Thursday, August 23, 2007

Postdoc Carnival: What's up Postdoc? August 23rd

Hello everyone,

It's always a joy to host a carnival where you read things written by your peers that are so insightful, truthful and enjoyable. Thank you everyone who wrote to me with posts and those who suggested posts, and without any further ado, the carnival.

Regrets Regrets

I wanted to know what all of you would have done differently if you could, and the spectrum of answers was fascinating. Dr. Brazen Hussy wouldn't change a thing, barring the occasional drunken quarrels with her advisor. Day by Day wouldn't change much either in the balance, she regrets only not spending enough time with her friends from grad school. Lou proposes that we all appreciate the here and now and learn from our pasts rather than regret them, and Propter Doc has a detailed and insightful analysis of what she would have changed given her current perspective. Katie at Minor Revisions has a frank and honest essay on regretting the time she has wasted and the questions she should have asked. And comes up with one the most memorable quotes I have heard in a while: "Post-docs are a renewable resource here." and goes on to compare postdocs to plankton. Fabulous and fabulously apt. Ragey One, Apparently and I do have some regrets, Ragey would not have accepted her current position knowing what she knows now, Apparently would have done her postdoc experience differently, and I would have interviewed more.

Dealing with other diverse subjects, other postdoc or former-postdoc bloggers have some great things to say. Sunil at balancing life wonders why Ph.Ds are so long, Incoherently scattered ponderings has some advice for what not to have on a CV and YoungFemaleScientists discusses whether its easier for foreign postdocs to find jobs here as opposed to US postdocs looking elsewhere. Marianne at the Eternal Postdoc tells us why being a postdoc is so hard, and Chall at Dreams and Hopes of a Scientist believes that your PI will find it easier to believe in you when someone else does. Chris at Highly Allochthonous finds that the postdoc is willing but the equipment isn't and a group of postdocs formed the postdoc union (wonder how they are doing?). Also, no to be discriminatory, but I have to mention some lovely women in science, Micella Phoenix DeWhysse at Science Careers has a whole series on Educated Women, here's one, and women in science as always has cool things to say.

And finally, the utterly apt and necessary PostDoc Oath, from the Girl from Ipanema. Say it with me everyone, " I X postdoc, do solemnly swear that..."

What would I have done differently?

Interviewed more.

I don't believe in regrets and hand-wringing. I am self-aware enough to know that I made an informed choice and I saw most of the red flags in my current lab when I interviewed. I didn't expect them all to be true, but that is a different matter.

I interviewed over one long weekend, in one area. I did restrict myself geographically for personal reasons, and that geographical restriction is turning out to be the best past of this experience. Anyway, over that weekend, I interviewed with five PIs and three labs. One experience was excellent, saw some potential problems, figured awareness was half the battle. One experience was really good, but I would have ended up being the senior person in the lab and the PI wasn't even directly offering me the job anyway. The other three were washouts. I was already pretty fed up with the process, because I had a few pre-screening rejections based on the tight funds at the time and my average but not sexy CV. So I didn't send out more applications and accepted offer from said excellent interview experience.

Red flags and all. And everything I thought might possibly go wrong did. Everything possible. Which really sucks, but I thought they were all possible. I also think that every lab has its, shall we say, quirks. I didn't expect the personality of the PI and the community of the lab to be this negative. I have some wonderful colleagues, so it makes it easier, but otherwise, not good. And the general research environment is not conducive to one's greater professional development.

So, I made an informed decision and took a chance, it didn't pan out. I'm dealing. But, in restrospect I should have interviewed more, seen more places, other labs, other dynamics and then decided.

Oh well.

Tuesday, August 21, 2007

The Damage Response Framework

The Damage Response Framework of Microbial Pathogenesis is an idea, put forward by Liise Anne Pirofksi and Arturo Casadevall in 1999. I first heard of it when I heard Arturo Casadevall give a talk: and what a talk! If you ever get to see him speak, do so, its well worth it. The point of this idea, or framework of ideas, is to find a way to describe “pathogenesis” in the most universally applicable way.

