Cilantronomics

We had dinner last night in one of favorite local eateries, a wonderful little Mexican place in a neighboring town. When I sat down, my eye was drawn immediately to my sort of dish -- one with a rich sauce combining the tang of tomatillos with the zing of cilantro. I picked well.

I really do love cilantro. Despite an extensive garden growing up, it was only in my adult life that I encountered this herb. I've been making up ever since. It works well in so many situations, not only in Mexican but also a lot of Asian cooking. The excellent Tibetan buffet in Central Square uses it extensively, particularly in a salad that works equally well before the meal as after, with the bite of cilantro contrasting with sweet cherry tomatoes and mango chunks. I even have a pot of it on my desk, which I share with my neighboring cilantrophiles.

However, not everyone loves cilantro. And it isn't just some folks might not like that little edge -- no, for some it tastes awful. Rather than some herbal bite, they taste soap. Or weirder. What other herb has its own http://www.ihatecilantro.com/?

Is it genetic? Alas, there has been a dearth of research on cilantro tasting -- indeed, it doesn't seem to rate an OMIM entry. There is a compound called PTC which is known to untastable by some, including this correspondent, and is genetically linked (my father can taste it; haven't surveyed the rest of the clan). With the help of some research by one of my office neighbors (and fellow cilantro fan), I did learn that 23andMe includes cilantro taste in their questionnaire. It isn't clear whether the other public and private genome projects are tracking this key phenotype.

Okay, I jest a bit. But while the ability to taste cilantro, or PTC, or the host of other innocuous traits which are staples of grade school genetics labs (e.g. widow's peak, hitchhiker's thumb, attached earlobes, etc) aren't exactly critical to understand, they will be interesting to understand. Widow's peak doesn't change someone's life, but to understand it is to understand a bit more about how patterns are laid out. The sciences of smell and taste have advanced tremendously over my lifetime; a whole new taste was found! Identification of smell receptors (recognized by a Nobel) and taste receptors have given great insights -- but we still understand very little.

Are there practical applications for smell & taste research? Of course. But to me the most interesting part is to figure out how it works. PTC doesn't seem so complicated, as the test paper doesn't have any flavor other than paper. But cilantro seems like a much more complicated, and interesting, question. Why does it taste bad rather than just not taste?

Is there an underlying soapiness which I just don't taste? In this case, tasters have a receptor for the magic compound (which is what?) and non-tasters simply lack it. Or does a different receptor bind the compound in tasters, in which case they have a gain-of-function mutation? Or, perhaps they have a partial loss of function -- there are a number of known compounds with concentration-dependent odor, probably due to differential binding to different receptors. In other words, at low concentrations these compounds bind to high-affinity receptors (yielding one perception) and at high concentrations some additional one Or, perhaps a partial gain of function in the non-tasters -- the same model could apply.

No, I wouldn't recommend basing an R01 application on the science of cilantro taste. Nor is it likely to tease a few million from some VCs as the core of a business plan. Cilantro haters will probably never have the option of genetic therapy to alter their perception. But it is still an interesting scientific question, and I look forward to personal genomics shedding some light on it.

The Blue Bus Grows Up

A striking characteristic of the Cambridge biotech scene is how it is concentrated in an urban setting. While there are a lot of biotechs elsewhere in Massachusetts, the Hub's hub is clearly a 2+ mile long zone. One challenge this offers is getting to work via Boston's transportation system.

Boston doesn't have an awful transportation network, but it isn't golden either. The transit system is decent, but the routes still largely follow a radial design, with routes that have changed little in the last half century (I kid not; I've seen a map that old & it takes a careful eye to find the differences). An extensive network of commuter rail feeds the downtown, but is split between two termini separated by a mile. The highway network has a number of gaping gaps, due to a mass cancellation of uncompleted highways in the early 1970's. However, this wasn't necessarily bad for biotech; I've spent half my career in offices that would literally be in the middle of the road should those highways have been built (for example, this very different vision for 640 Memorial Drive than a genomics-based pharmaceutical company).

The commuter rail option presents a particular challenge. One station, South Station, is connected to the Red Line subway which has two stops (Kendall & Central) proximal to many biotechs. The other station, North Station, has terrible connections to Cambridge, other than the perhaps future expansion of the zone into the Cambridge-Charlestown-Somerville interzone. But, if you live north of town it's either deal with getting from North Station to Cambridge or brave I-93. So, by multiple subway connections or a tortuous pedestrian path through Mass General's campus to the Red Line, a not tiny cohort of biotechies has made their commute this way.

