Breaking the Dogma - How Retroviruses Rewrite Our DNA
Cellsius, a community biotech lab in SF, hosted its monthly wetware meetup last Friday. I genuinely enjoyed all the conversations I had there. The atmosphere was buzzing with curiosity, and the topics we covered ranged from organoid intelligence and microscopy, to AI-driven drug discovery and RNA molecule shape prediction.
Among all these exciting conversations, the biggest surprise came from a conversation about retroviruses. I didn’t know that there is an exception to the central dogma of molecular biology: the flow of genetic information from DNA to RNA to proteins. Retroviruses flip the central dogma on its head.
A biotech startup founder explained this to me while walking me through his startup idea. He shared how retroviruses like HIV don’t follow the usual DNA-to-RNA route. Most viruses use DNA to make copies of themselves, but retroviruses use RNA instead.
Retroviruses enter a host cell and turn their own RNA into DNA using an enzyme called reverse transcriptase as they reverse the transcription process (usually DNA to RNA). That reverse-transcribed DNA then travels into the nucleus, where another enzyme called integrase helps insert it into the host’s own DNA. It becomes part of the host’s genetic material, which means its cells start making more of the virus as the cells replicate themselves. Since the virus is now part of your DNA, it’s very hard to get rid of. That’s why some retroviruses can cause long-term infections.
At home, I learned that retroviruses are just one example of reverse transcription. Other instances include retrotransposons, genetic elements that can copy and insert themselves into different parts of the genome, and Hepatitis B virus, which also uses reverse transcription as part of its life cycle.
Interestingly, I also learned that reverse transcription is just one of several exceptions to the central dogma of molecular biology. Other exceptions include prions, which are infectious proteins that replicate without nucleic acids, and RNA viruses, which replicate their RNA genomes without involving DNA at all.
Seen in this broader context, reverse transcription isn’t so surprising. In fact, the RNA World Hypothesis—which posits that RNA came before DNA in the early stages of life on Earth—suggests that the ability to convert RNA into DNA may have been a key evolutionary development. Over time, enzymes like reverse transcriptase may have enabled the shift from an RNA-based world to the DNA-based genetic systems we see today.
ChatGPT Voice Mode While Driving
I got my own car for the first time in my life late last year. Back when I was living in Tokyo, I never needed one—public transportation could take you just about anywhere. But now that I’m in the Bay Area, I’ve realized how inconvenient life can be without a car. Since getting mine, I’ve really come to enjoy the driving experience—well, unless I’m stuck in heavy traffic.
Naturally, I started thinking about how to make the most of my time behind the wheel. If I’m driving for an hour a day, that’s about 30 hours a month. That’s more than a full day—time I don’t want to waste.
I’ve experimented with different ways to stay productive: podcasts, audiobooks, and listening to short videos. But after trying them all, I realized the most valuable use of that time has been talking to ChatGPT in its advanced voice mode.
Here’s why. First, you’re in full control of the experience. With podcasts or audiobooks, content just keeps flowing—it’s not easy to pause or rewind while you are driving. And honestly, most of them, especially podcasts, don’t have high information density. With ChatGPT, I can easily ask it to stop, repeat, summarize, or go deeper.
Second, voice conversations with ChatGPT handle interruptions far better. While driving, your attention shifts. With podcasts or audiobooks, missing just five seconds can be frustrating. But with ChatGPT, it’s easy to pick up where you left off. Just ask it to recap or continue.
Third, I can review the conversation later. Having saved history means I don’t lose valuable insights I might otherwise forget.
Now, on my way to the office, I talk about goals I want to accomplish or reflect on what I learned the day before. On the way home, I review what I’ve learned and dig deeper through follow-up questions. Sometimes, I just ask for fun facts about biology or chemistry. Other times, I request an inspiring story. The variety keeps things fresh.
To make this a habit, I even set up a trigger: as soon as my iPhone connects to my Tesla via Bluetooth, ChatGPT’s voice mode opens automatically.
Never Too Old, Never Too Young
No matter your age, you are never too young or too old to achieve success. This is the modified version of this list.
