The Unsung Powers Of Moderation In Business
By Derek Hennecke, CEO of Xcelience
We live in a society that worships the new, the radical and the fast; yet we live on a planet that overwhelmingly favors a moderate pace to win the race. Can both be right?
Most innovation is gradual, organic, and moderate. In the cellphone industry before 2007, a new phone debuted every three months with one or two minor improvements over the previous model. The iPhone was a “leapfrog innovation”, a term coined by Apple’s Steve Jobs to capture the idea of leaping over your competitors’ heads with an innovation that is well ahead of the curve. Leapfrog thinking is the new management mantra and the topic of numerous management books and MBA courses.
From technological innovation to diet, our society glamorizes extremes. Is tea good for you? Then drink nothing but tea. Is gluten bad for you? Then don’t ever touch it. Do heights give you a thrill? Then bungee jump off a bridge. In this age of extremes, it’s easy to forget that most of the time, moving too quickly, growing too quickly, or doing anything in extremes is actually not a good idea. When extremes work out, they make great headlines, but the world contains far more examples to remind us that, in most cases, extremism doesn’t favor survival.
Huntington’s Disease: Too Many CAG Repeats
Over a period of about twenty years from onset, Huntington’s disease gradually but inevitably robs its victims of their minds, their mobility, and their emotional control. Many genetic diseases are capable of similarly unfortunate consequences, generally a result of a missing piece of a gene, or a gene with the wrong genetic letters on it. But Huntington’s is different.
Huntington’s is getting attention because of a mounting body of evidence to suggest it is caused by too much of a good thing.
In Huntington’s, the disease-causing version of the gene has too many nucleotide repeats, and the resulting protein, known as huntingtin, is different. Every huntingtin gene contains a stretch of repeating nucleotides: C, A, and G. This translates into a chain of the amino acid glutamine, and the average number of repeats is 17. Up to 35 repeats is considered healthy. Between 36 and 39 repeats may cause symptoms. Forty and above will definitely develop the disease.
The first clue that something was different about Huntington’s was its dominance, according to The Economist (“Brain evolution and diseases: a Faustian bargain,” March 7, 2015). Most genes are recessive; both parents must pass on the faulty gene, unless the child is male and the bad gene is on his single X chromosome. In Huntington’s, only one parent needs to have it to pass along. To make matters worse, symptoms usually begin in the mid-30’s, after the prime reproductive period. Natural selection really doesn’t get a shot at reducing incidence of this terrible disease.
The next thing that caught researchers’ interest was the fact that children as a rule tend to have more CAG repeats than their parents — a phenomenon called anticipation. This suggests that evolution is pushing us into a new direction; that somehow more repeats are better, though too many clearly leads to disaster.
What benefit could there be to more CAG repeats? We don’t know a lot about the Huntingtin gene, but because it is produced in the relevant cells, we know it has something to do with the construction of brains in embryos and the process of learning. We also know that the gene has a very long history. Even the unassuming amoeba contains a Huntingtin gene with no CAG repeats. Sea urchins have two repeats, zebra fish four, mice seven, dogs 10, and rhesus monkeys 15.
So there is a correlation between complexity and number of repeats. Correlation, however, is not cause. To determine cause, Dr. Elena Cattaneo, a cell biologist at the University of Milan, collected embryonic mice stem cells and extracted the huntingtin genes from them. Then she and her team mixed the remaining cells with growth factors and encouraged them to differentiate into a type of stem cell called a neuroepithelial cell. The hope was that these cells would organize themselves into a neural tube, which is a rudimentary brain and spinal cord. The experiment doesn’t work perfectly in vitro, but whole cells will try to organize themselves into sorts of rosette-shaped structures.
Without their huntingtin, however, the cells were incapable of organizing themselves into anything at all. Then, Dr. Cattaneo tried something really interesting. She introduced the huntingin gene back into the mix — not just the mice huntingtin gene though, but huntingtin genes from various different species. What happened? In every instance, the cells immediately began to organize again. How well they organized depended on the number of CAG repeats in the gene they received. More repeats was definitely better. CAG repeats seem pretty closely related to the evolution of neurological complexity.
Dr. Peg Nopoulos, a neurologist at the University of Iowa, tested this relationship with kids between the ages of six and 18. When comparing test performances and brains scans to CAG counts, she found significantly higher levels of motor coordination and intelligence correlated strongly with a higher CAG repeats, according to the Economist.
More CAG repeats, the evidence suggests, means more intelligence and motor co-ordination. Too many causes Huntington’s disease. Evolution favors growth, but not too much.
Too Much Broccoli?
Your mother always said that what doesn’t kill you makes you stronger. Granted, she was probably just trying to get you to eat your broccoli, but anyone who works in toxicology knows that this common advice is just the tip of a much broader theoretical iceberg. Hormesis is a fundamental principle of biology, whereby organisms exposed to low levels of stress or toxins get better at standing up to tougher challenges. Think vaccines and immunotherapy, but also vitamin A, vitamin B6, selenium, iron, and zinc. A little imparts a benefit; too much could hurt or kill you.
A 16th century Swiss physician and alchemist wrote, “All things are poison and nothing is without poison, only the dose makes something not a poison.” (“Best in small doses”, New Scientist, 9 Aug 2008).
How do low levels of stress or toxins make you stronger? When your body is threatened, it calls up an army of defense molecules to take on the threat, increase resistance to future threats, and if necessary, to repair damage. The precise make up of this army depends on the particular threat. When cells are exposed to high temperatures, toxins, or inflammation, heat shock proteins come to the rescue. They work to protect other proteins from damage by binding to them and shielding them. Other armies are capable of enhancing cell function while they protect. Growth factors, for example, are released in the brain during exercise and promote the growth of new nerve cells and synapses. They can even reverse existing damage, causing a proliferation of fresh healthy cells in damaged tissue, according to New Scientist.
Which brings us back to broccoli and why your mother, once again, was right. We all know that eating fruits and vegetables reduces your risk of cardiovascular disease, cancer, and some neurodegenerative disorders. The usual reason given is that fruits and vegetables are rich sources of antioxidants, which neutralize free radicals—those nasty chemicals we all produce as an unavoidable by-product of metabolism. Scientifically, however, this argument doesn’t stand up well. While it’s true that free radicals are implicated in all of these illnesses, and it’s also true that antioxidants can mop up those free radicals, the reality is, you can’t possibly eat enough fruits and vegetables to get the concentration of antioxidants in your body high enough to trigger this clean-up operation.
And yet, fruits and vegetables have been shown to improve your odds against these diseases. How? Antioxidants are part of a wider class of plant chemicals called phytochemicals that are—wait for it—toxic in high doses, but beneficial at lower doses. Think of antioxidants as a natural pesticide that evolved to deter herbivores. The amounts we eat aren’t enough to reach toxic concentrations in our bodies, but they are enough to wake up our army of defense molecules. They are hormetic stressors.
As a manager and a microbiologist, I love finding parallels between the business world and the natural world. I’m not going to argue that Apple was too radical or grew too fast—obviously this strategy worked for Mr. Jobs and Mr. Cook. But they are outliers. For every company that grew hard and fast and prospered, there are hundreds of bankruptcies and failures. Xcelience has quadrupled in the past nine years, and I’m feeling pressure to grow faster. We have plenty of opportunities to do it, but it might be too much of a good thing. In business as in nature, our chances of survival are better if we exercise a little moderation.