Student Bio Expo 2014 MOLECULAR MODELING Category Submission Template Before filling out this form, choose the “save as” function to rename this document. Label the document as follows:

Category Abbreviation_School Abbreviation_LastName For example, Lucy Lopez from Eastlake High School submitting a Molecular Modeling project would label her file: MO_MI_Mantchev Designated Category and school abbreviations can be found on the last page of this document. Please read through this form completely before beginning. After completion, use the “save as” function to save this document as a PDF, if possible.

Part I

Cover Sheet

Student Name:

Jessica Mantchev

School:

Mercer Island High School

Teacher Name:

Jamie Cooke

Grade Level:

12

Title of Project:

The Hidden Hazards of Poor Carbon Dioxide Filtration During Surgery

Mentor name, if applicable: Jan Chalupny

I understand that I need to supply any special AV or electrical equipment needed for my project (i.e. CD player, DVD player, laptop computer, extension cord).

Part II

Category Requirements

If you are unfamiliar with any of the elements listed below, please refer back to the Molecular Modeling Category Requirements. They can be found on nwabr.org Research Report Insert a photograph or detailed sketch of your Molecular Model in the grey box below. Images should be in .jpg format and should not be larger than 500 pixels wide (less than 400 kb):

If you need to resize your image, consider using www.pixlr.com. 1. Open pixlr editor (Advanced) 2. Open image from computer 3. From “Image” menu in top left hand corner, choose “Image size”

4. Set width to 500 pixels or less. Make sure you have selected “constrain proportions.” To view actual size, under “View” menu, select “Actual pixels.” This will be the size of the picture in this document. 5. Go to “File” menu and “Save” as high quality jpg. May need to add .jpg extension to title to save correctly on your computer. 6. Then insert the saved image into the grey box above.

Part III

Science Content

Copy and paste your 5-8 page Scientific Background paper in the gray square below: Molecular modeling allows scientists to physically hold and view atoms and molecules that are too small to even imagine. It allows us to hold a single water molecule in our hand when in reality we could only truly hold billions of water molecules. Models provide us a glimpse into this microscopic world that surrounds us. They allow scientists to see the bond angles, whether the molecular is polar or nonpolar, potential isomers, whether the bonds are single, double, or triple, and so much more. Back in the mid-1800s, molecular models were pretty basic: spheres represented the atoms and sticks represented the bonds. Overtime, scientists began assigning colors to each element so today it is universally known that white is hydrogen, red is oxygen, blue is nitrogen, black is carbon, and so forth. In 1860, August Wilhelm von Hofmann created with the first ever physical molecular model of a methane molecule. Notice the inaccuracy of the size of the carbon atom with respect to the hydrogen atoms (Chevalier, 2014). Also notice the inaccuracy of the bond angles of this molecule which should actually be a tetrahedral with 109.5° angles. Unfortunately, these physical molecular models began to seem a bit obsolete and inaccurate, especially after the rapid technological advancements in the 1970s. The scientific community quickly switched over to computer models which were easier to manipulate, easier to build large macromolecules, showed the energies of the molecule like electron density surfaces and electrostatic potential maps, and were much easier to store and duplicate (Hehre, 2007). Computer models, however, are a bit more difficult to assemble because they require mathematical functions and equations involving atomic radii, atomic position, and atomic

distance which are all used to accurately determine the molecular surfaces and the molecular energies (Gosper, 2003). Hundreds of discoveries regarding the structure of viruses, DNA, and vital molecular compounds such as coal and graphite are credited to the evolution of molecular modeling. Physically modeling structures that typically are invisible to the naked eye, allows scientists and doctors to observe patterns and properties that they normally would not be able to. These now-observable characteristics give way to explanations and cures further advancing the scientific, technologic, and medical industries overall helping the general public. Even in today’s ever-advancing, technology-based society there are still problems and conditions that require the aid of molecular modeling to solve. One of these being the negative effects anesthesia coupled with patient monitoring machinery used during surgery can have on the patient. In summary, the anesthesia when mixed with the machinery produces carbon monoxide which then binds exceptionally well to the hemoglobin molecules in red blood cells that should be carrying oxygen, but now carry carbon monoxide instead. This molecular model focuses on the latter part of this process and illustrates using different strength magnets how the bond between the iron molecule in the hemoglobin and the carbon monoxide molecules is far stronger and more stable than the bond between the iron and oxygen molecule. Anesthesia affects the central nervous system of the body. There are two main types of anesthesia: local and general. Local anesthesia works by inhibiting the ion channels on the cell membranes of nerve cells. Information gets relayed from cell to cell when an action potential is generated causing sodium channels on the cell membrane to open which depolarize the cell

