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It's beautiful!

This is a hellbender — a salamander, and the biggest amphibian in North America. Some people call them 'snot otters'. They're up to 2 feet long, they're slimy, and they look a bit like turds. But I think they're beautiful, a marvel of nature! They've lived on Earth for 65 million years. We've been here for only about 2 million.

Who will last longer? The hellbender is threatened — but some people are helping it out! They're cleaning up streams and repopulating them with hellbenders. Check out this fun video:

https://youtu.be/48hSM2MC0hQ

Hellbenders live in many eastern states of the USA, and are especially common in Missouri, Pennsylvania, and Tennessee — but mining and other human activities have silted up many of the fast-moving streams that they like. Already by 1981, hellbenders were extinct or endangered in Illinois, Indiana, Iowa, and Maryland, decreasing in Arkansas and Kentucky, and generally threatened.

So, restoring hellbenders must go hand in hand with restoring streams. But that's a good thing in itself!

The hellbender is a 'habitat specialist': it's adapted to fill a specific niche within a very specific environment. They like streams with large, irregularly shaped rocks and swiftly moving water. They avoid wider, slow-moving waters with muddy banks or slab rock bottoms. They love to hide next to a big rock, where they can hunt crayfish and small fish. Unfortunately, this helps amphibian collectors easily find them - another reason for their decline.

They start out with gills, but when they're a year and a half old they lose these gills and develop toes on their front and hind feet. After this metamorphosis they can only absorb oxygen through the folds in their skin. And that's another problem: they can only live in fast-moving, oxygenated water! If they get stuck in slow-moving water, they can't breathe.

Now people are trying to help hellbenders by breeding them in zoos and releasing them in clean streams. They can survive out in the wild if they don't get the fungal disease that's wiping out amphibians around the world — the chytrid disease. We really need good biologists to tackle that disease!

People are also creating artificial structures for hellbenders to hide in:

http://precast.org/2013/04/saving-the-eastern-hellbender-salamander/

Read more about hellbenders at National Geographic, where this picture came from:

http://news.nationalgeographic.com/news/2013/12/131220-hellbender-salamander-conservation-endangered-animals-science/

The hellbender's real name is Cryptobranchus alleganiensis, and it has two subspecies: the Eastern hellbender Cryptobranchus alleganiensis alleganiensis, and the Ozark hellbender Cryptobranchus alleganiensis bishopi. It's the only species in its genus, and its family contains the only two salamanders that are even larger: the Japanese and Chinese giant salamanders. For more:

https://en.wikipedia.org/wiki/Hellbender

#biology
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DNA hackers

In new research they plan to present at the USENIX Security conference on Thursday, a group of researchers from the University of Washington has shown for the first time that it’s possible to encode malicious software into physical strands of DNA, so that when a gene sequencer analyzes it the resulting data becomes a program that corrupts gene-sequencing software and takes control of the underlying computer.

It's not a realistic threat now - but it's cute enough to make a cute SF story, at least. Here's the idea, as described by Wired:

The researchers started by writing a well-known exploit called a "buffer overflow," designed to fill the space in a computer's memory meant for a certain piece of data and then spill out into another part of the memory to plant its own malicious commands.

But encoding that attack in actual DNA proved harder than they first imagined. DNA sequencers work by mixing DNA with chemicals that bind differently to DNA's basic units of code—the chemical bases A, T, G, and C—and each emit a different color of light, captured in a photo of the DNA molecules. To speed up the processing, the images of millions of bases are split up into thousands of chunks and analyzed in parallel. So all the data that comprised their attack had to fit into just a few hundred of those bases, to increase the likelihood it would remain intact throughout the sequencer's parallel processing.

When the researchers sent their carefully crafted attack to the DNA synthesis service Integrated DNA Technologies in the form of As, Ts, Gs, and Cs, they found that DNA has other physical restrictions too. For their DNA sample to remain stable, they had to maintain a certain ratio of Gs and Cs to As and Ts, because the natural stability of DNA depends on a regular proportion of A-T and G-C pairs. And while a buffer overflow often involves using the same strings of data repeatedly, doing so in this case caused the DNA strand to fold in on itself. All of that meant the group had to repeatedly rewrite their exploit code to find a form that could also survive as actual DNA, which the synthesis service would ultimately send them in a finger-sized plastic vial in the mail.

