USEFUL ECONOMISTS

Where I first courted Linda

and made Murphy's acquaintance

As some of you know, before I became a geologist I studied economics.  In fact, I graduated from Stanford saddled with that dreadful degree.  I had intended to go on to law school, and eventually into politics.  At the time I was a fervent Taft Republican; I thought Eisenhower was a dangerous radical.  Good thing I ditched law school.

Anyway, a NYTimes article sent me by Dick Ingwall proves that even economists can be useful.  Here is the article:

http://www.nytimes.com/2015/12/29/upshot/why-preventing-cancer-is-not-the-priority-in-drug-development.html?smprod=nytcore-ipad&smid=nytcore-ipad-share&_r=0

The lead author is perhaps not your typical economist.  She is a MacArthur “genius” grant recipient and is on the faculty of MIT.  (She had two co-authors, no doubt worthy guys but perhaps lacking such sparkling credentials.)  Her name is Heidi Williams.

It appears that Williams et al have studied our friend Big Pharma, They asked the following question: Why do (cancer) drugs brought newly to market consist dominantly of stuff to fight late-stage disease (that is, buy the patient a few more months)?  In contrast, it appears, concoctions that may affect early-stage disease (and maybe thus affect a cure), or prevent the disease altogether, are relatively rare.    Why?  It might not surprise you too much to learn that this involves money.

But it MAY surprise you to learn that it’s not all attributable to capitalist greed.  Williams et al start from the assumption that drug companies have to make money.  (They are economists, right?)  Here, then, is the problem, in one oversimplified (by me) nutshell.  Suppose you are Merck, or Pfizer, or even some little start-up in downtown Seattle.  You work diligently for many months - probably years - to develop some sort of probably complex biochemical substance that you think might be useful against cancer.  The first thing you do is patent your discovery.  This gives you 20 years before two smart guys, a scientist and a chemical engineer in Moldova, in cahoots with a venture capitalist in NY, set up a plant that can turn out your stuff for next to nothing.  But this doesn't give you a 20-year head start; oh, no.  To sell your stuff, of course, you must obtain FDA approval.  As you know, a clinical trial will be required.  So, think about it:  To get robust statistical results for a drug intended to extend life for only a few months may only require a matter of a few years, whereas if your drug is intended to prolong life indefinitely the trial conceivably might require decades. Drug development and testing can cost billions.   Imagine how your stockholders would greet the news that your drug is ready for the clinic, but that the guys in Moldova will bgine selling their version in Walmart next Monday.

One obvious remedy for this, mentioned in the article, is to commence the patent period only after FDA approval.  This has complications, of course.  Other remedies also are discussed but, frankly, I am getting tired of typing exclusively with my right forefinger* – so read the article yourself.  The Comments also are useful.

*Read my last blog to understand this statement.





Are you a WATCH, or a RUBE GOLDBERG?

The Joyce sisters explore the Oregon wilderness, 2006

 

It is cold and windy outside and I have seized upon this fact as an excuse to stay indoors and play with my computer, rather than go outside and try to identify ducks, as consideration of  health would recommend.  (I typed that sentence rapidly and with confidence, with my head held up, just as Mrs. Basha Long taught me in 1948.  I made eight errors.  This is discouraging.  Hunt and peck for me from now on, I guess, although this crappy laptop may have something to do with it.)  Anyway…….

I am deep into junk DNA, learning gee-whiz facts about all the things that go on that depend on stuff that originates within the 98% of our genome that doesn’t code for proteins.  My guess is that much, maybe most, of the research action may lie here in the decades to come.  It is not clear to me how this new flood of knowledge will help conquer cancer – but surely, the more we know the better off we are.

One set of important “junk” actors are short segments of single-stranded RNA,  usually 20 to 23 nucleotides long.  These things help regulate which genes get “expressed” (turned into functional proteins), and in what quantities.  I wrote a blog once about a guy from the Hutch who was working in this field – he has left subsequently.  I thought he was the real deal.  Here is the blog:

http://ljb-quiltcutie.blogspot.com/2013/10/profiles-in-research-excellence-dr.html

But that is not what I am on about this blustery Sunday morning.  I have been searching for a book to supplement those by Drs. Carey and Parrington, both of which I have reviewed recently.  What I have found surprises me.  There are a number of books out there that claim junk DNA as evidence of Intelligent Design.  You know what that is, right: the notion that the overwhelming complexity of life requires a Guiding Hand.  Junk DNA has been used as a counter argument, viz – if there is a Guiding Hand, how come It was so slapdash and inefficient?  Now that the Junk has been shown to have function that anti ID argument can be set aside.  Hence, books – more theological than biological, I would bet.

