Nanites!

I am a moderate Star Trek fan.  I have never dressed up like Uhura and gone to Comicon or anything, but I’ve seen all the Star Trek movies (most of them since Star Trek V in the theatre) and have watched many of the original TV reruns.  This is mainly because my dad was a huge fan, not able to go on dates on Fridays in the 60’s because he had to be home to watch the show (life was so hard before DVRs).  I never got into any of the TV spin-offs though.  So, when my husband watches The Next Generation (TNG), I refuse to watch it.  It’s not the original.  Cheesy sci-fi in the late-80’s and 90’s just isn’t the same, especially without Shatner.  However, it’s sometimes hard to avoid hearing or seeing some of it in our one bedroom loft.

You might have to squint really hard to see the nanites.

So when my friend Kari sent me an article about how nanoparticles can control blood sugar in diabetics for up to 10 days, I immediately thought of a TNG episode that accidentally seeped into my ear canals (and also guest-stars Dr. Bob Kelso from “Scrubs”).  It was an episode in which nanites, or microscopic robotic devices, could be put into humans and programmed to do medical tasks.  The actual episode storyline revolves around how the tiny computers “evolve” and start attacking the ship.  Eventually the nanites are given their own habitat to live in as autonomous creatures (reason #835 why I can’t watch this show).  But I digress.

Are “nanites” for medical use becoming a reality?

Yes and no.  Actual molecular nanorobots that can perform work inside cells are not a reality yet, but nanoparticles are.  Most nanoparticles used in the medical field utilize coatings that allow drugs or other useful molecules to be transported in the blood stream, targeted to a specific site within the body, or shielded from the immune system to avoid degradation.   Cancer drugs such as Abraxane and Doxil are two examples already in use.  Abraxane is a common cancer drug (paclitaxel) bound to a naturally-occuring blood protein (albumin).  The nanoparticle exploits the feeding system of the tumor, which takes in nutrients normally bound to albumin that are circulating in the bloodstream.  Tumors basically eat themselves to death when Abraxane is present, because they “eat” the albumin…and the drug that is bound to it.  Doxil is another cancer drug (doxorubicin) that is enveloped in a polyethylene glycol-coated liposome (similar to a cell membrane) and is used to treat Kaposi sarcoma, which causes skin tumors.  The coating targets the drug to the skin and the liposome reduces cardiotoxic effects (heart problems) of the drug.  There are many more nanoparticles currently in use, and if you want to read further, Wikipedia has a pretty good article on nanomedicine.

Using nanoparticles for long-lasting blood glucose regulation is a real breakthrough in the treatment of diabetes.  In a normal pancreas, the beta cells transport glucose from the bloodstream into the cell and metabolize it.  The energy and metabolites from glucose metabolism cause a series of events in the cell to release the hormone insulin into the bloodstream.  This mechanism allows the beta cell to sense the blood glucose levels and secrete the correct concentration of insulin in response.  People with type 1 diabetes have lost their beta cells (due to an autoimmune reaction) and can no longer produce insulin.  What makes this new nanoparticle exciting, is that it creates a closed-loop system that releases insulin by “sensing” circulating blood glucose levels, similar to a beta cell.  I have previously posted about an external “bionic” pancreas, which is an open-loop system that consists of an external continuous glucose sensor, an insulin pump, and a glucagon pump.  This type of system relies on electronic automation and accuracy.  Nanoparticles rely on chemistry for glucose sensing and insulin release.

WARNING: this paragraph contains chemistry, read at your own risk.  The nanoparticle that the Anderson lab created consists of insulin, glucose oxidase, and catalase inside an m-dextran matrix surrounded by a chitosan or alginate coating.  Insulin is usually released by the pancreas in response to increased blood glucose levels and the nanoparticle is able to “sense” blood glucose levels with glucose oxidase, an enzyme that converts glucose into gluconic acid.  Gluconic acid decreases the pH of the nanoparticle to degrade the m-dextran sphere and release the insulin.  The chemical reaction of glucose + oxygen + water catalyzed by glucose oxidase not only produces gluconic acid, but also hydrogen peroxide (which is toxic at high levels).  Therefore, catalase is the other enzyme in the particle that converts the hydrogen peroxide back into water and oxygen (to keep the glucose oxidase reaction continuing).  The spheres are coated with positively-charged chitosan or negatively-charged alginate to form an electrostatic network of nanoparticles, or nano-network.  Creating this three-dimensional, porous structure of tiny spheres increases the surface area-to-volume ratio to make the “sensor”, or the interaction between glucose in the blood and glucose oxidase in the nanoparticle, more efficient.

Upper panel: The nanoparticle. Lower left panel: The nano-network. Lower right panel: Insulin release response of the nano-network in a test tube with glucose concentration changes (100 or 400 mg/dL) every 2 hours.
From: Gu, et al. (2013) ACS Nano, 7(5): 4194-4201.

