TO WALK IN BEAUTY

Tomorrow Linda will have been gone for three years.  I am going to post something I wrote about her several months ago.  For the next 10 or so days I will be in northern Arizona with two of my daughters,

This isn’t really about ovarian cancer at all, nor is it an attempt to be funny.  Off and on over the years I have been interested in Navajo culture.  So far most of what I know comes from reading the marvelous “Leaphorn-Chee” novels, by Tony Hillerman.  I have made an effort to read more “serious” things, but to no avail. Hillerman remains my only guide.

In his books Hillerman relates that the Navajo Way consist in part of “walking in beauty”.  I don’t pretend to fully comprehend that concept; all my life I have “walked” in a state of constant striving  and inner turmoil.  But I have come to realize that “walking in beauty” exactly describes Linda; on her journey through life she created beauty all around her, wherever she happened to be!  Those of you who knew her well will understand.  Even when she contracted ovarian cancer she continued on, in beauty.  There wasn’t a Sing that could save her, nor any trick of modern medicine.  But she walked on to the end, in beauty.

In her obituary I wrote that, with her death, the world would be a darker place.  For those of us who knew her well, it certainly is.

MEASLES, CANCER - and natural gas

Park in Greenwich, England

 

Diane Wiese posted a very important article on Facebook last Thursday.  It relates how Mayo Clinic has succeeded in reversing the imminent death of a woman suffering from the blood cancer myeloma – by giving her measles vaccine!  Enough, in one dose, to inoculate ten million people!  However, this isn’t your family doc’s measles vaccine – it has been genetically modified to kill myeloma cancer cells while leaving healthy cells unaffected.  I guess you would call what the Mayo people did a phase 1 clinical trial: “proof of principle”, which translates into showing that the proposed treatment can work.  Note, can work, not will work.  Another woman with the same disease, but situated elsewhere in the body, did not respond.   Apparently there is some hope of using this “viral kamikaze” method on other tumors, including ovarian. A phase 2 trial is planned; this checks things like maximum tolerated dose, serious side effects, etc.  Then comes the ponderous phase 3 trial,involving hundreds to thousands of patients, followed for years.  Given the track record of the NIH, as portrayed in the important book The Truth in Small Doses, we can hope to see something definitive around the year 2030.

Here are some links.  One is a bit tough going.

http://www.mayoclinicproceedings.org/article/S0025-6196%2814%2900368-1/fulltext

http://www.washingtonpost.com/news/morning-mix/wp/2014/05/15/womans-cancer-killed-by-measles-virus-in-unprecedented-trial/

I looked at the Mayo Clinic web site as part of this research and discovered another important – and not entirely unexpected – fact.  Despite what you were taught as a child, farting is good for you..

 

 



PROFILES IN RESEARCH EXCELLENCE: Dr. Michael S. Goldberg

Linda and Patches

both gone

 

As you will know if you read these blogs regularly (and at least six of you do), I have become greatly dissatisfied with NIH funding mechanism(s), and ever more strongly convinced of the absolute necessity of independent funding mechanisms to spur innovative cancer research.  The Marsha Rivkin Center has several such programs, aimed explicitly at projects that may make a major breakthrough, even an important paradigm shift.  (The culture pervading NIH/NCI grants rewards “safe” research that everyone strongly suspects will yield  moderate -  very moderate – improvement in some established therapy.)  Two MRC programs target support to young scientists eager to try something new in the field of ovarian cancer.  These are the Scientific Scholar Awards ($60,000 for one year) and Pilot Grants ($75,000 for one year.)  Frankly, I can’t discern much of a  difference between the two, although there must be one, at least in the minds of the grant-givers.  Anyway, there were three Scientific Scholar Awards given in 2014.  Disappointingly, from my point of view – all three went to members of large, prestigious, (but well equipped!) cancer-fighting organizations.  Of the three I like best the proposal by Dr. Michael S. Goldberg.

