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Engineers are problem solvers, and our own health is full of problems to be engineered. In this episode we discuss drug discovery and drug delivery. We’ll explore everything from classical and reverse pharmacology to the new field of synthetic biology. We’ll also look at how important good disease detection is and why we need more targeted drug delivery systems.

Crash Course Engineering is produced in association with PBS Digital Studios: https://www.youtube.com/playlist?list=PL1mtdjDVOoOqJzeaJAV15Tq0tZ1vKj7ZV

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RESOURCES:
http://www.engineeringchallenges.org/9129.aspx
https://www.nature.com/subjects/drug-discovery
https://www.nature.com/subjects/drug-delivery
https://www.bio.org/articles/synthetic-biology-explained
https://www.theguardian.com/science/2010/may/20/craig-venter-synthetic-life-form
http://science.sciencemag.org/content/329/5987/52
https://www.nature.com/scitable/topicpage/dna-sequencing-technologies-key-to-the-human-828
http://www.who.int/news-room/fact-sheets/detail/cancer
https://www.hopkinsmedicine.org/interventional-radiology/procedures/chemoembolization/index.html
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3275820/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4884743/
https://www.cancer.org/research/cancer-facts-statistics/global.html
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https://pdfs.semanticscholar.org/1a8d/ea8780d5e2e8ef07ff83aef4cf7579e9dc04.pdf
http://articles.latimes.com/1989-10-30/local/me-93_1_hot-pepper
https://www.med.uio.no/ncmm/english/topics/drug-discovery/
https://www.healthline.com/health/heart-disease/drug-eluting-stent
https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1464-410X.2001.00112.x

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Medicine matters, whether you're getting flu shot or just talking an aspirin. The medical field is vital to the way you live your life. New treatments are coming out nearly every day, all because of the hard work of scientists and engineers. Together, they are creating breakthrough medicines and figuring out how to get them where they need to go. These efforts are called drug discovery and drug delivery, and they're what you need if you want to engineer a healthier world.

[Intro music]

In today's world, it's pretty easy to get things with a personalized touch. Everyone's different, and people want a lifestyle that reflects those differences. Custom cars, tailored clothes, personalized electronics--the list goes on. But what about medicine? What if you could walk into a hospital and get a completely personalized treatment for whatever you had going on? That's the dream of biomedical engineering: a world where doctors can diagnose and treat a person on their individual differences.

This concept is called personalized medicine and it's the healthcare of the future. It's the idea that you could combine a person's genetic information with clinical data to best tailor a treatment to meet their specific and unique needs. Medicine is the field where all our knowledge comes together. You'll need biology to understand the problem, chemistry to figure out the solution, and physics to deliver that solution in a safe and targeted way. 

As an engineer, it's your job to bring all this together using concepts like bio-compatibility and fluid flow to create one east-to-use package that could save someone's life. Lucky enough, there's already some places where this kind of personalized approach is being used! For instance, genetic tests can reveal how likely someone is to get breast cancer and guide them onto an appropriate monitoring path early in life. Hopefully this leads to detecting the disease early on, when treatment options are less invasive and more successful.

But there are still many challenges to overcome before personalized medicine becomes widespread. You need to develop better systems to quickly assess a patient's genetic profile, create inexpensive diagnostic devices using that information, and find the best way to deliver a drug if anything comes up. And that's all after you come up with a good treatment in the first place! 

Drug discovery is all about finding the new treatment. It's the process through which you discover and create new medications based on what you know about your ingredients and how they'll interact with the human body. Even before modern healthcare, people found natural remedies, often by chance, that improved their health or helped them get over an illness. The early days of drug discovery were all about finding the active ingredients inside those remedies -- the part that was actually affecting the body -- and learning how to replicate or improve the outcome.

Hot peppers, for instance, were used for centuries to relieve the pain of things like toothaches, but today we know it's only the substance capsaicin that matters. You can now buy it to treat conditions such as arthritis and shingles -- all without the burning sensation created by other parts of the pepper! These days we have large chemical libraries of synthetic molecules, natural products, and chemical extracts that have been tested to determine their effects. 

This is called classical pharmacology. A new tool is genome analysis, the study of a complete set of an organism's DNA, including all of its genes. It's the result of the Human Genome Project, which successfully sequenced our DNA. Sequencing your genome is like mapping out all the genes in your body. 

It's about figuring out the order of all the DNA nucleotides, or bases, in your genome. For the Human Genome Project, researchers were able to sequence all of our 3.2 billion base pairs, which allowed for the rapid cloning and synthesis of large quantities of purified proteins. 

Genome analysis is the foundation of the modern approach to developing drugs, called reverse pharmacology. Reverse pharmacology starts by identifying which of those proteins is related to the condition you want to treat. You can compare that protein to a list of chemical reactions to find a molecule known to interact with it. If you find a match, you can test the substance on living cells to see if the reaction has any positive impact. From single cells, you can move up to simple animals and -- if all goes well -- eventually to human trials. 

By starting with the "problem area" and working backwards, reverse pharmacology is the more educated -- and often faster -- way to discover a new medicine. Regardless of which way you got it, once you have a treatment, it's on to drug delivery: getting the medicine to move through the body, find the site of the problem, and even attach to right parts of the cells.