(Perkins, 2005). The sodium channels then close and potassium channels open so that the cell can restore its negative charge. When one small area is depolarized, it causes a “domino effect”. The action potential spreads all the way down an axon until it reaches the end where the axon releases a chemical called a neurotransmitter which binds to the receptors on the dendrites of the next neuron. Now, the impulse moves along the second neuron from dendrites to axon and repeats the same process (Campbell, 1999). So when the local anesthesia inhibits these ion channels, mainly the sodium ion channels, the cell never has a chance of depolarizing so the impulse cannot spread through the body. This is exactly why it is called “local” anesthesia. It only numbs a certain part of the body near injection without causing changes in awareness or perception. General anesthesia, on the other hand, gets its name because it causes a general insensibility to pain. Even though there is a loss of awareness with general anesthesia, the patient is still capable of executing vital functions such as breathing and blood pressure. The fact that patients can maintain breathing on their own is extremely important seeing as the most commonly used general anesthetic agents are administered by breathing (Perkins, 2005). Since mainly all general anesthesia is volatile, the anesthesia machines that employ circle systems include carbon dioxide absorbers to remove the carbon dioxide exhaled by the patient. However, these absorbers coupled with the carbon dioxide can generate carbon monoxide which is then inhaled by the patient in the recirculating gas mixture occurring in the anesthesia machine (ECRI Institute, 1998). When these carbon dioxide absorbers do work properly, there are many benefits: rebreathing is made possible thus conserving gases and volatile agents, decreasing pollution in the actual operating room, and most importantly avoiding the hazards of inhaling carbon dioxide. Unfortunately, the strong bases in the absorber – NaOH and KOH – which are required to

activate the soda lime which then absorbs the carbon dioxide have been convincingly implicated in the carbon monoxide problem especially when the absorbent dries out. Fortunately, two possible solutions to this problem have recently arisen. One fix would be to use lithium hydroxide lime instead of soda lime as the absorbent because it does not require the use of strong bases like NaOH and KOH. The absorbent efficiency of the lithium hydroxide lime is similar to the soda lime. The other approach would be to eliminate the strong bases altogether producing an absorbent with similar physical characteristics as the soda lime, but with a lower carbon dioxide absorbent efficiency (Dosch, 2012). Post-operative cognitive decline (POCD) is mostly linked with either increased levels of carbon monoxide due to inefficient filtration of carbon dioxide or due to the long-lasting neurotoxicity of general anesthesia. The key characteristics of POCD are a change in mental status and behavior such as a reduced awareness of the environment and a disturbance in the patient’s attention span. This may be accompanied by hallucinations or cognitive symptoms including disorientation or temporary memory loss. Fortunately, a brain function monitoring device such as the bispectral index (BIS) facilitates anesthetic titration and has been shown to reduce anesthetic exposure which in turn would decrease the severity of the POCD if not totally eliminate it. In conclusion, if BIS-guided anesthesia is practiced, anesthetic exposure is reduced and the risk of POCD is decreased at three months after the surgery whereas it would take six months with no aid from BIS (MT, 2013). Keeping this medical practice in mind, the only option left that can result in POCD is carbon monoxide poisoning. Carbon monoxide (CO) is a notoriously poisonous gas. The reason it can go undetected so easily is because it is an odorless, colorless, and tasteless gas. CO typically results from the incomplete burning of natural gas and any other material containing carbon (OSHA, 2002). In

this case however, the CO is generated when the absorbent in the carbon dioxide scrubbers dries out and becomes highly reactive in the presence of the halogenated agent Desflurane (Suprane) resulting in the production of CO. Other agents such as enflurane and isoflurane have also been reported to produce CO (ECRI Institute, 1998). This CO that then gets recirculated and inhaled by the sedated patient is extremely toxic because it displaces oxygen in the blood and deprives the heart, brain, and other vital organs of oxygen. CO combines with hemoglobin in the blood to form carboxyhemoglobin (HbCO). Since the hemoglobin is already bound to a CO molecule, this prevents hemoglobin from releasing oxygen in tissues, effectively reducing the oxygencarrying capacity of the blood. Carboxyhemoglobin can revert to hemoglobin, but the recovery takes time because the HbCO complex is fairly stable. The affinity between hemoglobin and carbon monoxide is approximately 230 times stronger than the affinity between hemoglobin and oxygen (oxyhemoglobin) so hemoglobin binds to carbon monoxide in preference to oxygen. The human brain is able to detect high levels of carbon dioxide because as more and more carbon dioxide gets dissolved in the blood, the more acidic the blood becomes, and the central chemoreceptors in the brain are able to detect this drop in pH and respond accordingly (Scott, 2013). The same, unfortunately, cannot be said for CO accumulation which is why large amounts of CO can overcome the body within minutes without warning causing a loss of consciousness and suffocation (OSHA, 2002). Since the brain is not able to detect the rising levels of carboxyhemoglobin coupled with the fact that carboxyhemoglobin levels are not monitored during surgery, makes it extraordinarily difficult to identify whether or not a patient is being exposed to CO. Devices that are used to monitor the patient during sedation such as pulse oximeters and blood gas analyzers are not only incapable of detecting the presence of HbCO, but will often detect this molecule as

