Writing on interesting science, open science, science communication, and the occasional short story (sciencey or not).

Learning the Game of Life with Biosensors

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There are many ways to learn a new game. You might read the instructions. You might look at diagrams of the game board. You might watch other people playing. You might even play the game yourself.

Similarly, when trying to understand how a cell works, researchers do all of these things. They read the cell’s DNA to learn what it encodes, they use special microscopes to get high definition pictures of cellular components, they watch the cell grow, and sometimes they even try to build new cells.

For all of these techniques to work, we must be able to observe key components of the games or cells under study. For example, if you were trying to learn how to play soccer and couldn’t see what was going on, you’d have a hard time learning the game. To study how a protein works, a researcher must be able to observe the protein in cells. The same is true for chemicals, DNA, and many other molecules a researcher might like to study inside a cell - you must be able to observe, measure and identify these things in order to learn what they do.

What is a Biosensor?

A biosensor is one type of tool a researcher can use to observe molecules in cells. Biosensors are devices made of biological components like DNA or proteins (hence bio) and they detect or “sense” when different types of molecules are nearby (hence sensor). Biosensors report that they have detected something through an easily observable signal. You can think of biosensors like friends explaining a game to you for the first time, and showing you clearly what is going on. If the game was soccer, they could point to the goalie and say “That’s the goalie” and also scream “GOOOAAALLLLLL!!!” when a goal has been scored.

Biosensors work in many different ways but they often give researchers visual cues to show that they have detected specific molecules. For instance, some biosensors will start to glow red if there is a particular chemical in a cell. Other glowing biosensors will attach to specific sequences of DNA to show where those pieces of DNA are. Still other biosensors will make cells turn blue only if two proteins interact with each other.

What are Biosensors Used for?

One interesting biosensor that I learned about recently is called iGluSnFr. This cleverly named biosensor glows bright green when it detects a chemical called glutamate. This ability is useful because glutamate is transferred between some cells of the brain when they communicate. You can therefore use iGluSnFr to determine if cells in the brain are talking to each other and even measure brain responses to things like visual cues. In this particular case, detecting glutamate serves as a proxy to tell researchers “Hey! These cells are talking to each other!”

Of course this is just the tip of the iceberg for biosensors. Researchers have produced biosensors to measure levels of toxic waste, to measure the acidity of cells, and even to detect Zika virus. Everyday, scientists are using biosensors to learn the rules of life and, as they get more precise, you may see these cool tools used to diagnose and treat disease!


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Jargon - The Expert’s Delight and the Novice’s Bore: Supernatant

Check out this post on scientific jargon that I wrote for my friend Matthew Niederhuber's blog .jargon.

Every field has jargon. Marketers talk of leads and conversions, cyclists speak of cadence and derailleurs, and programmers speak of grooming, for-loops, and much more. Jargon is everywhere. Both a boon and bane to understanding, jargon makes it difficult for any novice to get started in a field but makes it easy for experts to quickly communicate complex ideas to those in the know. Any word used only by experts in a field can be considered jargon. Scientists however, are perhaps the most egregious users of jargon.

My good friend Matt Niederhuber recently started thinking about how scientists use jargon and has been working on a blog where he introduces readers to the history of scientific jargon. Interestingly, few scientists know where many of the words they use come from, but learning about a piece of scientific jargon’s history can both provide one with a new way to get someone interested in science and reveal something about how science has advanced - the artistry of language serves as a proxy for the story of discovery.

Supernatant

The word “supernatant” is a fantastic example of scientific jargon. I’ve used it a million times but, the first time I saw it I probably thought it meant powerful vapor or something… I was very wrong. Simply put, the supernatant is the liquid portion left on top when a process produces solids and liquids or multiple distinct liquids.

For example, say you put a bunch of muddy water in a glass and let it sit. After a little while the mud would sink to the bottom and the water would sit on top of it. The water would be the supernatant.

On the face of it, supernatant appears to be a boring, mechanical word, but it has power in its specificity. When doing experiments, researchers often use procedures that separate complex mixtures into liquid and solid portions or multiple distinct liquid portions. The liquid that rests on top is the supernatant. Separating the supernatant from its counterpart may make it easier for a scientist to isolate something for an experiment. For example, when finished growing a bunch of cells, a researcher could separate the solid cells from their liquid waste (the supernatant). The researcher could then continue growing/using the cells while measuring chemicals in the supernatant. If you tell a fellow researcher to remove the supernatant from a mixture, she will know precisely what you're talking about.

Interestingly, supernatant can also be used as an adjective to describe one thing floating on top of another. So, if you wanted to describe the whipped cream floating on top of your hot chocolate, you could call it the “supernatant cream.” While this seems somewhat superfluous (we just expect the cream to float after all), it does add a bit of flourish and specificity to the sentence.

Like the noun form, the adjective has been used extensively in scientific settings. For example, one could say “mix these two solutions together and then remove the supernatant liquid.” However, I don’t really remember anyone using it this way in the lab. This is possibly because you could just say “remove the supernatant” and there’s really no need for the adjective form. Indeed some of the adjective forms like “supernatant fluid, supernatant oil, supernatant liquid, or supernatant water” peak in their usage prior to “supernatant” according to google books so it’s possible that this use is going out of style.

Floating above - The Supernatant Breakdown

Supernatant’s two latin roots, “super” and “natant” make perfect sense for its scientific meaning.

  • Super - An interesting word on its own with a bunch of different meanings. Here it means “above” as opposed “great” as in “I’m super, thanks for asking!”
  • Natant - I didn’t actually realize this was a word before, but natant means swimming or floating. Natant has fallen out of popular usage, but the next time you go to the local pond, you might spot some natant ducks or, my personal favorite, a natant turtle.

Put these together and you get the adjective form “floating above.” When supernatant is used as noun, it’s just a thing that floats above. In our mud-water example, the water was “floating above” the mud - it was the supernatant.

Nonscientific Uses of Supernatant

Possibly because it’s meaning is so specific, you don’t hear supernatant being used much in nonscientific speech. However, it’s Latin progenitor (also supernatant) is just the third person present conjugation of the verb supernatō which means “to float.” Presumably you could use it to say something like “The ducks float down the river” if you were speaking latin. In this sense, it’s usage wouldn’t be that uncommon if we all still spoke latin. Alack we do not and must therefore look to other more contemporary uses.

Searching through the news, it was difficult to find examples of supernatant being used outside of science. One recent Market Watch article did use it to describe the current heights of the stock market: “Such a preternatural period of supernatant trade is bordering on insane….” Here supernatant is an adjective used to denote market growth without any apparent foundation - the market just seems to float upwards. Uses like this are rare, but perhaps they will pick up as scientific advances and scientists themselves seep ever further into the public eye.

Future Evolution for Supernatant

With the practicality of its roots, supernatant is, in some ways, an ideal word. It has only one definition with a very clear meaning. However, supernatant’s lack of use outside science and the outdatedness of it’s roots makes it a rather blatant case of jargon. If you’re a scientist writing a piece for the general public, trying to communicate your work to friends and family, or explaining a procedure to a lab novice, you’d be wise to avoid this word. Nonetheless, it’s interesting that supernatant displays the practicality and functionality that many scientists try to exhibit when designing their experiments. Why come up with a random word for the “liquid that floats above” when supernatant has that exact meaning and serves it’s purpose so well?

As scientists move out of their labs and into other careers perhaps we’ll see the specific meaning of supernatant applied in non-scientific but perfectly apropo situations. The next time I travel to San Francisco for work, I’ll be sure to point out the supernatant fog coming over the bay. The next time we hear about an oil spill maybe we’ll learn of the supernatant oil oozing over the ocean. Both of these uses, while true to the very specific definition of supernatant, serve to drive home the point that the fog and the oil each loom over their counterparts distinctly separate, distinctly unattached, distinctly other. The precision of supernatant’s definition gives us a means of describing anything the floats above and without any real attachment. If supernatant makes its way into common language, it may give people means to more easily describe ideas knocking around in their heads - the things that are above but separate. Supernatant leaders? The supernatnat 1%? Supernatant values? Even a seemingly boring word like supernatant, which already has great power is describing lab procedures, could have even greater power outside the lab because of its clear and specific meaning.

You’ll see this same theme come up again and again in scientific jargon. A personal favorite - while the name “sonic hedgehog” may have seemed totally appropriate for the name of a gene discovered in the 90s, even now it doesn’t quite hold up.


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Read all of Tilda and the Goja Berries here! Tweet at me and let me know what you think!


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This is chapter 4 of a short story I've been working on. Find Chapter 1 here and Chapter 2 here, and Chapter 3 here. Tweet at me and let me know what you think!

With her belly full of delicious flies, Tilda made short work of the Goja desert and quickly sifted her way through the dunes on a path trampled by hundreds of lizardy feet. Just as the sun was setting on a dry, but mostly uneventful day, she spotted the top of a gigantic tree peeking out over the summit of a particularly large dune.

