Tuesday, April 22, 2014

DIET AND CANCER. Complications.


Goofing off after our trip to Peru

Vegans are less likely to get cancer than dedicated carnivores like myself who eat as much red meat as they can afford.  Does this mean that vegetables somehow help ward off cancer, or that red meat invites it in – or both?  Maybe not.  It is well established that obesity is a no-no, where cancer prevention is concerned.   It is hard to get fat on beans and rice, but easy enough on rib-eye steak.    And, in the debate over diet and cancer preemption, there are many such confounding factors.  Thus says an article in the NY Times, brought to my attention by Dick Ingwall.  I am busy getting ready to head out (annual reverse migration , Borrego Springs to Bellingham.)  So read it yourself.


So, as the article says – it’s okay to eat fat, but it’s not okay to be fat.  (Maybe)

No more blogs until next month.

Saturday, April 19, 2014

CHROMOSOMES, FRANKINFOODS AND DESIGNER HUMANS


Have I used this before?
Who is this little girl?

As of five minutes ago my “hit counter” (furnished by blogger) had recorded 12,117 hits for the entire life of this blog.  I would like to believe that each “hit” corresponded to an actual human, reading a blog entry, but I’m not quite that naïve.  For instance: after about a week of getting six to ten hits per day, today I have had 80 so far – and 73 of them are from Poland!  Is there a dedicated, scholarly group of Poles sitting around eagerly assimilating my little essays?  No, there isn’t.  Just today I came face-to-face with “Vampirestat”.  Vampirestat is a “bot”; it crawls through the internet surveying what’s out there, presumably looking for something its master can use to make money.  Vampirestat is not the only bot doing this; I also have been crawled over by bots called things like “semalt”,” bloopish”, and even “thetaoofbadass”.  The flesh creeps to think of such things.  How many of my hits represent real people?  I doubt if I will ever know.

Maybe vampirestat is headquartered in Poland, although Romania seems like a better fit.

Well, you army of bots, there is a good article in a recent issue of the Economist.  It relates the efforts – successful to a point – of scientists to produce a totally artificial chromosome.  They are working with the yeast molecule.  Yeast, as most of you know, is a eukaryote – it arranges its genetic material on chromosomes, and stores it in the nucleus.   Yeast has been important to humans for thousands of years – think bread and beer – and lately as a “model  organism” for medical science to experiment upon.  The researchers in this study (conducted at Johns Hopkins) aim eventually to produce a completely synthetic yeast molecule.  Apparently this work has become feasible because of the falling price of DNA synthesis – and the availability of an army of unpaid undergraduates to do the grunt work, the nature of which was not explained. 

The designing of this model was done in silico, meaning on a computer.  It (the molecule) was based on the structure of a real (natural) yeast chromosome.  The Hopkins people left out things they deemed redundant or downright malicious: “transposons” , some genes for transfer RNA, and certain stop codons.  They also tinkererd with the structure of the chromosome in other, more complicated ways, trying to explain the nature of which would take all afternoon.  Having created this synthetic molecule they inserted into a yeast cell and, low and behold, it worked.  They now are forging ahead, to create an entirely synthetic yeast cell.

This work has important implications all up and down the line.  For cancer, perhaps it would be possible to delete genes or even longer segments of DNA if they are found to be mutated and potentially carcinogenic.  Nobody would argue against that.  However, there are other profound implications.  Those of you who recoil from  GMOs and campaign against  “Frankinfoods” will shudder at the last paragraph.

Now let’s see if I can give you the link.
  

P.S.  The title of this article is “DIY chromosomes”, but nowhere that I can see is DIY defined.  If you figure it out, please let me know.

Thursday, April 17, 2014

MORE OVARIAN NEWS


Linda and Carolyn in Borrego Springs
Heading out for dinner.
I guess I was along.
The Fred Hutch Newsletter hit the stands today, figuratively – you actually get it through email.  It contains two articles highly relevant to ovarian cancer.  The featured article concerns Jeff Bezos – he invented Amazon.Com, as you very likely know – and profited hugely thereby.  His family has donated $20 million to Fred Hutch to support research on the use of the body’s immune system to attack certain kinds of cancer.  As we have discussed before, cancer has a diabolical ability to trick the immune system into thinking that all is well or, failing that, warding off its atacks.  There has been a lot of work done lately on ways to counteract these tricks.  If I understand correctly, some real progress has been made but – as always – more work needs to be done.  Bezos is paying for some of it.  I may even forgive Amazon its past transgressions and start ordering again.
Sometime in the past I wrote a blog about how, sometimes, great wealth can be a social good.  This is surely another example.  Thanks, Jeff.  In light of the problems with NIH/NCI-supported research hinted at in an earlier blog (The Truth in Small Doses), maybe we are going to need a lot more private support.
The second article (of many – I’m just reporting the ovarian ones) is a discussion of the desirability of having an oophorectomy at about age 35 – for women who are BRCA1 positive.  The advantages here are a much reduced likelihood of contracting ovarian and/or breast cancer.  The disadvantages include problems with menopause (because certain hormones are not being supplied) and, of course, the inability to have any more babies.  It is, as the article discusses, an intensely personal decision.   Know all the facts, mull them over, and  then decide.  Note that  this is meant for women with the BRCA mutations, and thus does not apply to the vast majority of women. 
Here are the links:
 
