Creating Melodic Landscapes in Antarctica

Question:  What are the origins of "Terra Nova," your \r\nAntarctic symphony?
DJ Spooky: \r\nWhat I wanted to try and figure out was, okay, in contemporary 21st\r\ncentury life the alienation between the self and the land around you or\r\nthe self and even the urban landscape.  You name it.  Most people walk\r\naround with headphones on.  They’re barely encountering or dealing with\r\ntheir fellow person, or if they’re in a car they’re in this kind of\r\ncocoon, stuck in suburban rush hour traffic or something.  The\r\nlandscape of their current experience is just really compartmentalized. \r\nAnd what I wanted to do with Antarctica was say let’s hit the\r\nreset button on that and see what happens to your creative process. \r\nLet’s go to the most remote place that you can imagine, set up a studio\r\nand see what music comes out of it. So I took a studio down to several\r\nof the main ice fields, and the basic idea was to give myself four weeks\r\nin these ice fields to create a new work and see what happens. And, you\r\nknow, it was really important to me to kind of think about the urban\r\nlandscape on one hand versus this hyper-abstract ice landscape\r\non the other. 
Antarctica, one of the things that was so\r\nremarkable about it was that the ice itself is a kind of pure geometry,\r\nso say, for example, if I was facing someone wearing I don’t know, a Joy\r\nDivision t-shirt with the mountains on it or something like that... \r\nSeeing that as a computer abstraction versus actually going to these\r\ncontinents and seeing a 40 mile chunk of ice break off that is the size\r\nof mountains the sense of scale was just awe-inspiring.  I mean just… \r\nI remember one time it took us several hours to walk out into a major\r\nglacier field off the Weddell Ice Sea Shelf, all right, so this is\r\nAntarctic summer, if you fall in the water you die in about two\r\nminutes, so you’re walking, the ice is creaking, the landscape is like\r\nsubtly you know shifting and if anyone out there has ever been in an\r\nearthquake this is like kind of a slow motion earthquake, but the land\r\nis shifting and groaning and creaking and you know if you ever walked\r\non ice and you’re like whoa, you could fall through.  It really you\r\nknow puts you in that for lack of better word, very cautious\r\nmentality. So the physicality of that and the just the sheer lack of\r\nurban noise and machinery—just the wind, the water and your breath,\r\nyou know that kind of thing—it was pure poetry and you know I\r\ntreasure that.  It was just…  I can only wonder what astronauts must\r\nfeel like or something like that when you’re really in the space of\r\nsilence and you are feeling and breathing in a way that you’re really\r\naware of your muscle and bone and the breath and the body and the\r\nmovement and all of those things that just you take for granted in the\r\nurban landscape. 
I felt like on one\r\nhand the clarity of thought was amazing, but on the other we went\r\nduring Antarctic summer, so the sun didn’t set the whole time we were\r\nthere.  It was permanent afternoon. And when I say permanent afternoon,\r\nyou know, I’m talking like crystal clear, crispy blue sky.  All the\r\nsudden you didn’t need to sleep as much because it just was difficult. \r\nAnd how that translated into my creative process I still am not quite\r\nsure, but it made my relationship to sleep a kind of abstract you know\r\nbizarre…  I can't put my finger on it, but I ended up\r\ndreaming very intense dreams because I only needed about four hours of\r\nsleep.  Meanwhile, we’d take you know four to eight hours hikes way out\r\ninto these you know kind of glaciers and so on you know all day and you\r\ncome back and you’d be tired and you still couldn’t sleep because the\r\nsun was up and it felt like you know it’s like two in the afternoon or\r\nsomething, even if it was midnight. So, yeah, quirky.  Sleep is crucial\r\nand I tend to find when the sun is shining I find it much more\r\ndifficult to get that sense of sleep. 

Question: Is \r\nthe  piece classical?

DJ Spooky: \r\nWhat I’m going for with the string arrangements for my Antarctic\r\nsymphony is a pun here.  On one hand you have a string quartet, which\r\nis not a symphony.  On the other hand is you have me sampling them and\r\nmaking it sound like there is many more people playing, so the whole\r\nnotion of, kind of, sampling applied to classical music is very\r\nintriguing to me because composers throughout history have borrowed\r\nmotifs and quotes from one another. So Bach, Beethoven, Duke Ellington,\r\nThelonius Monk, these are all people who would sort of rearrange or\r\ntake riffs from people. Same thing with rock, if you look at the\r\nRolling Stones doing a cover of Otis Redding or you know if you look at\r\nliterature James Joyce is pulling fragments of text from other people. \r\nSo the Antarctic symphony has a geometric relationship to the\r\nlandscape.  It’s saying that this landscape and the minimal kind of, you\r\nknow I’m talking like seeing ice, is visually kind of eerily minimal. \r\nBut there is a complexity and layering that goes on with this kind of\r\nthing, so the music is slightly repetitive and when I say repetitive\r\nit’s in the same tradition as people like Steve Reich or Erik Satie or\r\neven WC. So what I wanted to do is kind of invoke that and then dive\r\ninto that kind of repetition as a DJ thing because DJing you\r\nhear beats, like "boom, boom, boom, bap, bap."  You know hip hop, house,\r\ntechno.  So how do you translate between those electronic motifs and\r\nthe motifs of the landscape itself?  That is what I wanted to go for.
Question: What do you want people to get out of it?
DJ Spooky: \r\nAntarctica is one of the most remote and beautiful places on earth.  I\r\ndon’t think that everyone should go there.  I also think that we need\r\nto respect it as a kind of a national park for the planet.  It\r\nshould be you know put in parentheses.  You know, in the sentence of\r\nhumanity this place needs to be a parentheses. And when I say\r\nparentheses I mean I’m talking like you go around it.  Leave it alone.  \r\nLet it exist.  And what I want people to see with this\r\nfilm is not only a respect for this place from the bottom of my heart. \r\nI’m talking like just the beauty, but at the same time to get people to\r\nrealize that we should treasure it.  Maybe visualize it, but leave it\r\nalone. And it’s… there is a sense of awe with these huge landscapes and\r\nopen spaces.  Maybe someone living out in the American deep Midwest\r\ndesert can imagine the same thing, or somebody living in Namibia or the\r\nArctic is very different... but yeah, just awe of the landscape.  I know\r\nthat sounds like nerdy and corny and stuff like that, but you know let\r\nit be nerdy and corny.  It’s a beautiful place.  I could just sit on an\r\nice glacier and just watch the land for like days, months, years.

Recorded on April 8, 2010

"Go to the most remote place that you can imagine, set up a studio and see what music comes out of it."

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

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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