Simple things stated in a complex way

Sketch of a puppy

While I no longer do laboratory research, I still proudly consider myself a scientist and believe anyone can be a scientist if they have a curious mindset and fuel their actions with critical thinking. Nonetheless, those who consider themselves scientists do often have a few stereotypical quicks. One of these quirks is an infatuation with jargon and making communication more complicated that it needs to be. Part homage, part chastisement, in this blog post I provide examples of the complex ways scientists might say simple things.

*As a side note, the idea for this blog post came from a conversation about linguistics and my first example is the summation of that conversation.

Drawing of lips getting ready to pronounce something#1
Complex
: In many ways, language is shaped by biology and must conform to the shapes and structures of our mouths and airways.

Simple: We avoid saying words that are difficult to pronounce.

Drawing of a cancer cell evolving from a pile of cells doused with a chemical#2
Complex
: Continued exposure to damaging agents can lead to a series of genetic changes that ultimately enable otherwise quiescent cells to start dividing rapidly and dangerously spread throughout the body.

Simple: Certain types of chemicals and radiation can cause cancer.

Sketch of people having a conversation

#3
Complex
: The key to keeping a conversation going is to identify the activities, ideas, and people that excite your conversation partner and work these things into the conversation.

Simple: People like to talk about themselves.

Sketch of a burger, fries, and a shake#4
Complex
: If your metabolism is predisposed to store excess dietary calories in fatty acids and other macromolecules, you’re more likely to increase your body mass index on a given diet and activity regimen than someone who is predisposed to excrete excess calories.

Simple: Some people gain weight more easily than others.

Sketch of a puppy#5
Complex
: It can be easier to associate phenotypic traits in purebred dogs with particular genetic variations because of the level of genetic identity within and between different breeds.

Simple: Dogs are inbred and that can sometimes make their genetics easier to understand.

I should point out that the majority of these aren’t real examples and were just fun to come up with. Feel free to tweet your own whether real or imagined @tyfordfever.

The “properly” anthropomorphized flower

Drawing of an anthropomorphized flower

Very often, I anthropomorphize cells and other biological objects in my drawings. I’ve turned bacteria into pirates, phages into bandits, and muscle cells into builders. It is my hope that presenting biological concepts in this way helps you understand and remember them better or helps you think about them in a new way. In this post, I take anthropomorphism to somewhat of an extreme with what I’m calling a “properly” anthropomorphized flower. Reading this post, I hope that you’ll develop a deeper appreciation for what a flower really is as we approach Valentine’s day.

Drawing of an anthropomorphized flower
A “properly” anthropomorphized flower.

The problem with the smiling flower

Although you can find many cute flower cartoons depicting smiling faces surrounded by petals, it’s a bit odd to compare flowers to faces. You see, while plants can certainly sense many of the things we sense with our eyes, noses, mouths, and ears, they don’t have faces per se. For example, the mouths should be distributed more to the leaves and roots. The leaves “eat” sunlight and carbon dioxide while the roots “eat” other nutrients found in soil and fertilizer (e.g. nitrogen and phosphorous).

When thinking about its biological function, the flower itself is possibly the most lewd thing one could represent as a face. The flower is censored in my drawing because, in reality, flowers house the reproductive organs of many plants. Insofar as a plant’s reproductive organs can be compared to those of humans, single flowers often contain both male and female parts. In fact  some flowers can fertilize themselves. In the floral fertilization process, pollen constitutes floral sperm while eggs can be found within the depths of the flower. I find this all very cool but, were I to draw these parts only my anthropomorphized flower, I might turn away some of my audience.

If my drawing didn’t focus too much on the flower’s innards and instead focused on its petals, the censor bar might might not be required after all. This is because you might think of a flower’s petals as gorgeous clothes. These beautiful garments help attract pollinators like bees, much like we use clothes, jewelry, and hairstyles to attract mates when going out on the town (hence the dancing flower below).

A flower that's ready to dance
This flower is ready for a night on the town.

In any case, I hope you’ve found my “properly” anthropomorphized flower enjoyable. With a little more plant know-how, maybe you’ll further appreciate the complexity and life hiding behind the petals you see in your next bouquet!

More than dumb walls – how dynamic membranes enable cells to thrive

Drawing of a thirsty person getting some water

Cells use barriers to regulate their internal environments. Without their fatty barriers (membranes) cells wouldn’t function properly and we wouldn’t exist. Far from being static walls that prevent any movement or transport, these dynamic barriers enable cells to import and export the various materials they need to live.