- Shirley Temple became a movie star in “Bright Eyes” at the age of 6.
- Mozart composed his first symphony at 8.
- Anne Frank wrote her diary at 13.
- Magnus Carlsen became a chess Grandmaster at 13.
- Nadia Comăneci, a Romanian gymnast, scored seven perfect 10.0s and won three gold medals at the Olympics at 14.
- Pelé won the World Cup in 1958 with Brazil at 17.
- Malala Yousafzai won the Nobel Peace Prize at 17, making her the youngest recipient ever.
- Joan of Arc led the French army to victory at 17.
- Elvis Presley was a superstar by 19.
- Mark Zuckerberg launched Facebook at 19.
- John Lennon was 20 and Paul McCartney was 18 when the Beatles held their first concert in 1961.
- Bill Gates co-founded Microsoft at 20.
- Steve Jobs co-founded Apple at 21.
- Jesse Owens won four gold medals in Berlin in 1936 at 22.
- Roger Bannister broke the 4-minute mile record at 25.
- Albert Einstein wrote the theory of relativity at 26.
- Michelangelo created two of the greatest sculptures, “David” and “Pietà,” by 28.
- By 29, Alexander the Great had built one of the largest empires of the ancient world.
- Sara Blakely founded Spanx at 29.
- J.K. Rowling finished the first manuscript of Harry Potter at 30.
- Jeff Bezos founded Amazon at 30.
- Oprah Winfrey started her talk show at 32, which became the highest-rated program of its kind.
- Edmund Hillary reached Mount Everest at 33.
- Amelia Earhart became the first woman to fly solo across the Atlantic Ocean at 34.
- Marie Curie was nominated for a Nobel Prize in Physics at 35.
- The Wright brothers, Orville (32) and Wilbur (36), invented and built the world’s first successful airplane, achieving the first controlled, powered, and sustained heavier-than-air human flight.
- Reed Hastings co-founded Netflix at 37.
- Jim Clark started his entrepreneurial career at 37, later creating three companies that went public.
- Neil Armstrong became the first man to set foot on the moon at 38.
- Masaru Ibuka co-founded Sony at 38.
- Gordon Moore co-founded Intel at 39.
- Mark Twain wrote “The Adventures of Tom Sawyer” at 40 and “Adventures of Huckleberry Finn” at 49.
- Soichiro Honda founded Honda at 41.
- Rosa Parks refused to give up her seat for a white passenger at 42.
- Robin Chase co-founded Zipcar at 42.
- John F. Kennedy became President of the United States at 43.
- Henry Ford introduced the Ford Model T at 45.
- Suzanne Collins wrote “The Hunger Games” at 46.
- Momofuku Ando invented instant noodles at 48.
- Leonardo da Vinci started painting the Mona Lisa at 51.
- Abraham Lincoln became president at 52.
- Dr. Seuss wrote “The Cat in the Hat” at 54.
- Morris Chang founded TSMC at 55.
- Colonel Harland Sanders started the KFC franchise at 61.
- J.R.R. Tolkien published the Lord of the Rings books at 62.
- Ronald Reagan became President of the US at 69.
- Nelson Mandela became President at 76.
- Masako Wakamiya started programming at 82 and launched her first app in the same year.
- Ruth Bader Ginsburg celebrated twenty-five years on the Supreme Court at 85 in 2018.
- Frank Lloyd Wright completed the design for the Guggenheim Museum at 91.
Rethinking Founder Vesting
The standard vesting schedule for founders in Silicon Valley might be too short. I believe it should be longer.
Vesting schedules ensure that equity is earned over time rather than granted upfront. Typically, Silicon Valley founders use a 4-year vesting schedule with a 1-year cliff. This means:
- 1-year cliff: No shares vest during the first year. If you leave before completing one year, you receive nothing.
- After the cliff: 25% of your shares vest at the end of the first year.
- Ongoing vesting: The remaining shares vest gradually over the next three years, usually monthly (1/48 of the total grant).
- Fully vested: After four years, you own 100% of your granted shares.
