Turning Microbes Into Living Factories

Frances Arnold Turns Microbes Into Living Factories – NY Times – By Natalie Angier May 28, 2019

I’m posting this just because it fascinates me and I hope it stirs interest and curiosity in my readers as well.

The engineer’s mantra, said Frances Arnold, a professor of chemical engineering at the California Institute of Technology, is: “Keep it simple, stupid.” But Dr. Arnold, who last year became just the fifth woman in history to win the Nobel Prize in Chemistry, is the opposite of stupid, and her stories sometimes turn rococo.

…another of Dr. Arnold’s maxims:

“Give up the thought that you have control. You don’t.  

The best you can do is adapt, anticipate, be flexible, sense the environment and respond.”

This is how I have lived my whole life. It may not have changed my fate, but it certainly relieved me of the responsibility of trying to bend fate to my own purposes.

Of course, this freedom also has a dark side: knowing I didn’t “earn” and don’t “deserve” any of the beneficial circumstances life has granted me.

This is definitely a source of anxiety for me, even though I know darn well that life rarely provides us with what we “deserve” as evidenced by the ancient conundrum of bad things happening to good people (and riches going to the most brutal, unprincipled, and narcissistic leaders).

Overall, I believe my system of adaptive flexibility is the best one for me. I’m acutely aware that I can never know in the moment what would be best in the long run so I consciously allow “time” or “life” to make most decisions for me.

This is surprisingly similar to any other expression of faith: I believe the Universe will make choices for me that are as good or better than choices I’d make myself. So perhaps I, without religion, live and trust in my “universal” faith more than most people who profess to follow a religion.

As it happens, Dr. Arnold, 62, has built a spectacularly successful career on her willingness to cede control in the laboratory to a force much greater than any armed guard or head of state: evolution.

Dr. Arnold won fame and the Nobel Prize for developing a technique called directed evolution, a way of generating a host of novel enzymes and other biomolecules that can be put to any number of uses — detoxifying a chemical spill, for example, or disrupting the mating dance of an agricultural pest. Or removing laundry stains in eco-friendly cold water, or making drugs without relying on eco-hostile metal catalysts.

Rather than seeking to design new proteins rationally, piece by carefully calculated piece — as many protein chemists have tried and mostly failed to do — the Arnold approach lets basic evolutionary algorithms do the work of protein composition and protein upgrades.

You start with a protein that already has some features you’re interested in, such as stability in high heat or a knack for clipping apart fats. Using a standard lab trick such as polymerase chain reaction, you randomly mutate the gene that encodes the protein.

Then you look for slight improvements in the resulting protein — a quickened pace of activity, say, or a vague inclination to carry out a task it wasn’t performing before, or a willingness to operate under conditions it deplored in the past.

You mutate the improved version again and screen the output for even better performance. Repeat as needed.

Through directed evolution, Dr. Arnold’s lab has generated microbes that do what organisms in nature have never been known to do.

“In the lab, we’re discovering that nature can do chemistry we never dreamed was possible,” Dr. Arnold said. “We’re adding whole swathes of the periodic table to the chemistry of the biological world.”

Diana Kormos-Buchwald, who directs the Einstein Papers Project at Caltech and is a close friend of Dr. Arnold, said, “Frances essentially invented the field of evolutionary chemistry. Instead of analyzing materials and trying to produce them through standard chemical synthesis, she found a way to use nature itself to populate the landscape of all possible variants of biologically or chemically important molecules.”

Dr. Arnold has another favorite mantra: “Nature doesn’t care about your calculations.”

Analyzing the evolved mutations that proved most effective at tweaking a protein’s performance, the Arnold team found the changes in all sorts of unpredictable places.

“It was far from the active site of the protein, or it was on the surface,” she said. “It was where everybody said it wouldn’t matter but it did matter. I gleefully took the results to the biochemists and said, ‘Nyeh nyeh nyeh, you can’t predict that but I found it, and I’ll do it over and over again.’ That really pissed them off.”

As a “card-carrying engineer” with an undergraduate degree in mechanical and aerospace engineering from Princeton, and a doctorate in chemical engineering from the University of California, Berkeley, Dr. Arnold also is motivated by a desire to make useful things.

And because she is an ardent environmentalist, useful means good for the planet.

Directed evolution methods can yield specialized enzymes that will carry out desired reactions far more cleanly and efficiently compared to standard chemical processes, with their reliance on solvents, plastics and precious metals.

She has started a number of companies, including a business heartily endorsed by Jane Goodall called Provivi, which is devising techniques for synthesizing insect mating pheromones cleanly, cheaply and on an industrial scale, with the goal of fending off agricultural pests through confusion rather than extermination.

She has traveled and lived around the world, crisscrossed South America and Indonesia on her own, motorcycled through Europe and Turkey. She speaks five languages and plays guitar, piano and pipe organ.

By now, it’s clear that she is no “ordinary” person and I suspect her wide areas of interest are related to this exceptional discovery – either as a prerequisite or corellation.

…a charmed life, except — terrible things have happened to her.

Her first marriage, to biochemical engineer Jay Bailey, fell apart in the early 1990s, and he died of colon cancer in 2001. In 2004, Dr. Arnold was diagnosed with breast cancer that had spread to her lymph nodes, and she underwent 18 months of grueling surgery, radiation and chemotherapy, all while raising three young boys and working 60-hour weeks.

“I used to have a photographic memory,” she said. “Chemo knocked that out.”

It’s still rare to hear about the very serious damage caused by chemo. For decades, it was considered almost sacrilegious to say anything negative about these potentially lifesaving drugs/procedures.

In 2010, Dr. Arnold’s common-law husband, the cosmologist Andrew Lange, committed suicide, leaving behind a crater of emotional devastation so deep that Dr. Arnold still struggles to forgive him.

Worse by far was the accidental death in 2016 of her middle son, William Lange, at the age of 20, an event that Dr. Arnold says she is not yet ready to talk about.

I don’t believe I could survive such multiple heart- and body-breaking disasters.

Dr. Arnold grows impatient when people express awe at the strength of her spine.

“Nobody is guaranteed an easy life,” she said.

“Look at the people in Syria. I have friends who are Holocaust survivors. What was I supposed to do — give up, say I can’t go on? No. I had other children. I had a group of young people in the lab. Why would I give up?

1 thought on “Turning Microbes Into Living Factories

  1. Susan Brucks

    So true, you’ve got to keep on keeping on. Not always easy, in fact often hard to do. By the way? Do you know we’re i can get some of the stuff to confuse the pests on my tomatoes? 😁🐛🍅

    Liked by 1 person

    Reply

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