Bespoke genetic circuits rewire human cells

Cool! Article from Nature News: Engineered DNA device could coax cells to differentiate - or die - on demand.

Original paper: Culler, S. J., Hoff, K. G. & Smolke, C. D. Science 330, 1251-1255 (2010). | Article | OpenURL

best story ever

Cookies by Douglas Adams (author: “Hitchhiker’s Guide to the Galaxy”)

This actually did happen to a real person, and the real person was me. I had gone to catch a train. This was April 1976, in Cambridge, U.K. I was a bit early for the train. I’d gotten the time of the train wrong.

I went to get myself a newspaper to do the crossword, and a cup of coffee and a packet of cookies. I went and sat at a table.

I want you to picture the scene. It’s very important that you get this very clear in your mind.

Here’s the table, newspaper, cup of coffee, packet of cookies. There’s a guy sitting opposite me, perfectly ordinary-looking guy wearing a business suit, carrying a briefcase.

It didn’t look like he was going to do anything weird. What he did was this: he suddenly leaned across, picked up the packet of cookies, tore it open, took one out, and ate it.

Now this, I have to say, is the sort of thing the British are very bad at dealing with. There’s nothing in our background, upbringing, or education that teaches you how to deal with someone who in broad daylight has just stolen your cookies.

You know what would happen if this had been South Central Los Angeles. There would have very quickly been gunfire, helicopters coming in, CNN, you know… But in the end, I did what any red-blooded Englishman would do: I ignored it. And I stared at the newspaper, took a sip of coffee, tried to do a clue in the newspaper, couldn’t do anything, and thought, what am I going to do?

In the end I thought, nothing for it, I’ll just have to go for it, and I tried very hard not to notice the fact that the packet was already mysteriously opened. I took out a cookie for myself. I thought, that settled him. But it hadn’t because a moment or two later he did it again. He took another cookie.

Having not mentioned it the first time, it was somehow even harder to raise the subject the second time around. “Excuse me, I couldn’t help but notice …” I mean, it doesn’t really work.

We went through the whole packet like this. When I say the whole packet, I mean there were only about eight cookies, but it felt like a lifetime. He took one, I took one, he took one, I took one. Finally, when we got to the end, he stood up and walked away.

Well, we exchanged meaningful looks, then he walked away, and I breathed a sigh of relief and sat back. A moment or two later the train was coming in, so I tossed back the rest of my coffee, stood up, picked up the newspaper, and underneath the newspaper were my cookies.

The thing I like particularly about this story is the sensation that somewhere in England there has been wandering around for the last quarter-century a perfectly ordinary guy who’s had the same exact story, only he doesn’t have the punch line.

(Excerpted from “The Salmon of Doubt: Hitchhiking the Galaxy One Last Time” by Douglas Adams)

things learned in medical school

Running list:

1. Patients are people, not their diseases
2. Each patient you see sees YOU as their doctor, and them as your only patient. You need to compartmentalize so that one patient doesnt influence the care you give another patient.
3. Every patient has their own story, their own lives, and their own families
4. So what if you've seen 10000 cases of the same thing? The case is a first for your patient, and they probably know NOTHING

i never knew i would say this but...

i'm actually thinking of considering pediatric oncology. it actually sounds like the most depressing thing in the world, but compared to adult oncology,

-no worry about super complicated histories, like HTN, COPD, history of heart attack, usually no UTI, usually very little instances of drugs, alcohol abuse, diabetes, HPL, 100drugs, etc etc. in short, kids are CLEAN
-most cancers are either genetic, or have some underlying cause that is special (instead of, say, smoking. or just being old. or a combination of many things compounded) I may be wrong, but I feel children with cancer usually have it because of SOMETHING special. kids are NOT supposed to have cancer
-healthy bodies to start out with?
-kids will actually most likely be on schedule with their meds, bc their parents will make sure they take it
-kids are so endearing...and i'm not sure if newborns or even toddlers get cancer, so at least most of my patients can still talk to me

Usually, kids are the ones that develop things like neuroblastoma, leukemia, or other rare cancers--the ones i'm actually interested in. so... next step--contact someone at CHOP!

I just don't know if I would want to go through a pediatric residency though :/

edit://
after reading the blog of a pediatric oncologist, there is NO WAY i can go into pedonc. the stories were SO SAD...It is true that you really DO need to be a special person in order to do pedonc. Those doctors are angels.

really?!

Oh, what a breath of fresh air it is to be reading (scientific) literature again. That doesn't necessarily mean I'm satisfied with what I read though :P

Peeves:
"In this study, there was an increased risk of hyperkalemia. In contrast, there was a decreased risk of hypokalemia"...... isnt that obvious??

Every time I see an article from JAMA or NEJM studying the effects of a drug, they always list how the doctor is paid/sponsored for the project. Most of the time, the doctor is endorsed by the pharmaceutical company making the drug. I can't help feeling uneasy every time I read that--it makes it seem as if the doctor did the trial only under insistence of the pharmaceutical company and not because of interest in improving the care of patients. Which I mean, of course if a drug is promising then it makes sense to test it in patients, and there needs to be some funding for the trial, but...pharm companies are still companies. I guess if the data presented is empirical enough, there is trust that the doctor acted purely objectively and presented correct data, not biased data.

