TO TIDE YOU OVER

Heron Island clambake, 2009

Heron Island is in Maine

Note large crustacean by my right foot

I am beginning to pack for Borrego Springs.  I plan to leave Bellingham on December 2^nd and, after a pleasant layover in Eureka with Linda’s sister Carolyn, to arrive in the desert on December 10^th – where I will remain, God willing, until the end of March.  This means that I will not be posting any more movie reviews until spring.  (I assume this will disappoint a few of you, although I have watched as the number of “Likes” each review stirs up has dropped from about 30 to about three.   No, my feelings are not hurt.  Not much, anyway.)  Also, I won’t be posting any new blogs for some time, although I will take it up again when I am settled in B.S.  I don’t even know whether my computer works, or whether I have cable, or even if I have running water down there, so “getting settled” may take a while.

But here are some articles to tide you biology aficionados over for a few days, at least.

The first discusses probable developments in cancer treatments during 2016.  It comes from a publication of the Economist called The World in 2016, which – as a subscriber – I get free.  It is a delightful collection of analyses of present circumstances worldwide, together with predictions of where various aspects of human endeavor are headed next year.   You apparently can buy it for $13.95.  Canadians get it for C$13.95, which means that they get a break of maybe 50 cents.  Gloat, Parkfriend.

Anyway, this article is a comprehensible summary of what is going on in immunotherapy.   All of you who are eager to learn more about checkpoint inhibitors will enjoy this little essay:

http://www.theworldin.com/article/10641/big-c.

The second article is wisdom straight from the horses’ mouth: the NCI.  It elaborates on recent research showing just how dammed complicated cancers are, and how knowing precisely which genomic mistakes are involved in each can help.  This comes under the category of targeted therapy, I guess.  There is nothing particularly new here, but this is a good summary.  Note particularly the number of acronyms showered upon you – this seems to be typical of biology, or maybe just molecular biology.  (If I had referred to “margin-parallel crustal displacement caused by oblique convergence” as MPCDOC  I would have been tossed out of the American Geophysical Union and showered with rotten fruit.)

Also, it helps to know that a tyrosine kinase is an enzyme that slaps a phosphate group on a tyrosine molecule, thereby providing the energy needed for a biochemical “cascade”.   Here is the article:

http://www.cancer.gov/news-events/cancer-currents-blog/2015/understanding-precision-medicine?cid=eb_govdel

Try to make do until I get back on line.



DRUG ADVERTISING MAKES ME PUKE

On a bridge somewhere

Deception Pass?

Somewhere recently I mentioned that Big Pharma spends more on advertising than on research and development.  I’m not sure how to react to this fact (if it is a fact – I suppose somebody might have made the whole thing up.)  My gut-level response is mostly a blend of anger and disgust.  The disgust portion stems from the annoying nature of TV ads touting new drugs, which invariably end with the words “ask your doctor if Fidoplex could be right for you.” Characteristic of most of these ads is the obligatory two minute litany of side effects, usually ending with “death”. I particularly like the one that always terminates with two people, of opposite sex, in adjacent bathtubs!  These prime time ads must cost a fortune!  Why not spend that fortune searching for new drugs or therapies? 

Not so long ago there were people called drug reps.  These guys each represented some particular drug company, and they were tasked with bringing the new pharmaceutical marvel of the moment to the attention of the clinicians who wrote prescriptions.  Before Linda became a physical therapist she worked at the front desk of a group of physicians; one of her primary responsibilities was to keep these gentlemen from totally disrupting the daily flow of business.  Still, the drug reps got in, spoke directly to the doctor, explained their new wares, and left samples.  The doctor then made up his or her mind.

I suspect that the earlier way of disseminating news of new therapies (drug reps and free samples) cost a hell of a lot less than today’s  big, splashy TV ads, and did the job better.  Surely the med people must have preferred it: imagine how annoying it would be to have half a dozen patients every day ask “What about this Fidoplex stuff doc?  Sure sounds like a world beater.”

I acknowledge that there has to be a means of disseminating news of new therapies.  Ideally, the meds involved would read about them in professional journals, or learn about them at professional meetings.  Ideally, yes, but our modern doctors are far too busy to read all those journals, or go to all those meetings.  They deserve to put up their feet and watch Jeopardy when they get home, if that’s what they want to do.  They are, after all, human.

So, bring back the drug reps.  I don’t know where they went, nor why. (As an aside: I used to get scads of free pills, and now I have to buy ‘em.)   Finally – Big Pharma – quit annoying me with your stupid, splashy ads, and plow the money you save into something useful.



PROGRESS IN EARLY DETECTION

Glacier Bay, Alaska

Do you know what a “metabolite” is?  Well, like me you probably could guess that is something that has to do with metabolism – the messy and biochemically complicated way that we turn thing like berries, butter, bread and bacon into the energy that runs our bodies and the stuff that makes them up.  The products of metabolism are known as metabolites.  How a biochemist would categorize them is something I don’t know – but it is pretty clear from this article that they are not proteins.

