Field of Science

Sports and stats and why it doesn't matter

The big news last week in Minnesota is that Brad Childress the head coach of the Minnesota Vikings was fired after leading the Vikings to a 3-7 start this season. Admittedly the Vikings had self-destructed and a large part of that can be laid at the coach's doorstep. So the coach has to go right? Well, I think a few questions need to be addressed first. For example, why did the team self-destruct? and is this season a good example of a bad coach or an aberration?

Is Childress any good as a coach? Current conventional wisdom says the answer is a definitive "NO!" However, conventional wisdom in sports is as good as thinking with your gut when making foreign policy decisions. Let's look at some numbers to maybe get a sense of things. Childress took over in 2006 and the Vikings record each year was:

2006     6-10
2007     8-8
2008     10-6 playoffs
2009     12-4 playoffs/NFC championship game
2010     3-7*

So in Childress' first 4 years the Vikings continually won 2 more games than the previous year and got within a field goal of the superbowl last year. A consistent winner.

For comparison, prior to Childress, we had Mike Tice

2002     6-10
2003     9-7
2004     8-8 playoffs
2005     9-7

So Tice hovered around 50% the entire time he coached. Childress showed consistent improvement until the trainwreck of this year. So either the team got consistently better from 2006-2009 in spite of Childress or maybe Childress had something to do with it. Since the head coach is the head coach, Ill go with the latter hypothesis as most likely.

So why the trainwreck this year? I don't know, but I have a few thoughts. First, it seems likely that there was at least one poisoned apple in the locker room (Im looking at you Favre). One personality can be enough to ruin the good work of the rest of the group. Advice I got when I started my lab and have given others is that it is more important to get good people in your research group than simply warm bodies. These people have to work together and have to have the same basic goals. If one person comes in and makes for an unpleasant work environment or is constantly undercutting the lab head or other important person in the lab, bad things happen. When Brett Favre, almost certainly a hall of fame quarter back, comes in and disparages the leadership of coach Childress, bad things happen. Maybe you're not working as hard as you should and don't know the play book as well. Favre gives you an emotional crutch to not think about your personal failings or mistakes. See its the coach's fault, his play book is stupid, ask Favre, so why should I learn it?

Before Favre joined the team, 2009, the Vikings hadn't made it to the NFC championship game since 2000. So Favre must have made a difference. No question about from me, but the team was already much improved since Childress took over. With the drafting of Adrian Peterson in Childress' second year, the only position of dire need was quarterback. That position has been filled by journeymen since Duante Culpepper was traded after 2005. In fact, Favre was/is a stop-gap measure. So 2009 was phenomenal until the end (interception thrown by Childress Favre). However, there were already Favre-Childress problems, but I think winning kept those problems from flaming. After the loss, Favre retired and the Vikings needed to do something for quarterback....

...and looked no further than Tavaris Jackson before plan Favre II was quickly worked out. At the last possible second, so he wouldn't have to practice and Childress was desperate to the point of losing his hair. What? He was already bald? OK, and Childress was desperate to the point of sending 3 players to Mississippi on the down-low to get Favre back. So, virtually no practice with his receivers (of course it wouldn't have been helpful throwing to the back up for a few weeks before the primary receivers went down), still recovering from surgery, oh and a grandpa, Favre returns...and lays an egg. Now there are many problems this year and it is BS to lay the 3-7 record at Favre's feet, but Favre, I believe, fanned the fires of discontent for the coach with many others on the team. Favre became a poisoned apple.

Childress had a history fielding a playoff caliber team; Favre had a history of retiring. So now the coach is gone, the season is kaput (barring a non-sectarian miracle), and the quarterback that made the coach expendable is gone this year. Its like Favre left the gas on in the stove right after he moved out of his apartment. Now the Vikings might be fine next year, they need a quarterback and a coach. What I find amusing is that Wilf, the owner, had a coach that took a repeatedly mediocre team without a quarterback and made them winners. Wilf had a coach that added a (formerly) great quarterback and fielded a championship team. So Wilf fires one and will lose the other thereby returning to 2006.

But of course, the team is 3-7 now. Who the hell needs to look at last year, that was last year. I mean we make our own reality right?