When she was at the top of the dune, the enormous tree loomed over her with a gorgeous grassy plain below it. Just beside the base of the tree lay a large pond with a small village along its rim. Tilda saw many tiny figures scurrying between acorn-shaped homes of the village.

“At last!” thought Tilda, “This must be the Goja berry tree. Before I get to the berries, I’ve gotta get some water. This thing’s been empty for hours.” She shook her canteen and was greeted only by the dry rattle of a few grains of sand.

Tilda ran down the side of the dune, across the field and began pounding on the door of the first house she could get to.

“Yeeeeesss?” asked the occupant opening the door slowly.

“Excuse my manners but ohhhhh!...” said Tilda surprised by the occupant’s appearance. The occupant of the house was what looked like a man-sized caterpillar or centipede with a human face on it’s head and human arms on it’s second segment.

Shaken, but resolute Tilda continued, “Can I bother you for a glass of water and… maybe… could you tell me where I can find a Goja berry?”

“Glass? No glass here, but I can certainly get you a wooden cup of water,” chuckled the occupant opening the door wider. “Goja berries will be a bit more difficult, but we can talk about that more once … maybe… you’ve told me your name.”

Upon closer inspection, Tilda decided that the occupant had a matronly and kind face. Tilda followed the occupant as she wandered off into the house. The occupant grabbed a wooden cup, scooped some water out of a large basin and handed it to Tilda.

“THANK YOU!” Tilda exclaimed sincerely before gulping down the whole cup and carelessly dribbling a bit of water down her shirt.”

“Have a seat” said the occupant gesturing to a large, but comfy looking bench in what appeared to be the living quarters, “I’ll grab you some more.”

Tilda sat down and said “my apologies, I’m just so thirsty after crossing that desert. My name is Tilda. I’m from Arborea - the forest across the desert. I’m here to fetch 3 Goja berries for my village.”

“My, that’s quite the journey,” said the creature, “My name is Madeline and you’ve come to the right place. This is the village of the Goja berry tree. I’m the local historian/librarian.”

Only then did Tilda noticed that the back of the house was filled with books. Some were shelved but most lay unshelved and strewn about the floor.

“Hello,” said Tilda smiling happily and putting out a hand, “It’s a pleasure to meet you.”

Madeline grasped her hand, shook firmly and chuckled saying, “You won’t be so happy when I tell you a little more about the Goja berries. I’m afraid the only Goja berries available are at the very top of the tree.

“You see, we Goja berry beasts love Goja berries… you might say we go a little crazy for them… hence the name. We pluck all the low-hanging Goja berries as soon as they grow.”

“And the upper berries?” asked Tilda.

“Well,” said Madeline, “Occasionally some beasts climb to the upper branches of the tree, but, more often than not, they fall to their doom in the process. Even when they do make it to the top… things don’t go so well.”

“What do you mean?” asked Tilda.

“It’s kind of a sensitive issue in town,” said Madeline, “but the last group of beasts to make it to the top became so obsessed with the Goja berries they found that they never wanted to come down. Unfortunately for them, we Goja berry beasts aren’t the only ones who love the taste of the Goja berries.”

“Oh?” said Tilda.

“The Goja berry monsters,” continued Madeline, “enormous, horrifying in appearance but actually quite nice to talk to if you can get in earshot without being crushed by them - they occasionally come in from the south and forage the upper branches.

“Like us, the monsters get a little too excited once they start eating the berries and, wouldn’t you know it, one of the monsters mistook that last beasts who went to the top of the tree for some berries. That monster swallowed a whole bunch of berries and Goja beasts whole and continued eating without skipping a beat. When there were no more ripe berries left, he stumbled off to the east, never realizing what he’d done.

“No Goja berry beast has dared climb to the top of the tree since that particular incident. We’ve learned to control ourselves and avoid such… accidents.”

“My! That’s awful!” said Tilda consolingly (and not to mention a little disturbed), “but I’ve got to get up that tree.”

“The tree climbing routes haven’t been used in years,” said Madeline, “So I’m afraid I wouldn’t recommend going up today. The sun is already setting and I’m sure you’ll lose your footing on that old path. We Goja berry beasts have feet that are especially designed for climbing, but I’m not even sure you’ll make it.”

“But I’ve got to!” said Tilda, “... I’m running a little late.”

“My dear,” said Madeline, “few things aren’t ever as serious as they seem. Why don’t you spend the night here and we’ll see what we can do tomorrow morning.”

Tilda was put at ease by Madeline’s calm and soothing tone. Madeline reminded Tilda of her mother - a little funny, a little wise, probably a little crazy, but always there to help. “I guess that’s probably a good idea” said Tilda yawning.

“Good,” said Madeline, “I’ll put you up in the library. I’ve got plenty of blankets and cushions you can sleep on.”

“Thank you” said Tilda, “I really could use a good rest.”

Tilda and Madeline chatted for a few hours more and had a light dinner before each went off to bed. In the middle of the night, a great storm sent wind blowing through the house and the pages of many books ruffled wildly. Tilda heard a few great cracks as branches of the Goja berry tree snapped.

She nearly ran out of the house thinking she could probably find some fallen berries, but weird scurrying noises outside paralyzed her with fear and she decided to stay in bed. She swore she could hear a chorus of chewing just outside her windows.

Luckily the storm only lasted an hour or so and Tilda drifted back into a long, comfortable sleep. She woke to the sun streaming into the library.

Madeline, who had what looked to be red-lipstick on her mouth, offered Tilda some breakfast, but Tilda just grabbed a handful of flies, thanked her gracious host and began her search for some fallen berries.

Despite the ferociousness of the previous night’s storm, Tilda couldn’t find a single berry on the ground outside. She couldn’t even find any fallen branches, but she did see patches of crimson-stained dirt.

“Weird... “ thought Tilda, “I guess I’ll have to try climb the tree after all.” Try as she might, however, Tilda couldn’t get a good foothold on the tree. She asked many Goja berry beasts for help, but none seemed willing. The villagers, all of whom were wearing the same red lipstick as Madeline, looked away shamefully whenever Tilda asked if they would help her venture up the tree. Afraid to cause offense, Tilda quickly gave up on that front and plopped down on the ground hoping to think her way to solution.

“I could throw something up there maybe?” she thought, “orrrr maybe If I give myself a running start I could jump and get a handhold. Orrrrr maybe ….”

“TILDA!” a far off voice interrupted Tilda’s thought.

“TILDA!” repeated the voice, this time a little louder.

“TILDA!” came the voice a final time.

Tilda looked up toward the voice’s source just in time to spot the little penguin, his rope apparently snapped in the night’s storm, slam straight into a bunch of berries about halfway up the tree.

The collision knocked the poor Penguin from his seat and down he came with not 1, not 2, not 3, but FIVE whole berries. 3 of them were roughly the size of the penguin, but two were the size of small cars.

At first, Tilda was elated. “Finally,” she thought, “I’ll have the berries and I’ll make it back only a day or so late.” Her elation slowly turned to fear as she realized the Penguin was falling to what could very well be his death.

Tilda dashed into position to catch the Penguin, but she couldn’t get under him - the larger berries had dislodged from the tree first and the penguin was more or less directly above them, just a few meters higher. Before she could fully wrap her brain around the problem, the first large berry hit the ground with a SPLAT, then came the second with a SPLURSH, the came the Penguin with the smaller berries and a plurp, plurp, plurp, glurp.

Tilda closed her eyes as the smaller berries hit and couldn’t bear to open them until she heard the little penguin giggling and saying “Hey Tilda! You should try this mush, it tastes great!”

Wiping away tears, Tilda ran over and hugged the strangely amused Penguin - his glasses only a bit dislodged in the fall and his body covered in Goja berry mush.

Caught in the embrace and completely distracted by her relief, Tilda didn’t notice the swarm of Goja berry beasts that had assembled around the hugging friends. Soon, however, not even her immense happiness could mask the sound of the beasts feasting on the Goja berry mush.

The slurping, smacking, sucking noises surrounded Tilda and the Penguin. As Tilda looked toward the beasts, she noticed that something strange was happening to them. Their eyes has become dark red swirls and they seemed to be more ferocious than she remembered. Pushing, shoving, and sometimes even snapping at one another to get a bit of Goja berry mush down their gullets.

Just before she slid into the frenzy herself, Madeline looked straight into Tilda’s eyes and mouthed “run…”

For the first time, Tilda noticed that the “lipstick” on Madeline’s mouth was the same color as the berry mush and she understood. Tilda reached down, put a smaller berry under each arm, convinced the penguin to grab the third, and together they ran all the way to the dune leading out of the village.

Tilda and the Penguin didn’t look back until they nearly collapsed at the Lizard’s Fly Hut.


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Tilda and the Goja Berries Chapter 3 - The Goja Desert

This is chapter 3 of a short story I've been working on. Find Chapter 1 here and Chapter 2 here. Tweet at me and let me know what you think!