I am incurably agnostic in matters of teleology and such: about the really important subjects of life and human existence I simply am not equipped to comment.  However, on Intelligent Design I do have an opinion.  As far as I can tell, biological processes are far more complicated than they need to be.  You may know the Watchmaker argument for Special Creation – that finding a fine-functioning watch in the street implies the existence of a Watchmaker.  Well, maybe so, but we are far from highly efficient Watches.  We are held together with wire and duct tape.  We use far too much energy.  We keep bad time.  We run down too quickly, and not at all gracefully 

  No one would design such a piss-poor watch on purpose, unless perhaps for amusement.  Darwin was right - but do not read too much into that statement. 

 Do you remember Rube Goldberg?  Well, if not – look him up.

 



ONCLIVE: Strictly for the enthusiast

Linda and Patches

Good friends, as you can see.

There is an outfit called OncLive that reports on developments in all sorts of cancer research.  The technical level of the reportage is somewhere between that of typical British tabloid (New Chemical Found in Carrots and Pipe Tobacco Cures Cancer in a Matter of Weeks,  says Noted Authority) and the New England Journal of Medicine (Well, I won’t try to characterize this approach: I wouldn’t understand half the words, anyway).  I have just read an OncLive article on a seminar or small meeting concerned with treatment of ovarian cancer.  It is informative, but more than a little depressing.  Here it is:

http://www.onclive.com/web-exclusives/adjuvant-hormonal-therapy-linked-to-improved-outcomes-in-ovarian-cancer

Much of the discussion revolves around the topic of which course of chemo is best used when gains made  by debulking + adjutant chemo begin to be reversed.  The debate seems to revolve around something called PFS – Progression Free Survival, or how much time elapses before the cancer begins to come back.  If I understand what I read, ultimate survival is not in question.  Whether a woman dies of the damned disease or not seems still to be in the lap of the gods.  That is why I mainly donate to the Rivkin Center nowadays: I get the impression that they are focused on genuinely innovative research.

Linda had a long stretch of PFS, and those months were amongst the best of my life.  I thank all the researchers patiently gnawing away at the immense hardwood knot that characterizes ovarian cancer.  Every nasty little chip removed helps.  However, I hope to live to see the whole damned thing blasted to Hell!

I want a cure.





ROCA AGAIN, FOR HEAVEN'S SAKE!

Linda with one of her more spectacular quilts

Probably 2010

Dear Lord above, is there no limit to the caution – pathological timidity might be a better term – of the medical profession?  For centuries medical practioners have been obedient to the stricture: First, do no harm.  Now they seem to worry almost as much about another: Whatever you do, don’t run up the cost of medical care.

 Dick Ingwall has alerted me to a nice article in the NY Times on use of the ROCA method for screening for ovarian cancer.  To read the article, click on http://www.nytimes.com/2015/12/18/health/early-detection-of-ovarian-cancer-may-become-possible.html?smprod=nytcore-ipad&smid=nytcore-ipad-share.  To learn what I think of it, continue reading.

I have written about ROCA several times in the past, the earliest being in early 2013.  ROCA seems to be the fruit of scientific labor at the MD Anderson Cancer at the University of Texas.  It is a protocol for estimating the risk of ovarian cancer – in fact, ROCA is short for Risk of Ovarian Cancer Algorithm.  To my untutored mind it seems straight forward, logical, easy to apply – and ready for prime time.  But no: all the scientific spokespersons quoted, discussing a big trial of the method in the UJK, are “disappointed”, or “cautiously optimistic”.  To generalize:  More trials are needed.  More money must be spent.  More post-docs are requiredd.  Well, nuts.

I admit that ROCA falls short of having ideal sensitivity (telling you you’ve got it, if you do) and specificity (not telling you you’ve got it if you don’t).  This entails, inevitably, more anxiety and expense associated with false positives, not to mention heartbreak from false negatives. I stack this up against the 14,180 American women expected to die this year of OVCA.  Can’t the medical profession put some version of ROCA to work right now, if perhaps only for high risk women?  Can’t the NCI get off its fat ass and at least make some recommendations?   As I said earlier, nuts.

And as you can tell, I am in an intolerant mood.

I have written five blogs about ROCA, which you might want to read.  I think I have found a way for you to search all my blogs for a particular topic.  Google Myrl’sBlog, then look for an inviting line (on my machine, it is on the upper left) and type in a search term.  You should get all the blogs I have written which contain that term.  I hope it works.  Please let me know if it doesn’t.





