Friday, June 27, 2014

THE WIDOW'S MITE: And why it helps.


Portland, 2007
Have your heard the story of the Widow’s Mite?  Well, believe you me, if you had been sent to Sunday School at the Beaumont Community Church in the 1940s you would know all about it.  Here is one version (Mark 12: 41-43). 
Jesus is teaching his disciples:
41 And Jesus sat over against the treasury, and beheld how the people cast money into the treasury: and many that were rich cast in much.
42 And there came a certain poor widow, and she threw in two mites, which make a farthing.
43 And he called unto him his disciples, and saith unto them, Verily I say unto you, That this poor widow hath cast more in, than all they which have cast into the treasury:
44 For all they did cast in of their abundance; but she of her want did cast in all that she had, even all her living.
I was reminded of this when I read a story in the latest Fred Hutch newsletter.  Here it is:
The article mainly concerns research in immunotherapy conducted at the Hutch – which seems to be in the forefront of this sort of thing.  I would be tempted to suggest that immunotherapy is the Next Big Thing in cancer therapy, had I not learned from my friend Cliff (The Truth in Small Doses) how few Next  Big Things pan out.  This effort was kicked off by a $20 million contribution from the family of Jeff Bezos – yes, the ,man who started Amazon  (The Economist recently published a cover illustration showing an astronaut making an Amazon delivery on – I think – Mars.  I guess Bezos has been pretty successful.)
I also contribute to cancer research.  My total contribution so far, divided by Bezos’ initial donation, figures out to about 2.5 X 10-4.  So why do I bother?  Well: (1) Like they say, every little bit helps: (2) I can direct my money toward what I consider the best avenues of research, and; (3) It makes me feel good.  I wish I had Jeff’s money to spread around, but what the Hell – we do the best we can.
This Quest article contains very little science, but you might enjoy reading it anyway.  In fact, the whole issue is interesting.  Just Google Fred Hutch/Quest


Wednesday, June 25, 2014

3-D MAMMOGRAPHY: What's not to like?


Linda bugging Coleman
Portland, 2007
 
Dick Ingwall writes that he is so busy supplying the Hyannis Port Food Bank with squash that he rarely has time to search the NY Time for cancer-related stories, so sometimes I have to do it myself.  Today I ran on the following interesting article, which I will comment on below.
  The gist of the article is that medical technology has come up with a 3-D scanner to use in mammography.  It catches more potential tumors, it uses only marginally more radiation – and it costs a hell of a lot more.  An individual unit will set you back a cool half mil, assuring that only the more affluent venues will have them – at least for now.  It is stated that some (most?) insurance companies will not foot the entire bill, and that the patient may have to ante up an additional $50 or so, which could be a burden to some.  Nevertheless, on balance this seems like a good thing to me, but wait…..  Not everyone agrees.
Back in February I wrote a blog entitled “To Squeeze or Not to Squeeze”.  It discussed results of a trial conducted in Toronto that compared the efficacy of having a mammogram and breast examination together as opposed to having the exam alone.  It was concluded that the mammogram added nothing to overall survival, while producing unnecessary expense and useless anxiety (e.g.,  false positives).  The counter-attack was, of course, immediate and ferocious.  Here is a quick way to access that older blog:
As you can imagine, the same sorts of arguments are being rolled out regarding this new (3-D) wrinkle.  Is it worth the cost in resources and human anxiety?  The battle rages on.
Personally, I would be very reluctant to disregard any promising new technology in the cancer field.  Cancer is too damned serious to discard any potentially useful weapon against it.  Yes, added anxiety and added expense are bad things - but death is worse.  If I were a woman over 50, or a woman with a family history of breast (or ovarian) cancer, I would get my 3-D scan, and screw the extra expense.  Read the article and see if you agree.
For me, daughter Karen said it best:  “Mammography caught mine so I’m all for it.” 
Damned right!


Wednesday, June 18, 2014

LITHUANIAN TRANSLATED: I did my best

 
August, 2007
Happiness is good scenery, a good dessert, and her sister nearby
 
Well, I have been feeling bad about giving up on Dr. Auersperg’s important paper – and the bumptious way I (sort of) dissed her in the appended Comment.  So I made another attempt.  Turns out the article isn’t all that hard to follow – if you have a computer at your right elbow to enable you to look up every fourth word.  I make no pretense of “translating” the whole article, but here is a stab at its conclusions.  One is pretty important.
The subject is the origin of HGSOC – high grade serous ovarian cancer.  The question:  where does it originate?  The answer: probably both in things called OSE cysts (OSE stands for ovarian surface epithelium), and in other things called ovarian fimbriae.  The latter are tentacle like objects  that extend from the fallopian tube toward the ovary.  (Contrary to my former visualization, fallopian tubes and ovaries are not physically attached.  Apparently, during ovulation these fimbriae gently stroke the ovary, inducing it to cough up  one of more eggs, then ever so gently sweep the egg into the fallopian tube – and hence onward, to greater glory.) 
The conclusion: HGSOC can arise in both places.  Why is this surprising?  Because cancers arising in both places are identical, genetically speaking.  This is unusual: cancers arising in different organs usually are genetically distinct.  Dr. Auersperg’s suggestion: They both arise from developmentally identical tissue – the Mullerian duct if you must know.  Moreover, they have not fully “differentiated”; that is, they retain some aspects of stem cell (pluripotent) behavior.  Which is bad, I guess.
Okay, so what do we learn from this?  For one thing – this stuff is so complicated that, at my present rate of progress it will take me 25 years to get up to speed.  That would make me the world’s first 106-year-old Nobel Laureate
More important, it seems to me to be saying that surgery to prevent ovarian cancer better take out both ovaries and fallopian tubes.  At times in the past I think I have suggested otherwise.  It seems that I was wrong.
 