In case you skipped the previous paragraph, what makes this nanoparticle so great, is that it uses chemistry (which is usually infallible) to work.  The nanoparticle is engineered with many layers to encapsulate everything necessary for glucose concentration to be sensed, insulin to be released, and no cytotoxic (cell-killing) byproducts to be created.  And it works pretty well in mice.

Usually people with type 1 diabetes have to inject themselves multiple times a day with insulin.  They must also calculate how much insulin they should inject based on multiple factors: food intake, blood glucose measurements, and physical activity.  In this study, after injecting the 150 microliters of the nano-network into a diabetic mouse, it took 10 days for the nanoparticles to deplete.  Some mice maintained normal blood glucose levels for 15 days.  Two weeks after administration, the glycated albumin ratio (a measure of diabetic control over a few weeks) in mice treated with nanoparticles decreased from 10% to 6% (from a diabetic to a normal range).  If this type of system can be used in humans, it would increase the quality of life for diabetic patients considerably.

The problem with this nano-network system is that it is injected under the skin and sits in a visible lump until the nanoparticles break down and get cleared from the area.  Even though all the materials in the nanoparticle are biocompatible (not harmful to the body), there is local inflammation at the injection site while the lump of nanoparticles are physically there.  This system has yet to be tested in humans, who are much larger than the mice used in this study and may pose different problems.  The authors also don’t mention any experiments with a second injection after 10 days.  Insulin-dependent diabetic patients need to continue their insulin treatment for the rest of their life, so if the nanoparticles or certain components never get completely cleared from the bloodstream or begin building up after multiple injections (the authors do not mention blood pH measurements), then this treatment is not as feasible.

For now, nanoparticles are very promising in many different medical fields.  However, as electronic technology becomes smaller and smaller, nanorobots are not completely out of the question.  There is some really cool science going on in the John Rogers lab at the University of Illinois.  They have created dissolving electronics, stretchable lithium ion batteries, and malleable circuits that could be integrated into the body in the future.  Scientists just need to create electronics that are as reliable as biology and chemistry – and make sure they don’t evolve and take over the ship.

Hotspot to the Rescue

Last week, my friend Lauren asked me to talk to her 5th grade class about my job as a research scientist.  Her class was learning about the scientific method and that not everything may be as it first seems.  When they were asked to draw a scientist, they drew very Einstein-looking men with white, crazy hair.  When the class brainstormed questions to ask me, one of them was, “Do you wear glasses?”  She was able to massage that one into “Do you wear safety glasses?”, but you can see how these kids were thinking.  She wanted to break those stereotypes and show her class that anyone can be a scientist.

Her school is a solid hour away from my lab, so she thought a video chat would be the best idea.  She had never tried to video chat from her classroom before.  She tried Skype, which didn’t work.  She tried Google video chat, which didn’t work.  I tried to Google video chat from my computer on the hospital network, but I couldn’t get it to work on my side either.  It amazes me that in 2012, places where free video-conferencing should be used often (schools, hospitals) are denied access.  I understand that there’s only so much bandwidth available on certain networks (or only so much they want to pay for), but blindly denying access to certain sites makes it very hard to communicate.  There is also the security aspect of video-chatting in schools, but Lauren told me that her public school district restricts internet access much more than her Catholic school did 4 years ago.  (The Catholic school was under the impression that kids are going to go home, go on the internet, and find websites that aren’t appropriate.  Why not teach them how to use it properly at school?)  Nevertheless, teachers should be able to access internet sites they find helpful for their classes, regardless of student access.

I have an Android phone and knew I could connect my computer to video chat via hotspot over my cell network.  Unfortunately, she had an iPhone that couldn’t hotspot.  Apparently you have to pay for such service on iPhones (except maybe some plans on the new iPhone5).  Luckily, her husband’s jailbroken iPhone could hotspot.  So we video-conferenced between a school and a hospital using 2 hotspots and a borrowed phone.

This is what it felt like:

In the end, the connection was successful, if not a little jerky with an intermittent humming sound.  I think the kids enjoyed it (especially seeing the magnetic stirrer in action).

Magnetic stirrer

And it gave me a good feeling inside to think that I may have planted the seed for one of those kids to become a scientist someday.

Or maybe not.

Is That a Pancreas in Your Pocket?

When most people hear the term ‘vital organ,’ the pancreas doesn’t usually pop into their head.  However, the pancreas is vital for survival, keeping your blood sugar in check. That’s why artificial pancreas trials are so exciting.  A majority of Type 1 diabetics are diagnosed as children or teenagers, and must live the rest of their life with insulin injections or insulin pumps, which they control themselves. Having a machine to automatically adjust insulin and glucagon injections based on continuous blood glucose monitoring would make diabetic life much easier.  This is especially important in young children and during times when awareness of low blood sugar is impaired by low blood sugar itself (or during sleep), as the brain needs 6 grams of glucose per hour to function properly.  When blood sugar levels drop too low (hypoglycemia), a person can go into a coma or die because their brain and organs are not getting enough glucose as fuel to survive.