A SIMPLE REVIEW OF A COMPLEX BOOK

Linda and Florence at a Relay for Life

Do you know that there are about 100 billion nerve cells in the human brain, about equal to the number of stars estimated to exist in the Milky Way galaxy?  Well, now you do.  Furthermore, each nerve cells make a vast number of connections with other nerve cells – amounting to the order of 100 trillion little entanglements.  That’s a truly staggering number.  In fact, the only larger number that occurs to me offhand is the odds against my Kalamazoo relatives voting for Donald Trump in the next election.  I cite these facts mostly to introduce the chief unifying factor of the book I am about to “review”:  complexity.

The book is The Deeper Genome, John Parrington.  It was published by Oxford University Press; Parrington seems to be an Associate Professor in the School of Pharmacology at that venerable and justly praised institution.  Parrington’s book intends to make sense of the recently verified observation that the vast majority of DNA does not code for proteins, and that the differences in protein-coding sequences in humans and worms (not to mention chimps and mice) do not seem sufficient to account for our obvious dissimilarities.  These differences arise from business conducted by processes that go on in The Deeper Genome: regulatory business.  Regulatory processes are why you don't grow toenails in you eyeball.  They also account for the fact that a human gene, while very similar to the same gene in a worm, can do a hell of a lot more.  Let’s face is, this stuff is, well – PRETTY DAMNED COMPLICATED!  And so is this book.

Nessa Carey’s latest book covered much of this ground, only better.  I read all of this kind of material that I can find because I think it is of the greatest importance for molecular biology, and cancer research in particular. However, I don't inflict it all on you - you would Unfriend me on Facebook!  Besides, what else would I be doing?  I figure that Dr. Parrington spared me from many dozens of hours of daytime television.  I have entered it in my blog “The Cancer Researcher Wannabe’s Bookshelf”

http://ljb-quiltcutie.blogspot.com/2014/10/the-cancer-researcher-wannabes-bookshelf.html

with a grade of B-



A POTENT VEGETABLE?

Lady Astor's little British getaway

On the Thames, above London

There I a flurry of publicity surrounding some new clinical confirmation that using birth control pills reduces your likelihood of getting ovarian cancer.  You knew that already, right?  The problem remains, however: by the time a woman reaches the age range where she is most likely to get OVCA, she is past worrying about birth control.   Now, if we had Abu Bakr al Bagdadi for a leader, instead of our kind and somewhat hesitant president, all girls would be put on the pill at age 11 and only permitted to stop when more future jihadi were needed.  So, bummer.

However, here is something you almost certainly didn’t know:  there is a vegetable that may help prevent/cure both ovarian and breast cancer.  The stuff is called Sojne danta, and seems to be popular in India.  If you Google it, you will find recipes.  Nothing that I have read explains how it does its thing – other than by "stimulating apoptosis"which, as you know, is short for “programmed cell death.”  A clutch of scientists from India are presenting a paper on this plant, and initiating a formal trial.  I am hopeful, but skeptical.

I had forgotten how much I hate this computer!



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.



BACON FOREVER!

Linda would not approve of this blog

WHO do they think they are, messing with the best meal of the day??? I refer, of course, to the World Health Organization,  Unless you were climbing in the Patagonian Andes or bushwhacking through Borneo in search of hallucinogenic plants, you will have heard that WHO has just classified processed meats – and that includes bacon – as a carcinogen, thus lumping it with smoking, alcohol excess, and sniffing asbestos powder.  I heard this pronouncement  on two news broadcasts last night,  It was front-page on the highly influential Bellingham Herald this morning.  All this upset me so much that I went out for breakfast (my usual: biscuits and gravy, bacon and eggs).  On the way to the restaurant I punched the radio button – and there was Rush Limbaugh, weighing in.  (He thinks it is a liberal scam, like global warming, evolution and the existence of poverty.)  So what is an elderly carnivore to do?

Well, first of all, look at the fine print.  WHO tells me that eating plentiful amounts of processed meats (in my case, almost entirely bacon) will increase my lifetime probability of getting colorectal cancer by 18%.  Scary, no?  However – according to official health statistics the lifetime chance of dieing from this type of cancer is about 15 in 100,000 (or was, in 2012), which figures out to about 0.015%.  18% of that is a very small number: according to these statistics, eating bacon in profusion raises your risk of death from colorectal cancer to a whopping 0.018%.  I can’t speak for you, but at 82 I will damned well take my chances.

I guess it boils down to this question: do you want to live a long life eating oatmeal and yogurt, or would you prefer a  (perhaps) slightly shorter life eating bacon and eggs?

In passing, I read somewhere lately about an interview with the current oldest person in the world – about 116, I think.  She states that she has bacon and eggs every day.



