A LEARNED ESSAY ON STEM CELLS

Daughters Karen and Kristen will re-visit this country with me next month

Sure wish this lady could be with us

 I have mentioned stem cells 47 times in this blog.  It is time to determine if I really know what they are and what they do.  (The smart money is on:  probably not.)  I am going to write this “learned essay” off the top of my head; not even Wikipedia will be involved.  I expect biologically sophisticated readers (e.g., daughter Kristen Beck, niece Rebecca Hunsinger, great friend and benefactor Dr. Joanne Ingwall, paleontology colleague and occasional social critic Dr. Sharron Sussman) to comment, correct, and even chastise, if appropriate.  Failing that I will continue to muddy the waters and roll science back on its haunches – and it will be your fault, not mine.

So, what’nhell is a stem cell?  Well, it is an “undifferentiated” cell that has the capacity to turn into one or more types of specialized cells – liver, muscle, skin, etc.  You read a lot about “embryonic stem cells”.  These little buggers are derived from embryos, natch, and seem to occupy a realm of constant warfare between science and (some flavors of) religion.  This is because they have the capacity to develop into a whole and complete human being.  (There also are murine embryonic stem cells, but nobody worries much about the immortal souls of mice.  Other mammals have ESCs too, of course.)  As I understand it, there are two kinds of ESCs: “omnipotent ESCs, which can give rise to an embryo plus a placenta to nourish it, and “pluripotent ESCs” which can’t do the placenta thing.  I am far from certain about this, but it doesn’t’ matter anyway.  The overriding problem is that there are lots and lots of well-meaning, intelligent people who regard using ESCs in experiments as murder.  I see their point, but disregard it.

Question:  Is a human zygote also an omnipotent ESC? 

There also exist many other kinds of less “potent” stem cells.  These are specialized stem cells (SSC) which can turn into only a single type of cell: liver, say, or blood, muscle, etc.  Actually, they don’t “turn into” anything; rather, they divide, with one daughter being the specialized, working cell in question and the other an exact (it is hoped) copy of the original SSC.  In this way the SSC is essentially immortal and hangs around doing its thing indefinitely.

Question:  I had always thought that ordinary somatic cells divide to replenish its organ.  For instance, if an old liver cell with tattered telomeres received orders (from where?) to croak, its near neighbor, another somatic liver cell, would receive orders to divide, thereby filling the gap.  That must be wrong, right?

Question:  Cancer is said to result from unlucky mutations or groups of such mutations.  Does this mean that the SSC itself is mutated, or its sister the specialized cell?  Or both?

So, I am vaguely aware that it has proved possible to take an SSC and, using almost magical biological sleight of hand, induce it to climb back up the developmental ladder and become equivalent to am ESC.  They call these things iESCs, which codes for “induced embryonic stem cells”, although maybe they should be called induced pluripotent stem cells (iPSC) because they have little to nothing to do with embryos. 

An aside:  If iPSCs are ever used to generate a human being – in effect, a human clone - expect all hell to break loose.

OK, I think that’s all I know about stem cells.  You are to be praised if you read this far.  Thank you.  BUT WAIT:

Overriding big picture question.  When, for instance, a liver SSC divides to make a functional liver cell and a duplicate of itself, if mitosis does its job correctly both daughter cells have identical DNA – although they have profoundly different roles to play.  The difference must be epigenetic. Different genes are silenced in the two sibling cells.  What in Heaven’s name controls this?

FRANCIS COLLINS, M.D.

A desert hike

Dr. Francis Collins is the Director of NIH and a prolific blogger.  His blogs concern medical matters, as you might guess.  I find them interesting, well written, important, simple – and short.  You could do worse than to subscribe to his newsletter to receive his blogs via email.  To do so, go to

https://public.govdelivery.com/accounts/USNIH/subscriber/new?topic_id=USNIH_74

Tomorrow I plan to summarize one of his recent blogs concerning stem cells.  I’d do it now but it is time to pop a beer and go watch golf on TV.

SUMMER RUN 2017

Saul

A nice young lady from the Marsha Rivkin Center for Ovarian Cancer Research called me yesterday to urge me to enter a team in their 5 km Summer Rub & Walk, to be held in Seattle July 17^th.  Many of you will recall that formerly I organized a “team” – Linda’s Team – and entered it, not in the Summer Run proper, but in an event I cooked up called Summer Run North; Hot dogs, beer, and good feelings, running or walking optional, here in Bellingham.  All to raise money for ovarian cancer research, of course. 

Well, sadly, I won’t be entering a team this year.  Age and existential exhaustion are the primary culprits of course, but I must admit to a little pique and exasperation as well.  I have been – nominally, I guess I still am – a volunteer with the Rivkin Center.  From time to time I have been asked for input, mainly in the form of writing.  In the past my contributions were taken seriously.  Lately, however, a new regime has taken over, and my little seeds of wisdom have languished in someone’s in box, or more likely in a round file.  I can’t even get them to correct an egregious error in their new web site!   So, nuts to them!