 


Tuesday, April 15, 2014

PROFILES IN RESEARCH EXCELLENCE: Dr. Jason Bielas




The title of this picture is "Linda in a red sweater"
Where?  When"  I have no idea.
But it certainly is Linda, in a red sweater.

As promised I am going to introduce you to a promising young scientist doing original work on ovarian cancer: Dr. Jason Bielas.  Dr. Bielas seems to have a joint appointment with Fred Hutch and the University of Washington.  I presume that he is a “young” scientist – he received his Ph.D. in 2003, from York University in Toronto.  That was only 11 years ago.  Of course, 11 years after I finally nailed down MY Ph.D.. I was almost 50.  Was 50 young then?  It seems so now.  But not to quibble: Jason Bielas is a certified early career investigator, as shown by the fact that he recently received a $2.6 million grant – one of only 6 awarded, specifically to “early career investigators”.  Also, he looks young.  In fact, he looks quite a bit like my grandson-in-law, James Wiese.  Maybe, like James, he is a martial-arts aficionado in his spare time.


So anyway, Dr. Bielas studies the effects of mutations on age-related cancers, of which ovarian cancer is one.  Partly he looks at mutations in mitochondria .  You know what mitochondria are, right?  They are the power generators for cellular activity; little compartments in the cytoplasm of cells, stuffed with DNA and many other things.  Apparently Dr. Bielas has reason to believe that mutations in mitochondria, accumulating with age, give rise to some types of cancer.  He also works on mutations in the more commonly discussed DNA: that in the nucleus.  And from the title of one of his publications he also seems to have an interest in developing a means of detecting the presence of cancer from types of cells in the blood.  In short, my kind of guy: a basic get-the-facts human biologist with his eye on solutions to important problems.  I am encouraged that there are people like Jason Bielas working in cancer biology.  Now, if only we could reform the way research money is handed out (see my last blog entry.)


Google Scholar lists about 30 publications authored or co-authored by Dr. Bielas since 2003. One of them already has been cited 253 times.  Nine of them concern ovarian cancer.   Pretty good, I’d say. 


Saturday, April 12, 2014

THE TRUTH IN SMALL DOSES: Part 1


A new Physical Therapist

I am not going to try to be funny or clever in this blog; the subject is, for me at least, too important for any of that.  I am going to try to distill some of what I have so far gleaned from reading The Truth in Small Doses, by Clifton Leaf. 

I have been reading cancer- and biology-related books for several years now.  Most of them have been worthwhile, and one, Nessa Carey’s book on epigenetics (which I have mentioned several times previously) is close to essential reading for any non-biologist who wants to wrap his or her mind around modern concepts in genetics.  I have read Carey’s book twice, and may start it again within a few months.  Leaf’s book I certainly will read again and – something I haven’t done in many decades – take notes.  For someone like me who is deeply concerned with the lack of progress in the so called “War on Cancer”, Leaf’s book is essential; a game-changer.  I urge you all to, at least, consider reading it.  It isn’t easy and it isn’t fun – but it’s very important.  You can download it to an iPad for $12.99, or you can pick up a new hardbound copy through Abe Books for $5.73.

Leaf is not a biologist, but rather a science writer who has published in Fortune magazine, and elsewhere, I imagine.  He has spent many years (indirect evidence suggests nine) studying the workings of our cancer “War” and looking for probable causes of its tepid success.  Some of the things he discusses and, especially, some of his suggestions are very like things that have been rattling around in my head for quite a long time.  I am going to do a systematic book report on this item in the middle-distant future, after I have gone through the book again.  What I will write below are some themes and impressions that occur to me at the moment – in no particular order.

We can’t eliminate cancer by simply smothering it in money.  The money has to be properly directed.  We may need an overall administrative structure; like a biochemical NASA.  However, from my perspective, curing cancer is vastly more difficult than reaching the moon.  The problem is far more diverse; not one “problem”, but many.