QUILT FOR A CURE

Linda at Mt. St. Helens

Did you know that there is a Glasgow in Kentucky?  Well, neither did I.  When I saw this article on Google Alerts I thought it was the big Scottish city, where you need a translator to get around.  But it turns out to be a place in Kentucky, where you can probably get along with West Coast English.

It seems that the ladies of Glasgow make quilts and auction them off to support ovarian cancer research.  Linda was an avid and skillful quilter, and I am sure she would have thrown herself headlong into quilting for cancer research.  Most quilters are women, and perhaps the most deadly form of cancer for women is ovarian.  I would like to suggest that quilt guilds everywhere consider doing as the Glasgow (KY) women do: make quilts, have a show, then an auction.  I know I would damned certainly buy one.  If you belong to a quilt guild, why not bring up the idea?

http://www.glasgowdailytimes.com/news/pattern-of-support-homemakers-to-auction-quilts-for-cancer-research/article_5aa90420-79cc-11e5-b504-3f917c2aaf83.html

May I also suggest that the money raised be donated to the Marsha Rivkin Center for Ovarian Cancer Research, at Swedish Hospital in Seattle?  I have written about them before; they are the whetstone that sharpens the cutting edge of OVCA research.  (Sorry, my gene for enhancing bad writing seems to have gotten out of control.)  They are at:

http://www.marsharivkin.org/

 

 



IN-VITRO FERTILIZATION AND OVARIAN CANCER

Linda in Borrego Springs

No, wait.  This must be England

As most of you know, I use “Google Alerts” to help me keep up with developments in the ovarian cancer field.  Google Alerts isn’t very selective; it will feature a lurid apocalyptic article in a British tabloid  sandwiched between news from sources that are so sober and serious as to be the next best thing to an academic journal.  Of course, I ignore the splashy stuff (and puzzle over the rest).  Well, between October 20 and 23 there occurred a flurry of articles concerning a correlation between IVF (in vitro fertilization) and the probability of contracting ovarian cancer.  In a substantial British study, women who underwent IVF were about one third more likely to contract OVCA than women who did not.  The researchers hasten to say that the fault lies not with the IVF procedure itself, but rather the need for it.  In other words, some molecular mistake contributes both to infertility and ovarian-cancer susceptibility.  They are now searching for the causative link.  Good, fundamental biology, I guess.  Nine articles on this same subject were noted in three days.  Here is the most informative:

http://www.foodworldnews.com/articles/45755/20151021/can-infertility-point-to-ovarian-cancer-risk.htm

It should be pointed out that several of these articles note that this (British) result contradicts the findings of a much larger study performed recently in Sweden,  I consider this kind of thing  major drag.

And, if you have begun to think that cancer researchers all are meticulous, cautious and not given to premature enthusiasm, read this:

http://www.eurekalert.org/pub_releases/2015-10/uosc-boc101915.php

It appears that there is evidence that having a BRCA1 mutation enhances the ability to smell, in addition to increasing the probability of contracting breast and/or ovarian cancer.  This is the conclusion of a murine experiment.  (Murine means mouse.)  The statistics can’t be too griping, however: the whole damned thing had an N of 4!



LETS KICK BIG PHARMA A FEW MORE TIMES

Linda had a good time in London

For those of you who need to raise your blood pressure to lethal levels every so often in order to stay awake, here is another article on drug pricing and Big Pharma that should do the trick.  There are some deliberate misrepresentations here (see below), but by and large the thing rings true.  Market forces aren’t designed to deal with a situation like this, and our politicized regulatory system is not making things much better.  We need a  re-think, and soon.  But, as FaceBookers seem to like to say: LOL.

Where this article asks us to stretch our credulity a bit too far concerns the implication that academic institutions develop drugs with public funding and that Big Pharma just manufactures and delivers.  In reality – insofar as I understand reality – many drugs are developed by the drug companies as part of self-supported basic research, and academic labs normally provide “proof of efficacy” studies only – that is, they demonstrate that some bio-molecule they have found may do the trick, whatever that trick is supposed to be.  And then, as often as not, these dedicated academics form a company, patent the molecule, and promptly sell out to – you guessed it – Big Pharma.  How do you think Porsche stays in business? 

So I believe the statements that new drugs may cost several billions of dollars to bring to market.  Part of this is the ponderous, sloth-like mechanism for gaining FDA approval.  But, yes, my blood pressure does rise to dangerous levels when I learn that more is spent on advertising than R & D, and that profit margins can be as high as 20 to 30%.

