A decade ago, I finished my teaching gig with the middle school in New Haven. I started this research journey to unravel the connections between chronic brain parasitism and neurological diseases. This problem impacts over 2.5 billion humans infected with the brain parasite Toxoplasma.
I did not how to answer such a big and complex question. But, my middle-schoolers screamed in my dreams, “Dr. Ngô, are you walking the walk, or just talking the talk?” (see Biography). So, I closed my eyes and took a plunge of faith.
The classical training stuck with me from past biology mentors such as Drs. David F. Parmelee, Gerald W. Prescott, David B. Czarnecki, and Ben G. Bouck. A biologist explores as many factors of an ecosystem as possible. A scientist must examine as many components of a research problem as viable. You don't take shortcuts. You do things the right way!
I left behind that foundation to chase the leading edge of science. Success at Yale Medical School taught me to be more linear and focus only into a small piece of the puzzle.
My gut told me I needed both approaches, but more so of the ole school thinking, to solve this complex problem.
Since most of this work done was in the shadow of established research programs, I chronicled this personal journey. It breaks into eight entries so the reader won't fall asleep and bonk their head on the computer screen. I took an unconventional, difficult route ‘to do things the right way'. It needs narration. I need catharsis!
Summary of My Journey.
In 2006, I expected the following decades would be an argumentative debate between the Toxoplasma traditional camp and a smaller emerging group of incoming researchers.
The first group posited without proof a long-standing dogma. Chronic brain infection had no significant consequence unless the host is weakened from being immunocompromised. It's ‘harmless’.
The second provided data and perspective linking chronic brain parasitism to other brain diseases such as schizophrenia. Epidemiology and serological surveys of the general population would start, but fail to carry convincing proof to the debate (see Brain Parasite Toxoplasma).
I bypassed this argument because the more logical dogma should have been: a eukaryotic organism living in the intricate brain of human host will have consequences.
The right questions should be: Which brain diseases are linked to the chronic infection of a protozoan? How? And what we do about it?
I chose the strategy of concentrating on a human cohort with the infection. We could identify critical human gene networks leading to brain pathology. I chose also the ‘ecological’ approach. Studying the micro-ecosystem of a protozoan parasite living in the human brain requires an integration of major inputs/causes and outputs/effects. A more holistic approach was needed to study an infected human organ.
One could predict obvious trends and be at least a decade ahead of the pack and simply avoid competition. This style of leapfrogging the pack has several major drawbacks. One is the lack of peer interaction and support. Second is the lack of institutional and financial support.
The current, protracted debate delay, or ignore, the most important question. How to solve the human disease problems? Hence, I built with a network of collaborators a platform of protein crystallographic structures (see Drug Discovery). The mission is find drugs to kill the brain parasite and to heal the neural damage.
The results are:
1. We decoded the neurological gene-protein network that may associate Toxoplasma brain parasitism to neural cancer, Alzheimer's disease, epilepsy and several movement disorders.
2. We built a base of protein crystallographic structures to use for future drug design in targeting the brain parasite.
The diagram below shows my map of this decade-long journey. It breaks into 3 periods.
Diagram 1. Huân's offbeat journey in developing the two-pronged strategy to find cures for brain parasitism and diseases.
The first phase is the one and half years spent working from my home. I learned basics of neurobiology. Then, I deep dived into an analysis of over 600 mammalian genes moderated by the parasite. The gene list assembled was based on studies published up to 2006.
I wrote a short document of my early “Neurocompromised Hypothesis”. It proposed that susceptible genetics compromise a human brain to Toxo parasitic effects, resulting in neuropathology. I did not publish this piece because the dataset was a largely artificial construct. We did not need more noises in the debate.
What emerged was my shift in the gene-environment paradigm. I changed it to gene-environment-development paradigm.
The second phase is my tour of scientific duty to Chicago armed with the new paradigm. I rebuilt my science network and laid the foundation for the 2-prong strategy of tackling brain parasitism (see Brain Parasite Toxoplasma).
For the last phase I was back at home. For 5 years, I deep-dived again into learning new sciences to solve the problem. I learned Neurobiology, Systems and Structural Biology while waiting for the grueling progress of my collaborators.
In 2015, I finally had proper datasets in hand. I took another deep-dive for seven months. I emerged with the Reconstruction and Deconvolution model. Most important is the satisfying maps likely linking Toxoplasma brain infection to cancer, epilepsy, Huntington’s and Alzheimer’s disease.
In 2017, an excessive version of my manuscript is published. The discoveries and thoughts from my home (see BrainMicro LLC) remain the meat of this publication (Diagram 2).
Diagram 2. Core paradigm and Reconstruction-Deconvolution of Toxoplasma brain infection.
In future journal entries, I will discuss more in depth the roadblocks and my solutions to find cures for brain parasitism and diseases.
Journal Schedule
Entry 1. Walking the Long Walk, posted November 5, 2017.
Entry 7. A passionate plea to my colleagues, posted November 5, 2017.
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Entry 2. The Roadblocks, 2018.
Entry 3. Preparing for the Walk (2006-2007), 2018.
Entry 4. Scientific Tour of Duty (2007-2011), 2018.
Entry 5. Two-Pronged Counterinsurgency, 2018.
Entry 6. The Lost Art of ‘Synthesis’ (2011-2017), 2018.
Entry 8. I walked the walk less travelled, 2018.