So, anyway, people at Georgia Tech have used some clever chemistry and computational tricks to recognize a group of 16 metabolites that are elevated in ovarian cancer patients, but not in the rest of the population.  They attained a specificity of over 90%, meaning that the test was 90% accurate in distinguishing women with cancer from women without cancer.  And the really good news is:  The cancer patients were in either stage 1 or stage 2 – meaning that metastasis had not begun.  As always, more testing is required, but still – maybe we have here the Holy Grail:  genuine early detection.

The Georgia Tech test would operate from a simple blood sample.  The group I attempted to help at
Fred Hutch also sought a blood test, but they were looking at proteins exclusively (I believe.  Remember, I’m just a dumb geologist.)  Some proteins definitely are elevated in ovarian cancer patients – CA125 and HE4 are examples.  Sadly, they don’t rise until the cancer is fairly far advanced.    Our work seems to have fizzled out.  I will keep an eye on these Georgia Tech people.  I am encouraged.

http://www.eurekalert.org/pub_releases/2015-11/giot-mpd111215.php



USEFUL WEB SITE

Wild guess:  Chile, mid 1980s

 

Trapped inside by bad weather and lethargy, I found this web site while piddling around with the computer:

http://www.ovarian.org/

I bring it to your attention because it has an abundance of important information about ovarian cancer, in an easily accessible format.  I was inspired to join a local chapter (of the National Ovarian Cancer Coalition) but, it turns out, the nearest is in Sacramento, California.  And, don't ask: I am too old and lethargic to start a new one.



CONFUSED ABOUT MAMMOGRAPHY? This may help.

We were thin once

Cat is Whiskers

Confused about mammography?  Sure you are.  Most everybody who cares a fig about it must be a little confused.  Not only do guidelines/recommendations change every few years, but the latest “revisions” to come out, from two noteworthy organizations, do not agree.  The organizations are ACS (American Cancer Society) and USPSTF (our old friend the United States Preventative Services Task Force.)  Their recommendations are not radically different, but they do not agree on everything.  Two things they do agree on, however, are: (1) Mammography saves lives; (2) You don’t need quite so much of it.  They also seem to agree that the individual woman should make up her own mind.  Here is the article that inspired this:

http://www.fredhutch.org/en/news/center-news/2015/10/New-ACS-breast-screening-guidelines-for-mammography.html

All women should read this, then decide. 

Personally, if I were female I would say “To hell with false positives” & get checked frequently.



ON CANCER RESEARCH FUNDING

Linda on a typical Bellingham summer day

Well, we have ten or twelve of them most any year

While fumbling around in the depths of the internet seeking enlightenment on checkpoint inhibitors (q.v.), I stumbled on an article I actually could understand.  It had nothing to do with checkpoint inhibitors, though – it was a report of NCI awards for SPORE grants.  NCI you recognize: a SPORE is alternatively a way that some plants reproduce, or – as in this case – a type of NCI award called a Special Program on Research Excellence, or (as I am sure recipients regard it – the jackpot).  These grants last for five years and (currently at least) are worth $2.85 million annually.  At the moment there are four active SPOREs in the field of ovarian cancer research.  Mayo Clinic received one this year.  I am going to study the Abstract for their proposal, and if I can make any sense of it I will report.

Needless to say, Mayo Clinic is top drawer.  I am encouraged.

Sadly, the program I attempted to help at Fred Hutch was not funded.  I don’t think it was my fault.



HAVE MORE BABIES

Part of the reason we bought the place in Borrego Springs

 

Most of you already know that having babies lowers a woman’s risk of developing ovarian cancer.  You probably also are aware that this is a correlation, not proof of cause-and-effect.  (But I think it is.)  Well, Oxford University has just verified what you already knew; they studied 5700 British women for (well, hell, they don’t say how long), and found that having one child lowered the probability of developing OVCS by 20% - and the more kids you have, the lower the probability. For some (rarer) kinds of OVCA the risk reduction was even greater.   (My grandmother had nine kids – and didn’t develop OVCA.  Anecdotal evidence, you say, and you are right.  Raising all those kids, and in Cripple Creek Colorado at the turn of the last century, left her exhausted, but healthy.  She spent the last 20 years of her life sitting in a comfortable chair, smiling.)   Anyway, the same study showed that women who have their fallopian tubes removed are at a considerably lower risk of OVCA than otherwise.  You already knew that, too.

So why am a telling you all this, if you already know it?  Well, first of all it’s a big deal: journals from Nature to the sleaziest British tabloids are writing about it.  In case you have nothing better to do, read this:

http://www.techtimes.com/articles/102463/20151104/mothers-lower-ovarian-cancer-risks-with-every-child-study.htm

And also, I suspect that a few of you need to be reminded.

Finally, this finding has profound demographic consequences, which you can work out for yourself.