God, that sounds petty – and it is.  My bruised ego aside, the Rivkin Center is a marvelous institution.  Its founder (pictured above) has raised more than $10 million for ovarian cancer research – and, as a young man of only 81 (and thus significantly my junior) is still at it.  Better yet, the funds are dispersed by a process that evades the pitfalls of government funding, thereby providing enhanced opportunity for innovation.  (I wrote a Rivkin Center blog about that months ago.  Round file again, maybe.)

So what I really set out to say in this blog is that the Rivkin Center is holding its annual race, and you might consider participating, or donating.  For more information, consult their web site

https://www.rivkin.org/

As for me, I probably will give some money to Fred Hutch:

http://getinvolved.fhcrc.org/site/TR/PersonalFundraisingPages/General?px=1148821&pg=personal&fr_id=1573

ISN'T THIS OBVIOUS?

Linda with the Kalamazoo Kids

Here is a short, simple article on a new cancer treatment that is raising hope.  It involves using drugs FDA approved for cancer A on cancer B, based on the fact that the cancer-driving mutations in both are identical.  I would regarded this as an incontestable slam-dunk, but apparently it isn’t.  The clinical trial that established this protocal and the drug it features - Keruda - was funded privately.  Keruda will be supplied by Merck at an estimated cost of $156,000/year.  The article estimates that 60,000 people in the U.S. alone are potential patients.  That multiplies out to $6 2/3 billion per year.  Got Merck in your portfolio?

This tip came from my trusted research assistants, Joanne and Dick Ingwall, who are at this moment enjoying their garden on Cape Cod.  Thanks, guys.

https://www.nytimes.com/2017/06/08/health/cancer-drug-keytruda-tumors.html?smprod=nytcore-ipad&smid=nytcore-ipad-share&_r=0

ASCO AND PROGRESS

At the Whitman Mission

ASCO codes for American Society of Clinical Oncologists.  ASCO recently held its annual meeting, in Chicago.  About 30,000 abstracts were submitted, from 80 countries around the world.  How many were accepted, I do not know, but I would guess – a slew.  In addition there were workshops, panel discussions, ceremonial dinners, etc.  Maybe even tickets to Wrigley Field.  In other words, ASCO is a big deal.

As you would guess, my OVCA news sources have been jammed with articles summarizing goings on at ASCO.  Many of them describe new drugs said to be “breakthroughs”, or at the very least important new developments.  Alas, on closer inspection most of these fall into the category “seven of ten women experienced significant PFS (Progression-Free Survival)”.  In other words, “this stuff looks promising.  Check back in a few years.”

As you might guess, lots of this chatter emanates from drug companies or stock-market analysts.  Nothing necessarily wrong about this; in fact, it can be useful, because these folks are trying to communicate with you and me, not cancer biologists.  The result often is something a person without an M.D. or PhD can hope to understand.  This is illustrated by the link below.  Notice that it was written by Fierce Biotech – definitely not a cancer research laboratory!

All that aside, I am encouraged that so many smart people are striving to cure cancer.  It will happen, piecemeal - all in good time.

http://www.fiercebiotech.com/research/first-class-drug-for-ovarian-cancer-shows-promise-at-asco

BIOMATH

We had just been to Ecuador

Memorial Sloan Kettering (MSK) is located in New York City (NYC).  People must like NYC, because an awful lot of them live there.  Me, I would hate to live in NYC – but I would, if I had the training to work for MSK.  MSK must be the best cancer research center in the world.

NCI (National Cancer Institute) furnishes proof of what I just claimed.  To read it, go to

https://www.cancer.gov/news-events/cancer-currents-blog/2017/mutations-metastatic-cancer?cid=eb_govdel

and you will learn a lot..

When I was in high school we had a science graduation requirement.  The sciences offered were physics, chemistry, biology, and general science.  You had to suffer through two of them.  Most kids who simply wanted to get out of school took general science and biology.  Kids who thought they might try college took biology and chemistry.  A few of us took chemistry and physics.  The ones who chose biology did so by reason of math anxiety.  The point is that biology was thought to be completely descriptive – no math, no formulae, only little knives and microscopes.  I regarded  bio types as nincompoops.

Well, it ain’t that way no more, Zeke.  At least it isn’t where cancer research is concerned.  MSK has developed a program they call MSK-IMPACT.  It involves rapid DNA sequencing of multiple cancer types and includes matching cancer mutations to “clinically actionable” drugs, as well as on-going or prospective clinical trials.  All this is a part of what has become known as “bioinformatics”, which seems to be a sort of polygamous marriage between technology, computer science, physics and math.  My cup of tea.

I’m not going to try to explain MSK-IMPACT and how it’s used.  If I did I would almost certainly screw it up.  Be satisfied to know that there are people out there who smile at the challenge of making sense of mountainous piles of obscure data.  And don’t let Donald Trump shut them down!