OF GOOGLE AND ME

 

Linda and a grand nephew, Heron Island, Maine

 



As you probably know already, I have arranged for Google to alert me whenever an article concerning ovarian cancer appears in the world media.  Well, appears in English, I guess – nothing in Lithuanian so far.  .  Many of the articles they cough up are inconsequential, and a few are downright stupid.  However, some useful references also emerge.  As an example of the former, the Mirror (a U.K. tabloid – possibly the one that prints a full-page nude female on page three of every issue) reports that fizzy drinks cause cancer.  What they mean is that: (1) drinking an improbable amount of fizzy, sugary fluid causes puberty in girls to come a month or two early, and (2) early puberty increases the chances of developing certain kinds of cancer, especially breast and ovarian.  So, I guess our lesson here is to avoid fizzy drinks – mainly because they are disgusting in taste, make you fat, and rot your teeth.  Fear of cancer would appear to be fairly low on the list of reasons.

As an example of a useful article, the American Society of Clinical Oncology refers you to the following report:

http://jco.ascopubs.org/content/early/2015/01/16/JCO.2014.59.9746  **

This is something like an annual report of what ASCO regards as important advances in cancer research.  I can’t pretend that this is “I just couldn’t put it down” literature, but it has some interesting sections.   As you probably could have guessed, it contains an anguished plea for more Federal funding – the claim is made that the purchasing power of the cancer research community has decreased by 29% in the past decade.  No word about rearranging the way the available funds are distributed, of course – ASCO is cancer establishment, bigtime.  I, too, am unhappy when cancer funding is cut, but I continue to argue that the funds could be put to far more effective use:  see the following fascinating little essay

http://ljb-quiltcutie.blogspot.com/2014/06/the-truth-in-small-doses-at--last_7.html

which you should re-read.  I’m sure my email buddy Clifton Leaf would agree.

In passing: a large percentage of “serious” articles that Google dredges up for me concern research that demonstrates that certain genetic mutations are related to certain kinds of cancer.  I guess such discoveries are cause for jubilation – or at least, a fleeting, grim little smile.  Clearly, simply knowing what aids and abets cancer-acquisition is of little value so long as we don’t know what to do about it.   So, your genomic investigation tells me that my daughter is carrying a mutation that may cause ovarian cancer.  So, what then?  Can we fix the mutation?  Can we reverse its malign effect?  That’s what I really want to know.  What am I paying your salary for, anyway?  Come on guys – get cracking

**I should warn you that opening this site may result in an obnoxious add – on my machine it does about half the time.  However, just close the add and the meat of the article will appears.

 

 

ZACH

Cousins

Linda, Carolyn, Elsie, David

missing: Richard, Karl

 

A quick little post:  I subscribe to something called “Google Alerts”: they “alert” me to items in the media that touch, however lightly, on ovarian cancer.  In following up one such  I  discovered the following:

http://www.wusa9.com/media/cinematic/video/22296609/

This video talks a bit about medical application of genomics.  The little boy featured here had some of the experiences of Seamus, my great grandson – but in spades, and with many more complications.  The Cordova contingent will be especially interested.

Please watch this video, and then ask yourself two questions:

How can they do such incredible stuff, and isn’t it wonderful that they can?

How in Heaven’s name can we (as a society) afford it?

 

 

 

 



A DEFINITE BUMMER

Linda and Ella, not so many years ago.

She was never happier than with a baby.

 

CBC radio broadcasts something called “White Coats, Black Arts”, which I’ve never heard.  Apparently this program dissects various aspects of medical science, successes and failures, leaving  warts and wrinkles in full view.  To me, this approach sounds like a welcome change  from the way it often is done on U.S. television – you know, Dr. Nancy Snyderman perched across the table from Brian, solemnly telling us something we already knew, or strongly suspected.  This strikes me as definitely better.  Yes, CBC is Canadian.  Face it, the Canucks are ahead of us, again.

