Thursday, January 30, 2014

NOT OC: MOSTLY TWADDLE, PROBABLY

Linda near the top of the world
Vardo, Norway - about the latitude of Barrow, Alaska
They fought heroically against the Germans in WW II.
But, in the end, they lost
In some parts of the world we Americans are the Great Satan.  Elsewhere we are a bunch of buttinskis who meddle, uninvited, in others' affairs.  Almost everywhere we are resented as the top dog, the rich guys, - the “1%” of the world.  Even where we do good works - and there are many instances -  we are disliked; as is well known, no good deed ever goes completely unpunished.  In short, the rest of the world may admire us, may envy us, may even try to emulate us– but they don’t much like us.  How did this come to be?
I hit on these uncharacteristically gloomy, introspective thoughts because I just ran on a passage in an old book which demonstrates how much things have changed.  The words I am about to quote are taken from a book published in the 1870s, written by an talented, exceedingly well educated, well-traveled, and well-heeled Englishwoman.  The name of the book is A Thousand Miles up the Nile”.  The author is Amelia Blanford Edwards.  Those of you who have read some of the Amelia Peabody mysteries will recognize this ladies’ character.  So here goes:
“……Of all these, our American cousins, ever helpful, ever cordial, are pleasantest to meet.  Their flag stands to me for a host of brave and generous and kindly associations.  It brings back memories of many lands and many faces.  It calls up echoes of friendly voices, some far distant, some, alas! silent.  Wherefore – be it on the Nile or on the Thames, or the high seas or among Syrian camping grounds, or drooping listlessly from gloomy diplomatic haunts in continental cities – my heart warms to the stars and stripes wherever I see them.”
Well, yes  - this is simply one woman’s opinion; no doubt there were equally well educated, well traveled, well-heeled Englishwomen who felt otherwise.  However, I feel certain that the global proportion  of Amelia Edwardses  has diminished over the past 150 years.  Clearly, acting as global cop has not helped our popularity.  Neither has involving ourselves, often forcefully (and sometimes underhandedly) in the Middle East to protect our energy supply.  Just as clearly, we should try to withdraw from places that hate us, by developing domestic sources of whatever it is we need from them.  Okay, so here’s to fracking and shale oil, as well as renewable energy.  Hooray for a nimbler and more potent strategic strike force, and perhaps a smaller conventional army.  Here’s to diplomacy, if it’s backed up by a big stick. The day of Teddy Roosevelt is over, alas, and the day of an effective Barack Obama is far, far in the future.    In the meantime it would be nice if our friends in Washington could manage to do their jobs. 
Yeah, so now I will get back to another topic I know virtually nothing about – cancer research.
My knee is healing rapidly and I will be in Borrego Spring by the end of next month.


Wednesday, January 29, 2014

A BOOK REPORT

Linda at the Khan al Khalil, Cairo
It is a fascinating place.  We almost got lost in there.
A few months later, someone detonated a bomb right about where she is standing.
I have been going easy on myself lately, at least in the reading line.  I realize that if I am to secure the Nobel Prize before I am 90 I must work diligently at learning biology, but in the past month or so I have read mostly – fiction!  I have re-read nearly all the Tony Hillerman Leaphorn-Chee books, for no better reason than that there’re fun.  I also read a couple of the Amelia Peabody series of which I have written previously.  They, too, are fun.  But as my knee heals my conscience is catching up with me, so I took up a serious book: The Epigenetic Revolution, by Nessa Carey.  This book is so packed with important facts presented in such clear and clever language, that this book, too – is fun!  I urge you all to read it.  About $15 from Amazon, or less if you have a Kindle.
There also is an article in the NY Times that is of interest to people following developments  in genetics and medicine.  You recall some time ago I blogged about two Japanese scientists who had succeeded in converting fully differentiated cells (skin, liver, heart, etc.) into pluripotent stem cells.  iPS cells, they are called.  iPS cells are important because they can be coaxed to turn into other kinds of cells that your body might need – e.g., turn skin cells into heart muscle cells to help repair heart attack damage.  Until recently the only available source of such plastic cells were embryos – hence, the “embryonic stem-cell” controversy.  Now, however, it appears to be possible to push fully differentiated cells back into a pluripotent state, then use them ON YOUR OWN BODY, thus getting around the immune rejection problem.  The Japanese scientists (who received the Nobel for their work) did it laboriously by adding four genes to the existing set.  This new way sounds like it will be much easier (and cheaper), involving as it does only an acid bath.  Anyway, read it yourself
‘cause I want to get back to Nessa.


