ANOTHER BREAKTHROUGH? Let's hope.

Guess where.  Guess when.  Guess what's in that bottle.

Did I ever tell you that the amount of DNA contained in a human cell, if stretched out, would be about 6 fee long?  Probably not:  I usually save up such gee-whiz facts to use when I am a little low on creativity, like right now.  It must be true; I learned it from a Teaching Company course on genetics taught by one Dr. David Savada , a cancer researcher associated with various institutions in the L.A. area.  It is a very good course, and when you have as much free time as I do I’m sure you’ll buy it. 

Anyway, what I got from Dr. Savada and my previous reading  is that DNA (famously arranged in a double helix) is a very long, fragile molecule that must be protected from damage at all cost.  To accomplish this it is armored with something called chromatin, and to save space tightly wrapped around little nodules called nucleosomes, constructed from histone proteins.   That way you can stuff six feet of DNA into a space much smaller than the head of a pin.  Sounds farfetched to me, but that’s what they say. 

Fragile though it may be, pieces of tumor DNA may be detected, extracted and studied – from the blood.  These things are referred to as ctDNA:  circulating tumor DNA.  In a recent study by a group of about four dozen scientists it has been shown that ctDNA can be used as an easily-accessed (needle in the arm) biomarker for various kinds of cancer.  (Ovarian was mentioned.)  Even early stage disease leaves its molecular signs.  This may be the long-sought early-warning biomarker that my group at the Hutch has pursued for years with, I am sorry to say, not a heck of a lot of success.

These ctDNA things have other uses.  They can help determine disease-stage, for instance.  They can help oncologists determine which drugs will work best, and why a drug – once efficacious – suddenly loses its efficacy.  They can do other things, which I probably don’t understand well enough to try to explain.  In short – a wonderful breakthrough!

But it is possible to be gloomy.  There have been other wonderful breakthroughs, most of which have turned out to be modest advances at best.  Some have turned out to be total flops.. I am reading a book right now that recounts and explains some of these historical things.  So far it has been relentlessly negative; I am sure the author is going to conclude with a wholesale condemnation of cancer research in general.   The book, which I will review sometime in the future, is so depressing that I am going to lay it aside and read a spy novel.      

I was alerted to this article by my friend Kathy O’Briant, mainstay of my group at the Hutch.  Thank you, Kathy.

FINALLY, A COMPUTER I CAN LOVE

Out to dinner.  Where?

Many years ago I was an avid reader of science fiction.  I liked it so much that, while supposedly working

on my M.S. degree in geophysics, I took time out to submit a story to Amazing Stories, which at the time was the premier magazine of that type in the world.  In due course I received a polite rejection from the head editor, who encouraged me to try again.  Real life intervened and I never did.  That’s probably for the better, but who knows?

Anyway, I vividly remember a short story from those days, in which a computer was being awarded the Nobel Prize in medicine – for curing cancer.  It made an acceptance speech, if I recall correctly.  Did it wear a tux?  Or an evening gown?  Can’t remember.

So, maybe that wasn’t such a far-fetched concept.  Dick Ingwall, trapped in his house like me by gale force winds ripping through the Borrego Valley, has studied the NY Times and come up with the following article, which I will comment upon shortly.

http://www.nytimes.com/2014/03/27/science/enlisting-a-computer-to-battle-cancers-one-by-one.html

The deal is, sequencing DNA has become so easy, rapid and cheap that it is possible to take a sample of a tumor and quickly and economically determine which of its genes are mutated.  This doesn’t get you very far, however.  Some of these mutations will turn out to be harmless and should be ignored.  Others are probably harmful, but it isn’t always apparent how they harm, nor what you can do to stop them.  Here is where Watson comes in.  Watson is the IBM super-computer that apparently just starred on Jeopardy.  Watson is busily devouring the abstracts of medical articles – it is up to 23 million or so.  Give Watson a list of mutations and it will spit out a list of drugs, or drug cocktails  that might help.  Then, of course, humans enter the picture.

Obviously, Watson can only make suggestions based on the reported research.  If the research is crap, Watson will mislead.  That’s hardly Watson’s fault.  The familiar adage “garbage in, garbage out” applies, even to a super-computer.  We need lots of basic research for Watson to devour.  Lots of good basic research.

This approach to cancer therapy is going to be tested on a group of 20 victims of a nasty form of brain cancer, glioblastoma.  Prognosis from glioblastoma is dismal.  Let’s hope Watson gets it right.

NOT OC: My grand daughter Olivia Kelly graduates from Western Washington University

I was privileged to participate in Olivia's graduation ceremony.  Despite much trepidation, I did not trip over my own feet and fall off the podium.   The baby is Evelyn Beck Smith, often known as Her Royal Cuteness.