 



OLAPARIB: Not a wonder drug, but it helps

Linda and Carolyn, on a nice Bellingham day

Men have prostates, women have ovaries.  Right?  There are, however, similarities.  Both are located in the same general segment of the body, both have a role in reproduction, and both can cause lots of trouble when they develop cancer.  Maybe they develop from the same swatch of embryonic tissue, and proceed along divergent pathways only after the XX/XY thing kicks in*.  So perhaps it should not be surprising that a drug developed for ovarian cancer has proven to be useful in fighting certain types of prostate cancer.  The drug is OLAPARIB.

It turns out that men have defects in the tumor-suppressor genes we call BRCA1/2, most commonly associated with a hereditary predisposition in women to develop breast and/or ovarian cancer.  Olaparib is a PARP inhibitor. And if you can’t remember what that is click on this link:

http://ljb-quiltcutie.blogspot.com/2014/12/happy-new-year-now-for-little-biology.html

 Olaparib will not cure OVCA, or prostate cancer for that matter, but in certain cases it prolongs remission appreciably.  Every little bit helps.

Here is the link to the news article that initiated this blog: 

http://zeenews.india.com/news/health/health-news/ovarian-cancer-pill-can-help-men_1816548.html

*Nope.  In trying to understand "homologous recombination" I ran on the perfectly obvious fact that "after the XX/XY thing kicks in" the same fetal tissue goes to gonads in men, ovaries in women.  I bet you were worried about that.

 

 

 



CRISPR: Another mystery of life.

The Joyce family, 1951

I think Linda had just pinched Carolyn

It is a gloomy day, today.  I feel sorry for the little kids who will be swarming the local sidewalks, paper bags in hand – it is Halloween, and it is raining.  But that’s the PNW.  I won’t be here to pass out candy, anyway; I am going to the movies, and then out to dinner.  They shouldn’t eat all that bad stuff, anyway.  Now, if I could only pass out bacon…..

But before the movie starts, I decided to do some work.  Specifically, I decided to really wrap my mind around the CRISPRCas9 business that I have alluded to before.  It is very important, no doubt about it.  For instance, when I went in search of information I asked Google Scholar to give me a list of articles containing the acronym CRISPR published in the last two years.  I got 18,000+ hits.  And, tragically, not one of them can I understand.  Even Wikipedia leaves me mired in impenetrable biochemical slop.  So I decided to first look at what I had had to say previously about CRISPR in this blog.  Here is the only informative blog. I urge you to re-read it.

http://ljb-quiltcutie.blogspot.com/2015/08/forget-frankinfoods-how-about-designer.html

Alternatively, you could go straight to the Economist article that inspired it:

http://www.economist.com/news/briefing/21661799-it-now-easy-edit-genomes-plants-animals-and-humans-age-red-pen

I can’t tell you how CRISPRCas9 works – because I don’t know – but I can tell you what it does.  It allows us (that is, we fallible humans) to cut the double-stranded DNA molecule precisely at any particular specified place.  Used properly, then, it should allow us to remove a gene we don’t want, and substitute a new and improved model.  The biological, ethical, and even economic consequences of this technology are enormous.  Learned discussions are ongoing.

So, how about ovarian cancer?  Well, it’s not mentioned specifically, but I can see some useful applications.  For instance: what if you come from a family that carries the BRCA mutations (and others that contribute to breast and ovarian cancer)?  Using CRISPR technology it should be possible to “edit” those mistakes out of the germ cells that you will pass to your offspring – and substitute a working copy of the gene.  So maybe you will still be subject to higher cancer odds, but your kids won’t.  That’s progress.   Also, it should be possible to “engineer” T-cells to attack cancer cells; in fact it already has been done with total success, in mice.  (Some scientist was once quoted as saying “If all we wanted was to cure cancer in mice, we’d be out of a job”.)

So, I can’t explain CRISPR technology to you, but even so the serious minded of you (surely most) will happily devote a half-hour or so to the subject.  Read the links, above.

Here are some study aides:

CRISPR stands for Clustered Regularly Interspersed Short Palindromic Sequences (now, wasn’t that a big help?)

Viruses reproduce by injecting their DNA into other cells, principally bacteria.  Bacteria have responded by evolving RNA molecules that “recognize” the virus DNA, and cut it out. CRISPR technology is based on this.  Not all viruses are bad.

A palindrome is a sequence that reads the same forwards or backwards.  Since we are talking about RNA, there are four “letters” to consider: a, c,, g, and u.  So here is an RNA palindrome:  aucggcua.  Thus a CRISPR RNA sequence might read something like this: aucggcua (some other stuff, “interspersed”) aucggcua (more interspersed stuff) aucggcua and etc.  Since the “Sequence” is “Short”, there aren’t too many of these things.  SOMEHOW this structure guides the CRISPR RNA to the proper spot, where it uses the enzyme Cas9 as a cutting tool.  How, I haven’t a clue.

Okay, you get a reprieve; my ride has arrived.  I am going to see “The Martian”, about a botanist stranded on Mars.  Sometimes I feel like a geologist stranded in an organic chemistry lab.

More on CRISPR if I ever figure it out.  Don’t hold your breath.