As presently organized, the NIH/NCI “protocol” for doling out money is needlessly tedious and complicated.  One result is that cancer PIs spend far too much time writing grant proposals, at the expense of time spend on actual science.

The NIH/NCI “culture” discourages innovation and what Leaf calls “risk-taking”, but rather rewards cautious, incremental science – science that aims at making slight, sometimes wholly insignificant, fiddling “improvements” in existing protocols.  No home-runs allowed; bunts are welcome.

There is implicit in the way the system works an almost religious adherence to the phrase: “First, do no harm.”  However, there are harms of commission (you administer an experimental drug to a very sick patient and he dies) and then there are harms of omission (you  deny an experimental drug to a very sick patient, on the grounds that it might do something harmful – and he dies anyway.)   Which sin is worse?

Okay, that is enough for now.  I will do a much better job in a few months, after I have re-read the book and thought a bit more about its message. 


Wednesday, April 9, 2014

DIET AND CANCER: round 3, or maybe 4.


With Coleman, 2004.

In Tucson they say that “the ice broke in the San Pedro River” on the first day of the year that the temperature reaches 1000.  Well, the ice was supposed to break in Coyote Creek today  (here in the north Borrego valley) but it only groaned and cracked a little.  Maybe tomorrow.

But, as it reached 990 I did as I had said yesterday – went for a hike early, then spent the bulk of the day indoors.  This gave me a perfect opportunity to investigate a lead sent me by Carolyn, concerning diet and cancer.  Here is the link.  It is remarkably uninformative:


This link basically is an ad for a book, by Tamara St. John, the title of which is Defeat Cancer Now:  A Nutritional Approach to Wellness and Other Diseases.  I have not read the book, and probably won’t – but some of you may.  If so, please get back to me.

Ms. St. John says she has had cancer twice, and has been at death’s door since 2009.  She has used diet – apparently very high to vegetable matter – to hold her cancers at bay.  It is very difficult to excavate any concrete information from her blog, which is actually a Facebook page.  She is not a scientist; rather, she is an MBA and motivational speaker. 

Well, dammit!, more power to her!  It goes without saying that none of her suggestions have ever been tested with an NIH-approved clinical trial.  Dr. Ioannidis and his METRICS cohort would smile and shake their collective heads.  But so what?  Just because a hypothesis has never been robustly verified doesn't mean that it's wrong..  Novartis and Pfizer sell drugs to combat cancer; they are, one and all, various kinds of bio-active, mainly organic,  molecules.  So are carrots.  So why can’t a diet of carrots (and brown bananas) help keep cancer at bay?  Maybe they can.  My guess, though, is that – if carrots and bananas are truly effective – their value would have been discovered long, long ago.  So probably this is pseudo-science, and cancer patients certainly should NEVER rely solely on diet.  But, as I've said many times before – what do I know?


Tuesday, April 8, 2014

TREATS SOON TO COME YOUR WAY


In our home, probably 2010
The blank space on the wall now holds one of Linda's wonderful quilts.

It hit 980  in Borrego Springs today and is supposed to reach new levels  of discomfort tomorrow.  Then it may cool off.  My estimated date of departure is Wednesday, April 23rd, and (after my usual stay in Eureka), my ETA in Bellingham is April 30th.  My cats will be happy To see me, and I can begin to put in a garden.  This year I propose to grow lots of turnips.


I am going for a hike tomorrow, in Font’s Point wash – at 6:00 am.
     
Friday of this week I am scheduled  to deliver  two talks to the ABDS Paleontology Society.  The first, The Terrane Concept in  Geotectonics is something I can do in my sleep.  However, the second talk – New Ideas about the Origin of the Grand Canyon – concerns ideas and methods I know almost nothing about.  I took it on so as to force myself to learn something new (besides cancer biology, of course.)  Now I wish I hadn’t, but it is too late.  I will bluff my way through


But not to neglect my blog:  I have several things I want to discuss, but time and energy are lacking right now.  This current blog is something like a Preview of Coming Attractions.  Waiting in the wings are:


1)      Another episode in the series Profiles in Research Excellence.  There is a young scientist at Fred Hutch who has made important discoveries in the field of ovarian cancer genetics.  His name is Jason Bielas.  I would like to meet Dr. Bielas and intend to do so as soon as possible.
2)      I want to do a book report.  The book is The Truth in Small Doses, by Clifton Leaf.  Mr. Leaf is not at all pleased with the way the “war” on cancer is being waged, nor of the way cancer research funds are allocated.  In fact, he is pretty sour on the whole philosophical underpinnings of official anti-cancer activity.  I am nearly through with the book, and so far, reluctantly,  I agree with him.
3)      Finally, Carolyn has sent me a reference to an article on combating cancer through diet.  It appears that bananas – the browner the better – are recommended.  I haven’t read the whole article – but I will.
So, stay tuned.  I have to get back to the Grand Canyon and the mysteries of 4He/3He thermochronography.

