Ting Zhu, PhD, of Westlake University is a molecular biologist with an engineering background. He was selected as one of the Cell Press 50 Scientists that Inspire for his forward-thinking work on mirror-image biology and artificial living systems.

Dr. Zhu received his Bachelor’s degree with highest honors in Engineering Mechanics from Tsinghua University in 2003, MS in Mechanical Engineering from Massachusetts Institute of Technology in 2005, PhD from the Harvard-MIT Division of Health Sciences and Technology (HST) in 2010, and postdoctoral training from the Department of Earth, Atmospheric and Planetary Sciences at MIT and Massachusetts General Hospital. He joined the School of Life Sciences at Tsinghua University as an assistant professor in 2011 and was promoted to associate professor in 2016 and professor in 2019. He joined the School of Life Sciences at Westlake University as a chair professor in 2022.

His research aims to realize mirror-image biology systems, highlighting the potential of mirror-image biomolecules as a unique class of therapeutic and informational tools. In this Q&A, Dr. Zhu shares how moments of solitary reflection helped him find direction in his career and explore the meaning of life.

What are you most excited about in your field right now?

Despite biology’s seemingly limitless diversity and the vastness of its territories—permeating virtually every corner of the Earth—at the fundamental level of biochemistry, all known forms of life are narrowly defined by a single version of molecular machinery based on L-amino acids and D-nucleic acids.

The overwhelmingly homochiral nature of life and the fact that no known laws of physics and chemistry preclude biology’s use of either of the two chiral systems—which are mirror-image twins of one another—leads to an intriguing question as to whether a mirror-image world of biology running on a chirally inverted version of molecular machinery could also exist. Although the concept of mirror-image biology was proposed over 160 years ago by Louis Pasteur following his discovery of molecular chirality, it has not been discovered in nature or realized in the laboratory.

We reasoned that an imperative step toward building mirror-image biology systems is to establish a chirally inverted version of the central dogma of molecular biology. We initially developed a proof-of-concept mirror-image genetic replication and transcription system, followed by a more efficient and thermostable mirror-image polymerase that led to the realization of mirror-image PCR, gene transcription, and reverse transcription, as well as mirror-image DNA and RNA sequencing. The next step in establishing the mirror-image central dogma is to realize mirror-image translation through building a functional mirror-image ribosome. Such a self-sustaining mirror-image molecular system could become the evolutionary root for a new form of life, independent from terrestrial life as we know it. It would be more than another branch on the tree of life: it would start a new tree. Nonetheless, creating a mirror-image (or even natural-chirality) cell from scratch would require unprecedented technologies and vast resources that are currently unavailable and unlikely to be available in the near future. Meanwhile, it is imperative for scientists to be extremely cautious, avoiding the creation of living organisms of either chirality on this planet without ensuring total safety.

What does innovation in science look like to you?

I once interviewed for a position with the idea of building mirror-image biology systems. During the interview, a prominent scientist raised two tough questions.

Her first question was: “How many years will it take you to realize mirror-image translation?” She wasn’t convinced it was possible. But I felt encouraged: to me, the fact that others thought it couldn’t be done made it even more exciting to try.

It was her second question that got me: “Others have attempted the chemical synthesis of mirror-image proteins and nucleic acids. What makes your work to build mirror-image biology systems original?”

In the end, I didn’t get the offer. But her questions made me think deeper: if all scientific discoveries and inventions build on previous ones, if we all stand on the shoulders of giants, then what makes certain studies more “original” and “important” than others?

I pondered this question for a long time until one day while teaching a class on the evolution of species, I showed an image of a fish crawling onto land, leading to the emergence of land animals. That’s when it dawned on me: the progress of science bears a resemblance to the evolution of species. All creatures on Earth, all organisms, all species, descend from others. So then what makes certain species more significant than others in the course of evolution and, by extension, certain studies more important than others?

First, the fish had mutations that didn’t make it swim faster but allowed it to do something drastically different from others: crawl onto land. Second, these mutations were heritable, producing offspring that led to other species, like opening a new door that leads to more doors inside, starting a new path that leads to more paths beyond.

