When you have different ideas than everyone else, you are either considered eccentric, crazy, or a fool.  This is, indeed, a real problem in science and engineering, where folks postulate ideas and then, often,  prove them.  But, when one is ostracized for one’s ideas, it takes a strong personality to persevere.

Think of Copernicus and his concept that the planets orbit around the sun. (This theory was called heliocentricity).  And, the problems Galileo had when he propounded that same theory- which he ‘recanted” to (literally) survive in 1633.

Well, that could include Dr. Michael Wigler.  Oh, he’s accepted now- a member of the National Academy of Sciences. But his efforts in cancer and engineered animal cells were not well received at the outset.

And, now, he’s doing it again with his autism research. (He started on this path about a decade ago, when the Simons family contacted him to work with the eponymous Simons Foundation.  The Simons began this effort because their daughter was diagnosed with ASD- autism spectrum disorder.)  Based upon what Wigler learned (and theorized) from cancer research, which he determined often arises from spontaneous mutations in our cells’ DNA.   But, he found – as opposed to what folks like me were taught years ago- that these mutations are not just one or two- or even a few base pairs- but complex changes- with enormous chunks of our DNA  changing at a moment’s notice.

He discerned that these changes seem to occur in specific, (mistake-prone) regions of our chromosome. He has determined that many autism cases also arise as last minute glitches in the formation of sperm or egg cells. (These sort of mutations in germ cells are called “de novo mutations”.)  He first reported (with 31 co-authors) in Science his findings that autism arises from de novo mutations.  (There were FOUR pages, single spaced of those affected genes that were reported within the supplemental material.)

This approach is radically different from the more conventional theory that small genetic aberrations are the cause of the autistic behavior. But, Wigler shows that these novo mutations are what leads to the dramatic effects on neurological function and development.

What Wigler and his fellow researchers did that was different was NOT look for similarities in mutations that led to multiple cases of autism in families.  Instead, he sought out those who were the single autistic candidate in the family and discerned the mutations that caused this difference.

Now, Wigler is no longer alone in this hypothesis.  Dr. Evan Eichler (University of Washington) started with studying the “fragile X” syndrome and progressed to studying what he termed ‘segmental duplications’- 10,000 or more nucleotides of DNA that repeat within the genome. Eichler recognized that these could lead to significant genomic changes- changes that would be those de novo mutations in the germ (that is- sperm and/or egg) cells.   This phenomenon actually is a major driving factor in evolutionary processes, when such changes are passed to the new generation, but generally lead to either missing or extra strands of DNA (called copy number variations- CNV).

These changes are exactly what Wigler found when he studied those children with autism- and with no sibling or parental incidence.

Wigler and Eichler are now collaborating- along with Dr. Matthew State of UC San Francisco  (actually, it’s the entire labs of these researchers; the Nature publication had more than 40 co-authors) .  They revealed in this October 2014 publication that some 300 genes may be related to autism; 27 certainly yield a much higher risk of incidence.  (While any one de novo mutation may be present in far less than 1% of those subjects exhibiting ASD, all of these mutations as a group account for about ½ of all ASD incidence.)

Moreover, some of the mutations demonstrate their effects during prenatal brain development, while other manifest their changes after birth.  (Those during prenatal period are active REALLY early- between 8 and 16 weeks post fertilization.  Which means there is a potential for not only early diagnosis, but early intervention.  That won’t thrill a whole bunch of folks who already don’t let us effect stem cells- and this sort of intervention could alarm an even larger segment of the population because of the changes in embryo that will be made.)  We also now know that every child born has some 60 new changes in DNA sequences- and one in every 50  have a significantly large rearrangement.

The problem is that these are all research papers.  Parents- both those expecting and those who already have ASD children- want results.

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