The star of the show seems to be a Dr. Brian Goldman.  Dr. Goldman trained as an ER doc, has written a book on that subject, and apparently is a popular fixture on Canadian media.  In this article he takes on the efficacy of cancer screening.  He lobs us an 80 lb. medicine ball – a real downer.  Here it is:

http://www.cbc.ca/radio/whitecoat/blog/cancer-screening-not-all-it-s-cracked-up-to-be-1.2918080

In this article he reports on a new study published in the International Journal of Epidemiology and authored by some people at Stanford - which concludes that, in general, currently available cancer screening methods simply  don’t work.   (It should come as little surprise that one of the authors is our old friend John Ioannidis  – see, for instance:  http://ljb-quiltcutie.blogspot.com/2014/04/metrics-scourge-of-sloppy-science.html, and several other articles mentioned therein.)

To write the blunt truth, after my experience of the last few years I don’t find this surprising. 

Ioannidis and his crew define “work” as improving the chances of not dying.  Some tests do help, but most don’t.  Here is a paragraph that summarizes the problem:

“There are several possible reasons why these screening tests have performed so poorly..  The screening test may not detect the cancer early enough to save a life.  It may be that no matter how early the cancer is detected, there is no good early treatment that cures the cancer.  In some cases, there is a treatment but the risks of the treatment are so great that they cancel out the benefits of early cancer detection.  Or, early detection leads to treatment that cures the cancer but the patient is more likely to die of other causes not related to the cancer.”  Tell me this isn’t a bummer!

However, Dr. Goldman’s piece does include some silver lining for this particular dark cloud.  Several new prognostic processes are mentioned, including one currently being tested on ovarian cancer that involves looking for the presence of a certain abnormal protein in the blood.  It also might be useful for other cancers, including breast cancer.  Let us hope! 

There’s more good stuff in this short article; I recommend that you all read it.  And, when I get back to Bellingham, near the Canadian border, I’m going to see if I can tune in on White Coats, Black Arts.  Not much hope, here in Borrego Springs.

 

 

B



KEN BURNS AND CANCER

An early quilt

Definitely a toddler quilt

Wonder who has it now.

On October 10^th of last year I wrote a blindingly insightful analysis of current “popular” literature about cancer.  I looked at a dozen or more books and “graded” them, as you might expect an old fogy academic to do.  Only three were rated as “must reads”.  The most ponderous and menacing of the three was The Emperor of All Maladies: A biography of cancer, written (in his spare time?) by a young cancer researcher, Siddhartha Mukherjee.  I didn’t really expect you to consume this work – unless you are as driven as I seem to be.  Well, be golly, you are in luck.  Ken Burns is making a documentary out of Mukherjee’s book!  It is set for release next spring.  When I find out precisely when I promise to let you know.  There are few things in this world that I anticipate more.  (Remember: I’m 81, and I’m realistic.)

Read about it yourself: http://www.cancertodaymag.org/Winter2014/Pages/Emperor-of-All-Maladies-Biography-of-Cancer-Documentary-PBS-Ken-Burns-Siddhartha-Mukherjee.aspx 

Oh, I should have told you about my adventures today.  I went with some birders to the southern end of the Salton Sea.  I saw about 1000 snow geese (at times flying in circles overhead - raining their little treasures upon us), and perhaps land-based 500 sand hill cranes.  It was wonderfully impressive and I enjoyed it - but by next year I won't be able to tell one of these birds from the other!  No hope for me, Brad.
 

 



ORPHAN DRUGS

The Agora in Athens, 1983

I will start this blog with a scolding.  My last blog was designed to induce you to read a Wall Street Journal Op Ed by an M.D. in Bozeman, Montana who – if not our answer to Mother Teresa – is a close second.  But, it turns out, the WSJ (profit-grubbing capitalist swine that they are) will not let you read their articles on line unless you are a subscriber.  I have concocted a way around this impasse and have asked those of you who want to read about Dr. Bob to let me know by email.  Google tells me that over 20 of you already have looked at that particular blog.  However, only two of you have asked for the article!  More proof that most of you simple look at the picture of Linda and then flip down to the next cute baby or scenery picture.  Fie!  My email is myrlbeck@msn.com.  I expect some action.

