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.


12 comments:

  1. Thank you for the review! However, you seem to be missing important pieces in your interpretation of the cancer culture. Example, unlike your claim that we need "work to understand the basic biology of cancer" this biology has long been known to medical science, and your view on the deterministic nature of genetic mistakes is also misguided (discussed in "The Mammogram Myth" by Rolf Hefti). But this reflects what Leaf had pointed out: the present system slows progress. The current system is dominated by corporate interests, where scientific facts are subordinated to dogma and ideology.

    ReplyDelete
    Replies
    1. It is encouraging to receive a Comment from someone obviously situated outside my usual “Comment circle” of relatives, friends, and friends of friends. Not that I don’t appreciate Comments from Inside the circle; I relish them – even though 95% refer to the picture of Linda that accompanies each blog. This is natural: a glimpse of Linda is worth way more than any number of words from me.
      That said, I feel I need to respond to Anonymous, if only to explain my ideas a bit better. I wish Anonymous hadn’t placed me at such a disadvantage, though. Am I engaging with a biochemical professional with a string of degrees and designations an inch long trailing his/her name, or with someone as pristinely innocent of formal biological training as myself? I will assume someone somewhere in between. So, anyway…
      I continue to maintain that basic research in cancer genetics, in the large sense, is valuable. I strongly disagree that “(the basic biology of cancer) has long been known to medical science”. In the last 10-15 years there have been important additions to that knowledge: the significance of micro RNAs in modifying signaling cascades for instance, or the importance of epigenetic markers. It seems to me that vital discoveries about how genetic mistakes are transformed into harmful combinations of proteins are being made every year. I would agree that more attention – and funding - ought to be devoted to translating this basic research into the clinic. I am (was) a practicing scientist myself – and I am morally certain that it is never wise to assume that everything important already is known, about anything.
      According to Anonymous “(My view on the deterministic nature of genetic mistakes (is also misguided)” I’m not sure what that means. “Genetic mistakes” are surely stochastic – random, depending on chance. Some are Inherited – BRCA mutations in ovarian and breast cancer, for instance. But, even given a harmful inherited mutation, it is my understanding that it takes one or more additional mutations, acquired randomly, to set off a signaling chain that will result in cancer. I believe Leaf would agree that we need to search for external environmental conditions that contribute to the mutation rate (nicotine and asbestos leap to mind). So, I really don’t know what this criticism means.
      Anonymous and I certainly agree that the present “system” is broken. He/she blames “corporate interests”. To that I would add the academic predilection for peer review and “one more publication”. Until a method is devised for divvying up the money in such a way as to reward innovation and not massive publication lists, cancer research will just inch along.
      As always: remember, I am a geologist, and an old one at that. So – what do I know? (Not talking to you here, Anonymous. But thanks for your Comment. You made me think.)


      Delete
  2. Where is the review you refer to?

    ReplyDelete
  3. I find it curious that Ukraine, a small country with many big problems, should contain so many people interested in this blog. Hits from Ukraine are second only to hits from the U.S. this last week Ukraine also stands third in hits for the past month- and fourth all-time. Go figger.

    ReplyDelete
  4. Wow, Myrl! Thank you so much for this extraordinary review—and for the very generous assessment—of my book. I really appreciate your sharing this with the world.
    All the best,
    Cliff

    ReplyDelete
    Replies
    1. You are abundantly welcome! Thank YOU for systematizing (and backing with evidence) so much of the stuff I have been worrying about for several years. I wish I knew where to go from here. If you ever can use partner in crime, I’m your man!
      Myrl

      Delete
  5. Apropos of my suggestion that more private funding of medical research is required, if only to overcome the NIH/NCI/FDA institutional reluctance to fund innovative projects, read this interesting article in the Wall Street Journal.
    http://online.wsj.com/articles/eric-lander-and-louis-gerstner-private-money-pays-off-for-medicine-1407710070
    If only there were more of us with $650 million to spare, and a mission to conquer disease!

    ReplyDelete
  6. In (2), above, I suggest Steve Jobs as a potential Cancer Tsar. I have been reading “Jobs”, his biography by Walter Isaacson. I am nearly finished. It is a good book. My take on the matter now is: if he were alive, and we had such a things as a Cancer Tsar, Steve Jobs would be the man for the job. But I sure as hell wouldn’t want to work for him.

    ReplyDelete
  7. This for Clifton Leaf. The rest of you needn't read it.
    Damn it, Cliff! I have been reviewing research proposals to the NIH & I need to vent! Why don't you fix it so I can email you. I promise not to share your secret address with the NCI, or anyone or anything else who/that might want to throttle you.

    ReplyDelete
  8. Pierce Brosnan has lost his wife and his daughter to ovarian cancer, and he is using his celebrity status to lobby for more cancer funding. Good for him! Now if only funds could be allocated in a more effective manner, as suggested in this blog, things would be looking up.
    http://www.washingtonpost.com/blogs/reliable-source/wp/2015/03/17/cause-celeb-pierce-brosnan-urges-congress-to-step-up-cancer-funding/


    ReplyDelete
  9. New work on prevention, worth a Comment but probably not a Blog.
    http://www.medicalnewstoday.com/articles/299413.php

    ReplyDelete