Thursday, October 23, 2014

THE FRED HUTCH NEWSLETTER

Enjoying a Michigan Autumn
With her brother Richard, niece Rebecca, and several Hunsinger boys
What looks like a bald-headed walrus surfacing in her lap actually is your faithful correspondent
 
I don’t get the Ukraine.  It is a poor country, engaged in a civil war.  Its people speak a Slavic language, written in Cyrillic script.  And yet I have more “hits” from Ukraine that fror any country other than the United States.  Twice as many Ukrainians ostensibly read my blog than do citizens of all English-speaking countries combined, again excusing the United States,.  What gives?  Obviously there aren’t dozens or hundreds of Ukrainian citizens avidly consuming my blog.  Some computer algorithm is doing the “reading”.  What ever can it be looking for?
The Fred Hutch newsletter is out, and you can read it by clicking on https://bay172.mail.live.com/?tid=cm1fAI-XxZ5BGUuWw75af65g2&fid=flinbox. 
There are several important articles in this issue.  One describes how Hutch scientists have developed a “tumor paint” which somehow will cause tumor cells to glow.  This should make it easier for surgeons to detect all the places where a spreading tumor is lodged.  The molecule that allows this was isolated from, of all things, a scorpion!
Another significant bit concerns the “Angelina Jolie effect”.  As you probably know, this prominent movie start went public about her troubles with breast cancer and urged women at elevated risk to get tested for the BRCA gene mutations.  Apparently since she did this, the number of women complying has doubled.  Good for her!
There are, of course, the usual pleas for money.
Several other articles in this edition of the Newsletter deserve mention, but my shingles hurt and I’m going to swallow two pills and take a nap.


Monday, October 20, 2014

ANOTHER DISMAL LITTLE ESSAY

Linda and the Kelly girls on Orcas Island
Impudent, but -- nice hair
 
A recent Wall Street Journal  raises some difficult and interesting  questions.  Here it is:
At least the questions are interesting to me.  I am writing this as a tool to clarify some issues in my head.  You are free, even encouraged, to correct or dispute my musings.
So, a hypothetical question:  What if a particular mutated gene made it inevitable that you will come down with an incurable, fatal disease?  Would you want to know if you had the mutation?  How about if the disease were curable?  Well, for me, the answers are, respectively, “no”, and “yes”.  If I’m certain to contract the disease and die, why would I want to go through life worrying about it?  There would be some small advantages to knowing, involving arranging your life to minimize the impact of your death on your family, but they would hardly repay living years or decades in a state of constant low-grade anxiety.  So, don’t tell me.
However, what if the disease were curable?  Then, of course I would want to know.  Then I could arrange close monitoring, enabling treatment to kick in in the early stages of the disease, when the chances of cure usually are greatest.  So, tell me.
These musings concern diseases that are inevitable, if you have the targeted mutation.  But what if the mutation merely predisposes you to the condition, such as the BRACA mutations in the case of  breast and ovarian cancer.  In my view, the situation doesn’t change: if the disease can’t be cured I don’t want to know about it, but if it can be cured, even if there is only a forlorn hope of cure, then tell me.
God!  This is one of the bleakest and most depressing blogs I have ever written!  I apologize.  Maybe my mood is darkened by the fact that my shingles hurt, and that a power outage last night fried my cable TV connection as well as wrecking communication between my computer and printer.  I have spent most of the day working on these twin problems: the computer problem is fixed, but my TV still is on strike.
But here is something from the WSJ article that might interest you.  Apparently there is a gene (PSEN1) that, when mutated, leads inevitably to early-onset Alzheimer’s.  (Note: only 2% of Alzheimer patients have this genetic flaw, but if you have it you are up a creek.)  So, let’s say your mother died of EOA (early onset Alzheimer’s.)  If she passed the gene to you, your goose is cooked.  But suppose that you want to have children but are terrified of passing your mutation on to them.  In the case of one woman undergoing in vitro fertilization, the lab tested her eggs for the mutation, and then implanted the ones that were clean.  All this without informing the mother whether or not she was positive for the mutation.  She chose not to be told if she would get EOA, but she knew her children are safe.  What would I do, I wonder?  What would you do?
This stuff is abstruse but not hypothetical.  Gene-sequencing techniques are improving so fast (and becoming commensurately cheaper) that inevitably we will have to deal with lots more of it in the future.


Friday, October 17, 2014

SHINGLES

Linda and the twins, on a winter day in Michigan
 
I am enjoying a world-class case of shingles right now, so I haven’t much energy to spare for digging into the cancer literature.  Ebola has chased all other health-related stories from my usual newspaper sources, and Dick Ingwall seems to be in transit to Borrego Springs so I haven’t been able to count on him.   Rather than sit around feeling sorry for myself, I decided to see if other people are busy in the ovarian cancer field.  I used my old friend Google Scholar, and confined my search to articles published since January 1, 2012.  I searched for “exact phrases” but left the author line blank.  It seems that in the last 34 months there have been 37,400 papers published containing the phrase “ovarian cancer:.  Getting more specific, I find that over 1000 of them relate to early detection, slightly over 300 deal specifically with prevention, and the rest – presumably – with therapy.  I guess I should be pleased that there is so much attention being paid to ovarian cancer, but I am mildly disappointed that early detection and prevention are so conspicuously under-represented.  And that’s all the energy I have for today.  My main reason for posting  this blog, if you must know,  is to share this wonderful picture.