Tilda left the Penguin happily floating above the canopy and continued on her journey. To her surprise, the path to the Goja berry tree led straight out of the woods and, just as dusk began to settle, she reached the abrupt end of Arborea and it’s beautiful stands of trees.

Stretching before her was a not-so-vast desert, but Tilda figured it would take at least the next day to travel the distance of the road through the dunes. She considered trudging out into the darkness and thereby making some progress through the evening, but then she thought better of it, “far too cold and I’m apt to get lost without any moon tonight,” she thought.

“Wait… no moon,” a voice in the back of her head murmured, “wasn’t the moon nearly full last night?”

Tilda’s head jerked toward the sky and sure enough, dark clouds covered her view. As the first rain drops began to fall, she deeply regretted giving the Penguin her canvas and took shelter under the final tree where the forest met the desert.

Despite the rain, Tilda was able to get a few rather uncomfortable winks and woke up to find her clothes and pack soaked. She rang out as much as she could and stuck her hand in the pack for her breakfast, but quickly jerked it out. The bread and sandwiches she packed for the journey were disgusting piles of mush lining the inside of her pack.

She looked around her makeshift camp for anything to eat but could only find two acorns.

Just as she was about to head back into the forest (Tilda was far too smart to head into the desert without any food) Tilda heard a scratchy voice yelling “Get your nice warm breakfast here!”

It seemed to be coming from just over the first dune not more than 200 meters away, and so Tilda decided to try her luck.

Tilda followed the well-kempt path around the dune and, sure enough, she came upon a lizard selling brown, roasted masses on sticks. Between yelling about his wares, the lizard swept the path leading to his little stone shelter with more varieties of roasted… something on display.

As she got closer, Tilda called out, “excuse me Mr. Lizard, but can you tell me what you’re selling?”

“Oh! A customer… and from the forest!” exclaimed the Lizard. “I usually sell my flies to other reptiles coming in and out of the dunes. What brings you here from the lush forest?”

“Nevermind that,” said Tilda, a little groggy and with a rumbling stomach. “What have you got for me?”

“Well,” said the Lizard, “I’ve got the finest roasted flies this side of the Goja desert.”

“Roasted… flies…?” asked Tilda.

“Yes, my dear mammalian friend,” said the lizard, “The most tasty, most crunchy, most nutritious flies you’ll ever eat.” We’ve got all varieties. Chubby, curly wings, stubbly hair, and, of course, our prized CRAZY BIG FLY … not a very original name, I know, but come over here and you’ll see. It’s apt.”

The lizard brought Tilda over to a stone countertop where, true to his word, there were at least 10 different types of fly and even one fly that was bigger than Tilda’s hand. This piqued Tilda’s interest more than her appetite.

“Why only one big fly?” asked Tilda.

“That’s a CRAZY BIG FLY!” said the Lizard, “Always gotta stay on brand you know. I normally keep that a secret, but you’re not salivating like the others… you seem more intellectually interested. A fly breeder yourself?”

“Well, no,” said Tilda a little nervously, “I just…”

“Nahhhhhh. Don’t be modest!” interrupted the Lizard. “I know a fellow fly enthusiast when I meet one. You see, to make all of these varieties, we take a few live flies from our farm just on the edge of the forest and bring them out into the desert where we let them bake until just moments before they perish. We then snatch them out of the death grip of the sun and breed them with others on the farm. Sure enough, we always find a few children with unusual traits.”

“Now, for most of these traits, if we breed the children with other normal flies, at least some of their children hatch with the trait themselves. We separate these out and throw the normal ones back. We keep breeding the flies with the traits together until they produce no more normal children and then we can sell all we want!”

“The CRAZY BIG FLIES though… they’re rare and, when we breed them back with the normal population, they never have CRAZY BIG children… hence the hefty price tag on this one. It’s a total mystery.”

Tilda, however, didn’t think this was a mystery at all. While she hadn’t bred many flies, she did breed many flowers on her uncle’s farm and had seen this type of thing happen many times. Her uncle called traits like the “CRAZY BIG” trait “recessive.” She therefore saw an opportunity not only to teach the lizard but also to get a free breakfast.

“Actually…” said Tilda, “what you’ve probably got is a recessive trait.”

“Beg your pardon?” asked the lizard as his wide grin turned into a perplexed frown.

“It’s a little complicated and doesn’t alllways work this way,” said Tilda, “but if you promise to offer me some food, I can tell you how to breed more CRAZY BIG FLIES.”

“How bout you tell me first and then I’ll decide on the food,” countered the Lizard.

“Hrrmph… alright…” said Tilda. “The next time you get a CRAZY BIG fly, breed it’s children with each other even if they aren’t CRAZY BIG. You’ll probably end up with more CRAZY BIG flies anyway. Bread these CRAZY BIG grand children together and there’s a chance they’ll only make CRAZY BIG great grandchildren.

The lizard stared at her blank faced saying “ummmmmm…”

“Look,” said Tilda a little irritated and getting annoyed with her own impatience, “I could draw you a diagram of how it works, but I don’t have time right now. Just give it a try and I bet you’ll have more CRAZY BIG flies than you know what to do with.”

“Really?!?” said the lizard getting excited.

“Yes.” said Tilda matter of factly. “... though there’s definitely a chance it won’t work...” she mumbled.

“Well then…” said the Lizard thinking and apparently having missed the mumbled bit, “I think you’ve made me one rich reptile! I’ll need to exchange my fly cart for a safe to protect all my gold. What kind of fly enthusiast would I be if I didn’t offer you some grub for such useful advice. You know what? Take a couple handfuls of whatever type of fly you’d like… all except CRAZY BIG of course.”

“Thank you SOOOO much!” exclaimed Tilda a little over-expressively.

Tilda sidled over to the red-eyed flies. “Here goes...” she said grabbing a handful and plunging the flies into her mouth.

To Tilda’s surprise, the flies were well salted, had just the right amount of crunch, and had a delightfully savory aftertaste. With four more quick handfuls, two more for her pack, and an eyebrow raise from the lizard, Tilda bid the lizard farewell and continued on her journey.

As she turned the corner around the next dune, Tilda could hear the Lizard exclaiming to his next batch of customers: “You’ll never believe it, soon we’ll have enough CRAZY BIG flies for everyone!”

“Ooo boy,” thought Tilda, “I really hope it’s that simple…”


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Tilda and the Goja Berries Chapter 2 - Penguin with Balloon

This is chapter 2 of a short story I've been working on. Find Chapter 1 here. Tweet at me and let me know what you think!

After a good night’s sleep, a few cups of coffee, hydration, and much filtration through her still young liver, Tilda was finally able to really focus on her task.

At first she was at a bit of a loss due to the incredibly small amount of information the head villager had given her, but she soon noticed a small envelope that he been slid under her cabin’s door. “FOR TILDA” was written on the front of the envelope in the Head Villager’s unmistakable all caps handwriting. “Always so precise,” thought Tilda a little admiringly.

Tilda tore the envelope open with as little precision as possible and found a note and a map inside. “INSTRUCTIONS FOR GOJA BERRY QUEST” the note read.

“Of course,” thought Tilda, “the Head Villager would never leave me so high and dry.”

The note stipulated that Tilda simply needed to follow the map out of the Arborea forest, through the Goja desert, and to the Goja tree in the Goja Oasis. Once there she would pick 3 berries, return them to town hall, and hand feed them to the Goja monster.

The map was quite detailed and must have been drawn by the Head Villager who often surveyed Arborea and the surrounding regions in her private hot air balloon. Tilda had only been able to up in the balloon once, but she was amazed by everything she saw. The map brought back memories of her maiden balloon voyage.

The Head Villager indicated that the trip would take 3 days and “NO MORE” and that she “MUST LEAVE IMMEDIATELY” … somehow these last two bits seemed more capitalized than the rest of the note.

Shocked, but energized by the challenge, Tilda began throwing some provisions, toiletries, and clothes into her many pouched sack. After triple-checking to make sure she had everything she needed, Tilda left the cabin, locked the gate, and began down the path indicated on the map.

Tilda loved to travel but she’d never gone more than a half-day’s journey from her cabin - it was beginning to dawn on her how awesome this opportunity was… even if she still didn’t really get why she was doing it.

As the sun begin to set on the first day, Tilda came across an adorable little penguin seated on a tree stump in a small clearing. Tied to his wing and surrounding the penguin were a large number of inflated balloons but all of them were resting squarely in the dirt. Though rather vibrantly colored and full of polka dots and other patterns the balloons had a somber look about them.

The penguin himself was far from somber and wore a red bow tie with yellow polka dots that complemented his over-sized spectacles quite nicely. The spectacles magnified his eyes to a rather comical degree as the penguin sat on the stump and determinedly inflated yet another balloon.

Once inflated, the penguin tied the balloon to a string, held the opposite end of the string and tossed the balloon into the air with a smile. The penguin let out a squeak of hope as a slight breeze pushed the balloon a few centimeters upward but his happiness turned to frustration as the balloon sank to join the others.

“Drat!” said the Penguin, “I really thought that would be the one.”

Coming upon this scene, Tilda interrupted the penguin, “Excuse me,” she said. “My name is Tilda. I was was just wondering, what did you hope that balloon would be?”

With a blank face, the penguin looked over at Tilda, scrunched up his eyebrows, pushed up his glasses, and said in a somewhat childish but hopeful voice, “I thought it would be the balloon that finally helped me fly like the other birds.”

Tilda gave the penguin a tender look and said “Oh my poor little penguin friend. You don’t need to fly through the air, you can fly through the water!”

“Sure that’d be enough if I were in my tropical ocean home,” said the penguin, “but I’ve been traveling for months now and have fallen in love with these woods. Without an ocean to swim in, I need to learn to fly!”

“I see,” said Tilda beginning to scrutinize the balloons. There were at least 100 balloons, each the size of the penguin and some even a little bigger. She couldn’t turn away from the little guy when he was clearly trying so hard.

“Well,” she said, “you’re not going to get to the sky this way. Your breath is no less dense than the air around it and won’t cause these balloons to float.”

“Dense?” inflected the penguin, “What do you mean? I’m not dense? I’m smart!”

Tilda laughed a little nervously and said, “oh no, not like that. What I mean is, in order for a balloon to float, the gas inside it must weigh less than the air that would take up the same space. Your breath weighs about the same as the air around it and takes up the same space so it won’t float.”

“Huh?” said the squinting Penguin.

“Hmmm…” said Tilda, “think of the balloon like a little boat. The reason a boat floats is that it’s hull is shaped so that it takes up a lot of space pushes away a bunch of water. When a boat’s hull has pushed away so much water that the water’s weight equals the weight of the boat and everything in it, the boat will no longer sink, it will float!”

“That’s why you can even make boats out of metal. The hull pushes away so much water that it’s weight is equal to that of all the metal. My dad makes metal boats for our village.”

“That’s neat!” squeaked the penguin.

“Your balloons are like little boats except that the air they push away weighs less than your breath and the rubber they’re made out of. That’s why they sink.”

“I think I’m getting it” said the penguin, “I just need some way to make the gas in the balloon reallllllly light.”

“Sure,” said Tilda, “but you’ve got an even bigger problem if you want to make yourself float using the balloon. In that case, the balloon has to push enough air out of the way that the air’s weight is equal to your’s and the balloon’s weight combined!”

“Oooooooh” said the Penguin “... so I just need to push a lot more air away and make my breath lighter… I need a bigger balloon with a super light gas!”

“Yes!” said Tilda, a little surprised that the penguin understood.

“But, how should we do that?” asked the penguin.

“Hmmmmmm…” thought Tilda. “Well, one way to make air take up more space is to heat it up, but I think your balloons would pop if we expanded them to the size we need to make you float and we don’t have anything to heat up the air in the first place.”

“O, no, no, no,” said the penguin stamping his little feet, “we’re so close…. WAIT! I have an air heater in my tent! It gets so cold in this forest at night.”

The penguin waddled over to a tent just outside the clearing and returned carrying a gas lamp above his head.

“Can we use this?” asked the penguin.

“Welll, yes,” said Tilda, “but we also need to figure out a way to capture the hot air…. I know, I’ll give you my waterproof sleeping canvas to capture the hot air… I don’t think it’s going to rain before my journey is over so I shouldn’t need it.”

“Good thing he’s such a little guy,” thought Tilda, “otherwise I’m not sure the canvas would be big enough.”

Tilda fastened the canvas to the gas lamp and positioned it to capture the hot air. Next, she fashioned a little seat from one of her shirts so that the penguin could sit in flight.

“It’ll be a little difficult for you to control,” said Tilda, “But I don’t think you’ll be up there too long. Just turn up the gas to heat the air and go up. Turn down the gas to let the air cool and you’ll sink BUT BE CAREFUL. Don’t go too fast either way!”

“Alright!” squeaked the penguin as he excitedly nestled into his seat and jammed the lamp to full blast.

Sure enough, the canvas began to expand as it filled with hot air. In a matter of moments, the little penguin’s feet were dangling above her head and, in seconds, he was clear of the trees. “Be careful!” called Tilda, “and don’t forget to lower yourself slowly and get some food later. Don’t stay up there too long!”

“I will! Thanks Tilda!” yelled the penguin clearly not paying attention and soaring ever higher.

Unbeknownst to the penguin, Tilda tied a rope extending from the Penguins seat to a nearby tree.

“That ought to keep him safe,” she thought as she left the clearing and privately pledged to check up on him on her return journey.


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Tilda and the Goja Berries Chapter 1

This is chapter 1 of a short story I've been working on. Find Chapter 2 Here. Tweet at me and let me know what you think!

Tilda had come age. Like all newly minted adults of Arborea it was therefore her duty to report to the Head Villager. However, also like all newly minted young adults she had spent the night before her coming of age in merriment and was, well… a little hung over.

Under her purple cape Tilda was therefore a bit of a sweaty mess and her temples felt as though rail workers were striking pins into them every few seconds. Just as the head pain would subside, a bout of nausea would rise in her stomach and she cursed herself thinking, “you can be the life of the party without getting drunk… ugggghhhh.”

With the most recent bout of nausea gone, Tilda sluggishly pushed through the doors to the great hall of the village elders. The hall was little more than an oversized cabin, but it was much prized by all the villagers and the only building with metal doors in the whole village. The doors were laden with metalwork wrought into the creatures of Arborea. Their coolness was soothing to the touch, but Tilda had little time to contemplate their beauty. As soon as the doors opened, Tilda was greeted by the scolding voice of the head villager - “You’re late.” she said.

The head villager was seated at the raised head of a large wooden table carved similarly to the door. Tilda was particularly fond of the badger bear napping near the closest corner of the table and, even today, it’s sleepy face gave her comfort and she smiled as she stared down at the cuddly bear.

“Your attention Tilda,” said the head villager sternly but also with clear boredom and annoyance. She couldn’t believe that she had to deal with yet another hung-over twenty something.

“Yes, head villager,” said Tilda throwing on a smile she wasn’t sure how long she could keep.

“Right.” said the head villager, “so you’ve come of age. Now you must complete your deed of service to the village. What you do after the deed is of no importance to us, but you must first earn your freedom through service.”

“Service?” asked Tilda. She was more than a little unsure of her belief in this ridiculous practice, but her brain was far too broken at the moment to mount any more thoughtful questions about it.

“Yes. Service.” said the head villager, “You should take pride in the fact that you even get to serve. Every person who comes of age in Arborea gets a chance to prove him or herself, but not all succeed. Don’t you want to prove yourself?”

Now, you might think that the head villager made the above statements with some sort of exuberance or pride, but true to her deepest self, it was all stated in dry, matter of fact tones.

“Oh…” said Tilda, “okay…” but really she was just confused and it wasn’t the hangover. You see, Tilda didn’t think it was that simple. You don’t just complete some task and therefore come of age and “prove yourself” … whatever that meant. She had seen plenty of people come home from their “deeds” after coming of age and all they did was go back and work on the family farm or whatever.

Being from a family of metal crafters Tilda dreaded completing her task and returning home just to continue the family business. Not that she didn’t think her parents and brother were great at metal work - really they turned it into a art, but she just didn’t get any joy out of it.

Unfortunately, Tilda didn’t have time to express all of this.

“Great.” said the Head Villager curtly, “Now for your task.”

The Head Villager began mumbling as she read down a piece of paper paper in front of her.

“Ah. Your task is one of the most prestigious in all of Arborea.”

“Errr Cool?” said Tilda, another wave of nausea streaming over her.

“You, Tilda, will find 3 Goja berries and return them to Arborea.”

“Um… right,” said Tilda a perplexed look on her face.

“Of course,” said the head villager, “we want you to be prepared. Please ask any questions you might have.”

“Right, soooo, what’s a Goja berry and also… why?” asked Tilda, her stomach churning.

“Easy questions.” said the Head Villager. “Goja berries are the only things known to keep the Goja monster asleep. Why? Because if the Goja monster wakes up, he’ll destroy the village.”

At the conclusion of the above statements, the chorus of pain in Tilda’s head swelled to its raucous climax and she could do little more than say thank you and slump out of the room desperate to rest her head on something cool.

Tilda could feel the Head Villager’s eyes rolling as she said, “Get some sleep and we’ll send a map with more details to your cabin.”

As Tilda was leaving the hall, her friend Granite entered. His coming of age had coincided with her own and he was part of the reason Tilda was in so much pain today. Though great friends with Granite, she couldn’t stand to let the brute outshine her at any party.

Tilda rested her head against the ice cold metal of the great hall’s door as Granite was given the details of his own coming of age task. The doors were her father’s work and, by all accounts, outshone the handiwork of the table. Tilda looked down and to the right, scanning for her beloved Goja bear. As she was searching, she distinctly heard the Head Villager speaking to Granite, “Your task is one of the most prestigious in all of Arborea. You will find 3 Goja berries and return them to Arborea.”

At the close of this statement, Tilda’s eyes found the region where the Goja bear should have been. Strangely, the Goja bear had been replaced with an enormous catfish.


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Experimental Approaches to the Best Fruit Salad

Fruit Salad Experiment

A recent episode of Bojack Horseman (love that show) reminded me that most fruit salads are awful. Usually they contain far too much honeydew melon and, really, no one likes honeydew. Of course, one can always look on the bright side. The aspiring entrepreneur might see this lack of good fruit salads as an opportunity.

If you could simply make a good fruit salad, couldn’t you easily take over the fruit salad market and become wealthy beyond your wildest dreams? It’s never quite that simple, but this opportunity leaves us with an interesting question: How do you go about making the best fruit salad?

There are probably lots of ways to make a good fruit salad, but I’ll quickly discuss two possible approaches that are representative of many others. The first approach we’ll call “biased” and the second approach we’ll call “unbiased.” First the biased.

The Biased Approach to Making The Best Fruit Salad

In this approach we’ll use prior knowledge and information to guide the design of our fruit salad. Indeed, the fact that we’re working off of prior information is what makes this approach biased.

To begin this approach, you might poll a bunch of people to figure out what their favorite fruits are. You’d then limit the fruits in your fruit salads to the known favorites. Your decisions on what to put in the final product will also likely be affected by your own preferences. For instance, I would never leave out watermelon because people who don’t like watermelon are clearly nuts.

This seems like a great way to g, and it might even work. However, there are definitely some caveats. Here are a few:

  1. Even if people like certain fruits separately, they might not like them mixed together in a fruit salad. Growing up, my brother was one of those people who absolutely hated to have certain foods touch whereas I would go as far as putting mashed potatoes in my milk.... Clearly preferences about food combinations differ.
  2. People may not have tried all the fruits in the survey prior to taking the survey - you may be missing out on some great fruits simply because most people haven’t tasted them. Friends often give me mysterious and delicious fruits that I can never remember later.
  3. You wouldn’t know what proportions of fruit to put in the fruit salad. Heck maybe even a very small amount of honeydew in a fruit salad is good for some reason… maybe.

The Unbiased Approach to Making The Best Fruit Salad

To get around these issues, you could instead take an unbiased approach (see drawing above). In this approach, you might start off with huge piles of many different types of fruit. You would then use these fruits to fill many different salad bowls as randomly as possible, record the contents of each bowl (recipes for each bowl), give them to many different people, and ask the people to eat/rate the fruit salads. After collecting the ratings, you would then make a list of the most highly rated salads and use their recorded recipes to remake them. You would then distribute these new salads to many more people and repeat the process again and again until you found the very best 1-3 salads.

This approach doesn’t have any of the caveats of the biased process and will likely lead you to a better fruit salad than the biased approach. What’s the drawback? It’s a HUGE undertaking. It will take tons of fruit, tons of time, and tons of people to make sure you’ve sampled enough combinations and preferences to get to the few salads that are generally well rated. Were I an entrepreneur trying to make a new salad, I might avoid this technique simply because of the sheer amount of time and money it would take.

Combining the Biased and Unbiased Approaches

There are many ways you could modify these approaches to make them better and/or use them to answer different questions (for instance, what’s the worse salad I could possibly make?... all honeydew… duh). You may have noticed that you could also combine the biased and unbiased approaches.

You could add a little bias to your unbiased method by limiting the initial number of types of fruit. You might use a survey to find the best fruits and then only make random combinations with these. Alternatively, you might only use the cheapest fruits available to you. This would make the entire process less expensive and more doable.

Why Are We Talking about Fruit Salad?

Good question! Mostly because of Bojack Horseman, but also because these biased and unbiased approaches are used by experimental biologists everyday. Luckily for many biologists, the unbiased approach can be far more practical in a biology lab than in our fruit salad example - it’s just easier to get the large numbers of cells and other small biological things needed for unbiased biology experiments.

Whether or not a biologist chooses a biased or unbiased approach will be determined by a variety of factors. Just like our fruit salad example, these factors can include time, money, and level of prior knowledge. Importantly, both biased and unbiased methods can lead researchers to discover answers to big questions. For example, researchers recently used the biased approach to make pigs impervious to a particular type of virus (this could be useful for organ transplants from pigs to humans or for making better chimeras), and the unbiased approach was recently used to make viruses that infect specific parts of the human central nervous system (these could be very useful research tools).


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3 Things I Learned Recently about Plant Biotech

Virus Gene Delivery

Plants! We’ve been experimenting with them through farming and breeding for ages and we’ve had many successes (just look how corn has changed from its ancestral form for a great example). Nonetheless, more can be done to lower costs, increase variety, and improve nutrition (among other things). Here are just a few things I’ve learned about recently - engineering more stable animal feed, changing flower color, and making apples that don’t brown.

1. Making More Stable Animal Feed

Cheese burgers are delicious. However, to keep making cheese burgers, we need to keep making cows. A lot of money and resources go into making the tasty animals we eat (a good reason to be vegetarian at least some of the time) and farmers are always looking for ways to decrease costs.

Luckily, plant researchers have taken note. One way researchers are trying to lower farming costs is by making plants used for animal feed more stable. The plants we feed to animals often need to be stored prior to feeding and their nutritional components can degrade during storage. Scientists at the USDA are specifically altering alfalfa (apparently a component of feed) so that it produces chemicals that keep its proteins from degrading. This stronger alfalfa could some day lead to healthier, less expensive animal feed.

2. Changing Flower Color

Japanese Morning Glory

Have you ever wanted a particular type of flower to come in a different color? Plant breeders have been changing flower colors for years by crossing different varieties together. The process of altering the genes present in a particular plant (really what you’re doing in plant breeding) may be more straightforward and controllable if performed using genetic engineering techniques.

Toward this end, researchers recently used the genetic engineering tool, CRISPR, to change the Japanese Morning Glory from violet to white. This specific color change isn’t groundbreaking as there were already white Japanese Morning Glories, but it shows that CRISPR can be used to quickly get a desired color if we know enough about the underlying biology.

The company Revolution Bioengineering is doing something perhaps a little more exciting - they’re making flowers that change color overtime. I’m intrigued to see how things turn out!

3. Making Non-Browning Apples (Arctic Apples)

Browning Apple

I often find myself cringing before taking a bite out of a brown apple slice that’s been out for too long so I was excited to discover that the company Okanagan Specialty Fruits makes genetically modified, non-browning apples (see description on their blog). They call them “Arctic Apples.”

Apparently these apples have been in production for a while but they’ve only been sold in the U.S. since early 2017. Full disclosure, I haven’t eaten them yet and can’t vouch for their taste, but I’d love to try them out.

There’s all sorts of other stuff going on in the world of plant biology and I’m hoping to touch on some fancy things like plant metabolic modeling and engineering carbon fixation in later posts. Stay tuned!


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Why Viruses Are Great Gene Delivery Vehicles

Virus Gene Delivery

Pretend that you’re a delivery man (errr… a delivery person). Pretend that you’re a delivery person. Now pretend that you have all the packages you need to deliver today. You step out of your delivery truck onto the street. You’re ready to seize the day and start delivering with a smile on your face, but, just then, some crazed urge overcomes you. You want to do the worst job possible. How are you going to satisfy this urge?

If I wanted to be an absolutely terrible delivery person, I’d walk down the middle of the street and throw my packages everywhere at random. I’d probably end up throwing many packages into the street and into random yards. I’d probably hit some people and their pets. I might even get hit by a car. However, if I threw enough packages, at some point I might at least get one into the appropriate yard or driveway.

Like letters and packages, gene therapies need good delivery people. For gene therapies to work, healthcare providers need to successfully and specifically deliver genes to broken cells. Once in the broken cells, the genes produce things that help fix the cells thereby treating or curing disease. In a gene therapy for blindness for example, you might deliver genes to cells in the eye that make the eye better at detecting light (Connie Cepko’s lab at Harvard is doing this).

Unfortunately, if we just inject genes strait into our bodies, the gene therapy will function about as effectively as our crazed delivery person - they don’t necessarily get to the right place, they might be destroyed in the bloodstream, and they could cause further dangerous effects if they get into the wrong cells.

So what makes a good delivery person? A good delivery person carefully walks down the sidewalk (avoiding cars and stray dogs) and delicately places packages and letters into the mailboxes of their intended recipients. That’s all well and good for big ole letters and packages, but how do we go about delivering genes with such tenderness and care? Nature provides the answer - viruses!

Viruses as Gene Delivery People

You’re possibly looking at your screen a little skeptically and thinking, “Don’t viruses cause disease?” The answer is, yes they do, BUT, to cause disease, viruses often must deliver their own genes to cells. We now know enough about how some viruses work that we can strip them of their dangerous genes and, instead, get them to deliver therapeutic genes to cells.