Barriers enable cells to create specific internal and external environments

Membrane barriers come in a variety of flavors. Some cells have more membranes than others, their compositions are often different, and their structural properties vary quite a bit. Nonetheless, all cellular membranes are fat-based and selectively allow the transport of particular materials.

Indeed, membranes are good barriers because of their fatty composition. The internal and external environments surrounding cells are both water-based. Fat-based membranes largely repel the water-loving materials in these environments and thereby prevent them from crossing from one environment to the other in an unregulated way.

To obtain nutrients, grow, and function properly, cells selectively import and export materials from the external environment. They do so using proteins embedded in their membranes. A cell will produce more or less of a particular membrane protein depending on its needs. Below I describe how membranes and their embedded proteins enable some critical cellular functions.

Transmitting electrical signals

Nerve cells can transmit electrical signals because of the proteins embedded in their membranes. These proteins specifically import and export ions to build up electrical charge. By releasing this charge, nerve cells communicate with one another and coordinate bodily functions.

Drawing of a brain transmitting an electrical signal to a hand through a nerve cell.

Detecting and eating dangerous invaders

Some of your immune cells have the ability to eat disease-causing pathogens. To do so, immune cell membranes attach to and surround the pathogens. Once eaten, the pathogens are destroyed.

Drawing of a macrophage detecting and eating an invader.

Absorbing ingested water

The membranes of intestinal cells specifically transport salts from the gut into the body. Water follows the salt into the body through a chemical process called osmosis. The water can then enter the bloodstream and travel throughout the body. Without membrane-driven water uptake in the gut, we’d all be dead :D.

Drawing of a thirsty individual getting water
This thirsty individual may not be absorbing enough water in his gut.

Overall, cellular barriers are incredibly useful because they permit certain materials to enter and exit. Far from dumb walls, evolution has honed these barriers into dynamic systems with a variety of functions. These functions enable us to do everything from think to eat cake. We wouldn’t exist without them.

Viruses aren’t just for humans

Cartoon of phage attaching to a bacterium

You’ve probably lived through the woes of various viral infections. Viruses cause the common cold, the flu, warts, and more. You may know that bacteria cause some similar health problems, but did you know that viruses can infect bacteria too? In addition to killing countless bacteria, bacterial viruses (or “phages”) also make useful research tools. I’ll introduce you to some of the fantastic uses these tiny killers here.

Phages help researchers manipulate DNA

Phages survive by attaching to bacteria, injecting them with DNA, and forcing them to follow the instructions in that DNA. These instructions drive the bacteria to copy phage DNA and make more phages. The new phages then encapsulate the DNA and, eventually, there are so many DNA-filled phages that they explode out of the bacteria. Then they start the process again.

Cartoon of a phage attaching to a bacterium
A phage attaches to a bacterium and is ready to steal bacterial resources.

New phages occasionally grab up bits of bacterial DNA instead of phage DNA. If researchers know that one bacterial strain has useful DNA, they can use phages to encapsulate it. The phages will then deliver the useful DNA to other bacteria. These bacteria will follow the instructions in the useful DNA.

For instance, say you had one bacterial strain with a gene that made it really good at eating sugar and a second bacterial strain with genes that made it turn sugar into gasoline. You could use phages to put the sugar-eating gene into the gasoline-producing strain. The resulting bacteria could eat sugar and turn it into gasoline.

Using phages to control genes

When phages inject their DNA into bacteria, they need to make sure the bacteria follow the instructions encoded within it. To do so, some phages have molecular machines that force bacteria to devote themselves to following these instructions.

We’ve figured out how to use these same molecular machines to force bacteria to follow the instructions in researcher-specified DNA sequences. With these tools, we have more control over bacteria. For instance, we could use these tools to force our sugar-eating, gasoline-producing bacteria to do nothing but produce gasoline from sugar. These would be more efficient gasoline producers because they wouldn’t waste any energy on doing anything else.

Using phages as antibiotics

Because phages kill bacteria, we can potentially use them as alternatives to antibiotics.  This may prove a bit tricky because, unlike current antibiotics, phages generally kill specific species of bacteria. As a result, we might have to make new phages for each new kind of bacterial infection we’d like to treat.

This specific killing could also be a benefit. Current antibiotics kill both beneficial and harmful bacterial species. Phage treatment may leave beneficial species intact.