Tuesday, October 14, 2014

THE AMERICAN ASSOCIATION for CANCER RESEARCH


Linda and her Mom
Two beautiful women
 
For more than two years I have been scouring the world of cancer news, looking for information that I can pass on through this blog.  Many of you have helped, by alerting me to items published in the NY Times, Wall Street Journal, local newspapers, various news magazines, and on line.  Somehow, though, I have managed to remain completely ignorant of what may be a totally wonderful and convenient way to keep up with cancer research: the newsletter of the American Association for Cancer Research.  Somehow I have managed to remain unaware of even the existence of this organization, even though I conducted an intensive computer search for cancer foundations for the Rivkin Center just a year or so ago.  Anyway, I blundered onto the AACR web site just today, and discovered that – for free – I can receive a monthly update of advances in cancer research.  I just signed up, so I can’t tell you how valuable this e-newsletter will turn out to be, but I am hopeful.  If you want to sign up, here is the web address:
I know that all of you have better things to do with your lives than to join me in my inept but persistent crusade against ovarian cancer, so if you ignore this tip I forgive you in advance.  However, some of you might find it useful.  And, this is another excuse to post a picture of Linda.
 


Friday, October 10, 2014

THE CANCER-RESEARCHER WANNABE'S BOOKSHELF

Beach time
Wasn't she beautiful?
 
 
In my continuing attempt to learn about cancer biology and cancer therapeutics without really studying, I have purchased and read a good many “popular” books.  Perhaps you would like some recommendations?  No thanks, you say?  Well, I’m going to give them to you anyway.  That way you will have no excuse. 
 Those books I have read I will give a  letter grades, just as you would expect from a retired academic.  Some of these books I have not read, usually because I started them and found them dull, annoying, or both.  These get question marks.  I have several more books laying around somewhere which I haven’t even thought about yet, and I get wind of more every week.  I will keep this list up-dated.
Books I particularly recommend are shown in red.
Alphabetical, by author: 
Ackerman, Jennifer, Chance in the House of Fate.  ??.  This falls squarely into the category of “books I started and then abandoned”.  Part science, part poetry, part I-don’t-know-what, this book promises to be tough going – but I bought it, so I’ll read it,  Someday.
Carey, Nessa, The Epigenetics Revolution.  A   Certainly one of the most useful books I have found.  Everything you always wanted to know about heredity but didn’t know whom to ask.  She is bringing out another book next year, and I will be first in line at the bookstore.
Francis, Richard, Epigenetics.  C+  Covers much the same ground as Carey’s book, but with far less style and grace.
Goldacre, Ben, Bad Science.  D+?.  This guy evidently writes a science column for a British newspaper, in which – apparently – he eviscerates stupid scientific ideas.  So far, so good.  However, his style gets on my nerves.  Moreover, there is little about cancer in this book.  Read it at your own peril.   
Goodsell, David, The Machinery of Life.  B-?  I have merely thumbed through this book and admired the pictures.  This book contains descriptions of various “things” encountered in organic chemistry, each with its own set of beautiful illustrations.  Not much here about cancer, which may explain why I haven’t really read it.  After cancer is conquered I promise to give it a go.
Greaves, Mel, Cancer, the Evolutionary Legacy.  ??  This also falls into the category of “book I started, then set aside”.  The tropic promises to be interesting, but I find his writing style annoying.
Judson, Horace, The Eighth Day of Creation,  B  This is an excellent history and explanation of developments in biochemistry through what might be called the “heroic era”.  Unfortunately, it was published in 1975 so isn’t up-to-date.  Nevertheless I recommend it to all who are really interested in this stuff, and who has enough time on his or her hands.
Leaf, Clifton, The Truth in Small Doses.  A+  I have effused about this book before, so chances are you already know what I think about it.  In this book Leaf explains why we are not winning the war on cancer, despite having spent enough money on it to finance several modern shooting wars!  He is absolutely right, and this book is absolutely essential.  Go buy it forthwith.
Mukherjee, Siddhartha, The Emperor of all Maladies  , A-.  This is another very valuable book, heavy to the history of cancer and our response to it.  It is very hard to read in places, not because of difficult language but because the subject matter is so gruesome.   Mukherjee is a cancer researcher; I hope he has time left over to write a sequel.  How about a summary  of new therapies and their likelihood of success, Sidd?
Ridley, Matt, The Agile Gene and Genome  C+  Both books are artfully-constructed traipsings  through the world of genetics.  As painless background they are perhaps worth reading, but – cancer-wise – they lead nowhere.
Watson, James, The Double Helix  B+.  This is the classical account of the discovery of the structure of DNA, which lead to genomic studies and eventually to gene therapy in cancer.  Everyone should read it, once.  Watson was a brash little smart-aleck, but a clever one.  , His book is very entertaining – and you will learn some biology reading it.  Please don’t take his tale as typical of the way science is conducted; not then, and certainly not now. 
So, many of these books should be available at any good public library.  Those that aren’t can be purchased cheaply and expeditiously by going to Google, typing in Abe books, and following instructions.  Or, patronize your local bookstore – they probably need the business.


