Category: Uncategorized

Kawasaki Disease: COVID-0?

When I was a medical student doing my pediatrics rotation, our cardiologist fellow came into work one day looking wan and distressed. I asked him what was wrong. Ironically, his young child had been diagnosed with Kawasaki disease, a disease that affects children and can affect the heart. Knowing exactly what the disease was, he was extremely concerned.

Kawasaki is one of many remaining medical mysteries. Striking young children, it causes inflammation of blood vessels. It can affect the blood vessels in the heart and if it does, it can be lethal. The cause is unknown. Most likely, it is thought that an unknown virus infects the victims, the victims develop an immune response to the infection, and the immune response gets misdirected toward the patient’s own tissue.

This is not an uncommon phenomenon. Many pathogens use molecular mimicry to avoid our immune systems. They try to make themselves look like part of our normal body, to evade the defense system.  In the process of clearing the pathogens, sometimes our immune system makes antibodies that end up attacking our own tissue.

We have been unable to find the virus that causes Kawasaki disease. There have been some candidates, including several coronaviruses, but so far it has eluded us.

Given that COVID-19 causes symptoms similar to Kawasaki disease, it is probably likely that Kawasaki is indeed caused by an unidentified coronavirus as well.

Here is my hypothesis: At some point in human history, a new coronavirus leapt to humans, and became established. It is now endemic and almost every single person contracts it at some point, usually when we’re infants. A small sub-fraction of the population then develop Kawasaki disease.

Imagine is the current COVID-19 were to become established across the world and everyone got it as a child. It would be asymptomatic for most people, but now there would be a Kawasaki-like disease in a small number of children.

This scenario is consistent with what we saw with polio, and consistent with my Viral Shockwave Theory. I posit that pathogens, including viruses, that are asymptomatic or mildly symptomatic in children, and can become more virulent in adults, can provide a strong evolutionary advantage to populations of its hosts.

Calorie In ≠ Calorie Out

The other day, I was reading a book, Leaf Defence by Edward Farmer. It’s a book about how plants defend themselves against insects and other animals.

Why am I reading about that, you ask? Well, I’m a drug developer, and most drugs are defense chemicals from plants. To understand drugs, you need to understand their provenance, and their provenance is plants. Developing drugs without understanding plant defense systems would be like trying to study Western art without understanding the Bible or trying to study Renaissance works without understanding the precedent Arabic works.

I’m pretty well-versed in plant chemodefenses–I know that for example yams from the Amazon (not the internet store, the rain forest)  produce high levels of estrogen to prevent herbivores that eat them from reproducing (and that those yams were the source of first birth control pills)–but I didn’t know wild carrots and certain parsleys were natural abortifactants. Obviously for the same reason, the plants are practicing population control  of animals that eat them.

I knew ancient ferns took up silica into their tissue but I didn’t know that modern plants did the same thing–essentially incorporate glass into their leaves to grind down the teeth of herbivores–and in some cases make sand stick to the undersides of their leaves to accomplish the same thing.

I knew that there were high levels of protease inhibitors in seeds to present digestion of the seeds, but I didn’t know there were enzymes in plants that specifically degrades essential amino acids to starve herbivores of those amino acids. I didn’t know that plants made diuretics to induce animals to lose sodium–and that sodium is often the rate-limiting nutrient in many herbivorous diets. I did know microbiome often made essential nutrients for their hosts but didn’t know that they are often reconstructing the amino acids that plants manage to degrade when the plant is eaten. There are enzymes that plants produce that are inactive until the plant is eaten. In the stomach of the animal, they activate, and they degrade the essential amino acids, rendering them useless to the animal (for example, threonine deaminase 2).

The take-away from the the above paragraph is that plant matter(food) is biologically active. What this means that there is an emergent phenoma associated with food–that the food is not just a collection of proteins, fat, and carbohydrate. As Pollan notes in Omnivore’s Dilemma, you can’t understand a particular food’s nutritional value just by looking at the constituent protein, fat, and carbohydrate content. Food is a complex chemical soup of very potent and active biological molecules. Depending on those molecules, your microbiome, and your genetics, the nutritional value can be very different. We also know there is microRNA in plants that seem designed to manipulate the herbivores’ gene expression–although there is debate about how well such microRNAs invade into the animals’ systemic circulation.

This goes along with several other theories and observations. For example, even with same caloric intake, people and animals can gain or lose weight, depending on what they eat. As another example, cooking food substantially increases nutritional value. This is probably partially due to the destruction of the plant’s defense chemicals and proteins.

In other words, calories in != calories out.

Membrane-less Organelles

I love this post, Bye Bye Stoichiometry by Luysii, for couple of reasons.

First, it is about a new, startling new frontier in cell biology, namely membrane-less organelles. These are phase-separated organelles in cells that are looking more more like they’re going to be really important. Instead being bound by a lipid bilayer, they’re bounded by a phase separation. You can read about it in this article, Protein Phase Separation: A New Phase in Cell Biology and in this one. It appears these membranes are important in gene transcription, in pathogenesis of neurodegenerative diseases like ALS, and many other biological processes.

For example, the DNA repeats associated with ALS appear to affect the phase separation-mediated organelles, because RNA containing those repeats are important in the phase separation.

Second, Luysii’s second order conclusion/observation is that this upends the normal flow of scientific knowledge: math->physica->chemistry->biology. This is a case of a biology observation that will lead to new work in chemistry, as physcial chemists get busy trying to understand these new organelles,