Viruses are fantastic because many already deliver genes to specific cells (remember how HIV targets the immune system for instance). In fact, using our knowledge of how viruses work, we can even engineer them to deliver genes to new cell types.

Limitations of Viral Delivery

So, why haven’t we used viruses and gene therapy to cure a ton of diseases? Part of the answer to this question is that we’re only now beginning to understand enough about diseases, genes, and viruses to make effective therapies. In addition, viruses do have limitations. Here are a few:

  1. Size - Viruses are very very small (way smaller than cells) and just can’t deliver all the genes we need to treat some complex diseases. This is like having a delivery person who is too weak to deliver all of your new Ikea furniture even though you know it will look awesome in your new apartment.
  2. Lifespan - Some viruses deliver genes to cells and the genes do their jobs for a while, but then they stop working. This is something like your favorite movie going off of Netflix. It’s delivered to you for a while and you’re kept happy, but then you can’t watch it anymore for unknown reasons leaving you in pain.
  3. Immune Responses - Some viruses used for gene therapy still have markers that tell the immune system that they’re dangerous. These can cause immune reactions that harm the patient. This would be like your delivery person dealing drugs on the side and getting confronted by the cops at your doorstep… you might get hurt in the exchange.
  4. Integration Problems - Though some viruses are very good at getting therapeutic genes into cells, sometimes they put them in the wrong place or they put some of their own genes into the cells leading to further damage and disease. This would be like your delivery person occasionally jamming a package down your toilet without you noticing or accidentally dropping his pet cobra in your mailbox.

Different types of virus-based gene delivery systems have different combinations and levels of these limitations (some of the advantages and limitations of viruses used in research are discussed in this guide). It is therefore up to researchers to pick or engineer the right viruses to reduce these limitations for specific diseases.

Excitingly, we’ve learned a ton about how viruses work and you’re likely to see many virus enabled gene therapies coming out soon. Heck Voyager Therapeutics recently described promising results from their work developing a virus delivered gene therapy for parkinson's disease. So keep your eyes open - I’m sure there’s much more to come!


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CRISPR Fails to Deliver New DNA to Human Embryos

CRISPR Simple

In a recent publication, researchers used a biological tool called CRISPR to remove a disease causing mutation from the DNA of a human embryo. Previous to the development of CRISPR, it was difficult (or at least more tedious) to remove similar mutations from cells, but not impossible (in fact companies are currently developing therapies using other technologies - Bluebird Bio for instance).

Excitement around CRISPR stems from that fact CRISPR makes it much easier to remove disease causing mutations from cells. In a laboratory setting researchers have also used CRISPR to engineer new traits (like making some mouse cells glow a certain color). This ability to engineer new traits awakens fears of “Designer Babies” - human embryos designed to have specific characteristics (like a certain eye color).

Whether we should engineer human embryos is a big and important question; however, the “Designer Baby” fear distracted many from the main point of this publication. More than anything, this work showed we don’t know enough about basic embryo biology to use CRISPR for embryo editing. In fact, the authors were not successful at using CRISPR to add any new traits (new DNA) to human embryos.

How Does CRISPR Work?

CRISPR is awesome because you just need 3 components to make it work:

  1. Tiny biological scissors that cut DNA
  2. A tiny biological guide that tells the scissors where to cut
  3. A new piece of DNA that cells will use to repair the cut

The first two components alone are what researchers call “CRISPR” and the third can come in a variety of forms. You can use long pieces of DNA, short pieces of DNA, circular pieces of DNA (called plasmids if you’re curious), and much more. The important discovery from this recent publication was that the new DNA was not used to repair the cut.

Repairing Dad's DNA with Mom's DNA

If the new DNA wasn’t used, how was the cut repaired? Remember that all human cells have two sets of DNA. One set of DNA comes from Mom and the other set comes from Dad. These sets have very small differences. Therefore, if you cut one set of DNA using CRISPR, say the set from Dad, it can usually be repaired using the set from Mom.

This is exactly what happened in the publication. The researchers used CRISPR to cut the DNA with the mutation (DNA from Dad). Then, instead of using the new DNA, the cells used Mom’s DNA for repair.

In this specific case, Mom’s DNA didn’t have the mutation and could therefore be used to fix Dad’s DNA. However, and this is an important point, depending upon the particular disease we want to prevent, the DNA from both Mom and Dad might be mutated. The findings from this publication argue that CRISPR cannot currently correct these sort of double mutations and prevent disease. The same would be true for any traits we might want to introduce into “Designer Babies.” Human embryos don’t appear to be particularly willing to take up new DNA we supply to them and therefore aren’t easily engineered.

More Research On Basic Embryo Biology is Required

Why won’t human embryos take up new DNA? I’m not sure anyone really knows the answer to that question. We just don’t understand enough about DNA repair in embryos to answer it yet. More than anything, this paper shows that we need to learn more about DNA in embryos before we start going crazy over fears of designer babies. We should definitely be having thoughtful conversations about what types of embryo editing we should allow in the future, but overblown fears should not prevent us from learning more about how embryos work.

Only by trying out experiments like the one in this publication can we determine where our knowledge ends and where more research needs to be done - we test our knowledge by trying to use it productively. We should think about the scary possibilities enabled by embryo editing, but we should also be excited that this work has highlighted a huge gap in our knowlege. It has shown that we need to learn more about the basic biology of human embryos. Filling this gap will make it easier to treat human disease in the future.

Of note - there are CRISPR derivatives (so called “base editors”) that don’t require new DNA to make repairs. These are very cool but their editing powers are currently quite limited.

Want to learn more? Check out this great article from Stat News and this article from Mary Gearing at Addgene.


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Tips to Decrease Your Travel Anxiety

Clouds in Chicago

Travel is exciting, but can also induce anxiety. I often travel alone for work. For the first few trips, I was a ball of anxiety - I had to meet with many researchers, stay on schedule, stay organized, and it would be ridiculous if I didn’t allow myself to see some of the city… even after hours of meetings that left me wanting to do little more than enjoy the hotel bed. After two years on the job, I’ve learned a few ways to greatly increase the possibility that travel will be fun and easy. Here are my top tips for enjoying yourself in a new city.

#1 Rent a Bike

Bikes are the best way to see and commute through tons of cities. By hopping on a bike, you can see more of the city than by walking or running (although I am a huge fan of going for a nice long run a in a new city too). While cars are quick like bikes, they make it difficult to really notice the world around you. Not to mention, renting a bike is usually cheap (especially compared to renting a car), and many cities have bike shares that allow you to ride all over the city (~$10 a day in Chicago if you keep track of your time between stations). Bike share bikes are often obscenely heavy and aren’t the comfiest things around but they’re fun nonetheless. Just a couple of things:

  • Be Careful
  • Obey Traffic Laws
  • Wear a Helmet

#2 Wander a Bit

It can be tempting to over plan and make sure you know exactly where you’re going to go for every part of your trip. If you’re scheduling business meetings, of course these need to be scrupulously planned, but, if you’re just going to grab a bite to eat somewhere, don’t be afraid to wander around. Sure, you can use your phone to get to the right area, but don’t pin yourself down. Googling limits your options to whatever you decided to search for in the first place. By wandering, you might find something new. Wandering led me to an Umami burger and a variety of beaches on a recent trip. Wandering has the added benefit of helping you find your way around the city (...if you’re being mindful as you wander).

Pro-Tip: Don’t be afraid of eating alone. If you feel weird, you can usually grab a seat at the bar… you might even meet someone new… I learned a lot about a trucker’s music preferences this way recently. He was very into Lady Gaga.

#3 If You’re Alone, Get a Room with Two Beds

This tip comes from my manager… probably the best manager I’ve ever had. If you’re traveling alone and, in particular, if you have a lot of materials to organize for a meeting, don’t get the room with one king sized bed, get the room with two queens. Use one bed to sleep in and the other to layout all of your stuff.

Other Quick Tips

  • Always carry a book (I recently finished How to Win Friends and Influence People this way…. interestingly, this is a tip from the intro of that book)
  • Let your phone die when you can
  • Only bring a small bag on the plane… if you need a carry-on, just check it
  • When waiting at the airport, go for a walk through the terminals while listening to a podcast
  • Go for a run

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The Smirking Lamp Post

Smirking Lamp Post

On any old walk to work, Julio would pass at least 5 works of graffiti. Though certainly not annoyed by the artwork (in fact he thought the graffiti added a background flavor to the neighborhood that he rather appreciated) there was only one piece that really stood out to him. It was a smirking face painted on the base of an otherwise industrially metallic lamp post.

Julio liked to think that this smirking face gave the lamp post a kind of character that stood in opposition to its standard construction and very corporate position just outside the CVS. The faced seemed to say “Of course I do my job, but I’m certainly not one of them.”

One day, Julio turned the corner to see that a slight flourish had been added to the smirking face. Just above the curve of the grinning check, there was a small scar that Julio thought was made of shimmering white paint.