   

Saturday, April 5, 2014

METRICS: Scourge of sloppy science.


Early on - maybe 1981

Back on 11/13/13 I posted a blog entitled “Beware Greeks Bearing Manuscripts”, which featured a very famous bio-statistician named Dr. John Ioannidis.  I had written about Dr. Ioannidis earlier (5/22/12).  Dr. Ioannidis almost singlehandedly has stirred the bio-medical  community into a froth.  His influence seems to have originated with a paper he published in 2005, entitled “Why most published research findings are false.”    At scientific meetings I’ll bet he eats lunch alone.

Dr. Ioannidis seems to turn up everywhere.  A recent article in The Economist:


informs us that he is starting an institute at Stanford , the purpose of which is to examine bio-medical research and judge how reliable it is.  The name of this menacing creation is the "Meta-Research Innovation Center at Stanford": METRICS for short.  One thing METRICS will do is to troll for studies with faulty statistics; that is, studies  liable to produce “irreproducible results”.  Science is supposed to test the validity of new discoveries or pronouncements by seeing if the results cited can be duplicated.  This process is explicitly performed  very rarely, however, for obvious reasons, mainly involving monehy and professional advancement.  

The goal of METRICS is to hold comfortable scientific feet to the fire.   METRICS also will look for evidence of" publication bias", an evil that is poorly explained in the Economist article, but apparently pretty bad.

The British medical publication Lancet highlights the need for quality control in medical research: they reckon that $200 billion in annual medical research spending (85% of the total) is “squandered on studies that were flawed in their design , redundant, never published, or poorly reported.”  Ioannidis and his METRICS buddies are taking aim at this situation which, if only partly true, is still outrageous.  Good for them.
Better to fund institutions like the Rivkin Center, which awards support only to carefully selected investigators with precisely designed and targeted experiments.  
  

P.S.  Oddly enough, the Greeks and Manuscripts entry has attracted an unusually high number of hits lately.  Why this should be is a mystery to me.  


Wednesday, April 2, 2014

ONE MORE BATTLE IN THE PROSTATE CANCER WARS. Nuts to this stuff, from now on.


Linda and Ella
About six years ago

Breast cancer and prostate cancer have some things in common.  For one, they are gender-specific: yes, men get breast cancer, but very rarely.  Women don’t get prostate cancer for the good and sufficient reason that they have no prostate.  (This, ladies, is a blessing.  Take it from someone with an old and cranky prostate.)  Each type of cancer is the most prevalent for its respective sex.  Also, breast cancer and prostate cancer generate lots of press:  pink ribbons abound (as well they should), and articles about prostate cancer choke the news.  Now there is even a book about prostate cancer or, more accurately, whether or not to use the PSA antigen as a biomarker.  I wrote about the Prostate Cancer Wars way back on March 27, 2012, and have reported new battles in a bunch of Comments.  Go back and read to get up to speed. 

A few weeks ago The Economist reviewed a book titled “The Great Prostate Hoax: How Big Medicine Hijacked the PSA Test and Caused a Public Health Disaster.”  Read it yourself (the review, not the book) at:

The authors of this book are strongly against using PSA for diagnosis.  They have the creds: the first author is a U. of Arizona professor who claims to have discovered PSA in the first place.  Apparently at times their opposition becomes hyperbolic, even shrill; The Economist firmly dislikes both.  (I cannot comment as I have not read the book, and don’t plan to.)   In spite of any literary deficiencies  the book apparently reports material for several valuable insights.  Two huge clinical studies are cited, one of which reported very little reduction of mortality by PSA screening, whereas the other found a definite benefit for men in 50-69 age range.  Both studies found high quantities of unnecessary worry and medical expense associated with PSA screening.  Many men have elevated PSA but no cancer; further (expensive) tests are required.   Many actual cancers discovered are “indolent”; they pose no real threat, but they scare the hell out of the patient and may result in unnecessary surgery.  A blood marker for cancer avidity is needed, but does not exist.  Maybe all men should get a “baseline” PSA done at age 40.  Or maybe not.


So, what they heck.  As an octogenarian I am going to use “watchful waiting” if my PSA goes up.  As a person mostly interested in ovarian cancer I am going to try to avoid prostate cancer articles in the future.  And as a sloppy eater:  Anybody know how to get peanut butter off your computer keys?