As we learn more about bacteria and human health, I’m sure there will be many more developments in the world of phage research. Heck, a quick google search for “Phage biotech companies” clearly shows there’s interest in this area. If you’d like to learn more about phage, I’d recommend this cool episode of Radiolab (a podcast) or this quick New Yorker article.

Teeny, tiny turkey basters, antibiotics, and problems with their funding

Just a few days ago I attended a free conference hosted by the Center for Emerging and Neglected Diseases at UC Berkeley. At the conference, attendees discussed ways to diagnose and treat emerging and neglected diseases – diseases that are on the rise or which research has left behind. At the conference I learned about one particularly huge problem in this field and about a ton of new research that gives me hope for the future.

What needs to change in emerging and neglected diseases: investment in diagnostics and antibiotics

You cannot effectively treat a sick person if you don’t what’s causing their sickness. This seems obvious but believe it or not we’re lagging behind in our ability to diagnose a number of diseases. For example, as I learned at the conference (and later fact checked on the WHO website), only 20% of the millions of cases of Hepatitis C were diagnosed in 2015. Being that Hepatitis C can have rather dangerous health effects including cirrhosis and liver cancer, this is clearly a problem.

Unfortunately, as new diagnostic tools will have some of their biggest impacts in poorer regions, they must be inexpensive. This means investors have less monetary incentive to back their development. There’s a similar problem in the world of antibiotics research. Despite the fact that antibiotic resistant bacteria are on the rise, new antibiotics won’t generate as much revenue as other drugs. Thus new antibiotics research won’t get funded until antibiotic resistance gets worse, demand for new antibiotics goes up, and prices increase.

The solution as discussed at the conference is to find ways to decouple the high costs of the diagnostic/antibiotic clinical development process from the cost of the final product. From what I could tell, this will require more philanthropic organizations, NGOs, and governments to grant more money to clinical development in these fields. For example, one awesome nonprofit at the conference, FIND, works to provide resources, funding connections, and research infrastructure to those developing diagnostics. We need more organizations like FIND and, in the absence of government support, donors who will fund this research.

Cool advances in diagnostics and antibiotics research

Despite the need to fix the funding environment, there are a lot of cool developments in diagnostics and antibiotica research! Here’s a smattering of things I learned about at the conference:

Cartoon of a nanopipette detecting a disease-associated toxin.
Conceptual depiction of a nanopipette with biological materials (purple) that can attach to disease markers (green skull and crossbones). See description below.
  • Tiny turkey basters for detecting diseasePinpoint Science is a startup creating tools for diagnosing disease. They’ve developed a device that uses nanopipettes (basically teeny tiny turkey basters) to detect disease compounds (think toxins and parts of viruses). When biological materials in the nanopipettes attach to disease compounds, they cause changes in electrical signals that tell users the disease is present. Pinpoint believes that it can provide these devices at incredibly low prices (in the $1 range) and use them to diagnose all sorts of diseases.

  • Cell phone microscopes – Aydogan Ozcan from UCLA is working to develop cell phone attachments that turn your phone into a mobile microscope. These can be produced at much lower prices than standard microscopes. Thus they’ll make it easier for researchers all over the world to analyze biological samples. I imagine these could be great for people in the DIY Bio space as well.

  • Developing new antibiotics with a little help from out gut bacteria – Believe it or not, the “good” bacteria living in your gut defend you against disease-causing invaders. Indeed, these gut bacteria produce compounds that kill the invaders. Manuela Raffatellu from UCSD is studying these compounds. She hopes to use what she learns to create the next generation of antibiotics. I’m absolutely fascinated by this work and will hopefully write a separate blog post on it soon.

This is just a smattering of the research going on in the world of diagnostics and antibiotics. Researchers are coming up with many creative ways to diagnose and treat emerging and neglected diseases. We just need to fund them better!

Transcribing copies at the genomic library

Cartoon of a cell with a library representing the genome.

Your cells require lots of certain proteins in order to function properly. For example, your brain cells use proteins to transmit electrical signals, your muscle cells use proteins to contract, your stomach cells use proteins to secrete acid, and so much more.

Your genome contains the DNA instructions for these proteins in the form of genes. Almost all of your cells contain two complete copies of your genome and therefore two copies of each gene (one from your mother and one from your father). With only two copies of each gene, but the need to create large amounts of certain proteins, your cells need to make more copies of particular genes. This post discusses how cells make copies of genes to drive the differential production of proteins that ultimately leads to various cellular functions.