I’d be curious to know where this standard originated. But regardless of its history, vesting is a necessary practice for companies with multiple founders.
Consider a scenario where one founder leaves after six months, while another stays for four years until the company is sold. It would be unfair for both to receive an equal payout from the sale.
Vesting is a great way to incentivize long-term commitment while protecting the company from early departures. That’s why, when I incorporated my company, I followed this standard too, as Stripe Atlas, an incorporation service widely used for founders here, used this standard as the default term.
The question is whether the vesting term should be “4-year vesting with a 1-year cliff.” Now imagine a company where one founder leaves after four years, while the other works for eight years until it goes public. It would be unfair for both to receive equal payouts from the IPO.
So why don’t we make the vesting period longer? For example, eight years of vesting with a two-year cliff.
There are some concerns with longer vesting.
First, unvested shares at the liquidity event. There is a chance that a company will be sold or go public before the founders’ equity is fully vested. However, this is an easy problem to solve according to our lawyer from Goodwin because you can add an acceleration of vesting clause in your terms; you can make vesting happen faster than otherwise scheduled at liquidity events. On top of that, everything is negotiable in an acquisition. So even your vested shares can be unvested at the point of acquisition.
Second, control. I’ve been discussing the economics of equity, but the other important aspect is control. This may be the biggest risk because you might end up giving your investors more power than you when your vesting takes longer. Investors should have a longer or the same vesting.
Third, investor resistance. Investors may prefer to follow standard terms. If you want to set up different terms from other startups, investors might stay away from your company.
It seems reasonable to have longer vesting as long as founders have enough control over a company and investors are willing to follow the same vesting schedule. That said, I may be missing other concerns, such as potential tax implications.
I’m open to criticism—what do you think?
83(b) Election Basics
Every founder should file an 83(b) election.
When a founder receives restricted stock (i.e., subject to vesting), they can file an 83(b) election within 30 days of the grant date. This means they pay ordinary income tax on the fair market value (FMV) at the grant rather than at each vesting milestone. If you don’t file it, then you pay income tax later when the stock vests, which could be worth much more.
Let’s think of some numbers. Imagine a stock grant with a 4-year vesting period where:
- You receive 10,000 shares.
- The Fair Market Value (FMV) at grant is $0.10 per share, resulting in a total value of $1,000.
- After 4 years, the company does well, and the stock price is $50 per share, resulting in a total value of $500,000.
Below, I compared the case where you file and do not file an 83(b) election. You can see why you can potentially save a lot of tax money by filing it.
| Case 1: Filing 83(b) Election (Pay Taxes Now) | Case 2: Not Filing 83(b) Election (Pay Taxes Later) | |
|---|---|---|
| Day 1 Stock FMV | $1,000 | $1,000 |
| Taxable Income at Grant | $1,000 | $0 |
| Income Tax Rate | 30% | 30% |
| Income Tax Owed at Grant | $300 | $0 |
| Stock Value After 4 Years | $500,000 | $500,000 |
| Taxable Income at Vesting | $0 (already taxed) | $500,000 |
| Income Tax Owed at Vesting | $0 | $150,000 |
| Capital Gains Tax Rate | 20% | 20% |
| Capital Gains Tax Owed | $99,800 (20% of $499,000 gain) | Depends on future growth |
| Total Taxes Paid | $300 now + $99,800 later = $100,100 | $150,000 (income tax) + capital gains tax later |
As shown in the comparison, paying a small tax upfront can lead to massive tax savings in the long run. By locking in the fair market value early, you avoid hefty income taxes on future appreciation and instead benefit from lower capital gains taxes when selling your stock.
What is the Job of an Actor?
Honestly, I couldn’t respect acting as a profession. I thought actors were merely entertainers who distract people from thinking about important problems, and unfortunately, most commercial entertainment is still garbage.
But when I heard Meryl Streep says an actor’s only job is “to enter the lives of people who are different from us and let you feel what that feels like”, it made me think that commercial entertainment isn’t all that bad.
In fact, I can think of some movies that have done an amazing job of making me feel what it is like to be another person: