On writing: What illuminates a story?

Don't be afraid to have the very experiences you aspire to write about — they will help you write more vividly, and from a genuine place of wonder.

MICHAEL POLLAN: So this was an enormously challenging book to write. First of all, I knew very little about neuroscience. I knew very little about psychology, psychotherapy. And I had very limited experience of psychedelics. I had these mushrooms a couple of times in my 20s, but it was what people call a museum dose — enough to make the world sparkle, but not to lead to any kind of profound insights. So I was faced with the challenge of mastering a new subject, and I was faced with the challenge of trying these psychedelics because I realized I could not describe the experience strictly based on interviews with other people.

And that's how I work as a writer. One of the very important parts of my work is to find a way to have an experience that will illuminate the story. So when I wrote about food, I bought a cow and followed it through the food system, through the meat industry. And I apprenticed myself to a great baker to learn how to bake. And I feel that these kind of experiences, especially when you're doing it for the first time, gives you an ability to see things very freshly. And you have that sense of wonder that comes with first sight, and you also get the common possibilities of a fish out of water, doing something that he or she is not very good at and the learning that comes from that.

So one of the things I always think about when I'm starting a project like this is, what are the different perspectives that I need to bring to bear on this subject? I don't believe any one perspective can unlock a subject as complex as psychedelics. So you need to look at it — and this was true when I was writing about food and plants. Nonfiction gets interesting when you multiply the perspectives or layer the different lenses that you bring to. So you can look at this through the lens of neuroscience, say. A very interesting lens illuminates a lot.

But that doesn't tell you anything about the lived experience. Because neuroscience cannot reach consciousness. It has no tools for penetrating or measuring consciousness, except the absence of it. And so phenomenology — the accounts of lived experience are very important. And I could get those from the volunteers I interviewed and from my own experience. So I needed a memoiristic element, as well as the neuroscientific element. And then there's the historical lens. History always illuminates things. How did we get here? Why did it take so long to get here? What have we learned along the way?

So I realized, O.K., I'm going to need to do a chapter of history, or two. I'm going to need to do a chapter of neuroscience, a chapter of my own trips, and it gradually comes together. Each chapter is going to represent a different lens on this subject, and I'm going to circle it from these different points of view. And that, to me, is how you make nonfiction rich. Otherwise, you might as well write an article. And what necessitates a book is the fact that no one perspective will give you the picture you need, the full dimensional picture.

Within that frame, the most challenging part was describing the psychedelic trips. And William James famously said that the mystical experience is ineffable — beyond the reach of language. Well, I had an effort. I couldn't just let that lie and just say you had to be there. But it's very hard to describe because these are kind of pre-linguistic experiences.

One of the researchers I interviewed said — I said why are these experiences so hard to describe? And he said, well, imagine a cave man coming to New York in 2019, and he sees subways going by, and planes overhead, and people talking on phones, and the noise of traffic. And then he goes back to his friends in the cave, and what does he say? He says it's loud and fast, and he doesn't have the words for cell phone or the bustle of urban life. The language doesn't exist.

But I had to find the language, and so I approach those chapters with a great deal of trepidation and as much trepidation as I had about the trips themselves. And it took me a while to figure out how to write about it. Because I was trying to write for a general audience. I'm not writing for psycho nuts. I'm writing for people who've never had this experience, but might be curious. And I want to tell them what it's like. And it took me a while, but I gradually found a voice in which I could do it. And this comes through trial and error of writing an account and reading it and going, that sounds crazy. Or that sounds really banal. "Gee, you've had an insight that love is the most important thing in the universe. That's a Hallmark card."

The solution I found to that was to be very candid with my reader and essentially tell the narratives. And then break the fourth wall at various points, step out of the narrative, and say, "Look, I know how banal this sounds, but let's talk about banality for a little while. There's a very thin line between the profound and the banal. What is a platitude? Well, it's a truth that's lost its emotional force from sheer repetition. So how do we recover that?" Or, in another moment, where if something crazy happens, I would break the wall and say, "I know how crazy this sounds."

So I kind of move in and out of the experience, sort of the way a memoir writer would juxtapose the point of view of the 10-year-old with the adult and go back and forth. Because if you just stayed in the head of the 10-year-old, it would have no perspective. It might have vividness, but no perspective. And if you stayed in the head of the adult, it wouldn't be evocative. So memoirs, I realized — and I realized this teaching them because I teach writing — get their savor or their edge from that going back and forth in perspective. And I kind of did the same thing, not in a temporal dimension, but on this inside outside of the experience.

So I found my voice to write about it, and once I did, it was great fun to write about the trips. I've never had more fun as a writer. I loved describing them. And I and I would license the absolute madness of parts of the experience by saying, "Yeah, I know, it's crazy, but this is what happened." So this book was great fun to write. I was learning new things. I loved being at the beginning of the learning curve on this subject, rather than at the end. One of the reasons I moved from writing about food to this was I realized I had become an expert after three or four books on food.

And I don't like writing as an expert. I think readers don't like experts. I think they want someone to take them on a journey. And my education becomes the story that you follow. I always start out as an idiot in my writing. I'm naive. I don't know what's going on. I'm confused. I have questions in my head. I'm reluctant. I'm skeptical. And gradually, I build my knowledge. We learn things. Things happen. And by the end, we are experts, but we're not at the beginning. And I think that's a really important lesson for writing in general.

I think even though when you finish a research project, you have your conclusions, don't put them on page one. That's like starting the joke with the punchline. Storytelling is you start from knowing less, and you move toward knowing more. So that the novelty of this subject, the fact that I was very naive, was a virtue, or at least, made a virtue. So we shouldn't be afraid of our ignorance. We should use it in our storytelling.

  • When it comes to writing a story, it's important to find a way to have an experience that will illuminate the narrative for readers — that is, an experience that fills you, the writer, with wonder and gives you a fresh take on things.
  • A good way to make a nonfiction story rich is by tackling the subject with different lenses, by circling it from different points of views.
  • Good storytelling is about taking readers on a journey. This said, instead of leading with your conclusion, begin from the time when you were naive about the subject at hand, and, as you relay the different things you learn, you will help your readers, in a down-to-earth way, move toward knowing more, too.

How to Change Your Mind: What the New Science of Psychedelics Teaches Us About Consciousness, Dying, Addiction, Depression, and Transcendence


CRISPR therapy cures first genetic disorder inside the body

It marks a breakthrough in using gene editing to treat diseases.

Credit: National Cancer Institute via Unsplash
Technology & Innovation

This article was originally published by our sister site, Freethink.

For the first time, researchers appear to have effectively treated a genetic disorder by directly injecting a CRISPR therapy into patients' bloodstreams — overcoming one of the biggest hurdles to curing diseases with the gene editing technology.

The therapy appears to be astonishingly effective, editing nearly every cell in the liver to stop a disease-causing mutation.

The challenge: CRISPR gives us the ability to correct genetic mutations, and given that such mutations are responsible for more than 6,000 human diseases, the tech has the potential to dramatically improve human health.

One way to use CRISPR to treat diseases is to remove affected cells from a patient, edit out the mutation in the lab, and place the cells back in the body to replicate — that's how one team functionally cured people with the blood disorder sickle cell anemia, editing and then infusing bone marrow cells.

Bone marrow is a special case, though, and many mutations cause disease in organs that are harder to fix.

Another option is to insert the CRISPR system itself into the body so that it can make edits directly in the affected organs (that's only been attempted once, in an ongoing study in which people had a CRISPR therapy injected into their eyes to treat a rare vision disorder).

Injecting a CRISPR therapy right into the bloodstream has been a problem, though, because the therapy has to find the right cells to edit. An inherited mutation will be in the DNA of every cell of your body, but if it only causes disease in the liver, you don't want your therapy being used up in the pancreas or kidneys.

A new CRISPR therapy: Now, researchers from Intellia Therapeutics and Regeneron Pharmaceuticals have demonstrated for the first time that a CRISPR therapy delivered into the bloodstream can travel to desired tissues to make edits.

We can overcome one of the biggest challenges with applying CRISPR clinically.

—JENNIFER DOUDNA

"This is a major milestone for patients," Jennifer Doudna, co-developer of CRISPR, who wasn't involved in the trial, told NPR.

"While these are early data, they show us that we can overcome one of the biggest challenges with applying CRISPR clinically so far, which is being able to deliver it systemically and get it to the right place," she continued.

What they did: During a phase 1 clinical trial, Intellia researchers injected a CRISPR therapy dubbed NTLA-2001 into the bloodstreams of six people with a rare, potentially fatal genetic disorder called transthyretin amyloidosis.

The livers of people with transthyretin amyloidosis produce a destructive protein, and the CRISPR therapy was designed to target the gene that makes the protein and halt its production. After just one injection of NTLA-2001, the three patients given a higher dose saw their levels of the protein drop by 80% to 96%.

A better option: The CRISPR therapy produced only mild adverse effects and did lower the protein levels, but we don't know yet if the effect will be permanent. It'll also be a few months before we know if the therapy can alleviate the symptoms of transthyretin amyloidosis.

This is a wonderful day for the future of gene-editing as a medicine.

—FYODOR URNOV

If everything goes as hoped, though, NTLA-2001 could one day offer a better treatment option for transthyretin amyloidosis than a currently approved medication, patisiran, which only reduces toxic protein levels by 81% and must be injected regularly.

Looking ahead: Even more exciting than NTLA-2001's potential impact on transthyretin amyloidosis, though, is the knowledge that we may be able to use CRISPR injections to treat other genetic disorders that are difficult to target directly, such as heart or brain diseases.

"This is a wonderful day for the future of gene-editing as a medicine," Fyodor Urnov, a UC Berkeley professor of genetics, who wasn't involved in the trial, told NPR. "We as a species are watching this remarkable new show called: our gene-edited future."

UFOs: US intelligence report finds no aliens but plenty of unidentified flying objects

A new government report describes 144 sightings of unidentified aerial phenomena.

Photo by Albert Antony on Unsplash
Surprising Science

On June 25, 2021, the Office of the Director of National Intelligence released a much-anticipated report on UFOs to Congress.

Keep reading Show less

Android has won the phone world war

A global survey shows the majority of countries favor Android over iPhone.

Credit: Electronics Hub
Strange Maps
  • When Android was launched soon after Apple's own iPhone, Steve Jobs threatened to "destroy" it.
  • Ever since, and across the world, the rivalry between both systems has animated users.
  • Now the results are in: worldwide, consumers clearly prefer one side — and it's not Steve Jobs'.
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COVID and "gain of function" research: should we create monsters to prevent them?

Gain-of-function mutation research may help predict the next pandemic — or, critics argue, cause one.

Credit: Guillermo Legaria via Getty Images
Coronavirus

This article was originally published on our sister site, Freethink.

"I was intrigued," says Ron Fouchier, in his rich, Dutch-accented English, "in how little things could kill large animals and humans."

It's late evening in Rotterdam as darkness slowly drapes our Skype conversation.

This fascination led the silver-haired virologist to venture into controversial gain-of-function mutation research — work by scientists that adds abilities to pathogens, including experiments that focus on SARS and MERS, the coronavirus cousins of the COVID-19 agent.

If we are to avoid another influenza pandemic, we will need to understand the kinds of flu viruses that could cause it. Gain-of-function mutation research can help us with that, says Fouchier, by telling us what kind of mutations might allow a virus to jump across species or evolve into more virulent strains. It could help us prepare and, in doing so, save lives.

Many of his scientific peers, however, disagree; they say his experiments are not worth the risks they pose to society.

A virus and a firestorm

The Dutch virologist, based at Erasmus Medical Center in Rotterdam, caused a firestorm of controversy about a decade ago, when he and Yoshihiro Kawaoka at the University of Wisconsin-Madison announced that they had successfully mutated H5N1, a strain of bird flu, to pass through the air between ferrets, in two separate experiments. Ferrets are considered the best flu models because their respiratory systems react to the flu much like humans.