What is pathogenesis?
It means the genesis and progress of disease. A pathogen (as described in the sidebar) is an organism that causes disease, a simple enough definition, and fairly all-inclusive one may think. Maybe not. What about an organism that doesn’t cause disease in a normal healthy “immunocompetent” host, but causes disease in hosts that have deficient immune system fro some reason? These normally harmless microbes cause harm only in immunocompromised individual (Immunocompromised: possessing a compromised immune system. A fine example of the immuno-rule, if you want to make a term immunologically relevant, add the prefix immuno to it). An extreme example from Casadevall and Pirofski: harmless useful baker’s yeast Saccharomyces cerevisiae is considered a non-pathogen most of the time, in fact we consume it with great gusto. However, in some severely immunocompromised people, it causes disease. So is it a pathogen?

The Damage Response Framework
The key words in the previous paragraph are immunocompetent and immunocompromised, words used to describe the host. As illustrated by the baker’s yeast example, a “non-pathogenic” microbe can cause disease depending on the immunocompetence of the host. So, the pathogenicity, or disease-causing potential of a microbe is partly determined by the immune state of the host it infects, and a disease is the outcome of the interaction between the host and the microbe. This is the (paraphrased) first tenet of the damage response framework. This may seem obvious, but it is a really novel way of looking at disease, as the interplay between the host and the microbe, with the microbe contributing virulence, and the host contributing either resistance or susceptibility. It is a fine balance in other words, with the occurrence of disease depending on the balance between said virulence and susceptibility at any given time.

The second tenet of the damage response framework refers to the definition of disease itself: that the degree of disease caused is determined by how much damage is caused to the host. If one accepts that individuals have different susceptibilities to a certain microbe, then is follows that they will be affected by it to different degrees. Some individuals will show no symptoms despite being infected, some will show moderate symptoms, and some will be felled. They are all infected, does that mean that they all have disease? Not if one uses the damage response framework to measure disease. It doesn’t matter if an individual is infected, i.e. the microbe has entered their body, it only matters if their body has suffered damage, and to what extent.

The third tenet of this framework is that the damage caused by infection with a microbe can be caused either by the host or the microbe. Microbes can cause damage in many ways: they can kill host tissues, they can form big aggregates that physically impede blood flow or digestion, they can alter the basic metabolic balance of the host. The immune system is fast, robust and precise for the most part, however, it works by sending cells and cytokines out into the body to whirl around and do their thing. Immune cells eliminate infection by killing host tissues that are infected; it stands to reason then that there will be some collateral damage. This collateral damage can be minimal and go unnoticed, or it can be measurable but worth it because the microbe is eliminated, or it can be so extensive that it causes most of the damage to the host. Tuberculosis is a good example of the third case, the granulomas that are such distinctive features of clinical tuberculosis are large collections of highly activated immune cells, raring to go and damaging large swathes of the host along the way.

The Practical Applications

The most useful direct application of the damage response framework is to eliminate the subjective classification of microbes as strong or weak pathogens, as opportunistic pathogens or non-pathogens. This is achieved by using a new system of classification (because everyone wants to be Linnaeus!). The damage causing ability of a pathogen is plotted on a damage response curve, and the pathogen is classified based on its characteristic curve. The curves plot host damage and benefit on positive and negative y-axes respectively and the host immune response on the x-axis, going from weak to strong. I don’t want to reproduce the figure from Nature Reviews here, but I’ll try and describe the curves. The most easily visualizable are Class 3 pathogens that have a U-shaped curve, with high damage caused when the host immune response is either too weak or too strong. The difference would be that the damage is caused by the microbe when the host response is too weak and by the host when the response is too strong.

