You know how we all look for that one key to a problem.  Which begs the question- what makes us so sure that it’s just one key?

Let’s investigate a real case that demonstrates that why seeking one key (like the “one” that causes “Alzheimers” or autism) is often a chimeric venture.

We know (to the best of our ability, based upon this 20 year old theory) that autism is a disruption in the balance between two types of nerve cells that populate our cerebral cortex.  That is the region of the brain that deals with thought, emotion, decision-making, and language.   The nerve cells in this region causes other nerve cells to fire (interneurons, which are inhibitory).  If the interneurons are overexcited, then the brain manifests epilepsy.

How does the body produce more interneurons?   These neurons start out in the subpallium section and then migrate to the cerebral cortex during gestation; the process ends with the first year of the infant’s life.   Sergiu Pasca (Stanford) [X Mena, D Yao, K Imaizumi, KW Kelley, N Reis, MV Thete, S Kulkani, MC Bassik], along with two from UCSF [AA McKinney, G Panagiotakos, both are also associated with the Icahn School of Medicine (Mt Sinai, NY)]  decided to study the 425 genes that are linked to neurodevelopmental disorders.  They hoped to find the gene that disrupted the generation and migration of the interneurons.  The team  published their results in the journal  Nature, Assembloid CRISPR screens reveal impact of disease genes in human neurodevelopment.

Not surprising, it’s a bit of a bitch to screen for 425 genes.  So, they manipulated the cells so that only the nerve cells that prohibit others from firing would manifest a green flow.  On top of which, they used CRISPR to create a slew of cells, each one missing just one of those 425 genes.  They sought out cells that manifested two defects- the failure to generate the interneurons and those where the interneurons failed to migrate to the cerebral cortex.  (All of these tests were effected in vitro, not in live humans, of course.)

They found when 13 genes were absent, interneurons didn’t form. Moreover, there were 33 other genes that (when missing) precluded the migration of interneurons to the cerebral cortex.  FORTY SIX genes!  (That’s not really surprising, since autism is not ONE disease, but a panoply of disorders.)  One of which genes, LNPK was manifested with seizures, validating the hypothesis that too much excitation of neurons and too little inhibition would result in seizures.

(To further complicate the issues, some autistic folks have microglia defects.  [The microglia regulates brain development, injury repair, and network maintenance [the one that processes information].)

Obviously, more research is needed to better deal with the issues.

I am recommending you obtain a copy of “One Bold Move a Day”, written by Shanna Hocking.  The book shares hard won advice and insights gleaned from 20 years as a successful manager of large teams.  Shanna helps you choose concepts and methods to reach your goals every your personal life.  And, the key point- the time to start is now!

Among suggestions in the book is seeking out a mentor, even a personal board of advisors,   as well as these suggestions- stop relying on external validation, stop trying to prove yourself, there is no such thing as perfect or a perfect time, celebrate the progress you make each and every day, and practicing gratitude.

I am asking you- my loyal readers- to provide me a short blurb of what you are doing to make yourself better each day, how you are helping to remove the bias against women and minorities in STEM and management, and the like.  (Use this form, please.) I will choose among those items submitted between today and the 1rst of November and provide you a copy of Shanna’s book, One Bold Move a Day.

Good luck!

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