On applying to graduate school

This was supposed to be a response to my collective blog partner Psi Wavefunction (who has one of the coolest first name pseudonyms).

Another blog partner Gw/W submitted a post on graduate school applications, to which Psi in part responded:
"I find it quite easy to get in contact with potential supervisors, but that's probably because I usually know about their work first, and then find out where they are and whether they take students, etc. I find meeting them in person at meetings and department seminars helps things a lot. Actually, come to think of it, I haven't contacted anyone I didn't at least have some connection with already, at least through someone else who knows them personally. Then again, I've specialised pretty hardcore already, and in a small field like ours, everyone knows everyone... 
My trouble is with the application process itself, as my grades and GRE scores are...well, shitty. So I have to tailor my application to sneaking past the admissions people rather than appealing to a supervisor. Kind of the opposite problem to what more typical applicants have, it seems. 
I can freely chat with faculty about everything from research ideas to my transcript issues, but blank out completely when faced with personal statements and other formal application stuff. Where do I even begin? That was semi-rhetorical, but some advice would be very helpful! =D"
I posted an, as usual, overlong response, which blogger told me was too long. Since I am not willing to cull my infinite wisdom, I will add even more and make this an entire independent posting (take that blogger!).

Psi my experience comes from personally applying to (as a graduate student) basic biology programs and reading applications to (as a faculty member) a biomedical graduate program. My responses here represent my assumption that you are applying to a PhD program in the biological sciences.

1. In my experience direct appeals to specific PIs do not amount to much. Any decent direct applications I get I forward to our program secretary to be dealt with the official way (most go right in the trash because the student is spamming for a position). However, if you are keenly interested in biofilms and the Univ. of East Bumfuck only has one biologist working on biofilms, it may be worthwhile to see if they are planning on retiring in the next two years. Of course I would point out that it is insane or at least asinine to go to a program for one lab. What if they find someone they want more after you enroll?

2. You mention specialization. Do NOT get yourself stuck in a specific field. You are young (Im assuming), why limit yourself? As an undergraduate I did plant molecular biology research, that was the best shit ever! I applied to molecular biology programs with great plant labs. I rotated in a Saccharomyces lab, that was the best shit ever!! So I got my PhD in molecular genetics in yeast, and then found a post-doc working on a pathogenic fungus with non-existent genetics, and you know what? It was the best shit ever!!!! My point is keep a broad outlook, I still learn so many interesting things in biology. You need to be conversant with Drosophila geneticists, T-cell cell biologists, bacterial structural biologists, etc. at least if you want to be more than a glorified technician. (BTW I am not suggesting changing your field, just not be immune to other fields.)

3. Applications to my program are scored based on GREs, GPA, letters of recommendation, and personal statement. Kind of in that order, although there is much room for variation. We have looked over the last 5-10 years of our program and found that GRE score is the only indicator associated with grad school success (although lack of real bench work is associated with a lack of success, probably because students don't realize what it is they will be doing).

4. So GPAs, they are what they are, but are they? Poor GPAs are problematic, but not all problems are the same. Was your GPA shit early on and get better? That's a good thing. Were your GPAs awesome then get shitty? That's a bad bad thing. Did you do well in your science classes, at least those related to the program you are applying to? If yes, good. In no, reconsider you program. If your GPA was due to a bad year hopefully (as bad as this sounds) there were some obvious extenuating circumstances, such as a death in your immediate family. The committees that look at these things really look at them, so if you suck at art histroy but for some godforsaken reason minored in it, the reviewing committee will know that your sucky GPA is do to the fact you are not a cultural maven (a plus actually to be a scientist). From personal experience, I stunk up the joint my first year of undergraduate (1.8 GPA my first semester). That was basically impossible to recover from, but I was 4.0 my senior year. Overall GPA was garbage, but a more careful analysis showed I was a great student who was too not ready for college from the outset. I survived. Regardless, you need to deal with your GPA in your personal statement.

5. GREs are important, particularly the math component. If you do well there and speak fluent English, verbal is given a pass and the essay is BS to begin with. Write as much as possible in the time allotted to increase your score (word count matters, but shouldn't). The math component is considered strongly, hopefully you did well there. If not you need to deal with it in your personal statement.