The topic of this blog is “orphan drugs”: what they are and how they are created.  We have talked about medical economics at excessive length many times before.  Swell, here’s more.  An orphan drug is a drug designed to treat a very rare disease.  If it is truly rare, there is no way that Big Pharma or anyone else can develop and market a drug specific to that disease, and turn a profit.   It may surprise you to learn that Big Pharma has no soul, and so is extremely unlikely to deliberately lose money just for the sake of the humanitarian buzz it may provide  Thus, to generate orphan drugs, the public must intervene.  Short of setting up a government owned and operated “Crown Corporation” to do the work, inducements needs must be applied to get Big Pharma rumbling.   These include tax breaks, extended patent limits, simplified approval procedures, and probably lots of other little tricks.  Anyway, these “tricks” seem to be successful, because there are some orphan drugs already on the market, and more in the pipeline.     One of these is “enadenotucriev”. This unspellable and unpronounceable drug (soon to be renamed something short and catchy, you can bet) is being developed by a smallish company in Oxford, England.  It is a treatment for epithelial ovarian cancer.  May it work wonders!





GOOD PEOPLE DO EXIST. We need more.

Carolyn and Linda

When?  Where?

 

This little entry has nothing to do with ovarian cancer, but it has a lot to say about how we should lead our lives.  What I am bringing to you is an Op Ed from today’s Wall Street Journal.  The author is an M.D. practicing general medicine in Bozeman, Montana, a high and desolate mountain village chiefly famous for the fact that my youngest granddaughter is a college student there.  I urge you to read it and then think for a few minutes.  I did just that, and came away taxing myself for not being a better person.  To signal a change in my character I hereby vow not to gloat if the Seattle Seahawks cream Green Bay tomorrow.  And maybe I’ll work on a few other things, too.

I don’t know why this little piece affected me so much.  Maybe it is because my desk is surrounded by pictures of Linda.  This is the way she lived.

http://www.wsj.com/articles/bob-flaherty-diagnosing-the-many-routes-to-homelessness-1421452324

 

 



 



WHY DRUGS COST SO MUCH

Richard, Linda and Carolyn, Kalamazoo, 1952

Throwback Thursday

 

From the Ingwalls comes this NY Times Op Ed, which is guaranteed to make your blood boil.

It concerns a topic we have batted around many times before: How have we arrived at a situation wherein a drug – a pill, say – that some people need to survive costs $2.29 to manufacture, but is sold for $2,290?  (I made those numbers up, but they are not improbably extreme.)  In no particular order, here are some of the answers: 

It costs billions to develop a new, effective drug, and Big Pharma must recoup those billions, plus a decent profit, to placate its stockholders.

The Feds gum up the works with preposterous rules and regulations, presented as means to protect us from the next Thalidomide but really represent a product of the normal evolution of a bureaucracy.

Capitalism encourages the proliferation of a class of blood-sucking leeches who prey on the innocent.

Foreign countries let us (the U.S.) spend cubic kilometers of large-denomination bills to develop healthcare procedures, then duplicate what we do for peanuts.

No medical practitioner dares NOT use a new drug for fear that he/she will get sued.

