The Fate Game II

Miracles can happen. No, not that I've seen one recently. But I heard a story on the radio this morning (from NPR's Story Corps) about a little boy whose life was saved. It was told by a man who had been the little boy, the story of a time when he leant out of his family's five-story window a little too far and lost his grip, a fall he never would have survived, except for the barber neighbor who had come home from work early that day and was at the door to the building just at that moment. In the right place at precisely the right time. He quickly ripped off his jacket, reached out, and caught the boy (who was presumably only about 5.5 ft from the ground by then). He saved the little boy's life, and it became the most important moment in his own life, as well. A miracle for both of them, this unfathomable chance of random events coming together.

This is the kind of miracle I can believe in: the wonder and amazement of the what-ifs, the literally fantastic luck of timing. When the tragic action (of a car, of a slip or fall, of a cell, of a clot) is caught by the reaction of someone with a jacket, who just happened to be there at the right time. Where there is simply an action and a reaction, and no claim of one or the other without its partner. This is the kind of miracle that isn't there for so many, all the people who wonder "Why me?" or "Why her?" So many opportunities for a different fate, missed by miles or by hairs, the extent is no comfort because the outcome is the same.

This is how I feel right now: I have been walking, trying to run, down this street towards the building, watching her fall inexorably and slowly for more than three years like time is molasses. I don't even have a jacket on, and it took so long to process what I was seeing (and denial is so powerful), and I wasn't there at the window and I wasn't there to see the hand slip and I wasn't there to grab it. And nobody else was there either: the doctors guarding the windows failed in their jobs to watch over and test the windows against this possibility (was it their hubris? ignorance? or the age-old problem of who is going to pay for it?). Why do some of these goddamn windows have so many guardians and others are barely noticed? Some very, very good people have tried in vain to reach out and catch from other windows along the way down, like her parents running from floor to floor to floor. Good people set up experimental superstrong magnets that they are trialing to see if they can use to slow the fall or even stop time. But none of these things have worked. We needed either for the windows to be better guarded or for someone to have been there with a jacket at the very first fall of the very first cells going wrong and pumping out cortisol THAT WAS THERE IN HER BLOOD FOR ALL THE WORLD TO SEE IF ANYONE HAD JUST LOOKED. There would have been the time to catch her, and change the course of history.

So here we are now, there is still room for hope. Hope that at the most, the fall is slowed enough to give her time to look around and enjoy the feeling of flying, the beautiful sunshine outside, and all the people down there reaching out their ineffectual arms wishing they could catch her with the sheer force of their love. And at the very least, hope that with the here and now, our unique position in history, that we are on the cusp of something better. We have the opportunity and are beginning to develop the understanding to create tools to be there, at the right place and the right time, when they need it and before it is too late. All we can do is hope for the miraculous: that we are there, with our jackets out, ready to catch people.

The greatest love of all

I hereby proclaim that if I ever obtain a Howard Hughes Medical Institute Early Career Award, or something like that, I will post an audio recording of myself singing "The Greatest Love of All." Not like I am applying right now or something, I just wanted to make sure y'all will hold me to that if I do achieve somesuch importance.

Chemical bilology research blogging

Okay, so here's a little example of the kind of chemical biology that I am not convinced has a point for biology, it seems much more self-serving for famous chemists to indulge their 'we made this complicated thing in an extremely complicated way' obsession.

On the one hand, I read this essay by Tom Muir, which is totally SPOT ON about the future of chemical biologists as functional members of the research society. He's been one of the pioneers of this new cross-branching, so it makes sense he would know what is going on.

Then there was this. Three papers came out in the recent issue of JACS, all from the same research group (very famous) and all in a row. They all seem to contain the same authors but in different orders, all full articles. They all focus on making various parts of a fully synthetic, homogenously glycosylated EPO. They use phrases like 'Our venture commenced with the preparation of' and 'Several strategies were entertained' and this doozy: 'difficultly predictable conformation' (emphasis mine to highlight the typical chemist way with words). They also spend valuable page space (and reader time) expounding on how they tried this or that method that didn't work but fortunately such and such other method did, and detailing every little aspect of every single specific reaction including rapidity of consumption of starting material, and how happy they were about that. It ends up sounding seriously medieval.

They try to lay it all out old-fashioned-style like this is some kind of hypothesis driven research into a general glycoprotein synthesis strategy that will somehow revolutionize the field of 'biologics,' rather than the ponderous, author-heavy, complex target-based total synthesis it actually is. Yes, maybe a homogenously glycosylated EPO would be useful for figuring out which glycoforms have particular biological effects. But these (not one, not two but three, count 'em) THREE papers don't clearly highlight any generality or modularity that could be used for any glycoprotein. Their side chains are covered with protecting groups. They don't demonstrate how you could easily clip on any homogenous carbohydrate modification to relevant sites. Nor do they describe some new jump in efficiency of synthesis, or a new exquisitely-selective and exciting reaction (they just use minor modifications of existing strategies). These are the kinds of things that would be necessary to address their proposed justification that these methods could revolutionize drug discovery for biologics.

