Why I quit Twitter and what's next

Also, how editing genes might help prevent heart attacks

This newsletter is going to be a little different from previous ones.

There’s a good chance that you found Gyandemic because you saw one of my tweets during the COVID-19 pandemic. Twitter was an awesome place to meet people and to build lasting friendships. It was a place to share thoughts and ideas and photos in real-time in a way that no other social media network could.

I met a lot of people on Twitter. I wasted a lot of time. Hopefully some of my tweets helped people at a time when they were worried about COVID-19. I got a book contract during a pandemic because of my tweets. It’s all good.

Life isn’t always transactional. We share and connect because we are human. You are reading a newsletter written by a stranger who is writing because he values that connection. This connection is sacred. No money is changing hands.

Twitter had a great run, but let’s be honest. The magic is gone. It is time to move on.

I’ll be on Mastodon. You can find me here.

You can also find me at ani.micro.blog and of course, this newsletter will still be around .

I’ve used Mastodon for a day and the nicest way to put it is that it’s a bit quirky . You can join any server and connect (which is a concept that takes getting used to if you grew up using social media platforms created by companies). It can be slow and frustrating, but I also get that the servers are swamped right now because of #TheGreatMigration.

But I’m willing to give it some time. No one is firing half of their company through a Hunger Games or Squid Game (take your dystopian pick) type-email Russian roulette there. And because it is a decentralized social network, I’m not the product. There are no ads. No one is making money off of content we create.

Will Twitter die? Probably not. Will a lot of people leave? Those that have amassed a lot of followers and see it as part of their identity probably won’t.

It wasn’t so much that the technology of Twitter was revolutionary. Despite changes in CEOs, staff increases to 7,500, and billions of dollars in investment, Twitter remained essentially unchanged through its life-cycle.

Twitter wasn’t for everyone either. I’ll admit that most of my family, coworkers, and the people I know IRL were never on Twitter. They never got the appeal. And maybe that was part of the appeal.

You didn’t feel the pressure to follow anyone because you went to high school with them. And unless you were a celebrity, no one followed you because you were you. They followed you for what you wrote in short, snappy messages.

But all of that is in the past now. And it’s time to move on.

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Editing genes to prevent heart attacks.

Instead of having to take medicine regularly, what if there was a one-and-done approach to reducing blood cholesterol which would reduce your risk of heart disease? Would you take it? What if I told you that the experimental procedure made changes to your DNA?

I wrote about a revolutionary study in a column for Hindustan Times. For anyone with high-cholesterol, the potential benefits are remarkable.

Earlier this year a volunteer in New Zealand became the first person to undergo editing of a chemical building block of a particular gene as a means of controlling blood cholesterol.

The trial will expand to include dozens of others and might revolutionize the prevention and treatment of heart disease. Heart disease kills more people than any other disease and it afflicts of millions of other people worldwide reducing their quality of life.

The new treatment for heart disease is spearheaded by Verve Therapeutics, a US-based company led by physician-scientist Dr, Sekar Kathiresan. Dr. Kathiresan, a cardiologist by training and a professor of medicine at Harvard University, is no stranger to heart disease.

Verve’s idea is to prevent heart disease through genetic modification of DNA.

Here’s how it works —

While the original CRISPR-Cas technique that won its discoverers the Nobel Prize involves cutting DNA, the technology used by Verve, known as base-editing, makes a single chemical change in a gene. This change inactivates the gene. This single edit leads to reduction of LDL (low-density lipoprotein) cholesterol, otherwise known as “bad cholesterol,” which is tied to hardening of arteries and heart attacks in lab animals. The hope is the results will hold in people.

The gene that is being edited is PCSK9, which is involved in regulating LDL cholesterol levels. Different people have different forms of the gene, but it can be turned down.

The treatment known as VERVE-101 is trying to treat a condition in which some people have very high cholesterol levels that can lead to strokes or heart attacks early in life. The first patient to receive VERVE-101 had inherited a form of the PCSK9 gene that led to high LDL cholesterol, but there are also people with forms of the gene that contribute to relatively low LDL cholesterol. So, the inactivation of the gene has some natural precedence.

There are other ways to treat high blood cholesterol. Statins are some of the most widely prescribed drugs to control cholesterol levels, but they need to be taken regularly and can have side effects. As I’ve noted in an earlier column, statins don’t work well for everyone. Statins also have another problem. They don’t reduce blood cholesterol levels at the source – the enzymes that produce it.

There are newer therapies that can reduce LDL through two injections of a drug a year, but Verve’s approach is presumably permanent.

VERVE-101 consists of a lipid nanoparticle with a guide RNA that helps to find the right base on the PCSK9 gene and an mRNA that serves as instructions for cells inside the body to make the base editor. Together, the treatment successfully makes the single change inactivating the enzyme in lab mice and monkeys.

Because of the use of RNA and lipid nanoparticles, the treatment has been compared to mRNA vaccines.

Verve had already shown that the treatment works in monkeys and that it is persistent months later. The treatment was very specific in monkeys, but specificity will have to be demonstrated in people too.

And this is where things stand, as of late October.

Cardiovascular disease has many risk factors other than blood cholesterol, like blood pressure, metabolic disorders, and smoking. There isn’t a single gene responsible for heart attacks either. Instead, there is a symphony of many genes. Each gene might contribute a percentage to someone’s risk.

Genome-wide association studies help to provide “polygenic risk scores” that show our individual risk to heart disease based on our genetic profiles. So this isn’t a magic bullet.

Still, the link between reduced LDL cholesterol and heart disease is very well established over decades of research, and PCSK9 has a very strong link to LDL cholesterol that has been shown clinically.

If clinical trials are successful, treatment will be available to those who are known to suffer from heart disease.

But the real potential is in preventative medicine. Heart disease is a silent killer with little warning. A quick and lifelong reduction in risk would increase longevity and improve quality of life, potentially for millions.