Discovering The Mysteries of Life

Next time you’re on a hike in a Redwood forest, running along Ocean Beach simply packed into a Muni car during your morning commute, spare a thought for the embryo.

Where does it come from and what does it become?

Every towering redwood, every tiny sand crab, every humpback whale, every fern and every friend or stranger you have ever known started as a single cell, from which came the embryo and finally the form we take for granted.

Astonishingly, this happens perfectly nearly every time. How does a single cell, with a single set of instructions encoded in its DNA, divide, cooperate and communicate to make this happen, to become animal and plant life?

UCSF Professor Daniel Hart has always had a taste for these big questions, and the drive to answer them.

“Knowing innear totality, as close at it is possible to know, how genes are regulated to achieve the miracle of development, is the thing that I’m most interested in,” he said while sitting in his Mission Bay office.

UCSF Professor Daniel Hart

Now 43 years old, Hart spoke fondly of his earliest exposure to science that the future it might bring about.

“I fell into watching, when I was about 7 or 8, the original series of Star Trek,” he said. “I had in mind that it was proximal: in 10 or 15 years, I thought that’s exactly what we’d be doing, living on spaceships and the like.”

The influence of science fiction soon lead to a personal epiphany.

“I wanted to be in an environment where we’re tackling big questions, where we’re trying to do things to shape the destiny of mankind.”

Hart’s background allowed him to be especially receptive to utopian ideals. His father was a Nigerian ambassador, and moved the family around the planet from job to job, in the service of diplomacy and togetherness, and a better world. It was an adventure that took the family to Egypt, Poland, Spain, Zimbabwe and back home to Nigeria during Hart's childhood.

Moreover, he was taught from an early age that education is transformative.

“My Dad came from a very poor background, and he managed to get to university at a time in the country when primary and secondary school education was free. So he saw the benefit in that. He ended up being ambassador and ran the Foreign Service at one point. He was a living example of what education could do.”

At the age of 13 or 14, the pieces finally fell into place, and Hart was shown the power of scientific inquiry to identify the important problems and find their solutions. One day in class, his biology teacher seemed to conjure a knowledge of a future world where the climate and biosphere had changed.

“She suddenly stopped and said, ‘You know, your children will ask you one day what elephants look like.’ She was painting a picture of a time when the climate would be bad off because of human impact. This was 1988, she had incredible foresight. Why, was my question, why did she say this? Where was this insight coming from?”

Yet, Hart was attracted to art, and had the talent to match. In high school, he won a prestigious national award for portraiture. His art satisfied an aspect of his personality that science did not.

Curious to see if medicine would quell his twin natures, he applied to medical school, and was accepted. But very quickly he realized it was not for him.

“I didn’t think that losing a patient was something I could ever get used to,” he said. “My bedside manner would be [of the sort] that I would form a bond.”

And so he threw himself into pure research. Soon he was pursuing a Master’s degree at the Roslin Institute. It was 1996, and he was at ground zero for what was to be one of the biggest science stories of the century.

“Sitting right next to me at the canteen, every day at lunch, was Ian Wilmut. A few months after I got there they announced the cloning of Dolly the Sheep,” Hart said, referring to the first cloned mammal. Wilmut lead the group that accomplished this feat, and their work ushered in the era of regenerative medicine.

“That kind of energy, that buzz, you taste it and you get a feel for it. These guys had done something incredible. They’d essentially created life! The boundaries of what was possible were pushed back.”

He was hooked.

“What Ian Wilmut and colleagues haddone was a technical advance. But what was going on in this organism they had [cloned]?"

To Hart, it was obvious that control of genes, which are at the base of all life in the cell, must be key.

His curiosity carried him to his PhD, where he studied a new strain of yeast that can digest a diverse array of foods. Here he was able to refine his questions and focus experiments.

He wanted to conduct a rigorous study of this new yeast’s diverse gene expression using the same established, rigorous techniques, previously used in baker’s yeast, to solve the riddle of how the information in DNA becomes life.

While finishing his PhD studies, Hart was offered a postdoc position in the UK. But the idea of America held a special allure, from stories he’d heard as a child.

“It’s all naïve, when you look back at the momentous decisions you make as a young person, but it was just as simple as that,” he said.

He took a position at the University of Massachusett. However, soon Hart found himself on a technically-intensive project that didn’t scratch his creative itch. On top of this, it was a project involving mice, which are notoriously laborious with long experimental time-horizons.

Hart was discouraged, but spoke with a more senior labmate, who posed a fateful question: “Have you considered zebrafish?”

“With fish, the imaging is stunning,” Hart said, and recalled the profound sense of possibility that had gripped him at the Roslin. “You have such rapid development! You have all of biology in your hand. You go from one cell to a whole organism so quickly. You can do things.”

Hart's eye's grew wide with excitement as he recounted the moment.

“If you’ve ever looked a plate of 200 [zebrafish] embryos, and you see them divide, and you see them grow into these perfectly formed, free-swimming organisms within 36 hours, how does that happen without a significant number of errors? It’s fundamental.”

This excitement about gene expression, zebrafish and the beauty of life carried him forward into his career as a professor, with an extra dose of stimulation from being at UCSF.

Looking out the window of his Mission Bay office, gazing wistfully at the SF skyline, Hart drew inspiration.

“Look where we are in the Bay Area. There’s science all around us, in different forms. If you [can live here and not] feel a little tingle of excitement about something new in that realm, you’re done with science.”

When asked how a scientist should go about achieving such a lofty goal, he didn’t cite protocols, quote numbers or invoke data. He spoke of people and networks.

“What I’ve learnt in my time as a junior faculty here is that it’s not the [professor] who’s responsible for the breakthroughs, it’s the people in the lab, and surprises come from that,” he said.

“I would want to assemble a team of people who are passionate about the idea, who are motivated, and from that team there would be new directions and breakthroughs.”