CANCER SCREENING: WHEN IS IT WORTHWHILE?

A Michigan Fall

She loved dry leaves

Essentially the entire issue of the November 27, 2012 NCI Cancer Bulletin is devoted to a discussion of cancer screening.  As both of the groups I try to help are engaged in just that, I read it with interest (and more than my usual comprehension.)  It is really good stuff, and (as always) I urge you to read it.  However, I know you won’t, so I will toss out a few observations and maybe some analysis.  I am tempted to weave a few egregious lies into some future blog, to see if anybody notices and checks.  I promise not to do it this time, though.

First, there is a long piece by Dr. Virginia Moyer, who is the head of the USPSTF: that is, the United States Preventative Services Task Force.  This is the group that has caught so much flack over their recommendation that healthy men not be screened for prostate cancer using PSA.  (All males over 60 will know very well what that is.)  To get current with the Prostate Cancer Wars, re-read the blog of the same name (3/27/12) and especially the appended Comments. 

It turns out that the USPSTF is an all-volunteer group of 16 and is substantially independent of control by government or anything else.  They were set up in 1984 to counter the perception that the medical community was neglecting prevention for cure.  They make recommendations for preventative measures, including screening.  They have had their bad days; one especially bad occurred in 2009, when they issued guidelines for mammography.  They recommended that women under the age of 50 – and over 75 – be not screened at all.  The AMA went ballistic.

Dr. Moyer does a good job of explaining their reasoning.  Any screening regimen involves false negatives.  False negatives engender anxiety, discomfort, and expense.  In the case of cancer, there are some which are easily cured – and others that are incurable.  It doesn’t make sense to screen for these.  Pancreatic cancer is a case in point; there is no viable treatment.  For the rest of cancers, screening might save lives, and whether to screen or not is a judgment call.  I reason that ovarian cancer is one of these.  If caught early, it’s completely curable; if later, rarely so.

The problem here is that one does not know how to value a few lives saved relative to a whole bunch of needless treatment and anxiety.  I tend to think that one live saved easily balances a mountain of anxiety, discomfort and expense.  But that’s just me. 

Another great article concerns the role of statistics.  You know Mark Twain’s famous analysis of statistics.  Well, it seems still to be at work.  Some statistics show that the life-span of cancer victims from diagnosis to death has lengthened dramatically in recent decades.   Good news.   But there is a problem: does this represent better treatment, or is it simply an artifact of screening?  For instance, assume treatment for cancer X is totally ineffective.  Persons not screened will be diagnosed later than persons in the screening arm of the trial.  Thus, the diagnosis-to-death interval will be shorter for the first group than the second, and it will appear the “progress is being made”, when in fact it hasn’t.  In fact, the screened group is less well off in that they had to live longer with anxiety.  So, I guess that screening is useful only for those cancers that are easier to cure in an early stage.  Ovarian is one of these.

NOT OC: TAKE CARE OF YOUR TEETH!

Whitman Mission

Kristen's graduation from Whitman college, 1986

I thought she looked beautiful in that dress.

For nearly 80 years people have been telling me to take better care of my teeth, and I have ignored them.  Probably since about age 4, when my mother stopped brushing my teeth and turned the job over to me, I have hurried through toothbrush time as quickly as possible.  Brush each tooth up-and-down?  Too much trouble, I mostly brush sideways.  Floss?  Forget it.  Check-ups every six months?  Only if somebody else made the appointment and then bullied me into keeping it.  Well, the chickens have come home to roost, to coin a phrase.  I am now paying the price.

A brief history:  At about age 12 I had my teeth straightened.  The braces were on for what seemed like many years (two, I think.)  There was a routine to follow to keep my teeth clean despite all that metal in my mouth.  Unless my mother nagged me I usually ignored it in favor of playing outside or getting to bed early.  The result: when the metal was finally removed I had 22 cavities, with a half-dozen or more yearly thereafter (until there was little tooth left to rot.)  When I went into the army all my left-upper molars were yanked by German dentists.  This shifted the chewing burden to other teeth, which – one by one – succumbed to the additional pressure.  The upshot is that I was finally down to seven teeth on my upper jaw, until this morning.  Now I have a full complement, and I hate it.

Yeah, I decided to get a removable plate.  (They call it a “flipper”; why, I don’t know.)  As I sit here writing my tongue never ceases to explore this alien thing in my mouth.  The coffee I am drinking tastes funny.  When I say the letter “s” it sounds like a snake’s mating call.  I am assured that it all will be better bye and bye, but they equivocate over how long “bye and bye” may be.  They also assure me that “not much taste” will be lost owing to the fact that there is a plastic coating covering much of the roof of my mouth.  What does it avail to acquire teeth able to chew a steak, if you can’t taste it?  My father had a full upper plate in his 50s and he managed, so – I guess – I will too. 

