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Got up and going today earlier than usual. Happy Wife said, “I have to get to breast conference this morning.” Naturally, I thought, “Honey, you stay in bed, I’ll go in your stead.” nyuk nyuk. Didn’t say it out loud, the humor having long since run dry from overuse.

And so here I sit, in the kitchen, tapping away, awaiting inspiration. It’s dark outside and astronomers I’m told know why. Stinkin’ warm too — feels like an early day in May. Certain people claim they know why this is, too.

I was arguing on the internet again, this time about something I think know something about, what a rarity, right! Often I argue about things I know less about and I make mistakes but they say you aren’t learning unless you make mistakes so I’m not one to shy away from an exchange only because I’m less than optimally armed. Knowing I was intellectually well-armed this time around doesn’t mean learning was absent, it was just asymmetrical — I found myself in the role of teacher, or at least it felt that way to me.

The “discussion” was about the future, and revolved around a blogger’s contention that before too much longer, by extending a known current technology to guide a yet-to-be-demonstrated reproductive technology, parents of the future would be able to “pick ‘n choose” specific heritable traits they themselves express which they want their child to express — for example, say the wife is musically gifted and the husband is a good writer of fiction. Of course, like all people, our would-be parents have many other “traits” too — for the sake of example let’s say dad has a weak heart and mom suffers from a mild form of prospagnosia, she has some difficulty recognizing faces. Now, our would-be parents desperately want a little girl, and they want her to grow up to be a good musician like mom with an ear for good prose like dad, but at the same time, of course, they don’t want to endow the child any cardiac or neurological deficits.

Okay, so that’s the goal.

Now, to achieve this, the blogger described an approach he read about in a science fiction book. His idea was that if you have enough information of the kind that comes from modern-day genetic screens, a method that detects changes (“variants”) in a person’s genome that significantly associate with some trait, say musical ability in our example, why then we could use a future reproductive technology (see below) to make sure that good genetic variants make their way it into the child’s genome, and at the same time avoid any known bad variants from getting in, the ones that associate with bad traits, like a bad heart or face blindness. In this way, the blogger argued, the “Designer Child” grows up predisposed to becoming an harmonic flutist, say, and/or the next T.C. Boyle, possibly, with a sturdy heart and an un-compromised  faculty for recognizing friends and family.

Now to the future reproductive technology, this is the hard part so stay with me here, I’ll be brief. The technology would involve using the list of genetic variants screened for above, those that are significant for both good and bad traits, and use them to guide a selective screen of DNA in dad’s sperm and mom’s eggs, depending on who has which good/bad trait. The idea being to isolate into one sperm and one egg as many good DNA variants as possible and as few bad DNA variants as possible. Then take that one sperm and egg, let them fertilize, implant the zygote in mom’s uterus (I suppose), stand back and let nature take it from there leaving our would-be parents ample time to prepare for the baby shower.

What’s the problem you ask? Here are the problems. Note especially comments signed by yours truly (“RKN”).

Enjoy your day!

Earlier today, in the Chugach mountains in Anchorage. The usual suspects.

BIGGER.

You can smell it on her breath, hear it in her voice, her highest reaches gone white — Mother Nature.

Winter cometh.

Accordingly, I deconstructed and stowed all implements of lawn management in the shed. You’re on your own now lawn. Sleep sleep…

Still, yesterday it was 53^o, although mornings have the unmistakable chill to let you know change is a comin’.

And yes it’s Mother nature, you never hear Father nature. Why is this? Or, more curiously, why does this sexism persist in our metaphors, especially in an enlightened age when diaper changing stations are found in the Mens room? Not trying to short shrift Moms here mind you, only to acknowledge that Fathers do their share of coddling the youngsters too. In some species fathers do it all.

Consider the Emperor Penguin:

The dad penguin keeps the family’s eggs on his feet, covered with his feathers, for 60 days or more! Contact with the ice will result immediate death to any of the embryos. During this ordeal the male penguin eats absolutely no food. Once the chicks hatch, he feeds them with a substance he produces in his throat. The female returns once the eggs hatch and she takes over just some of the care.

Of the Siamese fighting fish (Betta):

The female Betta lays her eggs and the father catches them in his mouth and drops them into a nest he previously prepared. The male Betta then guards the nest and baby fish when they hatch.

Still unimpressed? Okay then, how about Father Seahorse:

The male sea horse may be the animal world’s most unusual dad. The male seahorse has a pouch where the female lays her eggs, literally impregnating him! The male has a placenta-like pouch that supplies nutrients and oxygen to the eggs. The father then looks after the eggs for about two months until they hatch and can leave the pouch. He continues to protect the young until they are able to live on their own.

So, the next time you raise your glass o’ lemonade — spiked or not 😉 — skyward acknowledging a beautiful day, consider a paternal salutation: Thank you, Father.

Martin Short pre-party @ Subzero lounge. Gave the pic a noir look ‘n feel in Photoshop, but it made me look like someone who’d fallen asleep in a tanning tube. Happy Wife was stunning, as usual.