Additionally, it is super frustrating every time I see data that improved the outcomes of patients by <50% . I know, I know...if standards of improvement had to be that rigorous, medicine would probably be at a standstill, and pharm companies would never make any new drugs. But for end stage life care, is it really worth it to spend thousands, even millions developing (and using) a drug that will improve your life by 10%, compared to doing nothing? 

Quote: 
We evaluated the effect of adding eplerenone to recommended treatment for systolic heart failure in patients with mild symptoms (NYHA functional class II symptoms). The rate of the primary outcome, a composite of death from cardiovascular causes or hospitalization for heart failure, was 18.3% in the eplerenone group versus 25.9% in the placebo group. This effect of eplerenone was consistent across all prespecified subgroups. With eplerenone, there was also a reduction in both the rate of death from any cause and the rate of hospitalization for any reason. In conclusion, our study showed that, as compared with placebo, eplerenone added to recommended therapy for systolic heart failure in patients with mild symptoms was associated with a reduction in the rate of death from a cardiovascular cause or hospitalization for heart failure. Similar reductions were seen in rates of death from any cause, death from cardiovascular causes, hospitalization for any reason, and hospitalization for heart failure.

I guess the purpose of publishing articles like the one I read is more to highlight the SMALL effectiveness of the tested treatment, emphasize the need for more research, and show that there is more going on out there than known. After all, data is data, and anything it helps to rule out possibilities and prevents redundancy. My main peeve about this article is that they claimed the drug was associated with a reduction. To me, reduction seems too strong of a word; MILD reduction is more like it.

To give the authors credit, 25.9 - 18.3 = 7.6 and 7.6/25.9 = about 30% less risk compared to the control. But thats like saying, taking this $$$ drug will give you a 30% chance of improving your outcome, and a 70% of making things no different. -__-'

If the purpose of the study is to use the drug to REPLACE a preexisting drug, then I guess it is fair to say a better drug will at least improve the outcomes of all subsequent patients. Meh...I still feel there should be a bigger difference in order for the drug to completely replace the other one...

Ah, medical ethics. I'll be kicking myself for being too idealistic later, but for now I'll indulge myself and complain :P

original article: http://www.nejm.org/doi/full/10.1056/NEJMoa1009492?query=OF&#t=article

edit: Ah, the editorial alleviated some concerns, but also expressed similar sentiments:

"The EMPHASIS-HF investigators have added real value to the management of heart failure. Since spironolactone is available for pennies a day, one might reasonably ask whether the greater cost of eplerenone is warranted or whether it is reasonable to simply assume that the current findings also apply to spironolactone and reserve the newer, more expensive therapy for those few patients in whom the side effects of spironolactone are disabling. I believe this would be a reasonable tactic."
-Paul W. Armstrong (from http://www.nejm.org/doi/full/10.1056/NEJMe1012547?query=OF)

random and CT scans

Top 25 played on iTUNES:

Haha I knew I liked "Replay", but I didnt realize there was such a large discrepancy :P 239 plays vs 73 for the rest!? Thats a not 2, but 3x difference xD  

----

I read this article today that commented on a study that tried to see if regular CT scans would help patients detect lung cancer earlier. A seemingly innocuous and helpful study, but these were the implications:

-Getting regular ct scans = detect lung cancer early = study found it saved 1 in 300 patients' lives.
-However, couple things involved:
1. costs of CT scans
2. false positives/negatives, = more tests, = more costs
3. the patient population they studied were SMOKERS.

Am I the only one who finds this study illogical? There were even scientific people in the article that commented on the inability to draw practical applications of the study, since while the CT scans saved 1 in 300 patients, there were still issues with the fact that CT scans are expensive, so people not be able to even get them. I guess the main point was to figure out if it WAS possible to detect lung cancer early... I was just floored by the fact they used smokers, because from the perspective of the article it seemed like this testing was only to save smokers from lung cancer (which could probably be solved by telling them to QUIT). But I'm guessing (and hoping) they chose smokers bc smokers are more prone to get lung cancer, so its an easier-to-study population??

Ironically, we've been going through healthcare in class, and one comment is that our 'healthcare' system is really in fact a 'sick care' system, since we're great at treating sick people, but terrible at preventing people from getting sick. This is a perfect example of the wasteful spending that can go on. :/

original article: http://www.nytimes.com/2010/11/05/health/research/05cancer.html?_r=1&emc=tnt&tntemail0=y

updates on pancreatic ca

Mapping the genetic evolution and diversity of pancreatic cancer
by ecancer reporter Clare Sansom

Paper sources:

Campbell, P.J., Yachida, S., Mudie, L.J. and 22 others (2010). The patterns and dynamics of genomic instability in metastatic pancreatic cancer. Nature 467, 1109-1113.doi:10.1038/nature09460

Yachida, S., Jones, S., Bozic, I. and 11 others (2010). Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature 467. 1114-1117.doi:10.1038/nature09515

*Jones, S. et al. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 321, 1801–1806 (2008).