Dr. Richard S. Lord, nutritional biochemist extraordinaire and Chief Science Officer at Metametrix Clinical Laboratory (now Genova) recently retired after 25 years. Richard was the director of the Medical Education team when I was in Atlanta at the lab. Richard was and continues to be, my teacher. There has been no greater influence on my thinking as a clinician and scientist than Dr. Lord. He inspired me to always question, embrace the uncertainty, trust the data, and argue my point (with evidence, of course!) RSL, this blog is for you!
When I interviewed for the postdoctorate position at Metametrix Clinical Laboratory in 2004, I was a bright-eyed student finishing my final year in naturopathic medical school. I was nervous and excited. The lab was a marvel of glass and metal. Gleaming rows of instruments: LC MS/MS, GC/MS, HPLCs and on…. Lots of machines that go “bing” as Monty Python said.
There was a library with thousands of journals and almost as many textbooks – and a librarian, Cathy Morris, dedicated to obtaining full text article requests.
I was in awe.
My interview with Dr. Lord that day was not unlike skimming along the white tips of ocean waves on a speed boat. I may have only caught every fifth concept that he expounded on but I was transfixed. There was no other place on earth I wanted to be!
Richard’s focus in that 2004 interview and for some months thereafter was around the clinical implications of low plasma homocysteine. He was gracious in allowing me to participate in writing the company’s white paper introducing the concept.
I know, you’re a good integrative clinician, and low plasma homocysteine is old hat to you at this point. But at the time, virtually no one was thinking about its relevance as an essential precursor to glutathione, taurine and sulfate; that low levels of homocysteine suggested that the body’s ability to respond to oxidative stress with glutathione and to engage in phase II biotransformation, was at serious risk.
If we thought about homocysteine at all, it was as a cardiovascular risk marker, where only high levels were considered relevant.
Now, transmethylation and transsulfuration are key pathways memorized by all students of integrative and functional medicine. Methylated folate, B12, n-acetyl cysteine are prescribed routinely.
Dr. Richard Lord put low homocysteine on the map and educated us as to its relevance. Quest Diagnostics later adopted a lower limit after Metametrix started reporting it.
From Laboratory Evaluations in Integrative and Functional Medicine, Bralley and Lord, 2008
I was moved by the magic, the power, of nutritional biochemistry and the intellectual journeys I took with Richard. It seemed to me then–and it still does today–that the solution is present in understanding as fully as possible the question.
We could look “under the biochemical hood” of the individual, piece together their metabolic story and correct it with pinpointed nutritional and dietary interventions.
And it worked!
We could effectively reduce disease risk, oxidative stress, and inflammation; improve mitochondrial function, energy, mood, sleep; identify and reduce toxic burden and reverse neurological deficits and tweak the gut microbiome. Sometimes, we could turn the disease process around completely, uncover and successfully treat genetic conditions otherwise missed. Nothing was outside our reach of investigation. It was a grail quest.
I remember consulting with a doctor regarding a patient’s organic acid results. This individual had a seizure disorder, onset at 16, which was non-responsive to any medication.
Her organic acids revealed a very elevated beta hydroxyisovalerate (BHIV), a catabolic intermediate compound derived from the amino acid valine that accumulates with a biotin deficiency. In her case, given the severity of her condition, there was likely a mutation in the biotin-dependent carboxylase enzymes required to metabolize BHIV. The mutation wasn’t apparent at birth, when organic acids are routinely tested, looking for inborn errors of metabolism. It was too mild to be seen with the broad reference ranges able to identify only the severest cases. She wasn’t symptomatic until 16 years of age. It took the more sensitive reference ranges we employed at the lab to identify it.
The young woman was treated safely with high doses of biotin, which pushed the faulty carboxylase enzymes to function. And her seizures resolved.
Another great case involved a young man with Melnick-Needles Syndrome. MNS is an extremely rare condition caused by a mutation in the gene that codes for filamin A, a protein that provides structure for cells. Being such a fundamental player in sustaining life, a filamin A mutation is often fatal shortly after birth.
We carefully individualized his nutrient intake of amino acids, fatty acids, vitamins, minerals to meet his exact needs by looking at his laboratory data every six months. It worked for him.
At the time of my last consultation regarding this patient, he was graduating high school. He was the oldest known living individual with MNS.
Proteome, microbiome, metabolome, exposome.
These are the sexy, current terms used to describe what was started at Metametrix in 1984, when Dr. Andy Bralley began measuring plasma amino acids – the first steps of an investigation into the proteome. With Dr. Lord, our lab was the first to launch an organic acids test sensitive enough to pick up subtle nutrient perturbations correctible with diet and nutrient interventions: insight into the metabolome.
With the launch of DNA analysis of gut bacteria, fungi and parasites, we could look into an individual’s microbiome.
Taking everything together, including looking at toxic compounds, we were, and are, glancing into the exposome.
Andy and Richard, along with many other great folks, including our education team of Cass Nelson Dooley, Betsy Redmond and Terry Pollock, worked overtime providing the scientific rationale for these investigations in the form of a textbook: Laboratory Evaluations in Integrative and Functional Medicine. Published in 2008, with more than 3800 citations, it remains the functional laboratory standard.
The Medical Education department, led by Dr. Lord, knew its work was essential, important, reflecting the company’s mission statement: To improve health worldwide by providing clinical laboratory testing services in the areas of nutrients, toxicants, hormonal imbalances, biotransformation and detoxification, gastrointestinal function, and the microbiome.