6. Letters of recommendation. These are your get out of jail free card. If your GPA and GRE suck, this can easily salvage you. You should have strong relationships with your letter writers. I wasn't planning this ahead of time, but played poker with one of my professors every couple of weeks. Despite taking his money often, I gained a great personal relationship with him as well as several other faculty members. This is important, neigh essential. Be someone, not just a grade. If you have research experience great (although this is almost a requirement). If you have a publication, you are fucking set! Even if its a fourth authorship. The publication shows that you are able to work on a piece of research that is publishable and published, that is currency you should use to its fullest, which takes us to....

7. Personal statement. The personal statement is important, but difficult to write. You need to do several things.
A. Tell the committee why you are interested in their program (each letter to a program should be different at some level to hit this point).
B. Share your passion for science! But do NOT NOT NOT NOT NOT tell us you need to cure cancer because your dear grandma who helped you through the difficult time of middle school bullying died from cancer. Every statement like that makes me feel for the candidate while I put the application in the discard pile. All you convey is that you are only interested and focused on one specific thing. You will not cure cancer during graduate school or learn how do to it while in graduate school, so all you are telling the committee is you are naive and scientifically immature. (If you having an outstanding blog, this may be the place to note it. It demonstrates your writing skills, passion, and intelligence. Although I would not overplay this, because many people (old white guys) still view blogs with some distaste.)
C. Talk about your research experience, what you did, why it was important, what it meant to you. If you have awards flaunt them in you personal statement, don't leave them hidden just in your CV.
D. Finally, and most importantly, while you will obviously highlight your achievements you must address your weaknesses. When you write a scientific paper, you deal with the weaknesses up front, you don't hide them and hope for the best. If you deal with them, your reviewers understand that you are critical and thorough, thus they do not have to be (at least not as much).

Finally, don't take it rejections personally, a good lesson to learn early in science.

Best of luck Psi and other potential graduate students.

Nocturnal visitor redux

So we have been discovered by a "family" of flying squirrels, although I prefer the name Night Gliders.There have been up to three flying squirrels visiting the crook of the aforementioned silver maple. One of the coolest thing is to see one come gliding in from a nearby tree.  I've caught them gliding in twice and both times they appeared  upright (like a standing up person) not flat like a hang glider. Of course it may be useful, at least structurally, to be upright just before you smash into a tree (see figure 1) although its also possible I saw them just before landing.
Figure 1. How not to bonk your head as a flying squirrel.

Figure 2. Nightcrawler and flying squirrel
from here and here respectively.
Another thing I learned is that flying squirrels, at least Northern American flying squirrels, can teleport (Figure 2). It's possible, but unlikely, that they are simply small and fast and its dark out, but I think they can probably teleport up and down and all around the tree. Regardless, these rodents are about the cutest damned furry mammals I've seen in a while. For comparison sake, I have vast experience with your common gray squirrel, which frequents our yard daily for peanuts, seeds, and other sundries. The red squirrel, which is much more shy in the twin cities suburbs, but much less so in the Itasca woods (where gray squirrels are essentially non-existent). We also have several white and black (gray variants) squirrel visitors (named whitey and blackey respectively). Its a great backyard experiment in evolution. The white squirrels are true albinoes, having pink eyes to go with their white fur. The expectation is that the white squirrels survive predation better in the Minnesota winter than either gray or black squirrel. If true, then there should be more white squirrels, as well as some selective pressure for albinoism in gray squirrel populations that live environments with extensive annual snowfall. In other words, there should be fewer white squirrels in Mississippi.

Figure 3. Nom nom nom squirrel.
Cool gray squirrel factoid, when they eat peanuts, they hold the nut in their paws like you might expect (Figure 3). They then rip a few pieces of the peanut shell off, pull out a peanut with their teeth, wedge it between their thumbs, and leisurely eat the nut. Bust off some more shell and repeat for the next nut. The gray squirrels (and variants) are getting to the point of semi-domestication (as are the blue jays that come when you call). The reds not so much. However, the flying squirrels while shy, appear to be getting used to me. I can go outside and provide more sunflower seeds without them bolting to Wisconsin. In fact, they seem to use the 'freeze' defense mechanisms, which makes sense if you are using darkness as a way to avoid predators.