ONE SMALL STEP FOR WOMANKIND: I hope it helps

Freezing to death on our way to Victoria

Small victories are better than no victories at all.  It has just been announced that the cause of an exceedingly disgusting form of ovarian cancer has been found.  The disease is called “small cell carcinoma of the ovary, hypercalcemic type”, or SCCOHT for short.  Fortunately, it is very rare.  Unfortunately, it strikes very young women (average age 24, with some as young as 14) and is as nasty as these things get: it does not respond to chemotherapy, and 65% of its victims die within 2 years.  You see why I call it disgusting.  I have some even stronger descriptive phrases for things like this, things that attack young people and don’t give them a chance to fight back – but they are unprintable.  

Well, an outfit called the Translational Genomics Research Institute (TGen) has just announced that it has isolated the problem: a disabling mutation of a gene called SMARCA4.  The proper role of this gene is to produce a protein that forms part of a transcription complex, which codes for a bunch of proteins that help repress some genes and excite others. (Get all  that?)   Apparently if the SMARCA4 gene malfunctions there is nothing (or very little) to stop replication of these “small cells” in the ovary, resulting in SCCOHT.  Or so I surmise: it isn’t explained in the article which, by the way, you can read at:

http://www.hngn.com/articles/27334/20140325/genetic-cause-of-rare-ovarian-cancer-revealed-illness-usually-affects-young-women.htm

But I remain skeptical.  So we know what causes this type of cancer.  What can we do about it?  Maybe we could manufacture synthetic SMARCA4 protein and inject it in the patient.  Or maybe not.  So pardon me if I don’t jump up and down in joy.  On the other hand I take courage from the undoubted fact that every little bit of knowledge helps.  We’ll get this SOB yet.

By the way, check out the TGen web site. 

LINDA ON HER WEDDING DAY: Our 32nd.

March 19th, 1982

This is our 32^nd wedding anniversary, and this is the last of our wedding pictures.  She is radiant, as she was nearly all  her life.  I am, well – me.  The wedding dress still exists; I have it.  That tie also is around somewhere, although I never wear it.  The suit – well, it has gone on to a better life.  The wedding bouquet, so beautiful then and still a personal treasure, is in a box in my bedroom.  Many of our wedding presents are still in use.  Her memory has not faded, and it never will.

However, ovarian cancer is still out there.  Diagnosis no longer is a death sentence as it was a few decades ago, but it still is a terribly serious, terribly upsetting life event.    Cancer researchers are making progress.  There is reason for hope.  Our research scientists are clever, our technology is incredibly sophisticated – but the problem (problems, really) are far more complex than anyone dreamed only a few  years ago.  The world is filled with worthy causes, but cancer research must be near the top of the heap.  Give it all the support you can.    

    

Here is Linda’s tribute fund at Fred Hutch

http://getinvolved.fhcrc.org/site/TR?pg=fund&fr_id=1050&pxfid=2861

PROGRESS? PROBABLY

Linda with one of her more original quilts.

Probably 2010

The stooped figure on the left probably is me

It hit 93 at noon today.  Yesterday it was 91 at the same hour.  Both days I have bounced out of bed and headed for the desert to hike before breakfast, thus allowing myself a bit of exercise at minimum discomfort.  The rest of the day I spend indoors, sitting in front of this hungry damned computer.  I say it is hungry because at random times it suddenly eats a great chunk of whatever I am working on.  I wish I knew why.

I call it a damned computer because the heat has me out of sorts.  It is supposed to cool off soon; 93 is very hot for late winter, even in Borrego Springs.  If it hits 100 I’m out of here.

Yahoo featured an article on ovarian cancer yesterday.    It seems to have been distilled from a press release by Brown University and contains very little information that I can dig into.  I tried to obtain the original article using Google Scholar but with no luck.  There are four authors; three women in junior positions and one man who apparently heads-up  the lab.  This is a common pattern;men have the senior positions (and the better salaries), but most of the real work in is done by women.  Okay with me; women are smarter than men, and usually work harder.

The Brown group seems to have discovered that several related proteins, all called TAF with a number appended, are suspiciously represented in ovarian cancer cells.  Some are too prevalent, others too scarce.  These TAF proteins have been dismissed for years as just a workhorse in gene replication; they form parts of things called “transcription complexes” which are necessary for a gene to be “expressed”.  Now they also seem to be implicated in ovarian cancer.  How do they work?  They are always around; why do they suddenly go haywire?  If they are proteins, they must be “coded for” somewhere in the genome.  Is that where the problem lies?  Is there some epigenetic process involved?  Damned if I know; this stuff is fascinating, but it still is far beyond me.

 So, in my present state of ignorance all I glean from this article is that perhaps someday we will have another tool to combat ovarian cancer – and that molecular biology is very, very complicated.  The latter I already knew. 

MAN CONQUERS MACHINE. (for now)

Linda and Carolyn

Our house, probably 2010

Once again, perseverance and dumb luck enable man to triumph over machine.  It seems that I can post pictures using Google Chrome, but not Internet Explorer.  (Bill Gates: back to work!)  I have nothing to say;  I'll just try to post more pictures, as promised.  And this makes 200 blogs.  Onward to 400.  It is 91 here again today; I got in a nice walk before it got hot.

On San Juan Island,  not enjoying her margarita

You've seen this one before, but it is a nice one.