The mutations that gave the virus its ability to be airborne transmissible are gain-of-function (GOF) mutations. GOF research is when scientists purposefully cause mutations that give viruses new abilities in an attempt to better understand the pathogen. In Fouchier's experiments, they wanted to see if it could be made airborne transmissible so that they could catch potentially dangerous strains early and develop new treatments and vaccines ahead of time.

The problem is: their mutated H5N1 could also cause a pandemic if it ever left the lab. In Science magazine, Fouchier himself called it "probably one of the most dangerous viruses you can make."

Just three special traits

Recreated 1918 influenza virionsCredit: Cynthia Goldsmith / CDC / Dr. Terrence Tumpey / Public domain via Wikipedia

For H5N1, Fouchier identified five mutations that could cause three special traits needed to trigger an avian flu to become airborne in mammals. Those traits are (1) the ability to attach to cells of the throat and nose, (2) the ability to survive the colder temperatures found in those places, and (3) the ability to survive in adverse environments.

A minimum of three mutations may be all that's needed for a virus in the wild to make the leap through the air in mammals. If it does, it could spread. Fast.

Fouchier calculates the odds of this happening to be fairly low, for any given virus. Each mutation has the potential to cripple the virus on its own. They need to be perfectly aligned for the flu to jump. But these mutations can — and do — happen.

"In 2013, a new virus popped up in China," says Fouchier. "H7N9."

H7N9 is another kind of avian flu, like H5N1. The CDC considers it the most likely flu strain to cause a pandemic. In the human outbreaks that occurred between 2013 and 2015, it killed a staggering 39% of known cases; if H7N9 were to have all five of the gain-of-function mutations Fouchier had identified in his work with H5N1, it could make COVID-19 look like a kitten in comparison.

H7N9 had three of those mutations in 2013.

Gain-of-function mutation: creating our fears to (possibly) prevent them

Flu viruses are basically eight pieces of RNA wrapped up in a ball. To create the gain-of-function mutations, the research used a DNA template for each piece, called a plasmid. Making a single mutation in the plasmid is easy, Fouchier says, and it's commonly done in genetics labs.

If you insert all eight plasmids into a mammalian cell, they hijack the cell's machinery to create flu virus RNA.

"Now you can start to assemble a new virus particle in that cell," Fouchier says.

One infected cell is enough to grow many new virus particles — from one to a thousand to a million; viruses are replication machines. And because they mutate so readily during their replication, the new viruses have to be checked to make sure it only has the mutations the lab caused.

The virus then goes into the ferrets, passing through them to generate new viruses until, on the 10th generation, it infected ferrets through the air. By analyzing the virus's genes in each generation, they can figure out what exact five mutations lead to H5N1 bird flu being airborne between ferrets.

And, potentially, people.

"This work should never have been done"

The potential for the modified H5N1 strain to cause a human pandemic if it ever slipped out of containment has sparked sharp criticism and no shortage of controversy. Rutgers molecular biologist Richard Ebright summed up the far end of the opposition when he told Science that the research "should never have been done."

"When I first heard about the experiments that make highly pathogenic avian influenza transmissible," says Philip Dormitzer, vice president and chief scientific officer of viral vaccines at Pfizer, "I was interested in the science but concerned about the risks of both the viruses themselves and of the consequences of the reaction to the experiments."

In 2014, in response to researchers' fears and some lab incidents, the federal government imposed a moratorium on all GOF research, freezing the work.

Some scientists believe gain-of-function mutation experiments could be extremely valuable in understanding the potential risks we face from wild influenza strains, but only if they are done right. Dormitzer says that a careful and thoughtful examination of the issue could lead to processes that make gain-of-function mutation research with viruses safer.

But in the meantime, the moratorium stifled some research into influenzas — and coronaviruses.