Anyway, the other night I provided some feed for some flying squirrels, which they enjoyed immensely.

However I believe I may have used some genetically modified sunflower seeds,  because when I looked back about 45 minutes later my flying squirrel looked like this:

It was much slower and seemed to have lost its apparation ability. In fact when I went outside to provide some more seeds, it looked at me....

Clearly this is a mutant flying squirrel. It was in the same place only a little bit later the same evening. It was eating the same food, but it lost many flying squirrel properties. Besides its basic lethargy, it also did not bolt when I went outside. As I approached the tree with a fresh supply of seeds and peanuts, it slowly turned, opened its maw revealing a row of dagger-like death and made some demonic hissing noise. Obviously, the rapid growth undergone by the flying squirrel affected its vocalization ability. It also appears to have changed its ability to sexually reproduce with a placenta and immediately evolved a pouch-like sac for fetal development.

Name this nocturnal visitor

Although the title may having you thinking about the caption Brett Favre attaches to pics sent via cell phone, Im interested in the following animal. This little creature has become a nightly visitor to our house in the St. Paul area of Minnesota (actually have seen up to three of them at once). Any guesses based on this lousy digital photograph?

For the record Im focused on the animal not the Maple tree it is attached to.

Why batshit crazy politicians may want to favor science over belief

In 79AD near on the coast of Western Italy near the city of Naples, the Roman diplomat Shimkusius was walking with his friend Pliny (the Elder), a philosopher. They were discussing the recent increase in smoke emanating from Mt. Vesuvius.

"We should consider closing the port and moving the people further from the mountain" stated Pliny.
"Ha! That's absurd my good friend, why should we take such action? If we close the port, ships will simply go to Salernum or Misenum. Senator Gaius would love to get the trade and may entice the traders to continue using their ports. We cannot risk the loss in economic development." responded Shimkusius.
"But, my lord, what if the mountain bursts forth with noxious gases and molten earth? The risk to the people and city is too great!" Implored Pliny.
"You spend too much time with your epistles and lectures Pliny. The people of the town need to see strength of conviction. Have you seen the worried looks on the farmers and farriers? The people want to see from their leaders that there is nothing to fear from a little smoke." Explained Shimkusius.
"Besides my friend, have we not sacrificed our requisite virgins to Vulcan, god of the mountain? And you know we have already found a lovely virgin for the sacrifice in three days. We have been dutiful with rituals, Vulcan is pleased."
Pliny looked Shimkusius in the eye. "You are quick to look to old rituals and trivial gods to ignore real problems. You are supposed to be a leader, lead for once!"
Shimkusius placed an arm around his friend shoulder "Pliny you are a delight. You need to get down on the ground with real people. If the docks are not being used, people won't have jobs loading and unloading them. The merchants, many of whom pay you to tutor their children, will not be making the money necessary to keep the town growing. The people of Pompeii, the real people, believe Vulcan is happy. Why is that so difficult for you to accept? It is rather off-putting for you to discount their ancient beliefs."
"Sigh, I think you're making a mistake Shimkusius, but maybe you're right and as you say another sacrifice is coming up."
Pliny and Shimkusius stroll off to Shimkusius' home and split a jug of wine....

Several days later, Shimkusius and Pliny are on the docks. Shimkusius is beseeching his friend to get on a boat. "Damnit man, we must flee!" roared Shimkusius.
"My wife and sister are back in town, I must try and save them!" screamed Pliny. "Why didn't you listen to me you arrogant bastard." Pliny was livid with anger. "You said the sacrifice would keep Vulcan happy, admit it you were wrong and now the city is destroyed!"
Shimkusius shook his head in self-righteous pity. "Pliny my friend, you must realize, the girl was clearly not a virgin. The whore doomed us, all of us. Well, not us, but the others in the city. Vulcan obviously is full of wrath because of our tainted sacrifice."
Pliny stared at his friend a moment and pulled away running back towards town never to be seen again.
Shimkusius boarded the ship as it cast off and headed towards his winter home in Syracuse thinking all the while that the citizens of Pompeii, like Pliny, must have lacked the faith in the gods to protect them. It must have been their own undoing, because Vulcan would not destroy a city because a senator simply entertained a young woman prior to the celebration.

