Saturday, August 1, 2015

CANCER AND EVOLUTION

In Hawaii
She loved water.  Not me.  No, wait - that didn't come out right.
 
The NY Times provides a summary of a recent paper that treats of what you might be tempted to call the “philosophy of cancer”, by which I mean the nature of such aberrations as viewed in light of evolution.  All that sounds thick and stifling, but that would be an unfair assessment of this short article.  You should read it. 
http://www.nytimes.com/2015/07/28/science/cellular-cheaters-give-rise-to-cancer.html?ref=health
The gist, honestly (but perhaps erroneously, in part) summarized
Multicellularity (as in us, fruit flies and grapefruit) has evolved from single-cellularity at least seven times – mostly in braches of life I have never heard of before.  It evolves because it offers certain survival benefits.  However, multicellularity require sacrifice – cells must give up their absolute freedom to behave as they see fit, and instead assume certain definite roles and functions.  What we call cancer is simply one way to describe the result when a cell rebels against these restrictions and begins to do what IT wants to do, rather than what the ORGANISM requires.  The organism has devised many ways to snuff out such a rebellious cell, but sometimes they fail.  And that’s about it. 
I have pondered these concepts for, oh, easily 30 minutes, and I am somewhat puzzled.  Evolution is largely based on natural selection: everything else equal, that unit prospers that is most aptly suited to its environment.  The key is survival.  The authors of this article (web address given below) regard the success of a tumor as a benefit to survival – of the tumor.  However, in the end the organism dies, and so does the tumor.  Rotten kind of “success”, I would say.
Here is the original article.  I am going to study it and see if deeper understanding evolves.  However, my great grandkids are visting (with their mothers, of course), so I have better things to do right now.
 
 
 


Tuesday, July 28, 2015

COMPLICATIONS AND MYSTERIES

Linda and Kiley Henner
Hippy Era
 
Now, here’s one for serious people only.
If you are like me you always have assumed that cancer is the result of a mutation somewhere, in one or more genes.  These guys say that’s not precisely true.  They have been studying the effects of an “imbalance” of two proteins as a driver of certain types of cancer, including mucinous ovarian cancer.  The two proteins are “plc-gamma-1”, and “grab-2” (hereafter p and g).  These two proteins have a controlling influence on one of these things called “pathways”; in this instance a pathway called AKT.  AKT tells a cell to proliferate.  In the case of the “right” balance between p and g, AKT is kept within healthy bounds – cancer does not develop.  However, if p predominates, AKT goes wild. 
So, why does the balance get upset?  Apparently it isn’t owing to a mutation of the genes responsible for either p or g; they checked for that.  So, in the words of the King of Siam, “Tis a puzzlement”.  I have read the article a couple of times, and I can’t detect that the authors (from Leeds, England and MD Anderson in Texas) have resolved the puzzle.  I offer a suggestion:
Maybe the concentrations of p and g both fluctuate randomly, within certain limits and with (possibly) different time scales.  It might happen, then, that p (which promotes proliferation) hits a maximum just at the time that g (which discourages proliferation) arrives at a minimum.  Result: imbalance.  And if the imbalance is large enough and last long enough, AKT does its thing and causes cancer.  This is modeled on how rocks acquire a viscous remanent magnetization, for all you geoscience freaks out there. 
Whatever.  Anyway, it would seem that the p to g ratio could be used as a biomarker for cancer, and that injections of g should slow or halt some kinds of them.  No doubt I’m missing something.


Friday, July 24, 2015

DRUGS COST TOO MUCH. What can we do about it?