Then about five years ago a new option appeared. Little blue buses promising a single seat ride from North Station to Cambridge, with a twisting route designed to be near nearly every major employer in the zone. Called EZRide, for $1 anyone can ride, but better yet the larger employers offer ride-all-year stickers.

The service was a bit slow starting up & went through a few hiccups, but over time it has been impressive. If memory serves, the initial frequency was every 30 minutes; this has been steadily dropped so that now a bus shows up every 8 minutes during commute time. However, demand has grown even faster; during core commuting times the bus is at its legal limit, with only ~30 seats and less than a dozen legal standees.

But a couple of weeks ago the announcement came out: a new vendor would be running full size buses on the route. And last week they showed up. On the one hand, there are more seats -- but not as many as one might think due to the layout. On another, more legal standees and less of the EZRide shuffle -- having to exit the bus at the early stops to let people off, as if you were standing you were a cork in aisle of the old buses. The longer buses don't handle the tight turns as well but do away with the most unpleasant aspect of the old buses: their short wheelbase combined with Cambridge's potholes yielded an amusement-park quality bumpy ride (particularly unpleasant if you made the mistake of leaning against the wheelchair lift).

EZRide isn't run by the transit system, but rather by a quasi-public entity called CRTMA which is charged with improving transit into Cambridge. The director, Jim Gascoigne, is energetic and personable and often on the scene, particularly when weather or accidents snarl require emergency re-routing.

In some ways the EZRide highlights issues in Boston. The T does an okay job, but it apparently never occurred to them in several decades that a market existed for a route from North Station to Cambridge. I've also seen the truly surreal quality of Boston from the blue bus: due to some construction, one Boston police officer directed the bus to stop in a new location, where the driver was promptly berated & ticketed by a second Boston officer. This is the town where the mayor had major apoplexy when a nearby airport added Boston to their name; transportation issues are about turf battles as much as moving people around. The planners also have a fondness for expensive megaprojects (the current shopping list can be found here). Several of these would have important benefits for the biotech zone -- for example, the proposed Urban Ring would run right through it & connect the zone to the Longwood Medical Area.

However, perhaps what is more realistic are more EZRide-like services, perhaps connecting to the south (Brookline, Brighton/Allston) that have surprisingly poor connections, or to the large transit hubs to the north (Wellington, Anderson). A direct connection to Charlestown wouldn't be a bad concept either.

In the meantime, I'll keep riding EZRide. And anxiously awaiting my train line(s) getting the free WiFi service a few lucky commuters have gotten to pilot. One more good reason to stay off the road and out of my car!

Panda genome arrives

China announced over the weekend the completion of the giant panda genome.

For the benefit of presidential candidates who can't conceive of the value of scientific research on bears I'll suggest a few questions worth exploring in the panda genome (beyond the obvious direction of weapons development)

First, the panda genome is one more mammalian genome to add to the zoo. For comparative purposes you can never have too many. Since other carnivore genomes are done (first & foremost the dog, but cat as well), this is an important step towards understanding genome evolution within this important group. It is the first bear genome, but with the price of sequencing falling it is likely that the other bears will not be in the extremely distant future (with the possible exception of Ursa theodoris).

Second, completion of a genome gives a rich resource of potential genetic variants. In the case of an endangered wildlife species such as panda, these will be useful for developing denser genetic maps which can be used to better understand the wild population structure and the gene flow within that structure. Again, if you are running for president please read this carefully: this has nothing to do with paternity suits. If you want to manage wildlife intelligently and make intelligent decisions about the state of a species, you want to know this information.

Third, pandas have many quirks. That bambooitarian diet for starters. Since they once were carnivores, it is likely that their digestive systems haven't fully adapted to the bamboo lifestyle. Comparisons with other carnivores and with herbivores may reveal digestive tract genes at various steps in the route from meat-eater to plant-eater.

Fourth, as the press release points out, there are many questions critical to preserving the species which (with a lot of luck) the genome sequence may give clues to. First among these: why is panda fertility so low? U.S. zoos have been doing amazingly well in this century, but that's only 4 breeding pairs. The Chinese zoos have many more pandas & many more babies, but it's going to take a lot more to save the species.