Tag: Biology

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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.

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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.

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Building many different tools with a single blueprint – the power of introns

Drawing of a muscle cell following the instructions in a gene

Many bacteria can and do live as single cells. Humans, on the other hand, cannot. We are composed of many trillions of cells with various functions, shapes, and sizes. Considering this discrepancy, you might think that humans have many more genes than bacteria, but this isn’t the case. Free-living, single-celled bacteria generally have a few thousand genes and 37 trillion-celled humans only have about 20,000 genes. This is confusing because these 20,000 genes are supposed to contain all of the blueprints for our 37 trillion cells. So where do the additional instructions come from???

Changing genetic instructions with introns

Part of the answer lies in the way human cells read genes. Think of your genes as sentences explaining how to create cellular parts. For example, one of your genes might read,

“Make a red and white square.”

Even though the DNA encoding this sentence would be the same in all of your cells, some sections of the sentence can be ignored in some cells.

For instance, your immune cells might read the above sentence as:

“Make a red and white square.”

An immune following the instructions in a gene.

While a muscle cell would read it as:

“Make a red square.”

A muscle cell following the instructions in a gene

And a brain cell would read it as:

“Make a white square.”

By ignoring or including particular sections of genes, individual cells create different cellular parts. Biologists call the ignored sections of genes “introns.”

This differential reading of genes makes cells more diverse. You can imagine that if you had a more complicated sentence like:

“Make a red, white, and blue square and place it next to any green triangles.”

Cells could read these instructions in MANY different ways. Thus, you might reach the cellular complexity and diversity found in the human body.

Introns aren’t the only route to cellular complexity

Before closing, I’d like to point out that, even though bacterial genes don’t have introns, that doesn’t mean they’re simple. Single bacterial cells often perform different functions under different conditions and both bacteria and humans have means other than introns to encode this complexity. Perhaps I’ll write about these additional means in another post so you’ll have to subscribe using the box to the right 😀

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The toxic swamps surrounding cancer cells

Drawing of a tumor in swamp

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!

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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.
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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
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.

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3 Effective Cancer Immunotherapies

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

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

3 Types of Successful Immunotherapy

1. Adoptive Cell Therapy

Cartoon of a cell used in cell therapyThere 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 therapyYou 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.

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Why Viruses Are Great Gene Delivery Vehicles

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

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

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

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

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

Viruses as Gene Delivery People

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

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

Limitations of Viral Delivery

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

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

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

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

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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.

A cow feeding on food engineered to contain more protein1. 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.

Japanese morning glory2. 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!

Cartoon Tyler eats a browning apple3. 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!

 

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Experimental Approaches to the Best Fruit Salad

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

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

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

The Biased Approach to Making The Best Fruit Salad

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

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

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

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

The Unbiased Approach to Making The Best Fruit Salad

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

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

Combining the Biased and Unbiased Approaches

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

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

Why Are We Talking about Fruit Salad?

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

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