They don't appear to have a biological collaborator who might be able to make sure they are pointed in a useful direction, and regardless of their repeated assertions that the biological impact of their project is so lofty, as a chemical bilologist, nascent cell physiologist and protein chemist, I'm just not seein' it. This looks more like a classic case of misguided synthetic hubris combined with author-laundering to maximize publication number. I understand that students and postdocs want to get their first-author paper on the thing they made, but it really dilutes the report of the research unnecessarily to split up a common project in this way. This could have been one paper simply and clearly showing the synthesis of the three segments and that's it. That's all that is here. Or better yet, wait until you actually MADE the full EPO and publish ONE paper on it. We don't need to hear the stream of consciousness/chronological story of your trevails. We just want to know if you did something important.

They say at the end of the final paper that they expect to be able to use their fragment condensation strategy with the understanding that "with all complex target oriented total synthesis, intervention of the unexpected is predictable. That being said, we are hopeful that the convergent nature of our synthesis and its flexibility will enable its adaptation to reach our goals." Good, I'm glad they are hopeful!! It's much better than being depressed about how your long, long, tenuously important project is not changing anything significant about protein chemistry!

This is the kind of thing that bothers me about the divide between old-school and new-school chemistry. Young chemists are being misled into thinking this kind of thing has impact. They are not looking at these problems with biologists asking them critical questions all along the way (nor asking those critical questions of themselves). Ultimately, they are wasting a lot of their time on directions that could be much better informed by understanding how and why things like this might be useful, and the real requirements for making them so. I just don't understand why people still keep doing stuff like this.

Grantwriting pointers: Research Design and Methods

Hot off the internehts, fresh grantwriting help:

The long-awaited sequel to such ChemicalBiLOLogy favorites as "Specific Aims" and "Background and Significance" is now available on the Drugmonkey Channel! All hail the Physioprof Guide to writing Research Design and Methods!

If you are here about my K99/R00 guide, I strongly encourage you to use these resources for developing the scientific part of your proposal!!

The fate game

Denial carries us a long way in life. It's pretty much the only way humans maintain sanity. Destiny means nothing. It is just a construct: something we created to make us feel better about our fate, to feel like we have something to follow purposefully to reach our final destination and state. Fate is the real truth--it is the point on which the randomness drops our data dot in the histogram of variation. Lost in a sea of stochastic possibilities, hoping to cling to the middle of the road, the typical response, the average lifespan filled with average or superior experiences.

Hoping against hope that we will only win the good lotteries, like the kind you by a ticket for, or the kind where you magically grab the correct number of forks from the drawer without trying, or get a sunny day on your birthday; and not the bad ones, like being on a plane that crashes, or the kind where you end up with two exciting events happening at the same time so you have to miss out on one, or have some of your cells overcome their checkpoints and forget their jobs and take over their home and ruin it. Fear keeps us hopeful, because otherwise why and how would we go on? Being afraid prompts us to compartmentalize and keep bad possibilities separated. But reality is: some of us are the datapoints in the unfavorable side of the histogram, and no matter how much we tighten it up around the mean, there will always be randomness and always be a spread. Ultimately, no matter how hard we try, we can't control our fate. Biology wins in the end, and we don't even know how to play the game.

If you look from far enough away, the lines seem sharp and well-defined, but trying to pin down their tracks is like trying to outline a pencil drawing with an airbrush: most of it goes in the middle of your aim but countless pixels spray in all directions. How can we hope to ever describe and understand that? How can we console the outliers and explain to them that there's no way we could have known? How can we do anything other than hope for miracles, even if we don't believe in them?

On the limits to family-friendliness: Part II

All this discussion got me thinking about this. The fundamentals of what I am talking about might not be related to the other discussion from some people's perspectives, but I do think it prompts us to think about this as a bigger picture issue.

I believe that flexibility, support, making science and the family workable, needs to be a two-way street. It needs to come from the bottom up as well as the top down.

I believe that mentors/employers owe their mentees/trainees/employees the right to flexibility and support as long as their productivity is maintained, and indeed that by offering those to their people, they give them the space TO maintain that productivity.

I also believe, however, that mentees/trainees/employees owe their mentors/employers that same degree of support and flexibility. You should be ready to give the same support that you expect from others.