Friday, June 13, 2014

LITHUANIAN


Linda and Florence
2007 Relay for Life
 
Back on July 2nd, 2012, I wrote a blog called “Myc: Friend or foe?”.  The blog was inspired by a news release published  in the Fred Hutch newsletter.  In my juvenile eagerness to get on top of the subject I tracked down and printed the journal article upon which the news release was based – and attempted to read it.  HAH!  As I said at the time, it might as well have been written in Lithuanian.
Well, I am going to attend a seminar at Fred Hutch next Monday.  The principal speaker will be Dr. Nellie Auersperg, from the University of British Columbia.  Dr. Auersperg is a much decorated research scientist specializing in ovarian cancer.  She will be talking about the role of stem cells in the origin of OVCA.  This is right down my alley!  So much is it down my alley that I used Google Scholar to track down her relevant publications.  There, like a ripe fruit hanging from a low branch, was a review article on the subject – and with a free PDF to boot.  I printed it, made a cup of coffee, and sat down to study.  Surely, I told myself, over two years of study will make this article a piece of cake.  Guess what?  (Yes, I know – you’ve long since deduced where this is going.)  More Lithuanian!!  I still have a lot to learn.
So, I will report next Tuesday.  Enjoy the picture.



Saturday, June 7, 2014

THE TRUTH IN SMALL DOSES: At long last

Happy, and beautiful
Okay, I have stalled long enough.  It is time for me to explain why I think that The Truth in Small Doses, by Clifton Leaf, is so important.  In my view it is indisputably a classic; the most important book that I have read since I stumbled on Ted Irving’s Paleomagnetism and its application to (a bunch of things I can’t remember), back around 1959.  Leaf, to me as an ignorant outsider dabbling in cancer research, is the equivalent of Irving, to me as a general geologist getting turned on to paleomagnetism and tectonics.  Yes, Leaf is that good.  Please read his book, and take it seriously.
Like me, Leaf is not a biologist.  He claims that he almost flunked biology in high school.  Heck, that’s nothing,: I didn’t even TAKE biology in high school.  I took physics: biology was for girls, and sissies.
Not only isn’t Leaf a biologist, he isn’t any kind of scientist, nor even a science writer.  At the start of his cancer crusade he was an editor of a business magazine, for Heaven’s sake.  Outsider he may have been, but outsider he is no longer: even someone as fundamentally ignorant as me can tell he knows plenty.  And he lays out what he knows, and what he thinks, plainly, eloquently and – at times – even amusingly. 

Leaf came to his cancer crusade naturally, if tragically.  He lost his mother to a rare intestinal cancer after a long fight, and he himself had to confront Hodgkin’s lymphoma at age fifteen.    He has devoted much of his  energy to the study of the “cancer culture” for the past decade.  He seems to have become well respected in oncology and cancer research circles.  He also has written various articles on cancer, but the best result of all this study and effort is this book.
Now, having burned through nearly 300 words just introducing the subject, I am going to enumerate what I believe to be the most important points in the book.  Then I will read it again and see what I got wrong.

In the first chapter he makes the case that we are NOT winning the war on cancer.  In fact, in his view we are barely holding ours own.  To me, this is the weakest part of the book.  He makes this claim in spite of the fact that most commentators; even many wearing white coats and bearing distinguished titles, evince joy about our progress, and even moderate exuberance.  True, they would admit, more Americans die of cancer every year than the year before, but that can be explained by a growing and aging population.  If rates are compared – “deaths per 100,000” usually is used – much of the apparent increase is erased.  Similarly, if one allows for an aging population – by “correcting” to a standard population, things look better yet.  Leaf criticizes this later procedure on the grounds that the “standard” used can become out of date.  (The standard used currently is the year 2000; often the standard is not changed – while the age structure of the population evolves – for up to 30 years.)  In several passages that I find puzzling, Leaf concludes that things are getting worse, not better.  My thinking is that things are getting much better in some areas and a little better in others.   However, many cancers most, perhaps - still have us stumped.  Overall we are making progress, but at a miserable and, frankly, disgraceful pace.
Why is this? asks Leaf.  Here are his main arguments:

1)      We should be concentrating on prevention and early detection, and not so exclusively on cures for advanced disease.  Pick the low-hanging fruit, he might say.  My view: easier said than done.
2)      The existing machinery  for parceling out Federal research dollars is inexcusably slow, cautious and bureaucratic.  It is based on “peer review”, much like the process we geologists must use to get funded.  However, geology is a luxury; mankind could get along without it quite handily.  Cancer, on the other hand, is a serious subject; one we cannot fluff.  Apparently the earliest  Congressional bill initiating the War on Cancer (1971) called for a separate institute, run by a sort-of  “Cancer Tsar”,; someone empowered to allocate funds, enforce collaboration, keep egos under check; generally run the show like a business.  Elsewhere I have suggested Bill Gates for the job (which, of course, does not exist.)  Steve Jobs might have been even better.  This concept was deep-sixed by a combination of turf-protecting elder statesmen of oncology, and of course Republicans and other small government types shuddering at the thought of yet another Federal agency.  It was decided to simply add cubic kilometers of money to existing granting programs; to smother cancer in money.  This hasn’t worked.
3)       Leaf makes a convincing case, bolstered by many interesting examples, about how the present system stifles creativity, slows progress, and encourages ”incrementalism”; defined roughly as the tendency to creep ahead cautiously, fearful of the adage “first, do no harm”, thereby producing expensive, minute improvements in existing therapies – and not the breakthroughs we so obviously need.  As a stupid, overblown, made-up example:  Imagine that you are a young untenured Assistant Professor at some medical school.  What do you want out of life?  Well, of course you want diseases in your area of expertise to be conquered; for Heaven’s sake, who wouldn’t?  But of more immediate relevance, you want to get a nice grant, thereby demonstrating that you are worthy of elevation to the distinguished rank of Associate Professor, with tenure.  That way you can support your family and maybe even buy a house and a car.  So, what are you going to do?  You are going to submit a “safe” research proposal, that’s what.  You are going to suggest trying something that everybody knows works on cancer A, to cancer B.  Or you are going to show that substituting atom X for atom Y in an existing therapeutic drug will make it work 6% better.  You are going to do something safe.  What you would really like to do is to follow an educated hunch you’ve had for years, that injecting garlic juice into a solid tumor will cause it to wither and die.  No peer-group panel will fund you for that – but, if you could spin a good, scientifically compelling yarn, Steve Jobs might.  Bottom line: the workings of the existing machinery of cancer research stifle creativity.  I take this to be undeniable.

The final chapter is short and vague; in it he seems to be telling us what to do about the mess we’re in.  He writes about “preemption”, which I take to be synonymous with "prevention”.  He also mentions early detection, which obviously should go hand-in-hand with preemption.  There are many cancers for which early detection plus preemption has been shown to work: lung cancer, cervical cancer, even to some extent, breast cancer.  For ovarian cancer you can have your ovaries and fallopian tubes removed after you have hatched your family.  However, many cancers arise from routine genetic “mistakes”, and – so far- you can’t preempt that.  That’s why we need to continue to fund research on cures, and especially work to understand the basic biology of cancer.  The recent work on epigenetics and micro-RNAs (discussed in several previous blogs) offers hope for a  much better future.  But that is quite enough: if you have read this far, please go and buy a small gold star and apply it to your forehead.  I am proud of you.
I may return to this topic in the future.  Be warned.


Tuesday, June 3, 2014

INCREMENTALISM & ZENO'S PARADOX


I am surrounded by beautiful women.
Kristen, Karen, Linda (wife) and Linda (daughter)
Our first house, 501 Cowgill, in the background.
 
Carolyn has sent me a link to a Yahoo news article that is meant to be encouraging – its title is New drugs may make a dent in lung, ovarian cancer    I find it slightly depressing.
These new drugs – specifically the one aimed at lung cancer – give the sufferer a few more weeks of life, at considerable cost in comfort as well as wealth.  Despite this some medical types purport to be excited: incremental progress is better than no progress at all, they say.  I would agree, of course.  However, if your goal is to eliminate cancer then one of Zeno’s Paradoxes comes into play.  If you go half the remaining distance toward your goal every year, how long does it take to get there?
Here is the link:
A side bar to this article led to another, this one specifically aimed at ovarian cancer.  The British drug company AstraZeneca has announced*the results of a small trial using two of their drugs in tandem.  One is a PARP inhibitor; that is, a drug which impedes the ability of fast-dividing cancer cells to repair “mistakes” in the duplication of their DNA.  Presumably if a cell finds itself with DNA that is sufficiently messed up it spontaneously croaks.  The other drug inhibits “angiogenesis”; the process whereby cancerous masses recruit new blood vessels to provide themselves with everything they need to thrive.  Used individually on patients who had relapsed after standard chemo, each of these drugs prolonged the period of remission.  Used together they did an even better job.  What is called “progression-free survival” was increased by over eight months by use of the combination of drugs.  The effect on ultimate mortality has yet to be established.
Again I could invoke Zeno’s Paradox, but I won’t.  Linda had a long period of remission.  It was among the best periods of our life together. 
Here is the link:
My attitude toward incrementalism is shaped by arguments in The Truth in Small Doses, which I promise to review properly very soon.  I need to read it for the third time and write notes in the margin.
*AstroZeneca is under “attack” by Pfizer, which wants to devour it.  It seems that the early disclosure of these drug-trial results was meant to reassure stockholders that all is well.  That doesn’t mean that the results are flaky, of course – just hastily revealed.