Sunday, January 26, 2014

FOREST GUMP AND THE X CHROMOSOME

Covenant Gardens, London
2007
 
I guess I will never really understand genetics.  I know that we inherit a single copy of each of our 23 chromosomes from each parent.  Later the genes on these chromosomes are “expressed” as proteins, which inscrutably complicated and grotesquely misshapen blobs of amino acids go around doing everything important in the body.  I don’t really understand how the body decides which gene from which chromosome(which "allele", I should say) to use.  In some cases the gene on one of the aleles is completely “dominant” over the other – it, and only it, gets expressed.  But there are things like shared dominance, co-dominance, etc.,etc.  What’s a geologist to do?  In my field quartz always is harder than feldspar, gravity always acts straight down, hot things always cool off eventually.  That’s the way the universe ought to work- simple, invariant laws that, once understood, can be put to work.  Not so in genetics, apparently.  Who designed this Rube Goldberg thing, anyway?
I write this because I just read an article in the NY Times telling of how female cells will methodically  stifle one of their two X chromosomes.  You know X chromosomes: get two of them, you’re female, get an X and a Y, you’re male.  It appears that females somehow de-activate one entire X chromosome, by attaching some protein called Xist to it.  If the article is to be trusted, one cell can deactivate the X it got from Mom, while its neighbor deactivates the one from Paw.  Why?  You get one copy of, say, chromosome 20 from each parent, but neither is shut down completely.   Why only X?  Maybe they will figure it out and explain it to me.
This sort of thing has relevance to cancer.  If I understand, failure to deactivate one or the other copy of X results in a superabundance of stuff, some of which causes cell proliferation – e.g., cancer. 
As Forest Gump would say, that’s all I have to say about that.  Read it yourself at:
 


Saturday, January 25, 2014

FRONTIERS IN THE BATTLE AGAINST OVARIAN CANCER

 
Linda and Carolyn in Borrego Springs
Probably 2009
 
I try to build a little humor into these blogs, to reward you for reading them.  I’m going to be up-front about it.  Click on
and get a chuckle.  Then read the rest of the blog, which will be boring.
My good friend Kathy from Fred Hutch sent me a link to an article published in the journal  “Gynecological Oncology”.  This little two-page snippet contain a link to a “white paper” elaborating on the same themes.  The latter is 18 pages long.  Both articles are largely free of academico/biochemistry-research jargon and thus are intelligible to the public.  (They can’t resist a little fancy language from time to time, though.  Try “financially incentivize”, which is a ponderous way of saying “pay”)
These articles are reports of the deliberations of the Ovarian Cancer National Alliance, which met in late 2012 to consider “Current Challenges in Ovarian Cancer”.  The three most pressing challenges, in their view, are:
                Including Patient Reported Outcomes (PROs) in the investigation of the efficacy of new drugs and/or treatment protocols.
                Improving patient access to clinical trials.
                Personalized medicine (e.g., targeted therapies).
A typical PRO might be “I was on standard chemo for four sessions, then I developed neuropathy in my fingertips.”  Apparently the two most common side effects are neuropathy and “chemo brain”.  The problems that need to be overcome, it seems, are several fold.  First, such anecdotal evidence is hard to integrate rigorously into clinical trials and, second, these reports are seldom delivered directly to the research team but rather to the treating physician, who may or may not pass them on. 
Clinical trials are most common, and most commonly effective, if conducted at major research centers (like, for instance, Fred Hutch).  The authors of this report deplore this, and suggest ways to incorporate women from the boonies in trials.  The major stumbling block here is “financial incentivization”.  This should come as little surprise.
And finally, targeted medicine.  The idea here is to turn from “organ-based” therapy (e.g., hit all ovarian cancer patients with the same cocktail of drugs.) to a therapy based on an understanding of which mutations are aiding and abetting the cancer.  It seems to be true that a biochemical-pathway malfunction that produces ovarian cancer in one woman may cause, for instance, colorectal cancer in somebody else.  So, identify the pathway(s), figure how to correct or stifle them, test the cancer patient, and give him/her the right  stuff.  Mutation-based therapy I guess it could be called.  As you might correctly guess, this also will require considerable -- financial incentivization.

