Saturday, March 10, 2012

Human Understanding, Randomness, Free Will, and Delusion Part I

Just because something makes sense does not mean it explains reality. And yet we are always trying to make sense of a world that scientists increasingly believe is totally random. And if the world is totally random, why do I think I have free will?

I usually do not listen to Car Talk, but I did happen to be driving in Gladwynne when Sally of North Salem, New York proclaimed, “I stumped the Car Talk guys.” Their immediate response is important. One brother said, “No, we do not have any experience with it. We haven’t given you an answer, but we will.” The other brother chimed in, “It doesn’t mean we don’t have an answer.”

What baffled the Magliozzi brothers was Sally’s driving under power lines in Waccabuc, New York and hearing a loud sound “like an electric charge” and seeing a bright light envelope the entire car. She was calling trying to figure out what happened.

One automotive expert’s answer was, “You saw something that wasn’t there or you are nuts.” His sidekick opined that Sally nodded off, was startled by interference from her car radio, and she woke up with the sun in her eyes. Tom and Ray Magliozzi are both MIT graduates, and they realized they did not really know what to tell Sally. They decided to ask their 4 million listeners to make sense of Sally’s experience and labeled the discussion board on their website as Weirdness in Waccabuc. (

The responses demonstrate that humans are never at a loss for an explanation, even when they have no idea what they are talking about:

“She was hit by a random lightning bolt.”

“I’m a pilot. Occasionally when the atmospheric conditions are right, we get a thing called precipitation static building up on the windshield. When it eventually discharges it can create quite a bright flash or sometimes ‘dancing lights’ called St. Elmo’s Fire.”

“Sally had a seizure.”

“It’s obvious, and I’m stunned that you were not aware that she had been scanned by the MOTHERSHIP and more than likely transported to the MOTHERSHIP examined and returned in a flash of light.”

“What appears to be a flash of light can be a symptom of a serious retinal (eye) problem, and you should call her and urge her to see an ophthalmologist as soon as possible.”

“Did anyone consider she might have had a slight stroke? It’s called a TIA and this might explain things, as there was nothing wrong with the car. Maybe she should go to the doctor.”

“I wonder if this experience could be symptoms of a brain disorder, i.e., a brain tumor or seizure or even an aura of a migraine…. She should probably see a doctor.”

“Waccabuc is also rich in Indian history…. Some people claim that they’ve seen Indian spirits lighting the ovens, especially at night. Most of those who claim to have seen the lights have viewed them from their cars.”

“You need Nikoli Tesla. Sally experienced what is called “Ball Lightning.” The bright flash and cackle are typical. It’s a harmless but often terrifying ionization of air caused by a large static charge…. Her tires built up static on the dry pavement. She passed under the power lines at exactly the right moment, and the field she passed through triggered the ionization, just like the trigger capacitor and transformer trigger a camera flash.

My money is on the last explanation, and I am even surer that I truly understand what happened to Sally after consulting my books on Tesla, an eccentric genius who has always fascinated me. But are there some things that cannot be readily explained? And why is it so hard to accept the truth once it has been revealed? And why do we humans have to try to understand everything anyway?

We humans get ourselves into trouble all the time by thinking we understand things when we really don’t. A good story that makes sense is enough for many of us to jump to conclusions that reinforce our view of the world.

I am reminded of this problem by two books I recently read: Misha Angrist’s Here Is a Human Being at the Dawn of Personal Genomics and Ricki Lewis’ The Forever Fix. Angrist is uniquely qualified to explore the many issues surrounding those who want to understand themselves by sending off their spit specimens to 23andMe or Navigenics. Angrist has trained as a genetic counselor, received a PhD in genetics from Case Western Reserve, teaches at the Duke University Institute for Genome Sciences and Policy, and was the fourth subject in Harvard’s George Church’s famous Personal Genome Project. His book describes how the blogosphere warmly embraces the “Saliva Diviners” who truly believe that knowing one’s genome will allow one to progress from traditional medicine’s diagnose and treat to digital medicine’s predict and prevent. He also gives equal time to physicians and scientists who emphasize that knowing one’s genome does not really tell you how to prevent most diseases in 2012; there is not much actionable that one cannot get from a much less expensive detailed family genetic history. Referring to the CEO of Navigenics, one scientist told Angrist, “Dietrich is a nice guy. The 23andMe people are nice ladies. But I don’t know what this is going to do for anybody. It’s a waste of time and money.”

Angrist concludes his book by stating: “I had come and seen my genome…But of course I ignored most of their contents. Not because they were toxic, but because in the end, this journey of self-exploration had turned out to be more of a speculative intellectual exercise than a life-changing clinical one. I had arrived at the theater early enough to grab a good seat, but the carpenters were still building the set.”

Truly understanding genomics keeps getting harder and harder because nature is really complicated and complex. For example, an allele can predispose a patient to type 2 diabetes when inherited from the father, but the same allele can protect against type 2 diabetes when inherited from the mother. Epigenetics is the emerging study of how histone proteins and methyl groups attached to DNA control when individual genes are turned off and on during a human lifetime; their discovery has complicated the easily understood metaphor that genes are the software of our body. This week’s New England of Journal of Medicine had disturbing news for those of us who want to believe that personalized medicine means we can genotype malignant tumors to guide targeted therapy against the specific defective biochemical pathway caused by mutations in the tumor DNA. Genotyping of 4 renal cell carcinomas revealed that only one third of the 128 mutations were present in all sites sampled and that mutations were different in primary and metastatic tumors. (

During the 1990’s I thought I understood how gene therapy was going to revolutionize clinical medicine in short order. It seemed straightforward to identify the genes responsible for a particular disease; it seemed logical to fix the defective gene and load it into viruses to get the therapy into the affected cells. Many experts agreed with the director of Stanford’s Gene Therapy Technology Program who predicted in Business Week, “Within the next decade, there will be an exponential increase in the use of gene therapy.” Shortly after the publication of that optimistic prediction, Jesse Gelsinger died after undergoing gene therapy at the University of Pennsylvania for a genetic metabolic disease. Lewis’ book The Forever Fix brilliantly examines why gene therapy has not yet lived up to the promise many of us saw in the late 20th century.

Carl Zimmer in a book review of Lewis’ book applied Jackie Fenn’s Hype Cycle graph to grapple with why we get so excited about scientific breakthroughs that we think we truly understand.

“Again and again, she had seen new advances burst on the scene and generate ridiculous excitement. Eventually they would reach what she dubbed the Peak of Inflated Expectations. Unable to satisfy their promise fast enough, many of them plunged into the Trough of Disillusionment. Their fall didn’t necessarily mean that these technologies were failures. The successful ones slowly emerged again and climbed the Slope of Enlightenment.” (

Part II will continue our exploration into human understanding and delusion.

1 comment:

  1. we have known the sequence of the dystrophin gene since 1987. The benefit to boys with the disease? nothing. We still play around with steroids. So why would anyone think genome sequencing would be of any immediate benefit? Gene therapy is the same. So I want to treat someone with MS - how do I get the cells to JUST the right spot, myelinate JUST the right axons (at least the ones are no too far gone) and remain oligodendrocytes for the next 40 years and not change into an oligodendroglioma? You willing to take that chance? (oops there's that word again)