When you eat a meal, carbohydrates and other sugars get broken down or converted into glucose, which circulates through the bloodstream.  The pancreas contains clusters of endocrine cells (cells that secrete hormones into the bloodstream) called Islets of Langerhans.  The majority of cells in the islet are beta cells which secrete insulin and alpha cells which secrete glucagon.  The beta cells sense the glucose concentration in the blood and secrete insulin in response, which travels through the bloodstream to other organs.  The insulin signals to those tissues (such as muscle, liver, and fat) to take up the glucose from the blood into the cell to be used for energy or stored for energy later.  High blood sugar (hyperglycemia) results from lack of beta cells (in the case of Type 1 diabetics) and the tissues ‘starve’ because they are not getting the signal to take up and process glucose from the bloodstream.  The body then tries to remove the glucose from the blood through excess urine production.  This is why poor glycemic control over time can damage the kidney and transplants may be necessary, although hyperglycemia causes many other complications such as microvascular diseases and nerve damage.

Normally, when a person becomes hypoglycemic, glucagon is secreted from pancreatic islet alpha cells, traveling through the bloodstream to the liver.  Glucagon signals to the liver to break down glucose stores (stored in long, branching chains called glycogen) and release glucose into the bloodstream.  If both insulin and glucagon are provided in a regulated manner, blood glucose levels can be adjusted accordingly.

Copyright discoverysedge.mayo.edu

The current insulin pumps provide a basal infusion of insulin to help keep blood glucose levels steady, but they are under the control of the user and must be manually adjusted throughout the day, especially during eating (more insulin) or exercise (less insulin).  Most diabetics prick their finger several times a day to test their blood glucose levels, as continuous blood glucose sensors are not widely used and still need calibrated at least twice a day with finger pricks.  People using insulin must be aware of rapid declines in their blood glucose levels; if their blood sugar drops too low, they must eat or drink high sugar foods or injest glucagon tablets to restore normal glycemia.  It is imperative that artificial pancreas blood glucose sensors are accurate and able to sense downward trends exceedingly well.  If a person starts exercising, muscle tissue is more sensitive to insulin and can even take up glucose independently of insulin because the need for energy (glucose) is greater.  If the sensor cannot perceive the drop in glycemia quickly and accurately; confusion, coma, and death may follow.  Combining better automatic blood glucose sensing with insulin and glucagon infusion in a bionic pancreas is a major step towards creating a better life for diabetics.  Getting the technology reliable enough is the challenge.

Nerd Alert

If you thought science and discovery was only for nerds and PhDs, think again.  Computers and technology have allowed some researchers to collect so many pieces of data, that they cannot possibly sift through it by themselves.  Many times an algorithm cannot replace human recognition and analysis, and requires that the data to be examined piece by piece.  This led some groups to reach out to the public for help.

I was first aware of crowdsourcing, in a different form, several years ago when I downloaded Screensaver Lifesaver.  This screensaver used my computer to scan potential cancer-fighting compound structures while I was not using the computer myself.  The University of Oxford basically built a supercomputer through the networking of 3.5 million personal computers, even ones as crappy as my 16GB, 300mHz Dell desktop.  I was amazed when Amazon introduced Mechanical Turk in 2005, a website where anyone can post a project for others to do, or you can choose to do a project, usually for compensation.  Currently, there are projects that pay up to $17.50 for your time, but many are small tasks that can be done for pennies.  I was tempted to use the Turk to help analyze mitochondrial shapes within cells, but never did actually outsource my graduate work (much to the chagrin of my husband who also never understood why robots weren’t feeding my cell lines for me on the weekends).

Image by NASA/ESA

Most recently, SETI (Search for Extraterrestrial Intelligence) announced that they will begin crowdsourcing the search for life outside of Earth.  Although they have been using the virtual supercomputer screensaver concept since 1999 to hunt for radio frequency signals coming from stars likely to have alien life, they are now reaching out to humans.  They need people to go through this data because there are so many man-made interference signals, their algorithms cannot distinguish the differences as well as a person.  Anyone can sign up and help the search for E.T. at www.setilive.org.

The crowdsourcing model has proven to be effective, as new planets have been identified by arm-chair astronomy enthusiasts searching the public images produced by the NASA Kepler Mission.  The Citizen Science Alliance, which works in collaboration with other organizations, now offers many different projects through Zooniverse, where you can search for new planets, stars, and supernovas.  There are even opportunities to branch outside of astronomy, such as categorizing whale calls to try to decipher the language of our wet mammal brothers.

The possibilities of crowdsourcing seems endless.  I am excited that the power of many can accelerate science and discovery much more than previously possible.  Public participation also increases awareness of scientific research and scientific literacy.  If you are ever sitting at home, bored of watching TV, maybe you should pop open the computer and look at some cool space pictures.  You never know, you could be the one to identify a never-before-seen astronomical anomaly.  Projects like these might just bring out the nerd in all of us.