Tag Archives: Myostatin

Science fiction for the cognoscenti – III — not all the background you need will be explained

Now that every team in the NFL has its own molecular biologist and antiVirologist, you might be interested in knowing how it all started.  Like most technologies affecting our lives it had a military origin.

The escape of the Taiwanese pacifist virus started it all –https://luysii.wordpress.com/2018/11/19/a-science-fiction-story-for-the-cognoscenti-answer-to-the-puzzle-and-a-bit-more.

The technology of infectious gene transfer by recombinant adeno-associated virus  (AAV) was well advanced long before there were garage molecular biologists.

The NFL wars began with the New England Patriots, (who else?), they of deflategate and other nefarious ways to win.

Tom Brady was getting all set to win superbowl LVII in 2023 at age 45 when the first counterattack was successful.

His wife, the beautiful Gisele, hated the idea of him playing so long, being very worried about dementia pugilista from all the head trauma.  Tom had agreed to yearly PET scans with Pittsburgh compound B, an uncharged derivative of thioflavin T which gets through the blood brain barrier and which stains senile plaques.  They showed no evidence of plaques (although plenty of demented people don’t have them) so he kept on playing behind Belichick’s not so secret weapon — 400 pound linemen.  Even though he’d lost a step or two, his eye and arm were still good and the linemen gave him plenty of time to throw.

Football players have always been bulking up.  Even the early experience with extra testosterone (which causes testicular atrophy in high doses) didn’t dissuade them.  Newer anabolic steroids had somewhat fewer testicular effects.  Eventually players took to using HCG to help normalize things, but some testicular atrophy was a price they were willing to pay.  The cheerleaders felt a lot safer around those using them.

So how did the Patriots have 400 pound linemen when no one else did?  The answer goes back to Piedmontese and Belgian Blue cattle which were bred for their large muscles.  They turned out to have inactivating mutations in the gene for myostatin, a protein which causes muscles to stop growing.

Boston isn’t known as the home of biotech for nothing, and Belichick contracted with an as yet un-named biotech firm (their depositions having been sealed by the court) to come up with a small molecule (compound M) absorbable through the skin which inhibited myostatin.

No one caught on why Belicheck had separate showers installed for the lineman and defensive backs, but they had to use them and got  dosed that way.  Testing for performance enhancing drugs was always negative. The linemen loved it, as their testicles grew back to normal size.  The cheerleaders didn’t.

So there the Patriots were, about to play the Arizona Cardinals, a team only winning 3 games in 2018 in superbowl LVII. No one understood how the Cardinals turned around and how they got those very slippery running backs.

No one, except the molecular biologist they hired.  But that’s for next time.

Who wrote this?

“Illumina has a SNP chip with 50,000 markers that now costs
about $80 to run.  Public domain software platforms now exist where we
can deposit the markers and training data to increase the accuracy of
our predictions.”

A cattleman that’s who.  Someone I’ve known since he was 6.  His father, also a rancher was and is a friend.  His classmates at Harvard called him a cow farmer.  They were rather surprised when the profs picked him as their assistant, telling him as a Montanan, he was there for the bottom of the curve.  All that was 25 years ago but bicoastal arrogance hasn’t changed about flyover country as far as I can tell.

The full quote is “We are now moving into genomics to assist our population selection
strategies.  Illumina has a SNP chip with 50,000 markers that now costs
about $80 to run.  Public domain software platforms now exist where we
can deposit the markers and training data to increase the accuracy of
our predictions.  This is quite advanced in the dairy industry, but less
so in our beef sector.  ”

He knows what an SNP is.  Do you?  If not see — https://luysii.wordpress.com/2011/07/17/weve-found-the-mutation-causing-your-disease-not-so-fast-says-this-paper/

The family enterprise was always way ahead of the curve, doing in vitro fertilization and embryo transplants in the 70s.  I found it amusing that both of us have spent a significant amount of our lives trying to improve muscle (I founded and ran the local muscular dystrophy clinical for 15 years out there).  So I wrote him, after receiving a catalog about his latest bull sale,  and asked if he know about myostatin — which is mutated in two breeds of cattle (Piedmontese and Belgian Blue) which have lots of muscle.  He knew all about it.

“We raised and marketed a brand of natural, hormone free, Piedmontese
beef from 1999 through 2003.  That is what broke our company in Montana.
The product was good, but managing the supply chain was nearly
impossible.  Two owners later, the company is still going and seems
profitable at this stage.”

Fascinating that he’s using genomics — the problem is that it’s going to be very hard to find out which of the 50,000 SNPs is important to what he’s interested in (ability to gain muscle weight with minimal feed and to gain weight quickly etc. etc.  As most of you know, even when a human trait is known to have a significant hereditary component (e.g. height) and polygenic in nature, genome wide association studies (GWAS to you) explain very little of the heritability.  [ Nature vol. 465 p. 998 ’10 ] The 50 loci found in GWAS studies for height explain only 5% of the heritability of height (which has an estimated heritability of 80%.

Perhaps the cattlemen will do better than the human geneticists have done so far.