More lab lamenting

So we think we nailed down which of our plastics were giving us some of the background. But we still can't get any signal. So, we did some other controls and realized that the new lot of one of our reagents is about 1000X less sensitive than the old lot. A conversation with tech support later tells us that this is the only lot currently available. Hmmm. They even sent us a whole new batch (of same lot, though, since there aren't any others) and it is still only able to detect 1000X higher concentrations of the stuff we're looking for compared to our previous lot (which is all gone by now).

So, this sucks. We're stuck. This is a reagent I had already optimized as the most sensitive for what we were trying to do. We can try one other version of it, of which the company is sending a sample, but based on what I have done before I have a feeling it won't work as well. And this is all we need to publish our first paper. 🙁

Bite me LiCor!

F'ing LiCor scanner software, mysteriously throwing away my scan that took 26 minutes to complete you piece of crap! I needed to leave to go home on my 86 mile drive half an hour ago, and now I have to wait for your ass for another 26 minutes!


Update 26 minutes later again: Oh, and now my dye is dead. Thanks a lot. Now I have to start all over from the beginning.

Oh, plastics.

Lab plastics are the bane of our existence right now. In my postdoc lab, we had certain products from certain brands and they worked a certain way for all of these organic solvent/strong acid mixtures I used to put in them with my various types of experiments. Now, of course, we have tried to move to some different varieties and find that they leach all kinds of background-producing additives into our experiments, and nobody can make the crucial technology of the lab give them reproducible, usable data. GREAT! Who knows if my old lab even still has any of the exact type that worked for me before--so we may never know where to get more, and we'll just have to try a bazillion samples until we get something that works. All when this is the LAST THING WE NEED TO GET THE DATA ON for our paper that really needs to be submitted TWO MONTHS AGO, and meanwhile people keep wasting their precious sample, which we will need to re-run, on these non-working plastics. Sigh.

And she's gone.

It's so odd how, now that my cousin has gone (she died on Saturday at about 9 pm), now I can finally talk about her cancer in more than metaphors. I don't know why that was so difficult for me before. Especially since when I talked TO her about it, I could ONLY talk in science and medicine, I was crippled from talking to her about more metaphysical, personal parts. I kept holding up my analytical, informational side for her to talk through the science of what was happening to her, rather than HER.

She died from adrenocortical carcinoma. Only about 300-400 people in the USA are diagnosed with ACC a year. In Australia, there are only a few patients currently. It is such a rare, strange cancer: rather than being undifferentiated like many cancers, these tumors are often differentiated and functioning: they pump out hormones like cortisol, causing all kinds of other side effects that are really unpleasant for the patient. It's extremely lethal, but only when found past stage 3-4. If found instages 1-2 (where the tumor has not invaded other tissue and is still encapsulated), it can be removed and survival with NED is actually pretty good. Unfortunately, because it is so rare, not many doctors know how to recognize the early warning signs, they often get mistaken for other relatively innocuous hormonal/weight/skin issues and so many patients are not diagnosed until stages 3 and 4 when it has gotten so bad, and the cortisol/Cushing's symptoms are so awful, that finally they can see there is something else going on.

And herein lies the problem: our medical system is no good at looking at small numbers of things. When a given doctor may see 1-2 people in his/her lifetime with ACC, they just don't have their radar set to the right level for catching it. We just don't know what to do with small numbers. Large numbers, yes: skin cancer? Totally watched for. Breast cancer?: yup, hudreds of thousands of women mean a nice big histogram to have in mind for someone to fall in the middle of. To that perceptual bias, add the problems with funding for things that don't affect enough thousands of people (a. not enough donors! b. no company will make enough money off THAT treatment!), and we reach the limits of the abilities of our model for medical maintenance.

What's more, she did not have health insurance for the first 3-4 years (or more) that this cancer was probably growing inside her and starting to show its signs. She saw student clinics and other free care options, and was brushed off again and again. Finally the volunteer nurses at one of these free clinics (a woman's clinic in a city) decided to look more closely and figured out to test for cortisol levels. BANG. From there is was a rush to imaging and surgery. Finally the attention that was needed, but about three or more years too late. Stage 4, invading the vena cava. Removed surgically according to what is considered the "typical" protocol, but within six months little constellations of metastases were all over her lungs and liver (which, it turns out, is also extremely typical for this protocol). These cells have an incredible propensity to invade other tissues, and the tiny seeds left over from the cutting and ensuing inflammation just floated on out and germinated in whatever narrow constricted vessels they finally landed. Once that has happened, it is definitely too late to make any major headway in treating this disease.

On the physician side, treatment of this cancer is beset by inexperience, ignorance, hubris and confusion. There are a few experts in the world, and these people are truly excellent--compassionate, thoughtful, giving everything they have to understand how to do the best they can for their ACC patients. But the non-experts sometimes kill people without realizing it. The tumors are soft and easily broken, and also most likely to metastasize when that happens--yet surgeons argue and disagree and can't decide whether laparoscopy or full resection or what-have-you-their-expertise is the best way. They argue academically about adjuvant treatments, disagreeing on paper whether they should or shouldn't help. They talk about staging and survival curves. They forget that they are talking about individuals, people, human beings who are afraid and who can sense that nobody really knows what is going on and that terrifies them.