And so forth.  Some of these are fairly stupid, some are partially true, but even collectively they are not the entire answer.  According to the author of this piece (a prominent M.D.  employed by Memorial Sloan Kettering, itself a true major-league outfit), the problem breaks down something like this:  Drugs obtain approval from the FDA that (a) cost a lot, and (b) aren’t much more effective than existing treatments.  Nevertheless, insurance companies are REQUIRED to offer these drugs, and some physicians prescribe them, either out of primordial CYA instincts, or out of ignorance.  The suggestion here is to, in effect, let competition do its job.  In Europe, it is said, insurance agencies can say “no” to new drugs, and so – if a new drug is developed – it must be priced so as to make it attractive.  Let’s say I am CEO of NastyPharma and I have a new cancer drug in my bag.  Call my drug N, and let’s also  say there is a competing drug already known to work, called C.  I would like to price N at $10,000/month, but C sells for about half that.  The FDA has ruled that N is a little better than C, but not much.  In the U.S., insurance policies must offer both N and C, and for reasons afore said some physicians will prescribe it, or at least not argue too hard if the patient requests it.  However, in Europe the outfits that control such things can say “no” to N, at that price.  Hence, I must price it much lower.  If it must be priced so low that I can legitimately despair of ever recovering development costs, well : Tough stuff.  I should have figured that out early-on and worked on something else.  Benign Capitalism in action, more or less. 

There is more to this article than I have summarized here, but I am beginning to think destructive thoughts about this computer again, as it swallows entire paragraphs and pastes them elsewhere – mainly in cyberspace.  So I will give you the link, below, which you should read.  In my view this is not close to the entire answer to our drug-price problem, although it is a good start.  It may reduce the cost of a drug from $10K/month to $5K, but who can afford even that?  We absolutely must somehow learn to allocate our research dollars in such a way that not many people ever NEED either N or C.  Maximize prevention and early detection so we don’t need to worry so much about cure.

http://www.nytimes.com/2015/01/15/opinion/why-drugs-cost-so-much.html?smprod=nytcore-ipad&smid=nytcore-ipad-share&_r=0 



DO YOU APPRECIATE ALL I DO FOR YOU?

Linda, looking uncharacteristically gloomy, in Oxford

I think she was tired

You don’t properly appreciate the things I do for you.    Not only do I keep abreast of the evolving cancer world, ponder all I am equipped to ponder, then distill for you a biochemical cocktail you can imbibe, and even enjoy – I also wade through a lot of crap on your behalf.  This has been especially true lately since I subscribed to Google Alerts and asked them to “alert” me to articles that mention ovarian cancer.  Google, wise though it is, makes no attempt at quality control – that is left to me.  The result is that I examine many articles each week, at least 50% of which are irrelevant to our interests.  The remaining 50% breaks down into 30% of material that probably is important but that I don’t understand, 10% articles that I like, can understand, and report upon, and 10% of unadulterated crap!  I had intended to give you an example of the latter, but the publisher – the West Valley (Phoenix) Journal evidently noticed how bad it was and scrubbed it.  It appeared to be a translation, probably from the Swedish, into Lithuanian, then into English, both translations having been performed by computer algorithms.  Honestly, I have never seen anything funnier and more pathetic in print since I stopped reading geology journals.  How I wish I could show it to you, but it is gone.

However, in the same “Alert” came news of some work at MD Anderson (Houston) that is worth passing on.  If you watched Sixty Minutes last night /1/11/15) you may have gained the impression that MD Anderson is a medical clip joint, devoted to squeezing money out of desperate cancer victims.  It isn’t:  MD Anderson is one of the most highly respected research hospitals in the United States, if not the world.   This isn’t the first time that 60 Minutes has pissed me off.  Maybe I’ll stop watching it (again.)

Anyway, this news release is interesting to me partly because it involves use of micro RNA molecules as cancer-fighting agents.  I have been keen on miRNA ever since I learned about the work of Monish Tewari (read my blog for 10/20/13.)  Dr. Tewari was employed by Fred Hutch at that time, and attended seminars with the group I was attempting to assist; subsequently he transferred his activities to his home state of Michigan.  Monish works with micro RNA molecules (miRNA) which I would attempt explain for you were it not that this damned new lap-top keeps skipping all over hells half acre, putting text in the wrong place, or erasing entire painfully constructed paragraphs!   I have written about miRNA before: check my blog for 6/8/12, for instance. 