These curves are really nice and interesting, but ironically, their main weakness is that they are too subjective. Strong and weak are relative terms, so these curves have limited application until we can quantify both damage and the host immune response in amore universal way. Another thing is the role of time. Infections take various courses over time, for example some viruses infect the host and become latent, hiding out in the host till they become activated upon which they cause damage. If the host immune response manages to overcome the activated virus the damage is limited and the virus reenters a state of latency, and has the potential to reactivate, propagating the cycle. A necessary component of the damage response curves is time then, on a third axis. This is probably pretty complicated computationally, also we I don’t really think there is enough data yet to make these for many pathogens. Especially since data needs to be collected with these curves in mind, a mindset change that yet needs to happen. Effectively, we would also need a massive though exercise in which we place all the data we have on microbes and the host responses they provoke together with the damage they cause are placed in a kind of giant multidimensional matrix and look for correlations and points of intersection. The biologist in me quakes at the scale, and the extremely rudimentary mathematics training I have had leaves me bug-eyed at the thought.

Extolling the coolness and a Summary
The Damage Response Framework of Microbial pathogenesis is incomplete and imperfect, but it is simple, clear, and phenomenally novel in its simplicity. It takes into account the interaction of both the host and the microbe, for after all they both affect each other constantly and while convenient, it makes little sense to treat them as separate independent entities while studying disease. I like to think of the host and microbe as trains on two separate but curving tracks. The host is headed towards a state of susceptibility and the microbe towards fitness to cause damage. At a given time, the curves of the tracks get close enough together and if the host train loses its balance on the track a little, becoming sufficiently susceptible, it collides with the microbe train and damage results. The extent of the damage depends on the angle of the collision (host susceptibility) and the momentum of travel. A limited and involved metaphor, but it helps me to visualize these interactions.

If you’d like to read about this idea in Pirofski and Casadevall’s own words, a great review is in Nature Reviews Microbiology in 2003, Volume 1, page 17. I’ve only skimmed the surface, there are so many implications and possible applications- not to mention caveats- that I haven’t gone into. It’s a seminal idea, and makes for very interesting reading and thinking.

Monday, August 20, 2007

Postdoc Carnival: (Renewed) Call for Posts

Hello All,

We are definitely entering the plea category. If you have anything you'd like to say, or have already said, about postdoc-ing or postdocs, send me an e-mail with a link to

by Wednesday night. For the Carnival to be posted on Thursday the 23rd.

Looking forward to it!

Tuesday, August 14, 2007

Never feel bad anymore?

The saddest happy song ever.
Island in the Sun by Weezer “..We’ll never feel bad anymore..”. Lovely fifties-sixties-ish chords. The “ hey hey”. Gets me every time.

“…We’ll run away together
We’ll spend some time forever
We’ll never feel bad anymore…”

Definitely not one of those days. Feels like I will be borderline bored forever. I know that’s not true, it’s a phase of the project, It’s all me really, I should plan better, I should be proactive, do more, fulfill my potential.

Don’t want to. Sighs.

Off to culture cells.

Monday, August 13, 2007

The Lab Wardrobe

I played against type today, I am wearing a skirt, pretty shirt and cute shoes. To Lab. It's a good thing I have a lot of computer work planned!

Ah dressing like a scientist. The bleach-proof scruffy eternally dreary clothes. To be honest, there is something to be said for jeans, t-shirt and sneakers, after all that takes care of the general ick factor of exposed skin in the animal room or the slight overall scariness of working with radioactivity. But how long can one go on dressing "like a scientist"? Company t-shirts, jeans from six seasons ago. I'm tired of it, I have a whole wardrobe that doesn't get worn enough.

I think the true revolution is the ballet flat. They are great! Closed toes, flat, comfortable and go with everything. Practical and attractive, imagine that, whole new worlds have opened up. Bringing on the new wardrobe...

Thursday, August 9, 2007

More on Illegal Immigration

Something that concerns me a lot, as you can probably tell.

Today's Editorial in the New York Times

I could not agree more. Their basic thesis for those who may not be able to read it is that the US government's current policy about illegal immigrants is based on punishment and making people's lives miserable. I quote

Their one big idea is that harsh, unrelenting enforcement at the border, in the workplace and in homes and streets would dry up opportunities for illegal immigrants and eventually cause the human tide to flow backward. That would be true only if life for illegal immigrants in America could be made significantly more miserable than life in, say, rural Guatemala or the slums of Mexico City. That will take a lot of time and a lot of misery to pull that off in a country that has tolerated and profited from illegal labor for generations.

