So there's good news and there's bad news.

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Bad news first? Alright, the next chapter of the 'Covid-19. Explained' e-book is still not done :(

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Good news? Oh, but I've gotten such incredible details from two brilliant sources...

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So in today's email, I plan to share the story of the past week's work. How I stumbled upon those sources, the material I got from them and why I'm so excited to incorporate them in the story. Think of today's mail as a trailer. Or better, some behind-the-scenes footage from this project.

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Now, some astute readers might have noticed that I'm getting into the habit of delaying launches - and then narrating a story for why the delay is justified - for instance, this one when the podcast was delayed! (I'd make a terrible Projects guy).

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Anyway, the lesson you should (not) learn from this is: If you can't ship the product, at least ship the story.

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With that context, let's begin.

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A Crash Course in Immunology

In last week's email, I had mentioned a book that I had come across about the Immune system, written by an Immunologist.

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(The Immune system is the body's MOST important actor in our fight against Covid-19. It is important to know how it functions, hence my deep dive into the topic).

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The book is called 'The Beautiful Cure' and it's written by UK-based immunologist, Daniel M Davis.

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I picked up the book since it was praised by guys like Stephen Fry and Bill Bryson. But I still had my doubts. It was, after all, written by a scientist. And perhaps when these good folks were praising the writing, they were probably keeping a lower 'storytelling standard'.

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It turns out I needn't have worried. Daniel writes with the precision of a scientist, the curiosity and storytelling skills of a journalist, and the warm empathy of a caregiver. Like a good scientific paper, almost every sentence has a footnote to a source attribution; but like compelling non-fiction writing, it reads like a clear, coherent story. That is incredibly difficult to pull off.

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The book offers an account of the key discoveries and innovations in the immunology domain in the past few decades. In doing so, it also profiles the relentless, driven and sometimes colourful personalities who made these breakthroughs happen.

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Our immune system has evolved over time to accomplish probably the most challenging aspect of survival: keeping us safe from micro-organisms.

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It is essentially a mysterious network of billions of microscopic messengers and mercenaries which patrol our body identifying and neutralising (and in some cases just gobbling up) the untold number of unseen pathogens which can wreak havoc on us. Despite its criticality, however, it has long been an enigma.

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For instance, Prof. Davis says: "it’s been estimated – though it’s hard to calculate such a thing – that around 95% of our defences against microbes are attributable to innate immunity." (Innate Immunity is one part of our immune system; and given that we didn't understand this part very well till then), "until 1989, mankind had been studying just a part – arguably, as little as 5% – of what makes up our immune defence."

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The veil on the enigma is being slowly lifted however. Research on the immune system has seen tremendous breakthroughs in the past 20-odd years. In just the last 10 years, 2 of the Nobel Prizes in Physiology and Medicine (in 2011 and 2018) went to researchers from this field.

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And yet, there is a ton that we don't know yet.

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The book has some fascinating elements:

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Human stories:

• The bittersweet and yet heartbreaking story of Prof. Ralph Steinman, who died just a few days before he was announced as one of the winners of the Nobel Prize in Physiology and Medicine in 2011 (the Nobel Committee had made the decision before his demise).
• Science research can be a lonely, risky and unrewarding affair. Your ideas could be wrong, ridiculed, ignored... or worse, stolen. In such an environment, lone warriors who stick to a line of research despite limited support, are real heroes. Here's Daniel on the perseverance of Prof. Steinman: "Peering down a rabbit hole, Steinman opened up a wonderland of immunity; a world full of peculiar, strangely shaped characters that interact in a complex system, in which many types of cell share information to coordinate their activity in fighting disease. As Mellman puts it: ‘Here’s a guy who single-handedly started a whole field and stuck with it after the rest of us would have given up to save our careers.’"
• The story of the slighted Prof. Medzhitov, who narrowly missed out on a Nobel in that same year is also fascinating: "It’s not that these scientists would anyway celebrate others winning a prize in their research field; they don’t get along. There was a deep rivalry between Beutler’s team and Janeway’s. Medzhitov (part of Janeway's team) says that he made the same discovery in Janeway’s lab around the same time as Beutler, while Beutler says that he got there first and that, at the time, Medzhitov’s work was incomplete. To this day, Medzhitov refuses to attend a scientific meeting in which Beutler or Hoffmann have also been invited."

Analogies

• The use of evocative analogies such as: "Textbooks about the immune system tend to discuss the role of each molecule or cell in turn, but that’s like explaining a bicycle by describing what a wheel is, and then what a handlebar is, and then what a brake is. None of these single elements are properly understood without the others; their meaning lies in the relationships between them."

Thoughtful quotes

• "As the scientist who discovered vitamin C, Albert Szent-Györgyi, famously put it, the trick is ‘to see what everybody else has seen, but to think what nobody else has thought’."

Surprising insights

• Why immunity differs across people: "By and large, we all have the same set of genes – the 23,000 genes which make up the human genome – but around 1% of the genome varies from person to person, such as the genes which affect our hair, eye or skin colour. Importantly, the genes which vary the most from person to person have nothing to do with our appearance but are part of our immune system."

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This book does a great job of describing not just what we know, but how we know what we know.

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Anyway, after reading this book, I was mostly set to write the chapter. There was only 1 hitch though - this book had been written in 2018 - pre-Covid-19.

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And I had a bunch of questions on how the immune system actually reacts to our main villain - SARS-Cov2. I was actually super confused about a lot of stuff.

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I emailed Prof. Davis and requested him for an interview. He replied in a couple of days, thanking me, but graciously declined, given other commitments.

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And so here I was, with several unanswered questions and a (self-appointed) publishing deadline. I reached out to the only expert I knew - Dr. Karishma Kaushik, the scientist who had ratified the first chapter.

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"Hi Karishma, would you know a good immunologist I could speak to?"

"Satyajit Rath is an option. You can Google to find his email"

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Google him I did. And boy, was I blown away.

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A saviour cometh

Prof. Rath (he prefers to be called Satyajit) is THE person to talk to about Covid-19 Immunology.

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He's attached to the 'Indian Institute for Science Education and Research (IISER) Pune' - an apex research institute under the Ministry of Education, located essentially 6-7 kms from where I live!

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Searching on the web, I came across a video of him doing a lecture on Covid-19 to a group of young students (with a biology background).

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That video is Five. Hours. Long.

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Part of my mind (the instant gratification monkey) was like: YAY, more content to see!

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Part of my mind (the Panic Monster) was like: Why do I even bother with deadlines?

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Even as I started watching the video, I thought: I HAVE to talk to him.

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And with almost trembling fingers, I sent an email to him...

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(In the recent past, several of my emails - mainly for podcast conversations - have been getting rejected, or worse ignored. It's not a happy feeling).

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But thankfully for me, Prof. Rath responded - the very same day! He graciously offered me a time slot for a call the very next day. I grabbed it with both hands, giddy with excitement.

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That conversation with Satyajit was more than an hour-long and incredibly eye-opening. He clarified all my nagging questions and doubts and did so with patience, warmth and humour.

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I've recorded the conversation and would be going back to it to write the second chapter.

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---

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I remember reading in an ad once. 'The search for the perfect dish ends with the best ingredients.'

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I don't know how the final dish will come out. But boy, am I excited about the ingredients that are going into it.

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Thank you for your patience - hopefully this is worth the wait.

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Ravi

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