Being that the face was a sort of daily reassurance to him, Julio was a little annoyed at this change. He inspected the face a bit more closely and discovered that, rather than being paint, the the scar was actually a small divot in the metal that gave the face a more rugged, though not unappealing, look.

At first, Julio was put at ease by his closer inspection. The scar was added by the hands of time and not some malicious actor that, only moments ago, he was ready to chastise for this ridiculous act of vandalism. Julio shrugged thinking “this makes old lampy look a little more dignified” and continued on his way, a small grin added to his own face.

As the days and months went by, other divots and scratches appeared on the smirking face until Julio realized it no longer appeared to be smirking at all. Instead, the face just looked tired and, well, old. Still, Julio considered this to be the natural way of things and always gave the face an appreciative little series of pats as he walked by.

On one particularly sunny day, Julio was contentedly whistling a new tune as he walked to work, but was jerked to a stop when he came across the face. The sun was beating down upon it at just the right angle for Julio to see how exhausted it had become. White pocks marred every curve and crease of the face. Julio’s hand instinctively went up to his own face palpating old pores and new wrinkles and searching for signs of damage.

His inspection complete with no surprises, Julio tried to shake the strange feeling that the face had thrust upon him. He looked down at his watch and remembered that he had to hurry or he’d be late for work. As he restarted his determined walk, he took steps to restore his good mood, mindfully focusing on his gait and the pleasure of the morning sun and chirping birds. Just as he felt he was getting his groove back, a giant sign outside the CVS slingshotted him back into unease. “WE’RE EXPANDING” declared the sign and Julio couldn’t help but let his mind wander to thoughts of opportunities, opportunity costs, and opportunities lost.

The next day, construction of the expanding mega pharmacy began and the exhausted lamp post was unceremoniously removed. It was gone, but so was Julio.


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Science Brought Us Beer... and Other Thoughts on Science Communication

March for Science Signs

Yesterday I attended a march for science. If you’re not familiar with the marches, head over to my friend Stephanie Hay’s blog post to learn a little about why scientists decided to march. TLDR: There were lots of reasons, but, more or less, people want knowledge and facts to become stronger forces behind the decisions that guide government action. It was invigorating to see so many people out there in support of knowledge, but there are a few things we need to keep in mind as we try to make science and knowledge effective forces for change.

1. Empathy, Empathy, Empathy

Many scientists are angry about the way decisions are being made in the US and throughout the world. This is understandable. After having done my PhD work in renewable energy and climate change, it frustrates me to no end to see these fields pushed aside. BUT, no amount of angry chanting, slogan writing, sign making, or even informative explaining will convince people that the problems so many scientists work so hard to solve are important.

If you lived in a small coal mining town where it was once possible to work in the coal industry your whole life and make a comfortable living, you wouldn’t be supportive of regulations that shut down coal-fired power plants. In fact, seeing few other options available to you and believing your entire livelihood was about to be destroyed, you’d probably be happy to see mining jobs come back; even if the long-term costs could be problematic, at least you could live with some chance of adapting to the problems later. Don’t fool yourself into thinking that you can start a conversation about science with a coal miner who disagrees with you using a snarky, sciency, anti-Trump sign. How could you possibly expect that person to relate to you?

Now, you might ask, why do I need to relate? Shouldn’t the truth be able to convince people? I wish it could, but, as a recent study on protest tactics showed, movements are more likely to succeed and recruit followers when people can relate to them (see NPR article segment on the study). The more you can identify with someone you are trying to convince, the more likely you are to convince them.

2. Extreme Rhetoric and Extreme Protesting Are Probably Not Useful

Despite common belief, people don’t necessarily avoid behaviors that are believed to be extremely or insurmountably risky. I’ll call this the “Screw it, I’m doomed anyway” principle. For example, work in Malawi showed that if men believed they had a 100% chance of contracting HIV by having sex with someone who was already infected, they were far less likely to use condoms than if they knew the actual, much lower, 10% chance. In a recent NPR report, the authors explain this as a kind of fatalistic approach to risk. If you’re told that you’re doomed, you don’t bother to change your action because, hey, you’re doomed anyway.

This has important consequences for the ways we talk about challenges facing the global community. If we simply start yelling “THE ECONOMY WILL IMPLODE WITHOUT NAFTA” … we’ll probably shut people off. Instead we might say, “I love being able to get fresh tomatoes for cheap at any time throughout the year, don’t you? …. Did you know that NAFTA is part of the reason you can get fresh tomatoes so cheaply? Pretty cool huh?”.

“Okay,” you might say, “but people will only start listening if I get extreme.” While it may be true that extreme protests get more news coverage, the same study on protest tactics I mentioned above found that protests using more extreme tactics are less likely to recruit people to a cause and may, in fact, have the opposite effect (again, you gotta be relatable!).

3. Jargon Sucks

I work at a biotech non-profit and many of my coworkers are not scientists. Despite the fact that they work around biologists and biology jargon everyday, we recently discussed the fact that many, many times they get lost once a scientist starts talking. This wasn’t unexpected - biology and molecular biology in particular is choc full of words that either a) have no meaning outside of biology or b) have biological meanings that make no sense when compared to their more general meanings (a good example, the term “gene expression”). Jargon makes my co-worker’s jobs more difficult and makes it harder for them to speak up in meetings for fear of looking stupid or making the meeting run too long.

What does this have to do with science advocacy or science marching? Researchers need to remember that, when they get around groups of peers, they are prone to start using alienating jargon that is nonsensical to people outside their specific fields. One of the quickest ways we make ourselves unrelatable and even a bit pretentious is to use jargon. So, while many of the more sciency signs at the march were quite cool and the messages were very good (loved the “Be like a proton, be positive" signs) they could have been more alienating than many of us realized (go ask a random group of ten people what a proton is). It’s certainly possible to make a relatable science march sign with a positive message: “Science brought us beer!” (slightly altered version of one of the great signs above).

Before I go, I’d like to reiterate that many people at the March for Science Boston (and I assume elsewhere as well) seemed to understand these points and did a great job. Hopefully we’ll see more positive science communication that will bring about effective policy change and community interactions in the months to come.


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Open Science

This week I did a podcast interview with some friends of mine in the science communication student group, Science in the News (SITN). We talked about a bunch of things, but for part of the interview, we delved into open science - the push to make the products and process of scientific research available to all. Here are some things I learned:

Open Access Journals Are a Huge Part of the Open Science Movement...

Open Science money and information flow

While many scientific publications are closed - you have to pay for subscriptions in order to see the research published within them - the research published in open access journals can be read by all (scientists and nonscientists alike). Open access journals have gained popularity as the internet has grown because it is easy to host the research papers published within them on the web. This alleviates the need to pay for printing and distributing the physical journal.

Open access journal articles are available to anyone who wants to read them. Open access journals are particularly valuable to:

  • Small Schools and Small Businesses - Subscriptions to closed publications are prohibitively expensive (thousands of dollars per year for a single journal in some cases) and smaller institutions (including Addgene, the nonprofit that I work for) have great difficulty paying for access to important publications. Open access makes it easier for these institutions to access research results and put these results to good use. These results help future researchers do more productive work and could help small businesses develop more useful products and technologies.
  • Developing Countries - People working in developing countries could be the most highly affected by the latest research (think malaria research) and are potentially in the best position to know the most appropriate next steps. However, researchers in these countries, like those in small schools and businesses, often find difficult to pay high subscription costs. Open access journals put the latest research in their grasp.
  • The General Public - Say you have a relative who suffers from a rare disease and you’ve taken it upon yourself to learn as much as you can about that disease. It's likely that you’ll have difficulty accessing all the research on that disease because much of it will be in closed access journals. Open access journals make research (even if not easily understood) within the reach of all concerned parties, whether they do research or not. Without even getting to this more personal side of the debate, it’s often argued that research should be available to the public given that much of it is publicly funded.

Other Upsides to Open Access Journals Include:

  • Increased citations - Scientists partially judge the value of their published research by how often that research is cited in other publications. Many studies have shown that open access articles are more highly cited than closed access articles (reviewed here).
  • Improved ability to find information - There are literally millions of research articles published every year. Not all closed access journals can be indexed by academic search engines like Google Scholar. This can make it difficult to find small pieces of information contained within those articles. Open access articles are readily available for indexing by search engines.
  • Reusability of images - This one is particularly important for me. When writing about recently published research, oftentimes the images in the original publication are fantastic at helping explain the results. However, you often have to pay to use images from closed-access journals. Open access images just need to be attributed appropriately.

Downsides:

There are, of course, some downsides to Open Access and many of them stem from paying for publication. Because open access publishers don’t get subscription fees, one of the ways they make money is by having authors pay to publish. This presents an inherent conflict of interest for open access publishers; there’s the potential for low quality work to be published simply because the authors pay for it. Indeed, so-called predatory journals that do not have proper review but do accept publications and their associated fees exist. Of course, there is policing for this within the academic community and it is not an unsolvable problem. For instance, publishing reviews along with final articles (as some journals are already doing) shows potential authors that a publication carries out rigorous review. Finally, the need to pay for publication may also prevent poorly funded labs from publishing at all.

