Tyler J. Ford

December 24, 2018March 18, 2019

The toxic swamps surrounding cancer cells

The many different types of cancer are difficult to treat for a wide variety of reasons. They have different causes, evolve rapidly, and hide in different parts of the body. Despite their variety, all cancer cells are dangerous because they grow uncontrollably and multiply quickly. In the process, they can form tumors, sap up nutrients from their surroundings, and produce wastes that can kill other cells. They form veritable swamps of dangerous cellular waste and death that make them difficult to treat. These toxic cancer swamps can signal bad news for the cancer sufferer and can protect cancer cells from the immune system.

Drawing of a tumor within a swamp — A tumor surrounded by the toxic swamp of its own creation.

Getting trapped in the cancer swamp

Immune cells have ways of recognizing and killing cancer cells before they cause too many problems. However, immune cells have difficulty penetrating cancer swamps. Much like Atreyu’s horse in “The Neverending Story,” these cells get stuck in the swamps and cannot complete their quest. They fail to protect your body.

Indeed, even if they do manage to slog through the swamps, immune cells might not survive there long enough to kill cancer. In the swamps, immune cells have few nutrients to energize them and some of the substances produced by cancer cells directly harm them. Finally cancer cells can even produce molecules that specifically shut off immune cells.

More than creating toxic swamps, cancer cells can evolve to further remodel their local environments (their microenvironments in biologist jargon). For instance, tumor cells sometimes evolve the ability to attract blood vessels which deliver more nutrients to the tumor. Cancer cells can use these blood vessels to travel to new sites in the body, establish satellite swamps, and cause further harm.

Cleaning up the cancer swamp

Luckily, researchers are well aware of the swamps and other hazards surrounding cancer cells. They’ve already modified immune cells to make them better at fighting cancer and these “immunotherapies” have successfully treated certain blood cell cancers. To make immunotherapies more effective at fighting other types of cancer, researchers are actively looking for ways to clear out (dear I say “drain”) cancer swamps. We may not be stuck in the cancer swamp for long!

November 29, 2018May 1, 2020

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:

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.
Shimabukuro-Vornhagen, Alexander, et al. “Cytokine release syndrome.” Journal for immunotherapy of cancer 6.1 (2018): 56. PubMed PMID: 29907163. PubMed Central PMCID: PMC6003181.

November 25, 2018November 26, 2018

Bacterial Abilities in the Gut: Stealing Vitamin B12

Bacteria are cool. They can do all sorts of things that you might not normally think about as you kill millions of them with your favorite antibacterial soap. Some bacteria can break down and eat toxic wastes. Some bacteria can use sunlight and carbon dioxide to grow. Some bacteria can even be used to create medicinal compounds. Although we know a lot about what bacteria can do, we still need to learn a lot more in order to effectively solve the world’s problems. Bacteria are everywhere and will therefore somehow be involved or interact with any technique used to solve problems like global warming or disease.

Importantly for this post, it’s estimated that there are TRILLIONS of bacteria throughout the human gut and we are far from understanding all of the beneficial and dangerous things they can do. As a small but meaningful step in the right direction, researchers from Yale University recently discovered that bacteria in the human gut can grab and use vitamin B12 coming from our food. Essentially, these bacterial pirates can steal vitamin B12 that would otherwise be absorbed in the small intestine, but this isn’t necessarily a bad thing.

A bacterial pirate steals vitamin B12 from the human gut

To steal vitamin B12, these bacteria create a protein that latches onto the vitamin really tightly thus allowing the bacteria to pull the vitamin into their cells and use it for growth. While they may be pirating some vitamin B12 from us, these bacteria also don’t survive well in the gut if they lose the ability to steal from us. Given that these bacteria likely play important roles in helping us digest foods and maintain healthy mixtures of bacteria in the gut, we can forgive them a little bit of pirating.

Now that researchers know how these bacteria grab onto vitamin B12, they might be able to use this knowledge to prevent the bacteria from stealing B12 in humans who don’t get enough B12. They could also potentially use this information to create new therapeutic bacteria that are better at surviving in the gut. For example, if researchers wanted to engineer bacteria that could live in the gut and create a nutrient for us, they might give the engineered bacteria the ability to steal B12 so that they are better at surviving in the gut. The researchers could also make it so they could shut off the stealing ability. If things started to go wrong, the researchers would just shut off the bacteria’s stealing ability and they’d be eliminated from gut.

As you can see, many new opportunities have been opened up simply from learning a little bit more about what bacteria can do. At first glance, the ability to steal B12 from us seems like it must be a bad thing, but, not only does this ability help useful bacteria survive inside of us, it potentially gives researchers new ways to manipulate bacteria for beneficial purposes.

I’m hoping to write more about cool bacteria and all the things they can do in the future so stay tuned!

References

Wexler, Aaron G., et al. “Human gut Bacteroides capture vitamin B12 via cell surface-exposed lipoproteins.” eLife 7 (2018): e37138. Pubmed PMID: 30226189. PubMed Central PMCID: PMC6143338.

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, 2018November 1, 2018

The Smirking Lamp Post

A photo of a lamp post with a face painted on it 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 face 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 cheek, 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 close 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, the pleasure of the morning sun, and the 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.

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, 2018October 31, 2018

Tilda and the Goja Berries Chapter 1

This is chapter 1 of a somewhat science-y short story I wrote called “Tilda and the Goja Berries.” Read all of “Tilda and the Goja Berries” here.

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.”

A Goja Bear from Tilda and the Goja Berries — A Goja Bear

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.

Goja Monster from Tilda and the Goja Berries — A sleeping Goja Monster

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.