Okay, I am going to stop here.  The author group-suggests remedies in all three cases outlined above.  Some are nebulous, in my view, and several are downright incomprehensible.  My computer skills being what they are, I have been unable to figure out how to give you the links, so you can read for yourselves.  So, next best thing:  I will forward an email to any of you who are curious.  The email will tell you how to get the other stuff up.  Really, it isn’t all that tough to read this material.  Maybe between plays on SuperBowl  Sunday.
 


Saturday, January 18, 2014

I ESCAPE THE HOSPITAL. Barely


Those Fabulous Joyce Sisters
1968
Well, I’m not sure why anyone should care over much, but I am going to give a personal health report (in lieu of some useful stuff about ovarian cancer.)  First of all, I had my left knee replaced last Friday (1/10/14, that is.)  I came home the following Monday after three of the usual blissful nights we all learn to expect in hospitals.  I am doing all my exercises like a good boy – supervised by my daughter Linda, who won’t let me get away with anything.  (It is possible that she is paying my back for all those times we “grounded” her as a teenager.  Actually, that’s not very likely because I remember her being remarkably easy to raise.)  I am starting my physical therapy next week and should be as good as new by the beginning of March – at which time I intend to go to Borrego Springs and enjoy myself.  In the meantime, for the next few days at least I haven’t got the energy needed to write proper anti-cancer blogs*.  As always, go back and read the old ones, and make comments.
In passing, let us discuss hospital practices.   Is it really necessary to check “vitals” every two hours?  Is it somehow better to draw blood at 5:00 am than at, say, 6:30?  Why must your nurse, on ending her shift, feel obligated to introduce you to her replacement – even if that occurs at 1:00am?  Do hospitals win awards for hooking their patients up to the maximum number of machines that will make it impossible to sleep?  In short – don’t they damned well understand that human beings cannot function – let alone heal – without sleep?  I suspect that there are lawyers and lawsuits lurking in the background – but, what do I know?  I’m just a patient.
*What I caught and corrected was “anti-cancer blobs.”  Maybe my computer is trying to tell me something.


Tuesday, January 7, 2014

OVARIAN CANCER, THY DAYS ARE NUMBERED. Unfortunately that number is still pretty large.


WITH ELLA
Frankly, I don't know what to say about this picture.  She was so brave.
 
We are not exactly winning the war on ovarian cancer; in fact, we’re barely fighting it to a draw.  (I wish I could figure out some way to post the graph on which that lugubrious statement is based.  I will keep trying.)  Anyway, OVCA is not in full-blown retreat, and probably won’t be in the near future.  However, its days are numbered!  I say that after spending many hours reading research proposals submitted to the Marsha Rivkin Center for Ovarian Cancer Research.  There are dozens and dozens of them, all submitted by smart young people with good ideas and the energy (and lab facilities) to follow their ideas up.  Unfortunately, we (MRC) can only afford to fund about 10% of them.  Even so that may total nearly $1 million.  Choosing the winning ~10% will be difficult.  It will involve quite a few experts in the field, each donating time to read and evaluate a selection of the proposals.  Then, presumably, there will be a run-off amongst the best.  I will submit my own evaluations, but don’t worry – nobody will pay any attention.
The ideas run the gamut from attacks on cancer stem cells, approaches utilizing the immune system, using micro RNA to mess up aberrant proteins – to interfering with the cancer blood supply, increasing the efficacy of chemotherapeutic techniques – to early detection,  and even prevention.  And more.  Damn, I wish I knew more about genetics and cancer biology; this stuff is fascinating.
So, anyway, OVCA is doomed.  I only hope I live to see the day.
This is Tuesday.  In three days I will receive my third joint replacement.  After that, only my right knee will be the original bone..  When I was in my 40s and early 50s I ran 12 marathons, one ultra-marathon, countless shorter road races,- and averaged about 20-25 miles/day training, mostly on roads.  After that I hiked every chance I got, until I was 60-something.  Nature designed me to be a weight lifter, not a runner.  I am living proof that bicycling and/or swimming are superior ways to get exercise.  But they’re not as much fun.