The National Academy of Science whipped up some new guidelines, and in December of 2017, the call went out: GOF studies could apply to be funded again. A panel formed by Health and Human Services (HHS) would review applications and make the decision of which studies to fund.

As of right now, only Kawaoka and Fouchier's studies have been approved, getting the green light last winter. They are resuming where they left off.

Pandora's locks: how to contain gain-of-function flu

Here's the thing: the work is indeed potentially dangerous. But there are layers upon layers of safety measures at both Fouchier's and Kawaoka's labs.

"You really need to think about it like an onion," says Rebecca Moritz of the University of Wisconsin-Madison. Moritz is the select agent responsible for Kawaoka's lab. Her job is to ensure that all safety standards are met and that protocols are created and drilled; basically, she's there to prevent viruses from escaping. And this virus has some extra-special considerations.

The specific H5N1 strain Kawaoka's lab uses is on a list called the Federal Select Agent Program. Pathogens on this list need to meet special safety considerations. The GOF experiments have even more stringent guidelines because the research is deemed "dual-use research of concern."

There was debate over whether Fouchier and Kawaoka's work should even be published.

"Dual-use research of concern is legitimate research that could potentially be used for nefarious purposes," Moritz says. At one time, there was debate over whether Fouchier and Kawaoka's work should even be published.

While the insights they found would help scientists, they could also be used to create bioweapons. The papers had to pass through a review by the U.S. National Science Board for Biosecurity, but they were eventually published.

Intentional biowarfare and terrorism aside, the gain-of-function mutation flu must be contained even from accidents. At Wisconsin, that begins with the building itself. The labs are specially designed to be able to contain pathogens (BSL-3 agricultural, for you Inside Baseball types).

They are essentially an airtight cement bunker, negatively pressurized so that air will only flow into the lab in case of any breach — keeping the viruses pushed in. And all air in and out of the lap passes through multiple HEPA filters.

Inside the lab, researchers wear special protective equipment, including respirators. Anyone coming or going into the lab must go through an intricate dance involving stripping and putting on various articles of clothing and passing through showers and decontamination.

And the most dangerous parts of the experiment are performed inside primary containment. For example, a biocontainment cabinet, which acts like an extra high-security box, inside the already highly-secure lab (kind of like the radiation glove box Homer Simpson is working in during the opening credits).

"Many people behind the institution are working to make sure this research can be done safely and securely." — REBECCA MORITZ

The Federal Select Agent program can come and inspect you at any time with no warning, Moritz says. At the bare minimum, the whole thing gets shaken down every three years.

There are numerous potential dangers — a vial of virus gets dropped; a needle prick; a ferret bite — but Moritz is confident that the safety measures and guidelines will prevent any catastrophe.

"The institution and many people behind the institution are working to make sure this research can be done safely and securely," Moritz says.

No human harm has come of the work yet, but the potential for it is real.

"Nature will continue to do this"

They were dead on the beaches.

In the spring of 2014, another type of bird flu, H10N7, swept through the harbor seal population of northern Europe. Starting in Sweden, the virus moved south and west, across Denmark, Germany, and the Netherlands. It is estimated that 10% of the entire seal population was killed.

The virus's evolution could be tracked through time and space, Fouchier says, as it progressed down the coast. Natural selection pushed through gain-of-function mutations in the seals, similarly to how H5N1 evolved to better jump between ferrets in his lab — his lab which, at the time, was shuttered.

"We did our work in the lab," Fouchier says, with a high level of safety and security. "But the same thing was happening on the beach here in the Netherlands. And so you can tell me to stop doing this research, but nature will continue to do this day in, day out."

Critics argue that the knowledge gained from the experiments is either non-existent or not worth the risk; Fouchier argues that GOF experiments are the only way to learn crucial information on what makes a flu virus a pandemic candidate.

"If these three traits could be caused by hundreds of combinations of five mutations, then that increases the risk of these things happening in nature immensely," Fouchier says.

"With something as crucial as flu, we need to investigate everything that we can," Fouchier says, hoping to find "a new Achilles' heel of the flu that we can use to stop the impact of it."

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