Linda and flat-lying sandstone
Guess where
 
I have written about this before, as you certainly remember:
Newsweek has published another article on the subject, which contains some interesting examples of severely overpriced cancer drugs and some intelligent speculation about what might be done to remedy the situation.  The facts are well know, I hope:
1)      New drugs are very expensive to develop, mainly because of the intrinsic difficulty of doing biochemistry at this level, but also because of all the bureaucratic hoops that must be jumped through to bring something new to market.
2)      FDA rules require Medicare to cover any approved drug, no matter if it is or is not a significant improvement on existing standards of care.
3)      Once a drug is approved, it is the drug company that sets its price – no free-market competition is involved.
4)      Cancer drugs frequently cost much less in other countries, but may not be imported.  (Why are they so much less expensive?  Well, if I was from Singapore, say, and wanted to get into the Gleevec game, for instance, I would visit the United States, buy a dose, and then fly home.  I would then hire some smart organic chemists to analyze the stuff, and I would raise money to build a plant.  Thus, I could crank out my version of Gleevec with no development or regulatory costs whatsoever.  No wonder I can undercut the price of Novartis, the parent firm.  Actually, Gleevec is a bad example because Novartis is a Swiss company, although the drug in question seems to be manufactured in East Hangover, New Jersey.  Full disclosure: I own stock in Novartis and wish I had a lot more.)     
So, anyway, read this article and think about the problem.  Write some comments.  As the population gets older and the docs get smarter, medical costs are not going to just wither away.  Something needs to be done.
 
 


Wednesday, July 22, 2015

OUR PROKARYOTIC FRIENDS

LINDA, ENJOYING THE WEATHER AT THE TOP OF EUROPE

Not all bacteria are bad – in fact, many of them are among our very best friends.  For instance, we couldn’t properly digest our food without certain gut bacteria, including the much-maligned E-coli.  It turns out that certain other bacteria – including our old enemy Salmonella – may offer a cure for cancer.  The way this works is laid out in this interesting little article:

http://www.newsweek.com/programming-bacteria-kill-cancer-cells-355474

There are other useful bacteria as well, and some of these may be useful in “hacking” the immune system in such a way as to alert it to the danger of cancer cells.  How they do this is beyond my ken, but apparently it’s possible.

However, another twist seems to be to modify the bacteria itself in such a way as to make it toxic to cancer cells but friendly to the rest of the organism.  Apparently this is in the experimental/developmental stage – meaning that many mice are dying for a good cause.  As a relative once commented: Bless the little mouse that gives its life for ours.


One thing I learned from this article that you would have thought I had already figured out: immunotherapy, triggering as it does the natural immune system, leaves behind it a record of whatever bad guy it met and conquered.  Thus, if the f…ing cancer tries to return, it is toast!

Tuesday, July 21, 2015

ISOLATION, ICELAND, AND GENETICS RESEARCH

Two unusually clean copper miners
 
Here is an article that combines two of my favorite things – Iceland, and genetics research.
http://www.newsweek.com/vikings-might-slay-cancer-354895
(Don’t access it more than five times, or Newsweek will insist that you subscribe!).
You probably know the Iceland story, at least broadly.  Way back – say about 750 A.D. – Irish monks seeking solitude sailed (in skin boats!) out into the north Atlantic, hoping to find islands.  Some of them reached Iceland and set up shop (settled in caves, huts or volcanic overhangs, and began to pray and/or meditate.)  But, wouldn’t you know it, barely a century passed before Vikings from Norway arrived, seeking free land.  They brought with them people they had kidnapped in Ireland, to serve as slaves.  The pre-existent monks were either absorbed, fled, or exterminated*.   Henceforth these Viking-Icelanders spread throughout the island, cut down all the trees, occupied all the arable land, and – in biblical language – went forth and multiplied.  At one time there may have been as many as 20,000 Icelanders busy farming and multiplying.  But then came what is sometimes called the Little Ice Age, and most of them died off.  Ever since, Icelanders have been keeping meticulous records of who is related to whom; for instance, there is a document – the Icelendingabok – that dates births, deaths and marriages well back into the Middle Ages.  To avoid in-breeding, there is even a web site that you can consult before you ask a girl out on a date (or accept the offer): is your potential partner a second cousin thrice removed?  The motto:  Bump the phone before you bump in bed.
Well, what has all this to do with genetics research?  Quite a lot, it turns out.  For instance, using these data you can determine which lineage is particularly susceptible to ovarian cancer, say, or some other disease.  Then you can search that lineage for prevalent mutations.  This is possible because Iceland has embarked on a program of genetic sequencing: 2,636 Icelanders have had their genomes completely sequenced, and another 104,220 partially so.  In a cohort of only about 350,000 people, that’s a whopping big sample.  The program is called DeCode.  Their current focus is on the genetic attributes of Alzheimer’s disease and certain kinds of cancer.  I hope for rapid progress.
Karen and I noticed evidence of genetic similarity in our brief visit. Notably, there were an abnormal number of very large men with dark hair, a benign smile, and an air of easy self-confidence.  They were peaceable and friendly – but you easily could imagine them with a skin shield in one hand and a bloody battle ax in the other. 
 