I should remark that I had two alternatives.  One was to do nothing and live off soup and mashed potatoes for the rest of my life.  The other was to get implants in strategic places: they estimated four would do.  Cost estimate: $30,000. `   

So, take care of your teeth.  You never know how much you need them until they’re gone.





MICROBES MAKETH MAN

Our 28th Anniversary

Linda is playfully decked out in Mexican blouse and Navajo jewelry

and holding her bridal bouquet!

I returned from Borrego Springs Friday.  When my good friend Joanne Ingwall dumped me off at the Palm Springs airport the temperature was 76, the sun was hot, and there was no breeze.  Good T-shirt weather.  When I got off the plane in Bellingham the temperature was 48, there was a light drizzle, and the wind was blowing.  Sweater and raincoat weather.  This dramatizes the dilemma of the long distance north-south commuter; there is no way to avoid being dressed incorrectly at one end or the other.  But I shouldn’t complain; the weather gives me an excuse to stay inside and clean up stuff I have been avoiding for months.

Among the things I cleaned up this morning was a stack of old magazines.  Included among these was the August 18^th issue of the Economist.  It had a weird version of Da Vinci’s Man in a Circle painting on the cover, with the caption “Microbes Maketh Man”.  This rolled me back on my heels because it sounded very like the New Yorker article I had just blogged about: “Germs are Us”*.  Sure enough, it was: the two deal with precisely the same research.  Of the two the Economist version is longer, explores the topic much more thoroughly, and is nearly as amusing.  You could do worse than to read it yourself: online at www.economist.com/node/21560523.  I excuse myself for missing it because it came out at the precise time that I was fixated on my broken ribs. 

So, the Economist version of the story digs into the subject much deeper.  It appears that the so-called “microbiome” (the sum total of our single-celled inhabitants) may in part be responsible for obesity, under-nourishment, heart disease, diabetes, and even multiple sclerosis.  But not cancer, darn it; manipulating our bugs won’t cure cancer, although we all wish it would.

Some gee-whiz facts:

            An adult human is composed of about 10 trillion cells.  In his/her gut alone live 100 trillion bacteria.

            Together the micro-organisms that call us home weigh more than 2 lbs.

            We inherit about 23,000 genes from our parents.  If we include as “us” our microbial element we have more than 5 million.

             

There is far too much stuff in this article for me to summarize effectively; go read it yourself.  And – although there is no mention of transplanted earwax – fecal transplants are discussed at some length – although, being a British publication, the word is "faecal".

As an aside, directed at New York Times readers and other liberals:  The Economist is safe to read.  Yes, it likes market forces, limited government, moderate levels of taxation, and tends to be slightly libertarian, but it is no Rush Limbaugh nor even the Wall Street Journal.  It endorsed Obama.

*Actually, in a Comment to "GRANDMA'S CURSE"

CROWDSOURCING: A new tool.

In an English tavern.

No, that's not Guiness.  It's her coke.

 

 

Perhaps inspired by  various TV reality shows, the NCI has instituted a program wherein a cancer-related “problem” is defined and “teams” from around the globe invited to work on it.  Then, after the lapse of some time, NCI (or somebody) decides who came up with the best solution and rewards them – hold your breath – with a trip to San Francisco and a chance to publish a peer-reviewed paper in a prestigious medical journal.  It may seem like I'm scoffing, but I'm not:  I think it is a very good idea. 

The projects I just read about are part of a larger program called DREAM:  Dialog for Reverse Engineering, Assessments and Methods.  DREAM engages in “crowdsourcing”, which means taking advantage of expertise and knowledge across the research community to attack specific problems.  NCI-DREAM is a subset  focused on several aspects of breast cancer.  Apparently 52 teams elected to participate.  They were given a standard genome, then invited to: (1) using the genomic data and, I guess, anything else they could drum up, predict  the response of 18 breast cancer “lines” to 31 previously untested drugs, and (2) predict the activity of pairs of compounds on diffuse large B-cell lymphoma (again using a standard cell line.)  The value of this sort of research to individualized cancer treatment is pretty obvious.

A team from Helsinki won sub-challenge (1); a team from Texas . #2.    

There also is another challenge afoot, one to predict breast cancer survival rates.  It uses something called “computational biology”.  Around every corner in a cancer research institution one bumps into a statistician, a computer programmer, or this thing called a computational biologist.  And to think I  used to look down on biologists as hopelessly non-quantitative!  Like, geology uses higher math?

P.S.  I am back from Borrego Springs until after Christmas.
P.P.S.  I have used 88 pictures so far, and I am beginning to forget which.  If you catch me doubling up, please let me know - I have many I want to use.  For those who don't know:  myrlbeck@msn.com. 





GRANDMA'S CURSE

Linda Joyce Beck, mountain explorer

The Economist really is an excellent news magazine.  Not only does it discuss important matters from all over the world, often in an amusingly cynical way, it also publish interesting stories about medicine (as well as books, science in general, and other such matters).  For instance, in the November 9^th issue, on page 82, there is a short article you all should read*.  Its title is “Grandma’s Curse”.

Seems some scientists working in Los Angeles have discovered something important and very surprising about smoking rats.  Actually, the rats themselves didn’t smoke; rather the researchers, headed by one Dr. Virender Rehan, took pregnant mother rats and smeared them with nicotine.  Then they observed the outcome.  As was expected and well understood, baby mice from the F1 generation all showed smoking-related asthma-like symptoms.  Why not ? – they were developing when their mothers were dosed.  The surprising observation  made by Dr. Rehan and his colleagues was that even baby rats of the F2 generation displayed the same symptoms.  This was unexpected because neither these baby rats nor their mothers had been directly subjected to nicotine.  Obviously, Rehan is waiting eagerly for the F2 ratlets to grow old enough to produce an F3 generation.  If they, too, show the symptoms of smoking a Nobel awaits.

What this experiment seems to show is that these rats were capable of inheriting an acquired characteristic.  Inheritance of acquired characteristics – Lamarckian evolution – supposedly  was exploded by Darwin.  Francis Crick, famous co-discoverer of the DNA double helix, also is well known for denying the possibility of genetic information becoming modified by the environment or experience (baring mutations, of course.)  So Dr. Rehan is proposing that it is not the rat DNA that is being modified, but rather things they call “epigenetic factors”.  I don’t really understand epigenetic factors.  However, it seems that stuff secreted by the mother and placed into the egg influences the early development of the embryo in an all-important way.  The guess is that nicotine inhibits the activity of one or more of these “maternal determinants” – although I still fail to understand how this extends to the F2 generation.  I await enlightenment.

If you want to see the original article, go to Google Scholar, type in Virender Rehan,  then restrict your search to articles published in 2012.  If you do this and read the article, please explain it to me.

Anyway:  the take away message.  For one more reason, don’t smoke.  Especially if you plan to get pregnant.  Your grandchildren will thank you.

*Or, you can get it on line: http://www.economist.com/news/science-and-technology/21565573-some-effects-smoking-may-be-passed-grandmother

PROGRESS

Font's Point

As many of you know, the group I am trying to help at Fred Hutch is focused very strongly on discovering one or more blood “biomarkers” which, alone or in conjunction with other evidence, will indicate – with a high degree of reliability – the presence of early-stage ovarian cancer.  This has proved to be difficult, and at times the difficulties leave me a bit discouraged.  So I am happy to find that a similar test for early stage lung cancer has been found, and promises to save lives, not to mention reduce exploratory surgeries (and thus suffering, and cost).  Maybe my group will be so fortunate.

The lung cancer people work at something called Cizzle Biotech, in Yorkshire, U.K.  (You can’t help but like that name.)  They find that a protein they call Ciz1 (Cizzle 1?) is present in copious quantities in early stage lung cancers  but not at all in neighboring tissue.  Furthermore, they can obtain high “specificity” using only a tiny amount of blood.  They are stoked.  I used to think that lung cancer was an inevitable death sentence, but apparently if caught early enough it isn’t.  Good for our British friends.  Of course, there are hurdles to be leaped involving technology, and probably regulatory issues, but they will be properly leaped over in time.  Let’s hope the same happens for other cancers, including ovarian.

On another subject entirely, I spent the morning at the first general meeting of the Anza-Borrego Paleontology Society.  I gave a talk, about which the less said the better.  The proceedings were dominated – or should I say contaminated – by a representative of the Cal State Parks people, who described in painful detail the new forms all new volunteers MUST fill out in order to be allowed into the program.  When I joined there was nothing like that, and if I were ABOUT to join now I would think twice about it.  Some cabal of bureaucrats in Sacramento has extended its turf, at the expense of reason, common humanity, and the public at large.  I felt sorry for the guy charged with telling us all about these new impediments to paleontological progress.  I complained lately about the Swedish volunteer requirements (several times in fact.)  They are as nothing compared to this.  Fortunately, I’m grandfathered in.        

   

NOT OC: I AM A SORRY SACK OF STUFF

Linda Joyce Beck, desert explorer

But not in the summer.

Do you know that there actually are people – most of them Europeans, with Germans said to predominate – who come here in the summer to see what it is like to hike in 110+⁰ heat?   Even some Englishmen are involved.  (You know about Englishmen, and mad dogs, of course.)  Miraculously, some of these idiots survive.  At least the Germans should know better.

I write this because I just came back from walking up Hellhole Canyon, in what seemed like 110⁰ heat.  I walked for only a bit more than an hour – and I am exhausted.  To make matters worse, when I got back the lying bastard of a thermometer in my jeep said the temperature was only 72⁰!  (If it wasn't at least 100 degrees I will eat my walking stick.)  And to make matters doubly worse yet, my Internet is down.  (If you see this you will be able to deduce that I figured out what is wrong.) 

So now you understand the title of this blog entry.  I think I am being punished for voting for the wrong candidate today.  In my view Obama doesn't deserve a second term and Romney  doesn't deserve a first term – so, as usual, I voted for the Libertarian.  Since  Reagan the only candidate I have voted for with real conviction was McCain.  It may be that, in getting old and tired, I also am turning into a curmudgeon.  Can that be?

MITOCHONDRIA, GENETIC ENGINEERING, ETHICS: is there a conflict?

Linda points to a 2 million year old camel tooth she discovered whle hiking in the desert.

Yes, camels originated in North America, then migrated, and went extinct here

Where is that tooth located?  I'll never tell..

It hit 91 in Borrego Springs today.  I did my walk early in order to avoid the worst of the heat.  The desert I walk through not surprisingly is nearly devoid of trees, and thus of shade.  If it is 91 in the shade, you can bet it is a hell of a lot hotter in the sun.  That’s why I have been getting my exercise in the early morning, before breakfast.  Fortunately, it is supposed to drop to more tolerable temperatures later this week.  I suspect that those of you in Bellingham (and Eureka) would trade your wet, windy 50-degree weather for a little Borrego sunshine – not to mention those of you in Michigan, either digging out of a snowstorm or preparing to do so.  Only blog followers in Chile would be content to stay put; it is early spring there.  I can’t predict how my loyal readers in Latvia would feel –the blog has suddenly developed a following there, according to the Google blogspot “hit-counter”. Go figger!  Anyway, I will fly back to Bellingham on November 16^th and stay there through the holidays.  I should get my fill of PNW gloom pretty easily.

You will be excited to learn that I have finished the CITI exams and am nearly ready to be accepted as a volunteer with the MRC (Marsha Rivkin Center for Ovarian Cancer Research.) I still have a fat form to fill out and an interview to survive, but I should be okay.  My career in unskilled clerical labor is about to launch!

Okay, about mitochondria.  You may know what these things are.  They are “organelles”, meaning tiny sacks of stuff, floating around in most human cells.   Their primary function is to act as dynamos, converting the energy in carbohydrate molecules obtained from the food and alcohol we consume – into an energy-form suitable for driving cellular processes.  Without functional mitochondria, we die.  Interestingly, mitochondria are inherited only from the mother.  Equally interesting is that they have their own genes: only a few dozen or so compared to the several tens of thousands contained in the nuclear genome – but they still have them.  What these mitochondrial genes do I haven't much of  a clue; if I ever find out I will put it in a “comment” to this blurb.  You may have heard of “Eve”, the Ur-mother of us all and chief fact supporting the “out of Africa” hypothesis about where we all came from.  She was deduced from analysis of patterns of variation in mitochondrial DNA.

Anyway, there are some nasty diseases associated with damage to mitochondrial genes; the list is very long, and depressing.  British scientists, however, have shown that hereditary mtDNA diseases can be prevented by transplanting healthy genes into the mother’s mitochondria.  The resulting offspring would have, in effect, two mothers.  However, as the maternal nuclear DNA would all be donated from the lady who will raise the kid, nobody but the parents and a whole lab-full of biologists would ever know.  The method needs testing – and therein lies the problem.

Britain, the U.S., and probably every other country that know how to make laws, prohibit “genetic engineering” as applied to human beings.  God, don’t I know it – the two CITI courses I just suffered through talked about the ethics of things like that until I felt like pulling out my sparse but precious crop of hair!  In a sense, this is “human genetic engineering”.  It also is a potential medical breakthrough that promises hope and eventual relief to lots of unfortunate people.  So once again there is a conflict between medical progress and strongly held ethical beliefs.  The Economist – from which I got some of this information - says that this dispute must be resolved in favor of continued research.  I agree.