Of course, its totally different when its global warming and ignoring it because of an extremely suspect interpretation (justification) of a couple of lines from the Bible.

Of course when everything goes to shit, billions are starving, fresh water is virtually non-existant, and war suffering and disease are the norm, this jackass can righteously conclude that indeed the world wasn't destroyed. You know because it still exists.

In which I disagree with a Nobel Prize winner...

This last week my MRU had the privilege in hearing a talk by Dr. J. Michael Bishop entitled "The Cancer Genome of Therapeutics." It was an interesting talk and Dr. Bishop told several good stories, which isn't that surprising since I expect you don't get a Nobel if you can't give a good talk. However, just because you give an interesting, engaging, and thought provoking talk, doesn't mean I have to agree with you.

The thrust of the talk was based on the idea that by comparing cancer cells with "normal" cells, we can identify things that are different. Once differences are identified, these are now targets for therapeutic interventions. Now I want to be clear for those not knee-deep into the biological sciences, when I say "targets for therapeutic development," I am not suggesting that therapies exist. This is the 4000 lb. gorilla in the room no one likes to talk about in many scientific areas. Just because you identify a target, does not mean you have any way of hitting it. Two thousand years ago if a hungry hunter saw a fat elk on the other side of a 500 foot gorge (the target to solve the problem of hunger), there was nothing the hunter could do about it. Even if said hunter had a bow and arrow or more likely an atlatl, the elk is still a useless target, since the dead elk would be eaten by wolves, lions, and other animals long before the hunter could climb down the gorge and back up the other side. So having a target does not necessarily mean much.

One way in which these target identification approaches is done is to identify genes that are expressed in one cell type but not another, such as expressed in cancer cells but not in normal cells. This is usually the direction these approaches work too, we look for things that are expressed in the undesired cell, not things that are absent. (Its easier, but not impossible, to target something that's there not something that's missing.) Also, we generally go for genes and not proteins because it is currently much easier to determine what genes are or are not expressed over essentially the entire genome than it is to determine all the proteins expressed in a given cell population. This means our measure for expressed targets is somewhat indirect.

So lets say we find 12 genes are expressed in a specific kind of cancer cell, like breast cancer cells, but no in normal breast tissue. (The reality is many more than 12, but let's keep the numbers small.) Do these 12 genes specify 12 new targets? Well, the short answer is no. See these 12 genes are found in the genome because human beings probably need this gene for something other than causing uncontrolled cell growth in the breast. This is a huge limitation to this kind of approach. Just because you identify an expressed gene specific in a cancer compared to the otherwise normal tissue, does not mean and almost certainly doesn't mean the gene is not normally expressed somewhere. So your newly discovered cancer target may also be a pancreas development target or bacterial combating lymphocyte target too.

This is where I was left wanting. The nobel winning scientist begins their talk by establishing the overarching theme: by comparing cancer and normal cells/tissues, we will identify new targets based on these differences, and begin curing cancers at a previously unknown rate. Sadly, the first thing that came to my mind was all those microbes that have been killing us for generations and are still pretty damn good at it. Bacteria are about as different from us as you can get and you know what, we really have no new ways of combatting them. They kill more of us than cancer, but pharmaceutical companies have been shutting down their anti-microbial divisions to the point few actually exist anymore. (Don't blame the pharmaceutical companies, which can make a ton more money making guys hard, women skinny, and kids easier to oversee in factories schools.) Bacteria, fungi, protozoan parasites. All are extremely different from us at least when compared to cancer cells which are essentially clones of all your other cells.

So I am skeptical that knowing all the differences in expression between cancer cells and normal cells will pay dividends in any rapid way at least not as sold. However, I am not against this approach scientifically (I am against how it is sold to the public though). This will definitely tell us much about cancer biology, it will reveal commonalities and distinctions between different cancers, it may reveal genetic risk factors in patient populations that could impact screening and lifestyle choices (think about the current mammogram controversy), it may also lead to new treatments just not in the one gene = one target paradigm.

There are two ways I can envision genomics leading to targets that are susceptible to therapeutic intervention.