Innovation often emerges at the boundaries of disciplines, like the boundaries between sea and land, water, and air. It arises when intellectual diversity is protected and encouraged, when we choose to be selectively naive—to venture into unknown territories, without letting knowledge become a burden, to transcend the boundaries between environments, between what’s possible and what’s not. The mutant fish that crawls onto land or jumps into the air might not be a champion swimmer in water. It might even seem a bit “ugly” and “odd.” But it’s the odd fish that has the best chance to jump out of water.

And fly.

What inspired you to become a scientist?

There was a period in my life when I found myself sinking into a desolate abyss and I needed a way out. I needed a new life, separate from my daily routine. Science provided exactly that—an intellectual life, one to which I can escape when wearied by the incessant noise of day-to-day existence. Meanwhile, science seamlessly connects the two lives, in an intricate union, a profound dyad of our most heavenly inspiration, to wonder, to create, and our most earthly desire, to survive, to prosper.

Are there hurdles you have faced in your science? How did you navigate these?

I started my independent research group about thirteen years ago. When I began, I made the first important decision in my career: to move away from the topics of my PhD and postdoctoral training. There was only one problem—I didn’t know what to work on next.

I thought about it on my flight to Beijing, and by the time the plane landed, I had already found a problem to solve: air pollution. We began using metagenomics to study microorganisms in the air that were causing various respiratory diseases.

In the meantime, the CRISPR-Cas9 system was becoming a popular tool. Most labs had begun using it in vivo for genome-editing purposes, and I feared it might be already too late to enter this field. Thus, we decided to use CRISPR-Cas9 differently—in vitro, for cloning and sequencing long genome segments.

These were the two projects we initially worked on as I was poking around, experimenting with different directions. Thankfully, I made the second important decision in my career: to gradually phase out these projects and to start something new. One reason was that while we were productive and did make innovations in these directions, they were still following a popular trend, running parallel with the mainstream. They were too safe. Instead, I wanted to try something more adventurous, something different: building mirror-image biology systems.

Another reason for leaving these directions was a growing realization during my quiet solitude about what truly mattered in my career. The gradual shift in my slowly aging organic consciousness didn’t distract me from science; rather, it reinforced the idea that I needed a more meaningful way to approach it.

I wandered, until a confluence of relief and clarity overcame me: what matters is how we spend our finite time in this insignificant corner of the universe, what discoveries and inventions we make, what new knowledge we create. I began to be utterly honest with myself, acknowledging the opportunity cost of time; I began to publish less, refusing to let myself be diverted by readily achievable objectives, trapped in the endless loop of productivity. In the end, all the efforts we made, the joys we cherished, the pains we endured, the ones we loved, and lost, will come together in a simplified picture of the past, a reverential awe of the world, a gentle whisper in the ear: life is worthy.

What do you think the next 50 years will look like for your field or for science more broadly? What changes would you like to see?

Modern chemistry has systematically created a vast variety of biomolecules; yet whether they can abiotically give rise to viable biological entities remains a major scientific unknown. Through abiotically creating biological entities from scratch, humanity will become the first intelligent species capable of turning dull, inanimate matter into living organisms, building new life forms, and restarting the biosphere even after total extinction. The synthetic proteins and nucleic acids will become more than collections of chemicals, assemblies of structures, more than molecules of life; they will become alive.

Abiotically creating biological entities may also help us understand, at least in part, another billion-year-old mystery: the origin of life. Indeed, it’s disappointing, yet deeply humbling, to acknowledge the fact that we may never get to see the whole truth, only small pieces of it. We, like all inhabitants of this planet, are babies left on the doorstep of a cosmic orphanage, asking the ultimate question: Where do we come from?

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As part of the celebrations for our 50th anniversary, Cell Press is honored to feature 50 notable scientists who inspire us. Editors at each of our journals across the sciences have nominated scientists whose research and careers drive innovation, cross boundaries, and inspire the leaders of the future. Visit the collection of profiles for a window into the lives and labs of these exciting scientists—and their hopes for the future of science.