Natalie Jing Ma, PhD

The endless sea of ideas beyond the bramble of writers’ block

Hey reader!

It’s been a while since a post, hasn’t it? I’ve learned a few things in starting this blog that I want to share with you below because I’d wager a lot of people face similar problems. If you’ve been stalled on your blogging/writing, I give you 100% permission to borrow this post, blame it on one the problems below, and start anew:

Writing what you know well isn’t always the easiest. You get bogged down in the details and you want it to be perfect. This is compounded in academia because you worry about the balance between reaching people outside of academia and those who might read it in the academic circle. To make blogging easier, begin with subjects you know some about and you won’t be dragged down into the deep details. Yes, sometimes you’ll write things that won’t make sense later or might be wrong, but that’s FINE. We learn nothing by venturing nothing.
Don’t feel beholden to a post you said you’d do, and you can always postpone a post to later. This is a hard one for me because I feel strongly about commitments and following through. It’s the same feeling that gives us anxiety when we leave an email unanswered for what we think is ‘too long’ or haven’t posted on a blog in a while. You feel like you’re letting your audience down, whether it’s one person or a million people. But you don’t owe the internet anything—you’re a free person.
This is an extension of 3, but it’s important to say on its own: write what you want. The easiest way to kill a blog is by having writing ideas but putting them aside because you “said you’d do” a specific post next. Likewise if you’re writing just for likes/favorites/exposure. It’s going to feel like an awful chore if you don’t write about what you want, so write about what you’re interested in, what you want to learn about, what won’t leave your mind. Get your thoughts out into the world.

So I’m holding off on writing in-depth about my PhD work for now. But I also didn’t want to be beholden to #1, so I wrote you a six-sentence summary of what I did in my PhD. Is it perfect? No. But it is:

As I described in the previous post, if we want to use living systems (organisms, cells) as technology, we want them to work as expected because we can’t rely on them if they don’t. One of the biggest problems is that most of life uses the same genetic code, so engineered cells can pick up genetic information from the environment that messes with their intended function. It’s as if we were all running the same version of Windows; you could install a program on any of our systems and it would run–including viruses and malicious code. To solve this problem, my PhD showed that changing the genetic code of an engineered cell makes it harder for genetic information in the environment to mess with the cell’s function, making it more stable. It was like we modified the “operating system” in our engineered cells, making it harder for malicious pieces of genetic information such as viruses to infect. In the future, we can change the genetic code in living systems to ensure they work as expected, bringing applications of biotechnology and synthetic biology closer to realization.

What will I write about next? We’ll see what I feel like, although posts will probably remain infrequent while we travel around the world (more on that here). One of the big projects I want to do over the next year is learn the physics of aerodynamics and orbital mechanics, partly because both of these are really important for space travel and partly to dispel the persistent myth that you can’t transition from “softer sciences” to “harder sciences” later in life. Anyone should be able to learn anything regardless of their background.

What I wrote below highlights some of the risks of engineering living things, the goal of a field called “synthetic biology” . Is anything unclear? Email me! Ask questions! Your advice will make these posts better.

We’re at an amazing point in scientific history where we know enough about how living things work to begin tinkering with them. There have been thousands of studies in the last century looking at modifications of living things. At first, the tools we had were crude and the questions we asked were “what happens if make a bunch of mutations in a living thing? What kinds of properties does the living thing show? And what changed in the a living thing’s genes, in its DNA, that caused this change?” As our tools became more precise, so too did our questions. We began to ask what happened when we took out one gene, or added another. “What properties appear when we do this?” we asked. These two ages of research brought is much of what we know about how a genome, a collection of a living thing’s genes (stored in the DNA), work together to create life.

Now, we’re taking this knowledge and beginning to modify genomes with the goal of creating living things that exhibit specific traits, in a field dubbed “synthetic biology”. Want an apple that doesn’t brown when sliced? We’ve got you covered. How about a microbe that produces an extremely expensive anti-malaria drug, making it more accessible? Yep, we have that too. These advances are the products of the last three decades, where concerted effort and millions of dollars bore fruit to create life with an engineered function. But with the ability to do create living things with desired properties, a new problem arose: how do we ensure a living thing we create works the way we intended?

Sea life grows in a plastic cup washed up during a storm; we may one day engineer life to break down plastic in the oceans

To understand this problem, we have to look at the biological purpose of life. Every living creature has a sole directive: to make more of itself, as many copies of itself as possible. From single-celled bacteria to the complex mass of tissues and organs we call animals, all living things strive to give rise to more of themselves. This directive manifests everywhere around us: the battle for self-preservation, consumption and conflict over resources, the care shown to offspring. It also leads to extreme scenarios, such as when a male spider accepts his death for a chance to mate with a female; in this case, the chance to create more life overrides even the powerful instinct of survival. At every level, in every living thing, this rule acts to reward those that succeed at making more of themselves, as these offspring give rise to more offspring. The winners that are better at following the directive keep winning. The losers disappear from the menagerie of life.

This is where our aspirations of engineering functions into life meets reality. Living things aren’t interested in what we want them to do and our engineered functions are forever secondary to the sole directive of life. Even worse, the changes we make to create these engineered functions are often contrary to this sole directive: they make the living thing less capable of making more of itself. The result is that once we’ve created a living thing with a specific function, such as production of biofuels, it begins trying to undo what we’ve done. The offspring of our living things should have the same engineered functions, but those that manage to undo what we’ve done are better at making more of themselves. In as little as one generation, the function we engineered can disappear. The system is never stable.

A tree overgrows a wall in Hong Kong. Life has a tendency to escape any bounds put on it.

This is a serious problem because if we engineer a living thing and it doesn’t work as expected, what will it do? In the best case scenario, the living thing loses its function and we’ve got to find a way to get it working again. There are some straightforward ways to do this that I won’t cover here, but basically this scenario just costs some time and money. More worrying is a worse case scenario: where the function we engineered into a living thing to exist within certain limits or parameters, but it breaks free. This is the “Jurassic Park” scenario, where something meant to be contained and safe gets loose and wreaks havoc. And because the function of limiting a living thing to certain parameters is both incredibly useful and directly contrary to life’s sole directive, it’s less a matter of if and more a matter of when this happens. As Jeff Goldblum’s character Ian Malcom says, “life finds a way.”

For those of you now panicking, calling research institutions demanding they stop their work, hang on a moment. You’re right to be worried, and I want you to know that we researchers are right there with you. An overwhelming majority of us are driven to research because we want to do good, and the scenario in which our research creates something harmful is a nightmare. That concern is what drove a temporary moratorium of research on mutant varieties of the avian flu that could prove more dangerous. It’s what’s behind a push to keep the locations of certain extremely rare animals secret, to prevent poachers from decimating their populations. And for those of us making forays into engineering life, it’s why we’re already thinking about how the functions and safety mechanisms we build could fail, and how we can prevent that. These are the problems that keep us awake at night.

In my case, it’s also the subject of my PhD thesis. I’ll explain that in the next installment.

What I learned by starting this blog

Engineering Life to Work as Expected