Syringes are the classic solution to this problem. Just draw up some medicine and inject it right where it's needed. But those syringes used to need a lubricant to help the plunger -- that thing you press down on -- well, go down. This usually meant using silicon oil, which could be a problem. Silicon oil can react with the medicine inside and, as medicines become more and more specialized, the worse and worse the reactions can be. 

Many drugs also can't be delivered straight to the bloodstream, but have to be metabolized in the stomach or intestines first. So it's a good idea to have other options for delivering your drugs. We've talked about some possibilities before, such as nanomaterials or biomaterials. Researchers are currently exploring ways to engineer nanoparticles that could deliver a drug to its target in the body while evading your immune system's normal defenses. 

You've heard about smartphones and smart cars, but what about smart medical devices? The idea is to design something that's sensitive to the body's internal conditions, letting the drugs react in the right way at the right times. Take someone with diabetes, for example. You could design smarter devices with better materials so that insulin was only released into their system when their blood glucose levels were too high. 

In the new field of tissue engineering, researchers are combining the principles of biology with the applications of engineering to create novel biomaterials that could aid in the repair of damaged body tissues -- maybe even replace them! One goal is a type of "medical scaffold" that can attract stem cells and guide their growth into specific types of tissue using biological signals. 

Stem cells are the building blocks of the body. And, in the future, mastery of synthetic tissue engineering could make it possible to regenerate tissues and even entire organs. That's about as personalized as it gets! Even that doesn't cover the full spectrum of what we want medicine to do. 

Sometimes the problem isn't that you're trying to repair or regenerate the body, but rather that you're trying to stop something from spreading or growing in the first place. Cancer is the second leading cause of death worldwide, and it's responsible for millions of deaths every year.

Conventional treatments generally rely on a combination of surgery, radiation, and chemotherapy. Chemo is often the first choice for treating many types of cancer, but it's basically a poison that you hope kills the cancerous cells faster than the healthy ones. It's a similar story with radiation -- it's hard to limit its effects to just the bad cells. 

With conditions like these, a drug delivery system that only gets the treatment generally where it needs to go isn't enough. You need to have a targeted drug delivery and not hurt anything else along the way. This enables you to maximize the positive effect at a specific place in the body with few negative side effects elsewhere. It would also allow you to treat hard-to-reach places while also using smaller doses. 

The idea of this "magic bullet" approach has led to a number of new drug carrier systems. A great example of these are direct local delivery systems, like the skin patch. These patches can slowly release medicine into the body over a period of days. They're commonly used to administer birth control or help smokers with nicotine withdrawal. 

A drug-eluting stent, which is a mesh tube that delivers time-released medicine, can do the same thing from within the body. They're often implanted into patients with coronary artery disease to prevent dangerous blockages. 

Another promising tool is micro particles. They're small enough to travel through the heart as part of the bloodstream, yet big enough that they can't enter capillaries. A number of researchers have taken to this unique property and prepared biodegradable drugs made of things like starch. They can deliver a large dose of chemotherapy directly to a targeted site, a process that's also called chemo-embolization. 

The particles accumulate at designated spots in the body, kind of like a storage depot. As they break down, the drugs release slowly, but continuously into the targeted area. Want to speed up or slow down the release rate of the medicine? Try using a different material -- one that degrades at a different speed -- or design the particles to have bigger or smaller pores. 

But let's say you do want something that can enter the capillaries so that it can keep on circulating through your body. Then nanoparticles are the way to go. Particles around 110-140 nm in size seem to be ideal for most applications because they're large enough to avoid being cleaned out by the liver or kidneys, but small enough not to be attacked by white blood cells. 

The goal is for them to stay in the body's circulation long enough to be removed by the target tissue rather than something like your immune system. This approach might be especially well suited to treat cancer. Since the blood vessels connected to tumors are often quite large, the medicine is less likely to leak into the surrounding tissue, resulting in something called the enhanced permeability and retention, or EPR, effect. 

Basically, you're increasing how much medicine gets to where you want, while reducing it where you don't. Future techniques could be even more accurate. An idea currently being developed is micro bubbles, which are super small bubbles filled with gas. Someday they could hold a chemotherapy drug that would only be released when the bubbles experience the waves of an ultrasound. Te ultrasound would target a specific part of the body and burst only the micro bubbles at the site of the tumor, which would activate the drug only where it's needed most. Targeted carriers like these, along with good disease detection systems and a wealth of drug discoveries, will add up to that promised would of personalized medicine. 

Today we learned about drug discovery and drug delivery. We covered classical and reverse pharmacology, as well as the new field of synthetic biology and what people have been able to accomplish with it. Finally, we saw how important good disease detection is an why we need more targeted drug delivery systems. I'll see you next time, when we'll go one step further and talk about biodevices. 

Crash Course Augmented Reality Poster available now at DFTBA.com.Crash Course engineering is produced in association with PBS Digital Studios, which also produces Global Weirding, a show that explores the intersection among climate, politics, and more, hosted by climate scientist Katharine Hayhoe. Check it out at the link in the description. Crash Course is a Complexly production and this episode was filmed in the Doctor Cheryl C. Kinney Studio with the help of these wonderful people. And our amazing graphics team is Thought Cafe.