I had no idea before the show that Martin Short was 63. He was impressively acrobatic on stage for a 63 yr-old I must say, jumping on and off a piano at various times during the show. His performance consisted of stand-up comedy, amusing song ‘n dance, and a reprise of some of his SNL characters, vignettes of which were shown on screen during character transitions. Happy Wife thought these were the funniest parts of the show. While I kindof agree with her, I can truly appreciate a performer who travels from city to city, getting on stage each night to keep expectant audiences amused for ninety minutes or more. That can’t be easy or free of its own kind of tedium, especially for a 63 yr-old. I thought the funniest part of the show was when he transformed into Jiminy Glick, a character I’d never heard of, and “interviewed” our local weatherlady.

Jiminy interviews Tom Hanks:

I am infrequently asked — especially this time of year, Fall — “The drive to your “Nest” near Seward must be beautiful. Can you describe it?”

Not really. Especially yesterday, it was so indescribably pretty you wanted to stop and applaud for nature.

So instead of a description, a dash cam. Cheesy and a bit amateurish due to rotation & compression en-route to Utoob, but I trust my reverence for this place was not lost in translation.

Somewhere south of Turnagain Pass, headed south. The wavy margins of the video are in no way reflective of the videographer’s state of mind at the time!

~20 miles north of Seward. The lightness of Bryan Ferry’s voice together with the serenity of the mountains, why, it was like a well-paired wine with a gourmet dinner.

There are few things like a scientific conference to make one feel as if he has been suddenly transported out of the ordinary world, into a fervor of activity focused on important problems facing mankind.

You knew we haven’t cured^* cancer, right?

Maybe you did. But I bet you didn’t know that among the people who work on the complex complicated problem of cancer, some have given up all hope a cure will be discovered by one person or group. Unlike a hundred years ago when a mind-boggling problem could be solved by a lone frizzy-haired man who split his time between the patent office by day and lucubration over theory by night.

No. Today some people advocate we should turn to the wisdom of crowds.

Computational Models and Crowd-Sourcing Initiatives for Inferring Genetic Predictors of Cancer Phenotypes.

A catchy title of an interesting talk given in our session last week Friday. The basic idea was that if you can enroll a large enough number of groups of really smart people with different approaches to solving the same hard problem, then you just might. Take breast cancer for example. Determining a patient’s disease prognosis given her specific — “personalized” — molecular form of the disease (there are many), and then prescribing — “designing” — the best treatment so she won’t die from the disease, has been elusive. The literature is awash with failed attempts.

The presenter showed a rank ordered list of the performance of all the entries that had been submitted (~50) to a recent challenge in breast cancer. The challenge involved developing a predictive, computational model to separate a large group of breast cancer patients into two (or more) prognostic classes, given only the genotype (expression of ~20K genes) of the patients’ tumors, and suitable controls. Prediction accuracy of the models was evaluated on an independent “test” data set. In addition to gene expression, modelers were also permitted to use any other relevant bioinformatic data they deemed relevant. The group that submitted the model with the highest predictive accuracy on a “test” data set was awarded with a publication in a high impact scientific journal.

Interestingly, the second best performing model was also submitted by the winning group. So one of my takeaways was that it isn’t so much you need a crowd to find a solution to a hard problem, you just need to identify the right group in the first place. Although the presenter did mention to me over drinks later on that when aggregating the model predictions into one, performance was as good as the single best model, or possibly better, I don’t recall.

A question came up at the talk: What’s the incentive to participate in this kind of winner-take-all challenge?

It’s a good question, because developing a predictive model like this takes considerable time and effort, and if you win, sure, you get a decent publication, but if you don’t you not only get nothing (other than an acknowledgment of participation in the journal article), your scientific reputation potentially is tarnished. The presenter replied that yes, this was something they’d thought about, they’d considered spreading the wealth to all participants but couldn’t figure out how to do it since the award is not monetary. Even so, the disincentive is evidently not so large as to discourage participation — this year they received submissions from groups in over ten different countries.

* Unlike, say, smallpox, a disease that has been virtually eradicated by vaccination, “curing” cancer means stopping people from dying from their cancer, not from getting cancer in the first place. At least for somatic cancers, there is no chance we’ll ever be able to stop certain genes from mutating entirely.

Now that’s what I’m talking about.

And that ain’t the half of it!

 

Shout out to the La Fontana Sicilian restaraunt in Seattle. Superb stuffed chicken paired with a 2008 Zenato Amarone. Excellent service.

2nd & Blanchard

At the BMES meeting in Seattle thru Saturday. We’re presenting some of our latest work around biomarkers of multiple sclerosis severity. Friday morning in the Systems Biology track — 8:00 am, ouch!

Thank heaven for Starbucks.

Wood was wet. I asked at least twice before he came, Are you certain this is seasoned and dry birch?

Yes yes yes.

When he finally arrived at ~6:30 I walked outside, shook his hand and looked in the back of his truck. Crap. I pushed my forefinger into the rotted center of a 12″ round and just looked at him. “Dude, this will not burn. It’s neither seasoned nor dry.” I pointed to other pieces just like it.

It sucked that he had to come this far to learn this, plus having to deal with the hassle of a broken down trailer, which he’ll likely have to leave roadside until Monday, the first chance he’ll have to find a spare tire. Then drive back to replace the tire and drive back home again. I felt his pain and gave him $40.00 for gas.

Oh well, dinner out and wine with friends was fun, finished off with a dip in the hot tub.

Back to Anchorage tonight.