The result, finally, was a piece of attack software that could survive the translation from physical DNA to the digital format, known as FASTQ, that's used to store the DNA sequence. And when that FASTQ file is compressed with a common compression program known as fqzcomp—FASTQ files are often compressed because they can stretch to gigabytes of text—it hacks that compression software with its buffer overflow exploit, breaking out of the program and into the memory of the computer running the software to run its own arbitrary commands.

But here's the part that really makes it of merely theoretical interest right now:

Despite that tortuous, unreliable process, the researchers admit, they also had to take some serious shortcuts in their proof-of-concept that verge on cheating. Rather than exploit an existing vulnerability in the fqzcomp program, as real-world hackers do, they modified the program's open-source code to insert their own flaw allowing the buffer overflow. But aside from writing that DNA attack code to exploit their artificially vulnerable version of fqzcomp, the researchers also performed a survey of common DNA sequencing software and found three actual buffer overflow vulnerabilities in common programs. "A lot of this software wasn't written with security in mind," Ney says. That shows, the researchers say, that a future hacker might be able to pull off the attack in a more realistic setting, particularly as more powerful gene sequencers start analyzing larger chunks of data that could better preserve an exploit's code.

Luckily the article admits it's just speculative:

Needless to say, any possible DNA-based hacking is years away. Illumina, the leading maker of gene-sequencing equipment, said as much in a statement responding to the University of Washington paper. "This is interesting research about potential long-term risks. We agree with the premise of the study that this does not pose an imminent threat and is not a typical cyber security capability," writes Jason Callahan, the company's chief information security officer "We are vigilant and routinely evaluate the safeguards in place for our software and instruments. We welcome any studies that create a dialogue around a broad future framework and guidelines to ensure security and privacy in DNA synthesis, sequencing, and processing."

Here's the article:

• Andy Greenberg, Biohackers encoded malware in a strand of DNA, Wired, 10 August 2017, https://www.wired.com/story/malware-dna-hack/

I apologize for the sexist, cheesy picture here. It's the best I could find for the theme of 'DNA hackers'.

#biology
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Biology as information dynamics

Here's the talk I gave last week at the Stanford Complexity Group.

If biology is the study of self-replicating entities, and we want to understand the role of information, it makes sense to see how information theory is connected to the replicator equation — a simple but extremely general model of population dynamics for self-replicating entities.

But it's important to realize that the amount of new information you gain when you learn something should be measured relative to what you already believe. So, the relevant concept of information turns out to be the information of one probability distribution relative to another. So, I start with an explanation of relative information.

Then I show how this gives a new outlook on thermodynamics. Then I explain the replicator equation and show how relative information lets us see evolution as a learning process Finally, I give a clearer, more general formulation of Fisher’s fundamental theorem of natural selection.

There were a lot of really interesting questions at the end of my talk. The audience picked up on lots of subtleties that I felt I'd glossed over in my talk.

#biology

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Biology as Information Dynamics

I'm giving a talk at the Stanford Complexity Group this Thursday afternoon, April 20th. If you're around - like in Silicon Valley - please drop by! It will be in Clark S361 at 4:20 pm.

Here's the idea. Everyone likes to say that biology is all about information. There's something true about this - just think about DNA. But what does this insight actually do for us? To figure it out, we need to do some work.

Biology is also about things that make copies of themselves. So it makes sense to figure out how information theory is connected to the 'replicator equation' — a simple model of population dynamics for self-replicating entities.

To see the connection, we need to use relative information: the information of one probability distribution relative to another, also known as the Kullback–Leibler divergence. Then everything pops into sharp focus.

It turns out that free energy — energy in forms that can actually be used, not just waste heat — is a special case of relative information Since the decrease of free energy is what drives chemical reactions, biochemistry is founded on relative information.

But there's a lot more to it than this! Using relative information we can also see evolution as a learning process, fix the problems with Fisher's fundamental theorem of natural selection, and more.

So this what I'll talk about! You can see slides of an old version here:

http://math.ucr.edu/home/baez/bio_asu/

but my Stanford talk will be videotaped and it'll eventually be here:

https://www.youtube.com/user/StanfordComplexity

You can already see lots of cool talks at this location!

#biology
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Rats!

Medical research using mice and rats tries to control all the variables - making everything the same. But it doesn't work...

... and maybe it's a bad idea in the first place! Joseph Garner at the Stanford University Medical Center has some ideas about this:

The philosophy behind mouse research has been to make everything as uniform as possible, so results from one facility would be the same as the identical experiment elsewhere.