After some Web searching I tracked down Dr. Goldberg’s vita.  Apparently he  is about 37 years old (or younger, judging from his photograph).  Dr. Goldberg received his B.S. at the University of Toronto, a M. Phil from Cambridge University in the U.K., and a Ph.D. from MIT.  Then he post-doc’d at M.I.T.  for several years before settling into his present position; Assistant Professor at both Harvard University and the Dana-Farber Cancer Institute in Boston.  You have to admit: he is well connected and equipped, and blest with a super-abundance of sharp colleagues.. Tenure awaits.   He already has two post-docs working with him (I had three in my whole career). As of about 2012 he had 16 publications.  From the point-of-view of eradicating ovarian cancer, Dr. Goldberg is a catch, and the existence of young people like him gives me much encouragement.  .

What Dr. Goldberg is trying to do is develop nano-particles to penetrate “walls” set up by cancer cells trying to protect themselves from agents of the immune system.  (Think of cannon balls measured in billionths of a meter.)  As you all surely  know already, cancer cells can “evolve” to recover from conventional chemotherapy.  Immune cells, however, can evolve right along with them.  Thus it is vital to get them (the immune cells) through the cancer wall.  Maybe packing them into  Dr. Goldberg’s tiny missiles will do the trick.  Let us hope.



TARGETED IMMUNOTHERAPY: Still work to do.

Enjoying life in Split Mountain Gorge

 

Dick Ingwall is my oldest Research Assistant (in point of service, and probably other ways as well).  He has pounced upon an important article in the New York Times of May 8^th.  In addition to being my most prolific source of ideas, Ingwall is my best-remunerated RA: only last year I arranged for him to be inundated by shipments of squash; to save himself he took actions that earned him the title of Most Honored Donor of 2013 by the Cape Cod Food Bank.  Thanks again, Dick: without you I’d have to subscribe to the Times myself.  Let me know if you need more squash.

It seems to me that the two most exciting lines of research in the field of cancer therapy are immunotherapy and targeted therapy.  The first involves teaching the immune system to recognize cancer cells as enemies, and then attack them.  The second requires much genotyping in order to design a molecule that will interfere with the chain of biological events that causes proteins coded for by mutated genes to work mischief.  It appears now that a combination of the two is getting some scrutiny.  This surmise is based on work done at the National Cancer Institute laboratories by Dr. Stephen Rosenberg and his team.  What they have done is to develop immune cells specifically aimed at the tumor itself.  They do this by sequencing the genome of the tumor, then identifying specific types of immune cells that are attacking the deleterious mutations.  Next they extract some of these immune cells, grow billions of them in the lab, and inject them back into the cancer victim, -  and watch what happens.  So far they have done this with only a single patient, a particularly courageous woman from Billings, Montana.  Her tumors have “melted away”, and she is enjoying life many months after she had been expected to die.  Let’s hope the cure is really permanent; a heck of a lot more work will be needed to verify if this treatment really works.  It is targeted on solid tumors; epithelial ovarian cancer is one such.

There are aspects of this article that I don’t understand.  I am going to quote from it:

“By then, the team had sequenced the genome of her cancer, and done extensive studies on her immune system. And it had found what researchers had long hoped for: a mutation in the cancer that was unique to it and not found in normal cells, and a type of T cell that would attack the mutation.”

I don’t know how you “attack a mutation”.  Does the immune cell actually destroy the mutated gene?  Or does it just stifle the protein that the gene produces?  I guess I don’t need to know: if it works, it works, and that’s all I really care about.  (But I’m curious.) 

If it (this kind of therapy) really does work, it is bound to be very expensive.  Thus, a related question: how do we (society) pay for it?  If this had been available when Linda was alive we would have paid for it out of pocket if necessary, that goes without saying.  However, that option is not available to most people, even in rich countries.  Another business model is required.  Maybe economists are  useful, after all.

This is a particularly important article: why don’t you read it?

http://www.nytimes.com/2014/05/09/health/doctors-use-patients-immune-cells-to-shrink-cancer-tumors.html?ref=health

Happy Mothers’ Day!

