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On the heels of reading Creativity Inc, penned by Ed Catmull, I wondered if scientists are really creative. Researchers are trained observers that ascribe to the scientific method, gather data, and analyze their data using statistics.  Statistics is an imagination snuffer.

Great discoveries sprang from scientists that showed imagination and out-of-the-box thinking.   Are the greatest scientists artists, as suggested by Albert Einstein? Can you teach creativity?  The book suggests an environment that fosters creativity is possible, but can that be done in the laboratory? Add a few cats to lounge around?

The four stages of creativity are preparation, incubation, illumination, and verification.  Where does creativity live?  It is said the step between incubation and illumination is where the mind-magic happens. Mind-magic is an internal process, perhaps day dreaming. The verification is the analytical process and is a different neural circuit. When one is taught by rote, and SOP’s, creativity declines. There is a place for repetition, and that’s churning out data.  The creativity we are discussing here is a leap of faith to grasp a paradigm-shifting novel concept.

Each persons creativity is honed by tools they stumble upon for themselves.  It may be mediation, exercise, whatever tool will turn down the noise of the conscious mind to let ideas flow. Scientific creativity is a process. A path to finding an answer. That is a linear and logical process. Built upon ideas that came before. We agree with Ed Catmull, that success in solving a big problem doesn’t come from a brilliant idea, it comes from a great team. Part of the team is the past, researchers that paved the way using technology to leap into the future.

We have undertaken the problem of identifying and treating ALS by forming a team.

Our team is a group of nineteen scientists and reaches from British Columbia across the US and on to Brazil.  Our topics are secretome, the elixir of stem cells that may normalize a corrupted system.  We look at nucleic acids (DNA, RNA, miRNA), antibodies and peptides. Some team members harnessed fat mesenchymal cells to assay for toxic properties and seek chemicals to reverse the damage. We are borrowing ideas from our EPM and PNE work, from pathology to curative molecules.

What we’ve discovered is that removing information silos and blurring the lines between disciplines is fostering progress.  We anticipate sharing our discoveries with a platform available to all.  Keep listening, I’ll let you know when we launch!

As Buzz Lightyear said: "To infinity and beyond!"

When chemists envision novel products, they undoubtedly have a target in mind. A vast knowledge of chemistry allow them to examine the binding sites on the  intended target molecule.  Back at the bench, they combines basic ingredients, and by trial and error, a novel drug is created.  Of course, the careful chemist has an end game and that is a testing system for the new compound.

The new drug has to be relatively non-toxic at an effective dose. Organic synthesis can take years of work with many dead ends.  High throughput computer systems may reduce the discovery tasks and even identify potential compounds and targets. Bioreactors are used in the laboratory to grow organisms that produce a desired product. Biosynthesis is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms.

Sixty five years ago an inventive group of Belgium scientists fed a newly made drug to chickens and found it active against ascarids. The drug was also active against sheep ascarids, but it was inactive in the species infecting rats or mice.  They collected the chicken feces and separated out the drug metabolites that were passed in the manure.  Amazingly, the manure contained a new molecule active against another chicken parasite as well as parasites found in sheep.  This new molecule was active against those ascaris species infecting in rats and mice!  Further testing revealed activity against gastrointestinal and lung parasites found in cattle, pigs, horses, pigeons, pheasants, ducks, cats, tiers, monkeys and man! This experiment was great for discovery but is significant food for thought.

It is worth considering that the drugs that are given to horses can build up in pastures and water.  Many drugs are eliminated through the feces. Unintended contamination of the environment is a serious concern and one important reason not to chronically treat animals with unnecessary medications.  Not only are you medicating pasture mates at ineffective low doses or new compounds, you are treating the wildlife. Soil organisms, insects, small mammals, and pasture mates are all exposed. What effect do these metabolized drugs have on the environment? You can check the Freedom of Information Summary for the levels of compounds that are excreted and the types of laboratory experiments that were conducted to determine environmental safety.  However, if several animals are treated over long periods of time the unintended consequences can be significant.

Often neurologic diseases look alike.  For instance, two diseases that look like EPM to the untrained eye. The difference between equine motor neuron disease (EMD) and equine degenerative myeloencephalopathy (EDM) can be subtle even to the expert.  The onset of age should be considered, EMD is often diagnosed in older animals while EDM is present in younger animals, although signs of EDM may not be present until the horse is 5-10 years old.  Signs are weakness and muscle loss. EMD horses show weight loss and sweating, EDM horses have a classical presentation of symmetrical ataxia.  Both diseases resemble wobbler syndrome, EPM or EHV-1 infections.  The diseases are distinguished because EMD is a neuropathy of lower motor neurons (LMN) while EDM involves upper motor neurons (UMN), it affects the brain stem and spinal cord.  A veterinarian can determine if a disease involves the LMN’s or UMN’s and this distinction weighs heavily in the potential diagnosis and treatment plan.

EMD accounts for 23% of neurological diagnosis in horses seen at major universities and has been likened to amyotrophic lateral sclerosis (ALS) in people.  A treatment for EMD is vitamin E supplementation in horses that have a deficiency.  Deficient vitamin E levels are determined by analysis of plasma levels. Forty percent of EMD horses may improve, forty percent are expected to show no improvement, and twenty percent will decline.

EDM can sometimes respond to vitamin E treatment.  It is suspected that there is a genetic cause of disease that has an environmental trigger.  The treatment may stabilize the neuropathy, but the animals don’t improve. Once diagnosed these horses should not be ridden. They are retired and can often end up in rescue facilities.

It is interesting that these diseased horses have a pigment retinopathy. The retina has a high rate of oxidative metabolism and high lipid peroxidation in the outer photoreceptors.  Oxidative stress in tissues causes damage. Horses are animals with a tapetum and the pigment deposits left  by oxidative damage are observed in the retina during an eye examination.  Recently, the etiology of a unique retinal pathology was described in a former high incidence foci of Western Pacific ALS and Parkinson dementia complex, ALS/PDC, in Guam (USA) and the Kii peninsula of Honshu Island (Japan).  It was suggested that the ALS/PDC-associated retinopathy could be due to in utero exposure of a genotoxic metabolite. It is interesting that mice with a genetically induced form of ALS (SOD 1) show retinal ganglion cell loss and microglial activation. The microglia are mediators of inflammation the central nervous system. The mouse model indicates the nervous system pathology may be a result of oxidative stress. What is an interesting finding is that some inflammatory markers can be measured in the mouse using special histopathology stains. If the mice were treated effectively for disease-associated oxidative stress it would evident on histopath.

We are continuing to developing new treatments for neurodegenerative diseases in people and horses.  One encouraging new therapy targets issues found in lower motor neuron axons and another targets multiple pathways, including neuroinflammation.  We are using the ALS mouse models initially, and thenf10-09-9781437708462.tif we will look for the disease in equine patients. We continue to build our database for potential patients, if you have a horse with EDM or EMD, or have donated a horse to a rescue diagnosed with these diseases, please let us know.

This is a picture of the normal equine eye showing the optic nerve and tapetum.