  Ask yourself: what would Bernie do?

http://theweek.com/articles/583337/brief-guide-big-pharma



I LEARN SOMETHING - AND TEACH IT TO YOU

Linda in the Tower

(of London, that is)

 

Well, you learn stuff all the time.  For instance, today I learned that I have (actually, had) the only dental bridge in existence (in my mouth, of course) that has ever needed to be replaced because it has broken in half.  This little piece of knowledge will cost me $2492 – surely worth every penny.

I also learned something about cancer, or – more specifically – the mutations that cause them.  There is an article attributed to The Atlantic, introduced by a picture of Angelina Jolie, about new research involving the breast (and ovarian) cancer gene BRCA1.  Naively, I thought of a BRCA mutation in terms of all-or- nothing; the protein coded for by the gene works when the gene is whole, and doesn’t when it’s not.  Seems it is much more complicated than that.  BRCA is a whopping big gene, and it can mutate (get damaged) in lots of places.  Each of these qualifies as a mutation, but not all of them are dangerous.  They are called “variants of unknown significance” (VUS).  Thus, if you sequence a woman’s genes you may find a BRCA mutation – but you don’t know what it might or might not do.  So far about 350 VUSs are known – and the task of sorting them out is just beginning.  Heading the work is a researcher from the University of Washington, one Dr. Lea Sarita.  She has a long row ahead to hoe.

And, for those of you who like to boil your blood once in a while, there is a bit in this article about Myriad Genetics, the outfit that first developed the BRCA test – and is trying to patent it.  I am a confirmed capitalist and would never deny a company that has done good work a legitimate profit, but this seems to (even) me to be going too far.  Apparently they are sitting on a valuable data base about VUSs and have not shared them with the scientific community.  Sic Bernie Sanders on ‘em!

Here is the article:  http://www.theatlantic.com/science/archive/2015/10/filling-in-the-unknown-unknowns-of-cancer-genetic-testing/409828/

 

 



SCIENCE OVER LUNCH

Mock Gothic ruin, Somewhere upon Thames

What was she doing back there?

 

Sorry for posting two days in a row, but I have just returned from an “event” and am filled with enthusiasm.  The event was Science over Lunch, sponsored by Fred Hutch, and the science was provided by Dr. Johnnie Orozco, who seems to be both a practicing oncologist (at the Seattle Cancer Care Alliance) and a member of one or more research teams (at the Hutch).  He is an energetic young man, obviously enthusiastic and capable; he and his team are doing cutting-edge investigations in the area of targeted therapy.  It warms my heart to be reminded, as I often am, that so much talent, energy (and money) are being applied to the fight against cancer.  I’d give you his email if I could find it, but I can’t.  That’s probably for the best; I don’t want him wasting time answering emails when he could be working on just the perfect nanoparticle to blast epithelial ovarian cancer to hell.  Anyway: thank you, Dr. Orozco, for an illuminating talk and for all your efforts on the front line.



TO BLINDSIDE CANCER

Proof that Monkey Puzzle trees are hardy

This was taken in Stanley, the capital of the Falkland Islands

Yes, I still have plenty of Linda pictures, but I want to slip others in from time to time.

Here is a basic primer on the genetics of breast and ovarian cancer.  Most of you won’t need it, but you might want to recommend it to your friends.

http://www.good4utah.com/news/local-news/expert-explains-the-genetics-of-breast-cancer

Having nothing much to do these days, I find myself watching more and more NFL football.  I feel ashamed of this sometimes; watching all those young millionaires bashing out their brains for the amusement of a bunch of atavistic savages (us) surely must be deplorable.  Two centuries ago we enjoyed watching bears and bulls kill each other; or dogs; or roosters.  Now it’s humans.  Well, at least they (the millionaires - not the dogs or roosters) live it up for a while.

But why I brought this up is this.  It seems as though the NFL has ordered all their gladiatorial bands to wear pink during their battles, in honor of Breast Cancer Awareness Month, which is October.  September is usually Ovarian Cancer Awareness Month, and NFL games are played then, too.  Do you think that if we all wrote Roger Goodell and asked him for teal* next September, it would work?  Probably not, but I suggest we give it a try.  Maybe somebody can figure out how to contact him electronically,

Breast cancer is far more prevalent than ovarian cancer: in 2012, for instance, about 130 women per 100,000 contracted breast cancer, whereas 12 were diagnosed with ovarian cancer.  However, in terms of the seriousness of the diagnosis the picture is much less one sided:  21 0f 100,000 died of breast cancer that year, compared to 7.5 of ovarian cancer. 

So let’s put teal on the Pittsburg Steelers defensive line and see if they can blindside both cancers next year.

*You did know that teal is the OVC color, right?

You can contact the NFL this way:
http://www.nfl.com/contact-us