 



OF CANCER RESEARCH, AND TURNIPS

In Bellingham, 2010

 

It is a beautiful day here in “Rainville”: mid-70s, light breeze, almost no clouds.  I am supposed to play golf tomorrow, so I assume that all of that will change, but I am enjoying it now.  I went out back to continue planting my garden, and found it more difficult than it ought to be.  I can’t kneel comfortably on my new knee, and my back hurts if I stoop over for more than a few minutes.  I guess this is nature’s way of telling me to buy a condo with a large south-facing deck, and grow things in containers.  But again, there is always Ralph: I can have him do all the work, and then take credit for the outcome.  I think that’s the way to go.

The Rivkin Center newsletter just came out, announcing the recipients of their yearly grants.  Once again they raised, and distributed, more than $1 million.  I will blog a bit about selected recipients in a few days.  For now, I note that most of the successful applicants are focused on treatment: kill the damned thing once it rears its ugly head.  The book I wrote about recently would disapprove of that: “preemption” is its preferred strategy.  I guess I would agree, although I would insist on the equal importance of basic science aimed at understanding the cancer process.  I will blog about that pretty soon, too.

But in the meantime I need to go outside and plant some turnips.

 

 

 



YOU ARE NOT OLD UNTIL PEOPLE START HOLDING THE DOOR FOR YOU: oh oh!

About 63 years ago

 

I just emerged from my post-Borrego daze to the realization that I have a birthday coming up, on May 13 – at which time I will turn 81 (!)  If any of you happen to be inclined to send me a present, please don’t.  I have everything I need, nearly everything I want, and if I get an irrational urge to own something else – a Maserati, say - I will buy it.  So instead, please make a donation to Fred Hutch in honor of Linda:

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

Be sure to designate ovarian cancer.

Humorous cards or Facebook posting are, of course, more than welcome.



ORPHAN DRUGS

On the Greek island of Rhodes

Probably about 1984

 

This is something you all should read.  It is enlightening, engaging, and easy going.  The fact that I fell asleep half way through it – on each of two readings, two days apart – remains unexplained.

http://www.propublica.org/article/where-are-the-low-cost-cancer-treatments

If you read this article, here are some of the things you will learn:

What are “financial orphan” drugs and why are they orphaned?

Why Big Pharma wants you to take drugs at $10K per hit, rather than aspirin at 3 cents.

Why there are no cheap cancer cures, or damned few.

When reading this article, here are a few things to keep in mind:

Merck, Pfizer, Novartis, etc. – Big Pharma – are corporations designed specifically to make money for their investors.  They are not charities.  Exxon Mobil makes money selling gasoline to people who need it to make their cars go.  Big Pharma makes money selling drugs to people who need them to remain alive.  Both do what you might call Pro Bono work; selling at a loss or giving their products (or money) away, to benefit mankind.  They do it to stay in the good graces of the buying public.  Corporations do not have hearts; they do not get warm, fuzzy feelings from doing good.  To expect otherwise is foolish.

Medical practitioners practice in a fearsome world, where any mistake can cost them dearly.  Their CYA instincts are powerful.  They will not risk using a therapy that is not approved by the FDA, the NIH, and 95% of the other doctors in their field.  To expect otherwise is, well, foolish.

Obtaining such approval requires clinical trials that, currently, cost unbelievable amounts of money.  Part of this money, but less than half – and dwindling – is provided by the government.  The rest comes from private individuals, NGOs (charities like the Rivkin Foundation) and - overwhelmingly – Big Pharma. 

“Alternative medicine” can refer to the utterly unscientific – rubbing beet juice into your scalp to prevent hair loss  - but it  equally well can denote treatments with strong scientific underpinnings, but which – for economic reasons, usually – have not obtained official approval.   

So.  Read the article, and don’t fall asleep.  Sample questions for the exam:

What is Global Cures, and what is its web site?

How does a drug or treatment become a “financial orphan”?

What is “ketorolac”, and why doesn’t your doctor prescribe it for you?

I’m home and trying to plant my garden.  The house was spotless.  I have been home three days now, and it isn’t any more.