On the basic science side, because of its small sample size this cancer highlights what we all have been coming to know and accept about cancer: it is a heterogenous disease, a collection of many different diseases from person to person (and frequently even from tumor to tumor and cell to cell in the SAME person), constantly evolving under pressures to eradicate it. When a type of cancer has millions of patients, the statistical biology means that good portions of them will have extremely similar characteristics so they can be classified together, and treatments can be tested out to know roughly what characteristics will respond favorably to which treatments. When the cancer only has a few hundred patients, this process is hit or miss--like doing a blind taste test where even the testers don't know which product is which. And when that cancer is extremely aggressive, the timeframes in which you can test are only months--so it is extremely difficult to really know what is working and what isn't. By the time you finally find something that stabilizes the disease progression, you may have broken down the patient's body so much that they cannot hold on any longer to enjoy their new control over the cancer.

When every patient is their own test case, it is impossible to predict how things will turn out. And it shows the sorry state our knowledge of this biology really is in, that we still need at least thousands, if not millions, of N to be able to make decisions about what is going on and what to do about it. Until we figure out how to quickly and mechanistically understand each patient's cancer, this will just keep happening over, and over, and over and over again. A tragedy each time, that didn't need to happen this way if only we could figure it out. Isn't that our job, science?

Grad student recruiting survey

Hello current and future grad student and postdoc readers, I have some questions for you!

We have traditionally done pretty well with recruiting, but lately things have waned a bit and we want to know why. We want to improve recruiting in our department, so we can attract more applicants and convince more of them who visit to come to us for their PhDs. We are looking at ways to do this, and I wanted to get some brainstorming feedback from you all out there who are looking, or who have recently looked, for graduate school opportunities. I even created an email address just for this! Please email me (or comment here) with any responses you're willing to share with me:

1. Where do you look for information about a department? What venues (internet, your current school, your current mentors, conferences, etc.) have been most effective in introducing you to departments that you might not know about otherwise? How important is the department's website in your decision to apply or not apply?

2. What are your top priorities in a grad school department? For example, rank these things (and/or add your own): reputation of department/institution name itself, reputation of PIs and their science, types of grad support available (TAships vs. RAships), length of average graduate student time to PhD, attitudes of current graduate students, exposure to postdocs, friendliness of environment, stipend level, etc...

3. If you were on the fence between two equally solid offers, what kinds of things could the recruiters do or offer to change your mind?

4. On a recruitment visit, what are the most valuable and important parts of the trip? Should there be more time with PIs, or more time with students? How much do social receptions influence your feeling of a department?

5. From afar, who seems more interesting and important to talk to: junior faculty or senior faculty? Do you want to see them give talks about their research, or do you want to spend more time one-on-one?

6. Any other things that stood out as positive or negative from visits you have had, or departments you have looked at (without identifiers please)?

Thank you!! All survey respondents will get a little gold star sticker put on my wall for them! If you don't have a way to answer anonymously by email, please feel free to comment here with your answers. If you do decide to email me, your anonymity will be protected.

In which she goes completely off the deep end...

There's this theory in physics called string theory (I think it's currently called M-theory and has moved onto multidimensional membranes rather than loops, but whatever, this is close enough for my purposes), which says that when you get all the way down, down past molecules, down past atoms, down past electrons and to the most smallest fundamental particle that makes up our being, everything is made up of tiny loops of energy (the strings) that vibrate in different frequencies to make up the different kinds of particles.

If this is true, we could think of each of our cells as a collection of vibrating strings all playing a different tone: kind of like a big, deep, complex chord in music. All of our cells together, then, making up our bodies, make up this huge piece of perpetual music. It would also mean that rocks, trees, gas molecules in the air, stars and planets are all made up of the same vibrating strings playing their own particular songs, making us all pretty fundamentally similar.

Following along this thought experiment theory, that means that our 'selves' and the movements we make, or thoughts we have, or memories we build would all have two components: one is the strings themselves, and one is their pattern of vibration. Thoughts are essentially ion currents, in a way, and the movements of those currents would be movements of vibration patterns. Are those patterns just traveling and transposing along a fixed matrix of strings? Or are the vibrating strings picking up and moving around, displacing each other? Either way, kind of like how Plato described the "Idea" horse (the template or recipe for a horse) versus the "actual" horse (its physical manifestation), there is the song that is the pattern of vibrations that makes up "US" and there is the actual physical manifestation of that in a particular set of strings in our place and in our time. There is the sheet music of our being and there is our being.

This means that maybe we are all just songs being played on this planet right now. And our songs can be played anywhere that there are strings, and, fundamentally, a song will still exist even if it is not currently being played on strings. After all, time is just another dimension. To dimensionless things, it is just another axis on a plot to track along with occupancy points.

I know this probably sounded really whacked out and crazy, but even though I can't believe in the traditional ideas about life and death, I'm able to feel hopeful about this fantasy right now. It means my cousin's pattern could still be around forever (for whatever forever is worth to dimensioned things like us), even if her body is not.

Trudging along

I know science gears turn slowly. I have been experiencing this for 14 years (since starting research in high school). But still, it is still a grinding source of frustration to be waiting for other people to turn those gears. This is one of the most difficult aspects of my transition from data maker to PI.

The only thing that salves it is to have multiple people's irons in the fire so that at least SOMEBODY shows me SOMETHING approximately once a day. And this summer, I have to buckle down and do some work in the lab myself, so I am sure by the end of that escapade I will be extremely happy to go back to having other people bring me the data.

But MY GOD it feels slow!!!