But despite extensive efforts to be consistent, this setup hides a huge amount of variation. Bedding may differ from one facility to the next. So might the diet. Mice respond strongly to individual human handlers. Mice also react differently depending on whether their cage is up near the fluorescent lights or hidden down in the shadows.

Garner and colleagues tried to run identical experiments in six different mouse facilities, scattered throughout research centers in Europe. Even using genetically identical mice of the same age, the results varied all over the map.

Garner says scientists shouldn't even be trying to do experiments this way.

"Imagine you were doing a human drug trial and you said to the FDA, 'OK, I'm going to do this trial in 43-year-old white males in one small town in California,'" Garner says — a town where everyone lives in identical ranch homes, with the same monotonous diets and the same thermostat set to the same temperature.

"Which is too cold, and they can't change it," he goes on. "And oh, they all have the same grandfather!"

The FDA would laugh that off as an insane setup, Garner says.

"But that's exactly what we do in animals. We try to control everything we can possibly think of, and as a result we learn absolutely nothing."

Garner argues that research based on mice would be more reliable if it were set up more like experiments in humans — recognizing that variation is inevitable, and designing to embrace it rather than ignore it. He and his colleagues have recently published a manifesto, urging colleagues in the field to look at animals in this new light.

Here's the manifesto:

• Joseph P Garner, Brianna N Gaskill, Elin M Weber, Jamie Ahloy-Dallaire and Kathleen R Pritchett-Corning, Introducing therioepistemology: the study of how knowledge is gained from animal research. Available at http://www.labanimal.com/laban/journal/v46/n4/pdf/laban.1224.pdf

The quote is from the article I'm linking to - the whole thing is good.

#biology

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Making a new dog

Dogs are now considered to be the same species as wolves. They can interbreed with wolves just fine. They've just evolved to look and act different through interaction with us. They eat things wolves wouldn't touch. Dingoes, in Australia, are semi-wild dogs that went through a similar evolution.

Now that humans have taken over the world, there is very little true wilderness. In most places where wolves roam, they encounter people. They have the option of trying to get food from human sources. It's often easier than hunting.

This means that all wolves are evolving into something new. They're roaming less, getting less scared of people. We're "making a new dog".

That's what this paper is about:

• Thomas M. Newsome et al, Making a new dog?, BioScience 67 (2017), 374-381. Available at https://doi.org/10.1093/biosci/bix022.

And as humans encroach on their range, wolves are having more trouble finding mates. Sometimes they mate with domestic dogs. But mainly they're starting to interbreed with coyotes! This especially true in the northeast US. There are now zones where coyote populations are more wolf-like. They've got wolf genes affecting their body size and proportions.

So: nature is doing its thing. There is no sharp separation between nature and culture, civilization and wilderness. The rapid changes in human culture are rippling through the whole biosphere in a myriad of ways.

#biology
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Trillions of warriors, in a battle visible from space

See the murky cloud in the water? It's made of dying warriors - tiny sea creatures called coccolithophores who are fighting viruses, losing, dying and falling to the sea floor.

It's not an unusual event. It happens around the globe all the time. This war has been going on for millions of years. The combatants have evolved intricate strategies to outwit each other. And most interestingly, the way this battle plays out is crucial for all oxygen-breathing life on this planet.

Listen to the story here. You won't regret it! It's well-told, it's thrilling, and it will make you think of the world in a new way:

http://www.radiolab.org/story/190284-war-we-need/

#biology
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Synthetic biology

I met some cool people this week, and here's one: Kate Adamala. She's a postdoc at the University of Minnesota. She creates artificial cells in the lab.

These aren't full-fledged cells that can reproduce and metabolize on their own. They're much simpler - but they're made from scratch, not from existing cells. She calls them protocells.

A typical protocell has some RNA inside a little membrane made of fatty acids. She can get the RNA to copy itself, and she can get different protocells to fuse, building more complicated systems from smaller parts.

My own career as a postdoc was much more boring! Kids these days are amazing. :-)

Here's a paper of hers:

• Kate Adamala and J.W. Szostak, Non-enzymatic template-directed RNA synthesis inside model protocells, Science 342 (2013) 1098-1100. Available at http://www.protobiology.org/reprints/Adamala_Szostak_Science_2013.pdf

Abstract. Efforts to recreate a prebiotically plausible protocell, in which RNA replication occurs within a fatty acid vesicle, have been stalled by the destabilizing effect of Mg2+ [magnesium ions] on fatty acid membranes. Here we report that the presence of citrate protects fatty acid membranes from the disruptive effects of high Mg2+ ion concentrations while allowing RNA copying to proceed, while also protecting single-stranded RNA from Mg2+-catalyzed degradation. This combination of properties has allowed us to demonstrate the chemical copying of RNA templates inside fatty acid vesicles,
which in turn allows for an increase in copying efficiency by bathing the vesicles in a continuously refreshed solution of activated nucleotides.