...but Open Access Journals Aren’t the Whole Story

Beyond open access publications themselves, many within the open science movement also push for open data and reagent sharing. Open data essentially means that, any data that is used to create published analyses is made available for anyone to use and analyze on their own. Reagent sharing means that any materials constructed during the research process (particular DNA sequences, cell lines, or bacterial strains for instance) are made available for future researchers to use or re-test themselves. Proponents hope that open data and reagent sharing will make it easier to reproduce research results between labs, prevent researchers from recreating reagents unnecessarily, and accelerate future discovery.

In its purest form, open science also calls for results to be made available for review as they are obtained. This can be accomplished through online lab notebooks where researchers record their experiments as they’re doing them. This seems unlikely in the near term given that many scientists worry about their ideas and work being stolen - particularly by larger and better funded labs that could potentially take ideas that show early success and run with them. Nonetheless, this is a fantastic goal to aim for, and the less pessimistic viewpoint (my own view point :D) says that it could lead to greater collaboration that accelerates science.


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3 Effective Cancer Immunotherapies

You’ve probably heard that a lot of money goes into cancer research but haven’t heard enough about its impacts. Through a series of coincidences at work, I found myself reading quite a bit about cancer immunotherapy - using the human immune system to better fight cancer. I was astonished by how many effective cancer therapeutics are coming out of this field and thought I’d quickly describe how a few of them work here.

*A Couple of Quick Notes* - We need new cancer therapeutics because standard cancer treatments (things like surgery to remove tumors, radiation therapy, and chemotherapy) can damage our bodies in terrible ways and are often ineffective. Also, even though the therapies below have been successful in some cases, every cancer is different, and they won’t be successful for all types of cancers or even all patients with a particular type of cancer.

3 Types of Successful Immunotherapy

1. Adoptive Cell Therapy

Cell Therapy

There are many different types of cells in the immune system. These play a variety of roles in fighting disease causing agents (pathogens) like viruses, bacteria, and cancer cells (yes, our bodies naturally fight cancer). In adoptive cell therapies, scientists take immune cells out of our bodies, make the cells better at fighting cancer, propagate them, and then put them back into our bodies.

Before the immune system can begin fighting a pathogen effectively, the cells that do the fighting need to be told a pathogen is present and what it looks like. Dendritic cells do this by showing components of the pathogen to other cells in the immune system. In one form of adoptive cell therapy, doctors take dendritic cells from a patient, load them with cancer cell components, and put them back in the patient’s body where they can alert the rest of the immune system to the presence of the cancer.

For more information, read up on Sipuleucel-T, an FDA approved adoptive cell therapy for prostate cancer.

2. Antibody Therapy

Antibodies and Cancer

You may have heard of antibodies. These are proteins that our immune systems naturally produce. Antibodies bind to pathogens and prevent them from causing disease. Through years of research, scientists have learned ways to produce antibodies that bind to cancer cells and slow cancer progression.

For example, some cancer cells produce a signal that tells the immune system to slow down and stop attacking them. Scientists have produced antibodies that bind to and block this signal. These antibodies have been proven effective at boosting the immune system and fighting a wide variety of cancer types.

For more information, read up on PDL1 inhibitors and watch this great video from Dana Farber.

3. CAR T-Cells

CAR T-Cell

CAR T-cell therapy combines aspects of adoptive cell and antibody therapy. T-cells normally bind to and kill cancer cells, but can only do so if they have the appropriate binding proteins. In CAR T-cell therapy, doctors take T-cells from a patient and give them new proteins called chimeric antigen receptors (CARs) that are very similar to antibodies. CARs allow the T-cells to bind to cancer cells. Once put back into the patient, these CAR T-cells can be effective at binding to and fighting the cancer.

CAR T-cells are effective at fighting a few types of cancer and have completely cured some patients who were otherwise out of hope.

Read Up on CAR T-Cell Therapy.


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Human-Pig Chimeras

In a pair of recent publications, scientists showed the following:

  • Human stem cells can contribute to pig tissues in pig embryos (i.e. it’s possible to make human-pig chimeras)
  • Mouse pancreatic cells produced in a rat can be used to cure diabetic mice
In the future, scientists hope to combine these findings to determine if it’s possible to make human pancreatic cells in other animals. These cells could potentially be used to treat human diabetic patients.

What is a Chimera?

You can check out the wikipedia chimera page for the description of a chimera in mythology (essentially a beast consisting of a lion, goat, and snake), but that’s not we’re talking about here. In biology a chimera is a single organism composed of genetically non-equivalent cells. We normally think that all the cells that make up an organism have the exact same DNA sequences. This is true most of the time, but there are a few natural cases where our bodies will manipulate our cell’s DNA sequences (in the production of B cells for instance), and humans can sometimes be born with patches of cells that have non-identical DNA (check out this Scientific American Article for more information).

Beyond these natural cases, scientists have known for some time that you can take stem cells from one organism, implant them into a developing embryo, and they will grow along with the embryo. These non-embryo cells will ultimately make up some fraction of the cells within the adult. Scientists routinely make chimeric mice composed of cells from genetically distinct mouse strains in order to produce new strains with particular traits (see chimeric mouse image below).

Chimeric Mouse with Pups

It’s also possible to create chimeras between different species (like between mice and rats) as opposed to just between two different strains of the same species. However, it’s unclear how different the two species can be while still resulting in viable chimeras. Furthermore, while most would argue that creating chimeras within in a single species is okay, it’s ethically questionable whether or not we should produce chimeras between different species. You might even ask - why make interspecies chimeras in the first place? The answer: chimeras may allow us to cure disease.

Indeed the combined results from two recent papers (one published the journal Cell, the other in the journal Nature) show that someday it may be possible to use other species to grow replacement cells for people with diseases like diabetes.

Growing a Replacement Pancreas for a Mouse

The first paper showed that, if you take a rat embryo that’s unable to grow a pancreas and give it stem cells from a mouse that can grow a pancreas, the mouse stem cells will form a pancreas in the rat. This rescues the developing rat which would otherwise die.

You can then take the pancreas from the rescued adult rat and use the cells from it to replace broken cells in a mouse with diabetes. This mouse will then essentially be cured of its diabetes.

Now you might say…”Why grow the mouse pancreas in the rat in the first place? Couldn’t you have just taken those cells from another mouse? The chimera seems unnecessary.” Well, in the case of mice, you have a point, scientists could easily harvest the necessary pancreas cells from a mouse and cure the diabetic mouse BUT ultimately, researchers would like to use a similar technique to cure human patients with diabetes. You can’t just take one person’s pancreas cells and use them to treat a different person with diabetes. If, however, this same technique works between humans and other animals, you could potentially grow a new pancreas in another animal and use it to treat the diabetic patient. Does this actually work?

Growing a Replacement Pancreas for a Mouse

The second paper set out to determine if human stem cells could be injected into embryos from other animals (specifically pigs) and contribute to the tissues in these embryos. The long and the short of it - Yes, the process is inefficient and requires the human stem cells to be prepared a particular way, but they will contribute to the tissues in the developing pig.

Now, these researchers did not allow the chimeric embryos to fully develop, and it’s unclear if they even would, but this is the first evidence that it may be possible to do something like what the previous researchers did with mice and rats instead using humans and pigs. That is, grow a human pancreas in a pig and use cells from the pancreas to treat diabetes. HOWEVER, this is a long way off and a number of things need to be considered:

  1. Ethics - We have to ask the question, should we be making chimeras in order to treat disease? In my mind, chimeras as we currently foresee utilizing them have two big ethical challenges:

    • Unintended consequences: Just one example, we don’t have good ways of directing the human stem cells particular tissues - they can contribute to many types of tissues. If some of the human stem cells contribute to the pig’s brain, will that affect the pigs cognition? What other attributes might the chimeric pig gain?
    • Animal welfare: What about the welfare of the pig? A pure utilitarian might argue that the ends, curing human disease, justify the means, but should we focus our efforts instead on ways to grow organs that don’t rely on other animals?
  2. Human Pancreas Formation - While papers discussed above are very interesting and demonstrate important first steps, these researchers did not show whether or not a fully grown pig could be formed using this technique or whether a fully functional pancreas could be made in the pig.
  3. Immune Rejection - In the mouse/rat experiments above, researchers suppressed the mouse immune system so there wouldn’t be a drastic immune response to the replacement pancreatic cells (which contained some rat cells along with them). If replacement human pancreatic cells were taken from a pig, how would the human immune system respond to them and what efforts would need to be taken to circumvent this response?

Final Thoughts on Chimeras in Research

These are the 3 biggest challenges that I can think of at the moment and I’m sure there are many more, but this shouldn’t dissuade researchers from at least thinking about pursuing this work. Keep in mind that pig valves are already used to replace human heart valves and pigs were once a major source of insulin used to treat Type I diabetes - in a way, human-pig chimeras have been around for a long time.