Well, it seems that something called the 3q26.2 “amplicon” is an important player in some kinds of cancer, including ovarian.  An “amplicon” arises when a stretch of DNA is “amplified” – that is, duplicated.  This can be done artificially, in a lab, but it also occurs in nature.  For an example, if a stretch of DNA should read “abcdefg” but instead reads abcdbcdefg, or abcddcbefg, or even adcbbcdefg – an amplicon has arisen.  Apparently 3126.2 is  “upregulated”, and implicated,  in some cancers and can be attacked with miRNA569, one of our micro RNA friends.  And that is all I am going to write, because – if this computer mutilates any more text I swear I will toss it into the street! 

Here is the web address:  http://www.oncologynurseadvisor.com/targeting-microrna-may-benefit-some-patients-with-ovarian-and-breast-cancer/article/391213/ 

Tonight is the college football championship game.  Go, Ducks!



GLOWING, PULSATING, DEATH-DEALING NANOPARTICLES

More of Linda and Ella

 

A nanometer is one billionth of a meter, or one millionth of a millimeter.  (You remember millimeters – there was some TV commercial that described the millimeter as, “Well, like SMALL!).  Well, cancer folks are using things called nanoparticles in various ways to combat certain kinds of malignancies.  I have written about nanoparticles previously:  specifically 10/30/14 (Google will rule the world: Inside and out) and 4/2/12 (Good things come in tiny packages).  Now research worker at Oregon State have come up with a new use for nanoparticles.    You can read their press release by clicking on

http://phys.org/news/2015-01-nanotechnology-cancer-surgery-malignant-cells.html

In a nutshell:  The somehow manage to load up nanoparticles with a drug called naphthalocyanine.  This stuff has the property of glowing when irradiated with light of a certain wavelength, called near infrared.  At the same time it somehow produces something called “activated oxygen” (oxygen ions?) that are hell on wheels where cells are concerned; it kills them.  Somehow these loaded nanoparticles can be festooned with proteins that bind to cancer cells and not to healthy cells.  Then the nanoparticle penetrates the cancer cell and causes it to light up when radiated, thus acting as a beacon for the surgeon’s knife.  And, (we fervently hope) the active oxygen can be counted on to kill any tumor cells left over.   

The method has worked on ovarian cancer cells in vitro and also on mice.  Next they are going to try it on dogs.  (Yes, I know – that’s terrible.  Terrible, but necessary.)

You know, when I write these things I often am bothered by thoughts along these lines:” Why in hell didn’t they have these treatments when they could have helped Linda”?  Not particularly noble of me, I know – but you will understand.

P.S.  I just went to the living room to watch the Packer’s game on TV.  I have been looking forward to it all morning.  It turns out it’s tomorrow. 



BAD LUCK?

Linda and Richard, Kalamazoo, 1981

I was lurking  just over the horizon.

 

I wish I were smart enough to figure out how go paste graphs and such on these blogs.  I have run on one that is very interesting and well worth your trouble to ponder.  You can see it by clicking on the following:  http://news.sciencemag.org/biology/2015/01/simple-math-explains-why-you-may-or-may-not-get-cancer

This arises from my efforts to understand an article that has obtained significant press traction this week, which maintains that “2/3 of all cancers are due to bad luck”.

You may react at first as I instinctively did: “What!  So the other third represents good luck?  Hell, any cancer is bad luck.  Period.  What are you talking about?”

Well, they have a point, and here (more or less) is what it is.

BioBackground:  Cancers are the result of uncontrolled cellular proliferation.  They arise when the genes that tell the cell when to divide (sometimes called proto-oncogenes) get “stuck open”, so to speak.  There also are genes that tell cells when not to divide (“tumor suppressor genes”).  If a series of mutations affects both kinds of genes, in the wrong way, a tumor is the result. 