The genome as the library in a cellular city

Think of your cells as tiny cities that together make up the country that is your body. These cities have their own specialized roles that collectively help the country (body) function properly. To carry out its role, each city has its own specific mixture of workers. Some cities have more builders, others more farmers, others more tech entrepreneurs, and so on. These workers are like the proteins in your cells.

A Cell City with its genomic library poised to distribute mRNA transcripts of its books… I mean genes.

The libraries in these cities are like your genome. They contain all of the books required to train all of the types of workers that could possibly exist in a city. However, there are only two copies of each book. Because some cities require many more plumbers than dentists, they cannot simply loan out the two books and expect all of the their needs to be met. Instead the library creates copies of each book. The more copies of a particular book the library creates, the more of that type of worker the city can train. If the city needs more actors than philosophers, its library can simply make more copies of the acting books and fewer copies of the philosophy books. In fact, the library can stop creating some copies altogether and the city will have very few of that type of worker.

Transcribing genes into mRNA copies

Your cells work in a similar way. The instructions found in the two cellular copies of your genes are required in disparate amounts, in different places, and at different times. To account for this, your cells don’t create proteins by following the instructions in genes directly, instead they transcribe the genes into copies known as mRNA. Cells then use the mRNA copies to produce much more of the encoded proteins when they’re needed. Indeed, if your cells don’t need any of a certain type of protein, they can simply stop transcribing mRNA copies of the gene that encodes it.

Our various body parts take on their different roles through transcription. Brain cells transcribe specific genes to transmit electrical signals. Muscle cells transcribe specific genes to contract. Stomach cells transcribe specific genes to secrete acid. With transcription, we’re much more than blobs of cells all doing the same thing.

When an Effective Cancer Treatment Makes Your Cells Riot: Cytokine Release Syndrome

Researchers and doctors have found many effective ways to modify cancer patients’ own immune cells and use them to attack cancer cells. They have been so successful that one type of these so-called “immunotherapies” was even considered the “Advance of the Year” in 2018 by the American Society of Clinical Oncology. However, these therapies are not perfect. Some immunotherapies cause overactivation of the immune system, which can result in terrible side effects including damage to internal organs. Cumulatively, this overactivation and its side effects are known as cytokine release syndrome. Thankfully researchers are coming up with inventive ways to limit or stop cytokine release syndrome, which makes immunotherapies even more powerful.

Researchers don’t yet fully understand all the specific activities that cause the dangerous overactivation of the immune system during immunotherapy. You can think of this overactivation as something like a riot or stampede of cells. When doctors give cancer patients modified immune cells, they do a fantastic job of killing cancer cells, but they also sound the alarm and throw out a bunch of signals saying “SOMETHING NEEDS TO BE DONE!” These signals activate other immune cells, those immune cells send out more signals, and then even non-immune cells can begin acting irregularly.

Drawing a modified immune cell attacking a cancer cell and causing a riot
A cellular riot caused by a modified immune cell used to attack a cancer cell

This cellular rioting can lead to disruption of blood vessels, flu-like symptoms, and damage to organs; but, luckily, doctors know how to treat many of these things. Doctors can give patients drugs that will limit the negative side effects of the cellular riot and block some of the alarms. Nonetheless, these drugs aren’t equally effective in all patients, and there is no one-size-fits-all treatment that can be used in every case.

Recognizing this issue, researchers are working to make it so the modified cells used in immunotherapy don’t cause cellular riots. These researchers are further modifying the immune cells so that they send out fewer alarm signals in the first place and can be destroyed if a riot begins.

Importantly, even without these new modifications, immunotherapies are already very effective at treating cancers of the blood (read the Advance of the Year article for more). I’m hopeful that researchers will be able to make immunotherapies more effective against other types of cancers soon (think solid tumors), and the ability to control these cellular riots will be the icing on the immunotherapy cake. It’s an exciting and hopeful time for cancer researchers and patients!

References:

  1. Chakravarti, Deboki, and Wilson W. Wong. “Synthetic biology in cell-based cancer immunotherapy.” Trends in biotechnology33.8 (2015): 449-461. PubMed PMID: 26088008. PubMed Central PMCID: PMC4509852.
  2. Shimabukuro-Vornhagen, Alexander, et al. “Cytokine release syndrome.” Journal for immunotherapy of cancer 6.1 (2018): 56. PubMed PMID: 29907163. PubMed Central PMCID: PMC6003181.