                                                 The baby is Laura Hanson, now grown and out of the nest.

NEARING A MILESTONE

This is my 199^th blog posting.  The first appeared on March 2, 2012.  This means that I have written one blog “essay” every 3.6 days, or 86.1 hrs.  I would pat myself on the back, except that I am so stiff that I have trouble reaching my feet, let alone a part of me that  I cannot see. 

Gracing and justifying those 199 blogs have been at least 175 pictures of my beautiful wife, Linda Joyce Beck.  I know that many of you read the text of these things, but I am sure that all of you enjoy the pictures.  As most of you will have noticed, the technology gremlins that infest every computer operated by anyone over 70 lately have maliciously  prevented me from posting any pictures,  no matter how hard I try.  I am flying back to Bellingham on Thursday  to take part in the graduation ceremony of my second grand-daughter, Olivia Beck Kelly.  I will wear full academic regalia, thus looking like something out of the 18^th century, and I will march in the precession.  While I am in Bellingham I will use my newer desk-top computer to post some pictures.  A bunch of them, in fact.  I hope you like them.

However, to justify this blog I need to tell you something about cancer.  The Economist  for March 1^st has an interesting articled about how much more terrible the burden of cancer is in the developing world than it is in  rich countries.   Here is the article:

http://www.economist.com/news/international/21597962-burden-cancer-falling-increasingly-heavily-poor-worse-aids : 

The gist:  Many African countries have no oncologists whatsoever, and rely on phone calls to U.S. doctors for treatment.  Many communities are in a remarkably unsophisticated state, so lots of time (and money) are spent on traditional treatments that – mostly – don’t work.  Developing countries are plagued by cancers (lung, for instance) that are being eradicated in the developed world.  (Or large parts of it – more than half of Russian, Chinese, and Indonesian men still smoke.)   Mammograms and PSA tests are often unavailable  in poor countries and, where available, usually are expensive.  To some extent our aid packages are misdirected:  cancer kills more people than HIV, malaria and tuberculosis combined, but receives only a “tiny fraction” of the monetary support. 

  And so forth.  Read it yourselves.

Oh, p.s. - it hit 91 here today.  If I see 100 two days in a row I'm heading north!

 

YEAH, YEAH - STILL NO PICTURE. I'M WORKING ON IT!

Wouldn’t it be nice if there was a vaccine against ovarian cancer?  Well, there isn’t – but some of our star Fred Hutch/W. Washington researchers are trying to chase one down.  They are even running a Phase I clinical trial, now enrolling women with Stage 3 or 4 ovarian cancer who are in remission.  Other restrictions apply, as well.  I hope darned few of my loyal readers qualify for this trial, but any who do might want to check this link:

http://www.pocrc.org/project-5.html

POCRC stands for Pacific Ovarian Cancer Research Consortium.  The Hutch project I attempt to help is an important component of POCRC.  The PI of this particular POCRC project is Dr. Nora Disis.  I have never met Dr. Disis, but from random reading she seems to be a powerhouse.  Once again:  Go get ‘em, Nora!

 

SEVERAL UNRELATED ISSUES

OKAY, DAMMIT:  I AM USING AN OLD LAPTOP LOCATED AT MY BORREGO SPRINGS PLACE, & THE DAMNED THING WON'T LET ME POST PICTURES.  I will keep trying.  And I will post multiple pictures.  Don't abandon ship!

It is Saturday, March 8^th, 2014 and I have been at my place near Borrego Springs CA for nearly three days.  The high temperatures each day so far have approached 90, which seems pretty darned hot to someone accustomed to winter in the Pacific Northwest.  I have been telling everyone who asks that I will re-migrate when it gets too hot down here.  That nearly occurred about this time Wednesday as I descended from the San Gorgonio Pass (elevation 2216 ft.) toward Palm Springs (elevation somewhere in the negative range.)  My jeep doesn’t have air conditioning, but it does have a thermometer that purports to give outside temperatures.  I watched as it rose from 81 in Beaumont ,the summit of the pass, inexorably upward toward 90.  Something in me kept saying “You’re going to go home when it gets too hot: if it hits 90, fling a U-turn.”  Fortunately it topped out at 89, so I continued on my way.  I’ll get used to it, I guess.

Incidentally, they are making a movie here right now, starring Ewan McGregor.   There are about a half-dozen big vehicles (and many small ones) parked at the entrance to the Font’s Point wash.   Nobody seems to know what the movie is about.  Maybe a sequel to Lawrence of Arabia?  Or Dune? 

Unrelated trivia:  I have been here three days and soon will have been out to dinner for the third time.  Don’t feel sorry for me.

Bad news:  The outfit I attempt to help at Fred Hutch has had its grant-renewal application rejected.  The main problem, I am sure, is a tight budget.  We will press on.  I hope to help.

More bad news:  The number one ace in my old racket – paleomagnetism – has just died.  His name is Ted Irving, and for many decades he has been one of the people in this world that I most admired.  I had the privilege of working with him for many years.  He was 88.  Bladder cancer.