*Another possibility, rarely discussed.  They were monks, implying that they were all men.  There were no native maidens.  Maybe there was just one wave of colonization, and then they simply died of old age.
 


Monday, July 20, 2015

MORE EVIDENCE THAT TV AND THE COMPUTER ARE TOOLS OF THE DEVIL

Linda and Eben Henner, a long time ago.
Eben is now a responsible husband, father, and rock-climber.

It appears that nature has determined that men are destined to sit, read and watch TV while women run around and take care of them.  At least that is one conclusion one could (plausibly, but with effort) draw from a new prospective study of 69,260 cancer-free men and 77,462 cancer-free women followed for 17 years as part of the American Cancer Society’s Prevention Study II Nutrition Cohort.  During that period 18,555 men and 12,236 contracted cancer – type unspecified.  More than just nutrition must have been observed, however, because this article

http://www.medicalnewstoday.com/articles/296883.php

reports that simply SITTING was correlated with (and a cause?) of multiple myeloma, breast and ovarian cancer in women, whereas there was no correlation at all between sitting time and cancer in men  It also was noted that excess standing time had definite ill-effects on the health of both sexes.  So maybe we were intended to spend our lives in bed, tended by robots?  Not much fun, it seems to me.

By the way, this piece of news seems to resonate throughout the writing class – it has appeared three times so far, in journals, ranging in respectability from Medical News Today to a British tabloid.

My daughter Kristen, her long-time partner Joe, their three cats and Sunny, a talkative blue micro-parrot will be staying with me until they find a home – they have moved back to Bellingham from Flagstaff, Arizona – good for me, certainly and, I hope – good for them.  Oh:  I forgot to mention Buddy, the horse.  He is not staying with me, at least not yet.

Thursday, July 16, 2015

TREES ARE OUR FRIENDS

In the desert near Tucson, about 1985

We must cherish and protect our trees.  Why?  Well, beauty, shade and nurture for the soul are starters.  The fact that they absorb carbon dioxide and thus combat global warming is another.  And some trees give us cancer-fighting drugs.  End of argument.
You all probably know about Taxodium brevifolia, the Pacific yew, from which is derived Taxol, a common chemotherapy agent.  (Nowadays Taxol is manufactured otherwise somehow, leaving the noble yew to grow huge and combat global warming.)  Now, according to the following article

http://www.economist.com/news/science-and-technology/21657352-optical-switching-may-abolish-side-effects-cancer-drugs-colourful

science has discovered another oncologically useful tree (the South African bushwillow) that produces an organic chemical (called combretastatin A-4) which deals swift and certain death to cells that are trying to divide, as cancer cells do all too frequently.  This stuff has been known for some time but, because it deals death to any cell it encounters, not just cancer cells, it is little used (or used in weak dosages) because of its powerful side effects.  Now, two very clever people in Munich have figured out a way to turn combretastatin on or off – that is, from a harmless to a potent structure - using a simple and non-destructive beam of light.  The trick then will be to give the harmless stuff to the patient, then turn on the potent form in the cancer, but nowhere else. 

You should read this little essay; no advanced biology required.  The article ends with the warning that few clever ideas that originate in the lab ever emerge in the clinic, and that is true.  Maybe this one will fall by the wayside too.  However, it warms my innards to be so often reminded that there are so many extremely able people working on the cancer problem.