More BioBackground:  Some people are born with defective genes of one kind or another – BRCA1,2 are well-known examples.  Others aggravate the problem by experiencing environmental factors that conduce mutations: smoke, eat red meat, play with asbestos for instance.  The authors of this paper are trying to find out how many cancers are not attributable to this kind of bad luck and/or foolish behavior.  In other words, how many cancers are due to simple, dumb, bad luck?

The method used is really rather uncomplicated.  The authors estimated how many times in a lifetime tissue at a given potential cancer locus will divide.  Then, they assume, the cancer rate should be proportional to this number.  They found that, within wide error limits, this holds true.  For instance: they estimate that a colorectal stem cell divides about 10¹² times during a lifetime, whereas a stem cell of the duodenum does its thing about 10¹⁰ times.  Thus their hypothesis predicts that colorectal cancer ought to be about 100 times more common than cancer of the duodenum – which, within very elastic error limits – it is.  Thus, using this kind of simple mathematical reasoning, they conclude that 2/3 of all cancers are the result of (this special kind of) “bad luck”.

Well, yeah – big deal.  I have maintained all along that many (most?) cancers are the result of the accumulation of mutations, a process over which we essentially have no control (once we ditch the cigarettes, asbestos, etc.  of course).  I agree with the authors that this directs us to work hard on early detection (and, of course, treatment).  But the graph that you will now examine contains some mysteries.  For instance, why is it that ovarian germ cell cancers and cancers of the small intestine have about the same lifetime risk, regardless of the fact that small intestine stem cells divide about 10,000 times more often than do ovarian cells?  Maybe there is an obvious answer, but I don’t see it.  More need for well-directed and well-funded applied BioResesarch. 



 

 



BE NICE TO YOUR MICE

Linda at 25

 

Mice are back in the news.  Way back on 3/12/12 I wrote a blog called “Forget dogs: Mice are man’s best friend.”  This was, of course in recognition of the supremely important role mice play in cancer research: what you can’t inflict on people you can test using our murine friends.  Then nine months later I changed my mind (9/19/12), occasioned by the astounding news that some dogs can detect some kinds of cancer – by smell!  This has spurred all sorts of research into the possibility of detecting cancer by “sniffing” phonemes, without much result as yet.  But who knows?  Maybe someday.

Well, mice are making a comeback.  An article from the San Diego Union-Tribune reports that mice are being u3sed to test the effectiveness of various chemotherapeutic drugs.  The way it seems to work is something like this:  You acquire a few lab mice, take a slice of your tumor and graft it on to the poor little devil – and then test your drug.  For instance: maybe there are four candidate drugs but no way to know a priori which if any will work.  You acquire four mice and test a single drug on each.  This should work; provided, of course, that you can be assured that your mice are biochemically equivalent to you – which is by no means entirely certain.

There is a powerful disincentive to pursue this line of therapy, however – cost.  Apparently it runs about $10,000 per mouse, with no help from the insurance companies.  This is all highly experimental at present; stay tuned.

Another OVCA-related article appeared in a recent British publication.  It has long been known that eating red mean is conducive to the acquisition of all sorts of cancers.  The question has been: why?  It was thought that grilling produced some kind of toxin that was responsible.  However, grilling chicken or fish produces no such result.  Now it appears that a sugar molecule – specifically something called Neu5Gc does the damage.  This sugar is found in all sorts of different mammals, but not in chicken or fish.  Or, as it turns out, Homo sapiens.  Thus, when we eat red meat we effectively insert a “foreign” substance into our body, one which arouses the immune system.  Inflammation duly ensues.  And what does chronic inflammation do?  It somehow lubricates the cancer-acquisition process.  Why this should be true is a deep mystery to me, but apparently it is.

And how do we know all this?  Mouse models, of course.  As Bunny Schneider once Commented:  Bless the little mouse that gives its life for us.

Want to read the article?  http://www.dailymail.co.uk/health/article-2890243/Scientists-crack-red-meat-linked-cancer-SUGAR-molecule-blame.html