Though it's one of the most recent on her website, this paper is not so new; she's doing even cooler stuff these days. Check out her work here:

http://www.protobiology.org/index.php

and in her talk.

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Biology as information dynamics

I'm at the Beyond Center in Phoenix Arizona - a center devoted to understanding the origin of life. They're having a workshop on whether biological complexity can be measured in a quantitative way.

Why? One reason is that NASA plans an $800-million mission to Enceladus, to see if there's life lurking in the underground oceans of this moon of Saturn. How can they actually detect life if they see it? That's a hard question. I just heard a talk about this by Chris McKay. They're going to look at stuff like the abundances of amino acids, which are very different on Earth than on meteorites. But there's not enough theory about how this should work for life on another planet!

There's also something else, even more exciting to me: developing a mathematical theory of living systems. Some other talks will touch on that, including mine here:

• Biology as information dynamics, https://johncarlosbaez.wordpress.com/2017/01/31/biology-as-information-dynamics/

The idea is if biology is the study of self-replicating entities, and if information is important in biology, we should look at how information theory is connected to the replicator equation — a very simple model of population dynamics for self-replicating entities. In this model, the population of each kind of self-replicating entity grows at a rate equal to its population times its fitness. But its fitness can be any function of the populations of each kind of entity.

There are some nice results connecting the replicator equation to information theory. The relevant concept of information turns out to be the information of one probability distribution relative to another. This is called relative information, or often the Kullback–Leibler divergence - a term I hate, because it's completely undescriptive, and it hides the importance of the actual idea.

What's the idea? It's this: when you learn something, how much information you get some depends on what you believed before!

Using relative information we can get a new outlook on free energy, see evolution as a learning process, and give a clean general formulation of Fisher’s fundamental theorem of natural selection.

I had a lot of trouble understanding Fisher's fundamental theorem until I reformulated it. In rough terms, his theorem says:

“The rate of increase in fitness of any organism at any time is equal to its genetic variance in fitness at that time."

or a bit more precisely:

“The rate of increase in the mean fitness of any organism at any time ascribable to natural selection acting through changes in gene frequencies is exactly equal to its genetic variance in fitness at that time."

But there are a lot of assumptions required to prove this result, and there are lots of situations where those assumptions don't hold. My version, which is more general and incredibly easy to prove, says exactly this:

" If a population evolves according to the replicator equation, the square of the rate at which the population learns information equals the variance of its fitness."

You can see an explanation on my blog:

• Information geometry (part 16), https://johncarlosbaez.wordpress.com/2017/02/01/information-geometry-part-16/

The idea of "the rate of learning information" is made precise using the Fisher information metric - a way to measure distances between probability distributions, closely related to relative information. I explain this concept in my talk, and in more detail in my blog article.

Back to the talks! Now Kate Adamala is talking about her attempts to synthesize chemical systems that act a bit like life... but simpler. Her talk is called "Alive but not life".

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Creature of nightmares

This is the scariest insect I've ever seen: the giant toothed longhorn beetle from the Amazon basin in Ecuador.   It's not as big as it looks here, but it's big: one of the biggest beetles in the world, up to 17 centimeters long.  (That's half a foot, for you Americans.)  Its larvae are even longer! 

+Gil Wizen, who photographed this monster, writes:

Encountering this species was one of my highlights for the year. I know Macrodontia cervicornis very well from museum insect collections. It is one of the most impressive beetle species in the world, both in size and structure. But I never imagined I would be seeing a live one in the wild! Well let me tell you, it is hard to get over the initial impression. The male beetle that I found was not the biggest specimen, but the way it moved around still made it appear like nothing short of a monster. This species is very defensive, and getting close for the wide angle macro shot was a bit risky. The beetle responds to any approaching object with a swift biting action, and those jaws are powerful enough to cut through thick wooden branches, not to mention fingers!

Check out his favorite photos of the year:

http://gilwizen.com/2016-in-review/

and for more on this beetle, see:

https://en.wikipedia.org/wiki/Macrodontia_cervicornis

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