Wednesday, October 8, 2014

CHIMAERA: The mythical monster that fights cancer. We hope

In the main square of Quito, Ecuador
 
A new article in the Wall Street Journal has a direct bearing on some of the questions we have been stumbling over for several months, specifically: .  What kind of cancer treatment offers the most hope, and how can we pay for it.  Here’s the article:
The treatment described in this article  has been developed specifically for acute lymphoblastic leukemia, a common childhood leukemia (adults also are susceptible.)  However, it might prove useful in the case of other types of cancer.  It (the treatment) is highly specific to the individual patient – in other words, it isn’t possible (yet?) to affect economies of scale, by mass-producing a drug that would benefit everybody.  Instead, here is how it works, more or less:  (1) A blood sample is drawn from the patient; (2) A type of white blood cell called a T-cell is separated;  T-cells are part of the body’s inherent immune system; (3) The T-cells are modified by inserting (using virus "vectors") some alien DNA that will recognize and fight the cancer;  (4) These modified T-cells are cultured for a time, producing lots of them; (5) Finally, this new T-cell army is re-inserted into the patient, whereupon it seeks out the cancer cells and destroys them.  Hallelujah!  But curb your enthusiasm: so far this therapy has been applied to only 41 patients, in two separate Phase 2 trials.  The results have been exemplary so far, but a lot of testing still remains to be done – even though NIH has “fast tracked” this study.  (Three years instead of six?  I tend to be cynical about such matters.)  One important fact that remains to be determined is – is the “cure” permanent or temporary?
Another problem lies in the realm of adverse reactions.  A similar study recently conducted found that patients at risk for heart disease had a tendency to die when the modified T--cells are re-injected`.  They died of something called “cytokine-release syndrome”.  You can look it up on Wikipedia.  If you do, explain it to me.
Oh, by the way – these GMO T-cells are referred to as “CARs, which codes for “chimeric antigen receptors”.  “Chimeric”, in turn, refers to the fact that the modified T-cells are “Chimaera” – composed of two or more types of genetic material.    An “antigen” is something that “generates” an antibody (which are the dudes that fight infection.)  “Receptor” seems to refer to proteins or other stuff on the surface of cells that are shaped precisely to allow certain floating antibodies (or other kinds of cells) to fit into them, thereby precipitating  some kind of internal biochemical process.  That’s what the three words mean.  If you figure out what they mean when strung together, please let me know.
And, oh yes, the cost:  Nobody has come out with a definite number yet, but the estimates cluster around $½ million.  Let's puzzle about that later.
 


Friday, October 3, 2014

YOUNG, BRILLIANT & UNDERFUNDED


In Nogales
Back when it was safe to visit
 
In the 19th century and earlier many creative scientists could function without grants.  Some were wealthy men who did science for fun, or out of curiosity – Darwin, for instance.  Others had to work for a living and did their science on the side, as a sort of hobby – example: Newton.  But with rare exceptions you can’t do significant science today without financial support.  If you don’t work for a drug company or the like, you need a grant.  The National Institutes of Health gives grants to researchers in the medical field.  Who gets them?  Well, mainly old folks.  (Not  old , perhaps, but certainly mature.)  The median age of recipients of the most significant N.I.H. grant is 52.  More people over the age of 65 are funded than those under 35.  Does this make sense?
Of course it doesn’t.  A  government study  in 2005 reported that the bulk of Nobel Prize winners in science were between the ages of 35 and 39 when they did their significant work.  It is well known that even brilliant mathematicians flame out after about age 30.  Same way in physics.  Then shouldn’t we  be directing our resources toward younger scientists? Of course we should.  But we aren’t.
Patting myself on the back: I began to realize that this was the case several years ago, through my volunteer work.  I hinted at these opinions many times (in several earlier blogs), but it wasn’t until I read Clifton Leaf’s The Truth in Small Doses that I realized I had it right.  To read my review of Ciff’s book, click on http://ljb-quiltcutie.blogspot.com/2014/06/the-truth-in-small-doses-at-long-last_7.html 
Well, here’s more evidence, in the form of  a short essay by an ex NIH research scientist now serving in Congress.  He says what Cliff and I have been saying for some time: to conquer ovarian cancer, Alzheimer’s, or any of the other dreaded  human medical maladies, it will not do simply to attempt to smoother the problem in money.  Rather, the money must be used like a very sharp knife, precisely manipulated by the best, most original, most innovative workers in the field. In other words, by the young, the brilliant and the (currently) underfunded.  We are making shamefully slow progress in our “war on cancer”.  The problem isn’t lack of money.  The problem lies in how it is deployed.  Ii's as if on D-day we landed our troops on the beaches of - - Australia.  Pretty far-fetched and stupid analogy, I know, but the best I can do this morning.