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11/12/2022

The Day I Was Right, Lucky, and Wrong, and What You Can Learn From It

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I had just graduated with a PhD and had returned to do science in the developing country that I grew up in. I joined a laboratory that performed basic science research but that also had a service for screening of medical conditions called “inborn errors of metabolism”. These conditions occur when a child is born with a genetic defect in one or more enzymes, which are the proteins responsible for carrying out metabolic conversions of one chemical compound into another. When these enzymes malfunction as a result of a genetic defect, the chemical compounds that they act upon cannot be degraded and accumulate in the body at very high concentrations causing toxicity to many organ systems including the brain. Because my degree was in nutrition with a major in biochemistry, I was considered the “expert” in metabolism, and I was supposed to do consulting work for the service. Although I had never worked specifically in the area of inborn errors of metabolism, I was newly graduated and cocky enough to think that my general training in metabolism would be enough to allow me to make a contribution.

In developed countries, newborn children are systematically screened for these genetic defects, because early treatment can ameliorate the pathology. However, in developing countries which have scant resources, many people are reluctant to perform these screenings. Inborn errors of metabolism are rare conditions, and you have to screen thousands of children to find one that has a problem. The director of the laboratory where I worked, and founder of the service, faced an uphill battle to try to convince hospital administrators in the country to join the service and send blood samples from newborn children for us to analyze.
 
One day, one of the hospitals, which our director was trying to convince to join the service, contacted us with the case of a girl who kept having seizures despite being treated with virtually all anti-seizure medications that they had at their disposal. They were at their wit’s end and suspected that the girl could have an inborn error of metabolism. A blood sample from the girl was sent to our service and after analysis yielded the result that some chemical compounds were elevated in her blood. The director of the service contacted me and asked for my “expert” opinion. I armed myself with naiveté, picked up the textbook that I had used in my biochemistry classes, and looked up the compounds which were elevated in the girl’s blood. When I checked the enzymes required for the metabolism of these compounds, I noticed that a few of them required vitamin C as a cofactor. In other words, the enzymes required vitamin-C to function.
 
When an enzyme which requires a cofactor has its activity reduced due to a genetic defect, a very common strategy is to administer large doses of the cofactor to boost any residual activity of the enzyme. The diagnosis and treatment now seemed obvious to me. I thus stated that the girl probably had a genetic defect of one of these enzymes, and that therefore we should give her large doses of vitamin-C to maximize any leftover enzyme activity. My suggestion was relayed to her doctors in the hospital which proceeded to pump vitamin-C into the girl’s body.
 
A few days later the director of the service contacted me regarding my diagnosis and treatment suggestion. The girl had stopped having seizures and recovered! And not only that, the hospital decided to join the service and send blood samples from newborn children for us to analyze! My boss was impressed. My coworkers were impressed. I, the “expert”, had made the right call! Not only did my suggestion heal a girl, but it was instrumental in convincing hospital administrators to devote resources to working with us! Because of what I did, more children would be screened, and more children with genetic defects would be identified for early treatment, which would help them. And all it had required was me checking my book! It had been sooo easy. Veni, vidi, vici (I came; I saw; I conquered). For about a week I was on cloud 9, full of myself, walking on sunshine: and don’t it feel good!
 
And then it all crashed and burned.
 
When the real experts were contacted (people who had actually dealt with impairments of the enzymes that I thought were affected) they told us that the elevations in the concentration of the compounds we detected were not large enough to indicate a genetic impairment in the enzymes. Rather these experts stated that vitaminc-C is part of the body’s defense mechanisms against toxins (oops, I had not considered that). What probably happened was that the girl was malnourished (and therefore vitamin-C deficient) and she had been exposed to a toxin that her body was not able to clear and which caused the seizures. When we gave her the vitamin-C, her body was able to degrade the toxin, and she got better.
 
I was incredibly lucky. I had arrived at the right treatment for the wrong reasons. So I had to eat a very large slice of humble pie. Thankfully, when notified about the matter, the hospital decided not to pull out, and they continued working with the service. However, I learned a harsh lesson. Even though I had a PhD, I had only a “textbook knowledge” of the field with no practical experience. I was not a real expert, and I had failed to understand that fact.
 
If you are familiar with my blog, by now you have probably figured out what I’m getting at. Today there are individuals with no formal general training in science or practical expertise in any specific field, who are reading the scientific literature and interpreting it to support opinions and ideas which they disseminate on social media, blogs, and podcasts to thousands of people. I had been trained in science. I had a PhD. But because I was not an expert in a specific field, I screwed up. Why do these individuals feel they have the qualifications to do what they are doing? And why do others follow their every utterance as if it were gospel while ignoring what the real experts have to say?
 
The experts are called experts for a reason, and it is folly for people without training to try to replace them. Luck may not always be on your side.

Four leaf clover image from OpenClipArt by Firkin is in the public domain and has been modified.


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