Discrimination and prejudice are well-documented, prohibited by law and pretty thoroughly discussed with regards to hiring, recruiting, treating your employees. University (and other) policies are in place to protect trainees from being discriminated against, and to require their employers to support them for personal issues like medical and family situations. But nobody talks about the other side: students/postdocs/trainees/applicants unconsciously or consciously discriminating against young/pregnant/female/minority mentors or employers. You as the trainee need to make sure you are going to get the best possible opportunity, right? You expect that a mentor and institution owes that to you, right? And yes: we do, because that is our job and it is why we are where we are.

But when it comes to decision time and the top candidates are choosing whether to join a lab run by an older faculty member with no family committments (no kids or grown kids), who is on the top of the ladder in their field vs. a young assistant professor (promising, but maybe she's pregnant and you worry about how much time she'll be able to devote to your needs)... ISN'T THAT THE SAME DECISION as whether or not to hire a young, pregnant woman to work for you wondering if her productivity might suffer because of her situation?

WE NEED EACH OTHER TO SUCCEED. No, of course I'm not advocating that every trainee should perform bottom-up affirmative action in this way. But young and/or pregnant and/or minority assistant profs need you excellent trainees to believe in us just as much as you need us and the old greybeard moneybags to believe in you. And we ALL have to work together to make science more open to the people who keep getting lost out of the pipeline AT ALL LEVELS.

What are the limits of "family friendly" workplaces?

I was disturbed into posting by Damn Good Technician's reaction to her husband's PI setting aside a room for his children to spend time in after school during his work day:

DrDGT's PI is moving his labspace within his university - the lab just moved from one building to another, and they're moving again this fall. His PI had a discussion last week with the rest of the lab about blueprints & lab rooms. Evidently, his PI told the lab that one of the rooms they were promised - a room meant for some delicate equipment - is going to be used for his kids. Yeah. Seriously. His PI's wife told him that she thinks it would be "best" if he dedicated a whole room in his lab to his kids, such that when they hang out there after school a few days a week, they have their very own room in which to reside.

WHAT?? This is wrong on so many levels. First off, that a spouse could dictate to their faculty member spouse how to allocate space in their lab is fucked up - unless you're the Jans or something, this seems beyond the pale. Second, it is wholly inappropriate for a faculty to cordon off lab space for their own child care purposes. The university is not granting him space for his kids have a place to color three times a week; he's getting space to run a lab. Lastly, you're making it perfectly clear to everyone who trains under you that you are not committed to getting them the best lab space that you can - now this delicate (and might I add fucking expensive) equipment is going to be stuck out on a bench somewhere, getting dusty, abused by other labs, etc etc.

I was utterly floored when DrDGT told me. Can faculty do this? 'Cause, shit, if that's possible then I want DrDGT's lab to have a foosball room with a keg in it.

Reader, how do you react to that idea?

I don't think she or any of her commenters realize just what they are demonstrating: they ARE BEING the people whose first impression of a scientist having their family around is inappropriate.

If the PI was a woman, would they/you feel differently? A single mom without access to a good daycare? If the children were younger, still dependent for food and naps on their mom and dad? Why should the school-age children of a father have any different set of circumstances available to them? Why can't every scientist with kids have something like this available to them? Why does across-campus or far-away daycare access factor into this, when dumping your kids off in the care of someone else does not solve the problem of the struggle to balance family/work?

Having a room to set aside for your family is EXACTLY what would make science work for parents. Sometimes day care just doesn't cut it: you want to be near your children, available to them if they want to spend physical or emotional time with you. But you need them to not be right in your office, or they constantly distract you from the work you are trying to get done. This situation sounds perfect as a way to help balance family and science, and every institution should try to offer this to their PIs.

I'm sad that it provoked such outrage from the people who want to be understanding and inclusive, and I hope you guys will realize that this is a perceptual prejudice, and by holding fast to that reaction you are being the people that you think of as the enemy.

Frankly, lab member "inconvenience" regarding a piece of equipment or some yards of bench space should not trump support for scientists with families. We will only move forward and increase representation of women when this kind of thing is less appalling to everyone.


My brain feels like oatmeal: I just finished a 10-day trip to my husband's homeland for various family things, that just so unfortunately happened to coincide with the week before one of my grants was due and all the paperwork for the Concept Award is due (the date for both is tomorrow). Of course I could only get superficial work done while I was over there, both because of internet access problems and the demands of family and friends who only get to see us about once a year/every two years. We got back about four hours ago from about 17 h total of traveling and I just spent that whole four hours hammering through first some more intense science writing revision on one grant and then i-dotting and t-crossing on paperwork for the other. So much thinking, so much detail, soooooooooooooooooooo tiiiiiiiiiiirrrrreeeeeeeeeedddddd.

Whaa f'in' whaaa, right? And I couldn't even find any salt and vinegar Squares in the airport, so no snacky favorites to help me (I guess I did eat like 20 packets while I was there, so it's probably a good thing I can't get at them anymore).