1. Often cancer progression is associated with chromosomal rearrangements. One chromosome recombines with another making a fusion chromosome not found in normal cells. A recombinant chromosome is not necessarily a bad thing and normal cells frequently contain them. However, the recombination can lead to the generation a protein that would never normally be generated. If the recombination occurs in the middle of two distinct genes a fusion gene can be created. One famous case of this is Bcr-Abl, which is associated with certain leukemias. Abl and Bcr are both kinases, although the specific function of Bcr is still not clear. The Bcr-Abl fusion removes an inhibitory domain of Abl, which leads to hyperactive Abl and that is oncogenic (cancer promoting). These types of rearrangements can be detected using new deep sequencing genomic approaches. 

2. Cancer is complicated and not due to a single cellular defect. Cancer requires numerous genetic changes. What we often see is that for a given type of cancer a similar set of cellular pathways act differently, although in the same way in the cancer. Much like specific targets, like a protein, a pathway can be the target for a therapeutic intervention. Actually, pathways are much larger targets since a pathway can be targeted by disrupting any of the proteins that make up the pathway. As before these pathways exist in normal cells as well. However, we could target two or three different pathways that are hyperactive in cancer cells with different therapeutics, which could kill the cancer cells. A normal cell may require one or two of these pathways, but not all three and thus would be 'immune' to the treatment. Admittedly there are a lot of ifs associated with this approach, but it is a viable approach. In fact, this is the approach that has made HAART so successful in treating many HIV infections.

I don't mean to be all gloom and doom, but the scientific community has gotten a fair bit of well-deserved blow back from overstating the impact of our studies to the lay public. Also, the fact that a given approach may not lead to a life-altering new product does not mean it is not worthwhile. If we look back through the history of science, many of the biggest advances were not front page news at the time. One ready example is the initial identification of penicillin by Fleming occurred in 1928 (earlier reports existed but this was the one that stuck), however it took 11 years and another group (Chain and Florey) to purify it for use as an antibiotic. This is a rapid turn around time and probably a poor example, because penicillin changed our lives. None of us were alive when death from bacterial infection was common and normal. People did not generally die of cancer or heart disease. The splinter in your finger you got chopping wood, that could kill you, if you got the wrong bacterium in the wound. Of the ~350,000 Union soldiers that died in the US Civil War, ~220,000 died of disease. Or pre-penicillin, in WWI 16.5/1000 soldiers died of disease/year whereas post-penicillin, in WWII 0.6/1000 soldiers died of disease/year1. The take away point is that new treatments take time and are not often clear from the initial findings. The second point is that we'll probably never see another medical intervention that has the same societal effects as the antibiotic generation.

Vote for reason, that's your reason to vote

November 2nd tomorrow, Election Day. What are you doing? Are you blowing it off because the choices come down Republicans...ah, the golden days of 2008 when republicans were lying their way through 2 wars, the economy was crashing, the ultra-rich were gathering up a greater and greater % of all the wealth...and Democrats, the party of push-overs and dare I say accommodationists that don't want to turn away voters who wouldn't vote for them anyway.

I admit it seems a crapshoot. Not happy with Dems, so vote in Reps? The problem is that the Reps. bring primarily fear, hatred, and blind worship of ignorance. So, Im voting for Dems, but if the Reps actually presented a package that wasnt bat-shit crazy, I would give them the nod. But the Reps. don't appear to think that intelligence and thought are worthwhile activities. Reps. have a 15th century understanding of the world they live in and they like it, worse they call others elitist for actually knowing something more recent than Newton. Yep, that's the mentality I want in office. I'ld rather have the milquetoast party.

If we keep swapping crap for crap (albeit some crap stinks worse than other crap), it will never improve. So let's give a party a reason to stop giving us crap as a choice. If your Ford sucks, you may buy a Toyota, which also sucks but gets better gas mileage, you don't then buy another crappy Ford. Make Ford improve by buying another Toyota, at least you get the gas mileage. When Ford improves its product, Toyota better follow suit or its screwed.

FWIW. I will not vote for any person that has the idea that intelligent design represents a valid scientific theory. It means two things, 1. the candidate doesn't know jack about science (not a deal breaker for me, since there are many things I don't know); 2. the candidate is being advised by, and put their trust in, a bunch of fucking morons (and that is a deal-breaker).