The American people cherish lawfulness but resist cruelty, and have supported reform that includes a reasonable path to earned citizenship. Their leaders have given them immigration reform as pest control.

The thing is that this article is such a great example of American generosity. How many countries would be so generous about this issue? Do I think that governmental policy should be more generous? Resoundingly, yes, partly due to a visceral and admittedly unfair feeling that this whole country is founded on immigration and therefore has more of a responsibility to immigrants now.

Its a nice article at any rate and a strong statement from an extremely influential media source.

edited to re-format link

Wednesday, August 8, 2007

Call for Posts: Postdoc Carnival August 23rd

I am going to host the next What's Up Postdoc? carnival, and here is a call (appeal?) for posts.

The theme? What would you have done differently? If something, why and what? And if nothing (lucky you!), why?

Feel free to ignore the theme, and just write. Or send something from your archives. I'd really like to hear what you have to say.

E-mail posts to me at

Thanks and Happy Writing!

Stresses and Professionalism

Dissatisfaction is a common theme these days, whether the speaker/writer is a postdoc, a student, a financial professional, a software engineer, a insert-what-you-will-here. Which begs the question why? Is it because as a generation we have had things relatively easy? The struggles that may have defined life in earlier times are certainly less relevant to our lives, but we have a different set of stresses to deal with. Some are unique to the growing phenomenon of immigration, or migration, some are a function of increasingly isolated living situations and more nuclear families, some are certainly due to the fact that the bar for success is higher these days, to list only a few.

The question then is to what extent should these stresses influence one's performance professionally?

An individual is only as effective as the the sum of the stresses they are under. Simply put, one's life influences one's work. Some are better at compartmentalizing than others, and the result is often that they are able to separate the stresses of not-work from those of work, what is often the key to professionalism. And, as I've said before, I believe that professionalism is absolutely essential, both to work well and to maintain a pleasant work environment. However, are there circumstances when the stresses so far outweigh one's wish or ability to remain professional? What then?

Some obvious examples (only for the purposes of illustration!) that come to mind are pregnancy, clinical depression, serious illness, the serious illness of a family member. Many women don't have any problem working as usual through a pregnancy, what of those that are cripplingly sick? Or have complications that require them to take a lot of time off? And depression? Depression has degrees, and there are degrees of depression that are paralyzing, what then? If a colleague is seriously ill, its easy to see a way to be understanding, what if its a parent or grandparent? Is sympathy limited then?

For that is what it comes down to in the end, the ability to relate to someone's difficulties in a certain situation. It is much easier to make allowances for a colleague when one has been in a similar situation, and much harder to do so when one has not. Men, and many women, can be less than understanding about pregnancy related problems, and depression is such an amorphous thing that is is often quite difficult to feel for it, let alone understand it. Specific examples aside, what may not seem as stressful to an outside observer may be unbearably intense pressure to the person going through it. And it will, absolutely will, affect their work.

Some people have better coping mechanisms, for whatever reasons, physiological, emotional, mental or physical. It is inherently unfair that people who can cope better get less of a break, but that is the way it is. They need fewer allowances made for them, and often can be more professional in their approach to work, but they should not have that same expectation of everyone else. People are quick to perceive an inequality or an injustice, and are often justified in feeling put upon. But that does not necessarily mean that the people who seek more refuge from their stresses through less involvement in their work are doing so deliberately or as a means towards getting favours.

So my contention is that compassion is as essential a part of being professional as drive or discipline. No, one does not have to be friends with or confidantes of one's colleagues, but a little compassion for their troubles does not hurt. There are some stresses that do justify the loss of some professionalism. Burnt out late stage grad students, overloaded working parents, utterly demoralized postdocs, disorganized PIs who have lost control of their labs, all of these are real, if regrettable. It is hard, if even possible, to be patient with these people, especially if one hasn't been through these experiences personally. That is no reason not to try. And there will always be people who abuse compassion, with endless excuses and complaints, but is that reason not to be compassionate to anyone?

Tuesday, August 7, 2007

"Illegal" Immigration

A thoughtful adn though-provoking post by my dear Mincat, its a point of view, check it out.