made the talk show circuit, signed a book deal. Her nose got its own Facebook page, twitter account, marketing campaign, and a product line that could be bought from the official website; the best-seller has been scented tissues. For 59 days “Scarlett Johansson’s nose” was the top-searched item on Google, and that doesn’t include a thousand variations typed in by people who couldn’t remember whether there were double-Ts or Ns, added some more, left some out, or had missed school the day they taught the apostrophe.

Fame, however, is a double-edged sword. At first the attention was nice, but soon it began to take its toll. Entire fleets of paparazzi began following her nose around, to the point that it needed its own bodyguard. And not all of the public commentary was polite. Scarlett’s nose was made a political issue, particularly by the Tea Party, who managed to link her nose to the climate change debate, then held it as proof that the nose could not have arisen by the principles of Darwinian evolution. Donald Trump stated that if he were elected President, he would deport her nose, because it could not produce a proper birth certificate, and once it was outside the country, he would build a wall so that it could not come back in. Feelings on the issue intensified to the point that a single mention of Scarlett Johansson’s nose set off fist-fights, which usually ended in someone’s getting their nose broken.

As the nose was, literally, in the foreground of the media frenzy, many of the effects spilled over onto other parts of her face. “At the beginning it was very strange,” she said in a recent interview. “I’d do an interview on television, and the entire time the camera would be zoomed in on my nose. It had very little media experience on its own; I had to train it to hold still when I talked, for example. Everybody’s nose moves, but you never notice because the whole face is moving.”

People would come up to talk, she said, and during the entire conversation their eyes would be fixed on her nose. “They’d be thinking, What makes it so special, so much better than mine?’ You couldn’t catch their eye; they were always looking a little farther down on your face. It was as if my nose had developed special powers, some sort of irresistible force. When people realized it they tried to tear their eyes away, but within just a few seconds they’d be drawn back to it again.” The only way to get them to stop, she said, was to zap their eyes with a laser pointer.

* * * *

While the Perfect Nose had been found, the mechanisms that led it to develop on Scarlett Johansson’s face remained unknown. This week’s study provides a way of finding them, by comparing the sequences of four of her genes to those found in the rest of the population. Presumably she has a unique combination of sequences that explains both her Perfect Nose and the imperfect noses of everyone else.

The chances of these particular versions coming together in one person may be so small that they will never occur again, unless the actress engages in inbreeding and her descendants continue to do so for many generations. Alternatively, CRISPR/Cas gene editing technology may one day be advanced enough to introduce perfect nose genes into human embryos.

At the moment, ethical considerations would make this illegal. There is nothing, however, to prevent scientists from placing Scarlett’s genes in animal genomes. So in the near future we can expect to see mice, rats, and other model organisms, including zebrafish, flies, and worms, all bearing the perfect nose.

One thing the discoverers of the Holy Grail of the Nose might not have taken into account: It is currently impossible to carry out gene therapy to correct most defects in adult tissues. If these challenges can be resolved, however, it may eventually be possible to infect an existing nose with a virus that will rebuild it and render it perfect. In identifying the Perfect Nose, the scientists may have unwittingly triggered the demise of their own profession, by making the Nose Job a thing of the past.

 

References:

Kaustubh Adhikari, Macarena Fuentes-Guajardo, Mirsha Quinto-Sánchez, Javier Mendoza-Revilla, Juan Camilo Chacón-Duque, Victor Acuña-Alonzo, Claudia Jaramillo, William Arias, Rodrigo Barquera Lozano, Gastón Macín Pérez, Jorge Gómez-Valdés, Hugo Villamil-Ramírez, Tábita Hunemeier, Virginia Ramallo, Caio C. Silva de Cerqueira, Malena Hurtado, Valeria Villegas, Vanessa Granja, Carla Gallo, Giovanni Poletti et al. A genome-wide association scan implicates DCHS2, RUNX2, GLI3, PAX1 and EDAR in human facial variation. Nature Communications 7, Article number: 11616. 19 May 2016. http://www.nature.com/ncomms/2016/160519/ncomms11616/full/ncomms11616.html

 

Omar Ahmed, MD; Amrita Dhinsa; Natalie Popenko, BS; Kathryn Osann, PhD, MPH; Roger L. Crumley, MD, MBA; Brian J. Wong, MD, PhD. Population-Based Assessment of Currently Proposed Ideals of Nasal Tip Projection and Rotation in Young Women. JAMA Facial Plast Surg. 2014;16(5):310-318. doi:10.1001/jamafacial.2014.228.
http://archfaci.jamanetwork.com/article.aspx?articleid=1883794

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