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A Portuguese mother in labor and Throwback Innovation

The real voyage of discovery consists not in seeking new landscapes, but in having new eyes.

-Marcel Proust

One night when I was a medical student, I was doing my rotation through obstetrics at the Brigham and Women’s Hospital in Boston. It was about 8 pm at night, and I was exhausted from delivering several babies already.

Suddenly, a commotion erupted down the hall. An orderly and a nurse were wheeling in a pregnant woman. The patient was screaming incoherently, and writhing. She was obviously in tremendous pain.

We rushed to her and I set about taking her history, except… I quickly realized she sounded incoherent because she was speaking in a foreign language. She didn’t understand English.

My resident and I just stared at each other blankly, at a loss. We didn’t even know what language the woman was speaking. Then one of the delivery nurses told us the patient was speaking Portuguese.

Our nurses scattered throughout the hospital out to find a translator, and after quite a while, we located the one Brazilian nurse in the hospital who spoke Portuguese. It was a difficult delivery, and the mother was in quite a bit of distress, but fortunately the baby was healthy.

The next morning, I stood outside the room, and recited her history to the attending physician “26 year old Portuguese woman, G1P1A0 (Gravida 1, Para 1, Abortus 0, which means pregnant once, delivered one child, no abortions)…” At then end, I added, “and oh by the way, she only speaks Portuguese.”

But to our shock, when we entered the room, the new mother sat up, smiled brightly, and said “Good morning, doctors.” Surprised, and a little chagrined after I had just told my attending that she only spoke Portuguese, I said, “I thought you didn’t speak English!”

She looked puzzled, saying, “What do you mean? I was born in Portugal, but I moved to the States when I was three. I’ve forgotten all Portuguese. I only speak English.”

Indeed, she knew hardly a word of Portuguese, now that she was not in labor. But in the throes of labor, with the pain, she had forgotten all English and was tapping into Portuguese that she had learned as a child.

The point is this: in times of stress, we sometimes tap into abilities we didn’t even know we had. We are programmed to reach into our reserve and draw on talents we don’t — perhaps can’t — access under normal times. Portuguese was buried deep inside her, it had never disappeared.

History May Not Repeat, but it Rhymes

This has an important parallel in innovation.

We tend to think of great innovations as completely new inventions that have never existed before. And in some rare cases, that is true: steam engine, flight, polymerase chain reaction.

But many innovations, especially business innovations, come from reaching into the past and pulling forward into the present some innovation or business long forgotten. Just as the stress of labor allowed the re-emergence of Portuguese hidden deep into the recesses of this mother’s mind, many of the recent innovations emerged because internet allowed a previous suppressed product-market fit to re-manifest itself.

These are what I call Throwback Innovations. Like phoenixes, they are old ideas reborn. They include companies like Airbnb, Uber, Twitter, and eBay.

Let’s start with Airbnb. Almost all the people that Brian Chesky, one of the Airbnb Founders, talked to when he was starting his company thought the idea was crazy. No one thought people would want to rent out rooms in the their houses. Fewer still thought people would want to stay in other people’s houses.

The only exception was his grandfather, who said, “Of course that will work. That’s how we often used to travel when I was young – staying with people in their private houses.” (Indeed, for African Americans, sometimes the only way to travel was to stay in other people’s homes – hence the Green Book.)

Indeed, before modern hotels and motels, that’s how many people travelled – in other people’s houses. But with advent of hotel chains like Howard Johnson that offered consistent, reliable, and convenient service, the local home-stays couldn’t compete. People wanted to stay in hotels that they trusted. Mass market hotels took over. Until the advent of the Internet. Internet allowed Airbnb hosts to offer the same convenience and more importantly, trust, to travelers. It leveled the playing field and the lodging industry reverted back to the past.

One of the most important things for new tech startups is the product:market fit. They strive for, and often have difficulties with, finding a product that people want.

But, the markets are as old as the human race. Technologies change but people don’t. Airbnb didn’t discover a product market fit. It rediscovered it.

Similarly, Uber. is a reincarnation of jitneys. When cars were first invented, people would offer rides in their cars to strangers for a small fee. Often, they would race ahead of streetcars and pick up passengers waiting for the streetcars. Not surprisingly, the streetcar companies legislated the jitneys out of existence in most cities. (Although it hung on in a few cities, and in San Francisco, the birthplace of Uber an Lyft, it hung on until modern times).

Or, let’s consider Twitter. I must admit, it look me a while to understand Twitter. I didn’t understand why people used it.

Then, I realized what Twitter was: rumors.

I remembered that when I was a child growing up in pre-modern Korea, most of the important news didn’t come from newspapers or television. It came from rumors. Newspapers were censored and not reliable. And they only had 8 pages. Not much information could be crammed into a newspaper.

On the other hand, rumors were uncensored. Important news would fly on wings of rumors from one end of the country to the other in hours or minutes. People were plugged into rumor networks, and key information was transmitted from one trusted person to another like wildfire. Currency is going to be devalued. Price of heating coal is going to triple. A subway station is going to built on that block. It could make an enormous difference in lives. In times of war, it could mean life or death. The army is about to lose the city and we must flee. The bridge across the river has been destroyed.

Twitter reminds me of rumor networks – ultra-rapid, unverified (uncensored), decentralized information networks based on trusted sources. The way news was disseminated and consumed for hundreds of thousands of years. It’s a real throwback.

Similarly, eBay is a throwback to the era before packaged good era, to the times when the price of each item was separately negotiated between the shopper and the proprietor. And a throwback to the times when the reputation of each seller and buyer was known, because the communities were smaller. When reputation followed you throughout your life and therefore you guarded it with care.

And of course, Amazon did with internet and UPS what Sears did with mail order and railroads. Both became dominant because they could order broader inventory and lower prices than local merchants.


So what can we learn from this?

First, that as new technologies emerge, business models that made the most sense in a previous era can get toppled by old ideas reborn, not just by new ideas. And the forgotten old ideas may be the most potent ones–because those are the ones that are not immediately obvious to everyone.

Second, that as we search for a product:market fit, it may behoove us to look to the past to guide us. What was popular in the past, what worked in the past, may portend a new way of achieving the same.

Third, and most importantly, that history is important in innovation. History rhythms, even at the frontiers of technology. This is why when young aspiring entrepreneurs ask me what they should study if they want to do a startup, I tell them: first, study history.

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,