Sunday, January 5, 2014

MORE PROGRESS. CAN WE AFFORD IT?

 
With our friend Marilee Munizaga
From Chile
 
I am writing this while waiting for the 49ers-Packers game to begin.  The last word I heard was that the temperature (in Green Bay) would be about zero, with wind-chills around -20o F.  Frankly, I am less interested in the game than I am about how human beings – fans and players – can survive and pretend to enjoy themselves under those conditions.  Somewhere I read that the 49ers gave up plans to train this week on the Weddell Sea ice pack and went to Green Bay instead - it was colder there. 
So, there is an encouraging article in the latest Economist.  You should read it, at http://www.economist.com/news/science-and-technology/21592599-researchers-and-drug-companies-are-ganging-up-new-push-against.  It relates progress against cancer on two fronts: targeted therapy, and activated immune response.  Two things seem to behind this progress: the ability to sequence cancer genes rapidly, and lots of money.  As far as I can tell the approach still seems to be mostly empirical:  try a whole lot of things and see if they work.  Of course, which things you try depends to a large extent on knowledge of basic cancer biology: which mutated genes produce which proteins that don’t do their jobs right.  The problem is exacerbated by the fact that cancer cells, by definition rapidly dividing, produce new mutations which may also be deleterious.  It’s as if the House has stacked the deck against us.  But, we will prevail.  I may never get the Nobel Prize for curing ovarian cancer, but somebody will.  Someday.. 
One astonishing thing brought out by this article is how expensive some of these new treatments can be.  Try $100,000 for one year.


Saturday, January 4, 2014

VACATION ENDED, SICK-LEAVE ABOUT TO COMMENCE


Brave and Wonderful
She didn't let cancer spoil her life
 Yesterday I returned from enjoying the holidays with my family in Alaska, during which time (over two weeks), I added nothing to this blog.  Now, however, I hope to write several more little essays  before I begin sick leave (knee operation) in less than a week.  I need to keep writing, if for no other reason than to keep my “hits” up.  I can now boast that I have over 10K hits all time, with nearly 11K if you toss in the other blog (Fight Back against Ovarian Cancer).  However, during my “vacation” my hits-per-day dropped from about 15 on average, to just 2!  Clearly, I need to keep writing.  The situation is somewhat like the career path of an academic research geologist: do some research, write it up, present it at a meeting, “network”  while  there - so you can hope to get another grant, enabling you to do some  more research, write it up, etc., etc.  The only difference is that, in writing this blog, I am doing something useful, I hope – helping to make people aware of the causes, symptoms, treatments and cures of ovarian cancer.  I participated in the geological squirrel-in-a-revolving-cage exercise because it was fun, not because it did anybody (but me) much good
So, anyway, let me tell you about a worthwhile short article in the NY Times, which you can read by clicking on:  http://well.blogs.nytimes.com/2014/01/02/missing-a-cancer-diagnosis/?ref=health&_r=0.  This seems to be part of a series called “Living with Cancer”, written by Susan Gubar, who has advanced stage ovarian cancer.  In this column she discusses her symptoms – just those I have written about many times previously – and how she and her doctors ignored them.  She discusses her feelings once the truth was known; how she blames herself - and her doctors – and what she or they might have done.  She writes well and analyzes feelings carefully; I urge you to click and read. 
Following her one-page essay are 17 pages of “comments”.  These also are worth reading.  I did; why not?  I couldn’t figure out how to stop my printer from spewing out all 18 pages.  Fortunately paper is cheap – although printer cartridges certainly aren’t!
Finally, another old friend of mine has died of cancer: leukemia, in his case.  I had worked with him and shared jokes, complaints and successes with him, for 44 years.   He was 88, so I guess it’s all right, although I regret it.  Maury, you will be greatly missed.