Science Communication – Page 3

October 31, 2018April 29, 2021

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

Cartoon of a cell used in 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

Cartoon of antibody therapy 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

Cartoon of a CAR-T cell getting ready to attack a cancer 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.

October 31, 2018October 31, 2018

Open Science

Many weeks ago, 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 schematic showing money and information flow from government to research and back

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.

October 31, 2018April 16, 2019

Why Viruses Are Great Gene Delivery Vehicles

Drawing of a cartoon virus delivering a piece of DNA 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:

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.
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.
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.
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!

October 31, 2018October 31, 2018

3 Things I Learned Recently about Plant Biotech

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

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. Marking Non-browning Apples (Arctic Apples)

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!

October 31, 2018October 31, 2018

Experimental Approaches to the Best Fruit Salad

Diagram of 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:

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.
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.
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).

October 31, 2018November 1, 2018

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.

A drawing of turtle floating in an inner tube

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.

October 30, 2018November 1, 2018

Learning the Game of Life with Biosensors

Cartoon of a DNA Biosensor

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?

Drawing of a protein-protein interaction 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?

Cartoon of a biosensor for glutamate

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!

November 1, 2017March 26, 2019

Human-pig chimeras

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

Mouse pancreatic cells produced in a rat can cure diabetic mice
Human stem cells can contribute to tissues in pig embryos (i.e. it’s possible to make human-pig chimeras)

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 be used to treat diabetes.

What is a chimera?

Photo of a chimeric mouse You can check out the wikipedia chimera page for the description of a mythological chimera (essentially a beast consisting of a lion, goat, and snake). While cool, that’s not what we’re talking about here. In biology, a chimera is a single organism composed of genetically distinct cells.

We normally think that all the cells in an organism have the same DNA sequences. This is true most of the time. Yet, there are a few natural cases where cell’s change their DNA sequences (in the production of B cells for instance). In addition, humans can 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 use stem cells to create chimeric organisms. To do so, they implant foreign stem cells into developing embryos. These grow along with the embryo. Ultimately, they will make up some fraction of the cells in the adult.

Scientists routinely make chimeric mice composed of cells from genetically distinct mouse strains. Scientists use these chimeric mice to produce new strains with particular traits (see chimeric mouse image above).

It’s also possible to create chimeras between different species (like between mice and rats). However, it’s unclear how different the two species can be. Furthermore, while most would argue that creating chimeras within a single species is okay, it’s ethically questionable to produce chimeras with cells from different species.

You might ask – why make interspecies chimeras in the first place? The answer: chimeras may allow us to cure disease.

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

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 , 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 cells from the rat and use them to replace broken cells in a diabetic mouse. This mouse will essentially be cured of its diabetes.

Now you might say, “Why grow a mouse pancreas in a rat? Couldn’t you just taken pancreas cells from another mouse?”

In the case of mice, you have a point. Scientists could easily harvest the necessary pancreas cells from another mouse. However, researchers would like to use similar techniques to cure human diabetes. You can’t just take one person’s pancreas cells and use them to treat a different person with diabetes. If, however, you can grow a human pancreas in another animal, you could potentially use it to treat diabetes.

This sounds far-fetched, but the next paper makes it seem more likely.

Making human-pig chimeras

The second paper set out to determine if human stem cells can contribute to embryos of other animals (specifically pigs). TLDR – Yes, the process is inefficient and requires the stem cells to be prepared in a particular way, but it does work.

In this work, the researchers did not allow the chimeric pigs to fully develop. It’s unclear if they even could. Yet these results do provide evidence that it’s possible to grow human organs in pigs.

There are a number of important issues that need to be considered before similar research moves forward:

Ethics – We have to ask the question, should we be making chimeras to treat disease? In my mind, chimeras have two major ethical issues:
- Unintended consequences: Just one example, we don’t have good ways of directing human stem cells to particular pig tissues yet. This raises questions like – If some of the human cells contribute to the pig’s brain, will that affect the pig’s 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. However, there may be other ways to achieve the same goal. For example, should we focus our efforts on growing organs in the lab?
Human pancreas formation – The papers discussed above are very interesting and demonstrate important first steps towards the production of viable human-pig chimeras. However, these researchers did not show whether or not a fully grown pig could be formed using this technique. New techniques may be required for the creation of fully functional organs.
Immune rejection – In the mouse/rat experiments above, researchers suppressed the mouse immune system. As a result, the mice didn’t have drastic immune responses to the replacement pancreatic cells. If replacement human pancreatic cells were taken from a pig, how would the human immune system respond to them?

Final thoughts on chimeras in research

These are the 3 biggest challenges that I can think of at the moment. I’m sure there are many more, but these 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. Pigs were also once a major source of insulin for Type I diabetes. In a way, human-pig chimeras have been around for a long time.

April 23, 2017October 31, 2018

Science Brought Us Beer and Other Thoughts on Science Communication

Signs from the March for Science

Yesterday (April 22, 2017) 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, science-y, 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 un-relatable and even a bit pretentious is to use jargon. So, while many of the more science-y 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.