oxyhemoglobin, thereby giving the doctors present false information. Devices that can distinguish HbCO from oxyhemoglobin require fresh blood samples from the patient and the results can take between 10 to 15 minutes, a very impractical approach seeing as carbon monoxide poisoning can induce suffocation within minutes of exposure (ECRI Institute, 1998). A single red blood cell is filled with millions of hemoglobin (Hb) molecules; located in the cytoplasm of the red blood cells. These hemoglobin molecules are represented as “tubes”, but in reality these tubes are constructed out of over 500 amino acids (Chemistryland, 2013). Hemoglobin is a protein molecule made up of four subunits: two alpha helices and two beta helices. The alpha globin chain is comprised of 141 amino acids and the beta globin chain is comprised of 146 amino acids, but they both share similar secondary and tertiary structures making them appear fairly identical (Davidson College 2005). Each of these subunits surrounds a central heme group. In the center of this heme group is an iron atom which is where oxygen binds and then gets transported. A total of four oxygen molecules can attach to a single hemoglobin molecule seeing as there are four subunits and therefore four hemes. The first oxygen is always the hardest to bind, but the second and third are easier because the hemoglobin molecule changes shape as the first oxygen binds to the iron atom. However, the fourth oxygen molecule is almost as difficult to bind as the first one which gives way to sigmoidal (or logistic) curve (Boundless, 2014). In my own molecular model, I showcased these bonding characteristics by permanently attaching one iron atom to each of the four hemes per hemoglobin molecule (the irons are the

blue colored spherical magnets). I constructed the helices out of wire and dowels, adding one extra dowel to the beta helices because they our bigger than the alpha helices. The beta helices are painted blue and the alpha red. Because the conformation of hemoglobin changes after oxygen or carbon monoxide bonds to the first iron, I left the other 3 irons unattached because I am focusing on the bond strengths and not the change in formation of the hemoglobin molecule. The wire and dowels allow the molecule mobility which is important seeing as the conformation changes after the first iron atom gets attached to either oxygen or CO. The carbon monoxide molecule is made up of one black magnet and one red magnet, respectively, permanently attached together. The oxygen molecule consists of two red magnets permanently attached together. The magnetic attraction between the iron and carbon monoxide molecule is much stronger than the iron and oxygen molecule, which is the exact same relationship of the bond strengths on the molecule level. This is because iron is polar and the oxygen molecule is nonpolar so there is very little attraction between the two, causing there to be a weak bond. On the other hand, iron and carbon monoxide are both polar molecules therefore they form a strong covalent bond fairly similar in strength to an ionic bond due to their strong polarities. The reason that I used magnets is because the oxygen or carbon monoxide molecules can be removed from the iron and reattached, but by using different strength magnets, the viewer can see how much easier it is to attach CO to iron than oxygen and also how much more difficult it is to remove CO from iron than oxygen. This molecule lays down the foundation and showcases the interaction between these atoms on the simplest level possible. This incredibly strong attraction between hemoglobin and CO is extremely deadly and nearly impossible to reverse once begun. Therefore, the solution is not so simple which is why this is an ongoing problem in the medical world. There are some

solutions in the works, but for now the big idea is to constantly renew the carbon dioxide scrubbers before the components dry out. This way there will be no opportunity for the anesthesia to mix with the dried out scrubbers so no CO will be produced or recirculated. Anesthesiologists and surgeons must be constantly aware of this hidden hazard in the hopes that one day, patients will not have to suffer with the repercussions of POCD and CO poisoning due to negligence or faulty equipment.

Part IV

Connections and Collaborations

Insert your Connections and Collaborations Statement in the gray square below. I requested a mentor through the NWABR and got paired up with Jan Chalupny. She is trained in immunology, molecular biology, and cell biology and for the past five years her research has focused on developing treatments for cancer - things that will inhibit the growth of cancer cells or kill cancer cells without damaging normal cells. We have been emailing about once a week or so since the middle of January and she has been a vital resource to me: from editing and giving me critiques on my science background paper, to bouncing ideas around to spur my creativity regarding my molecular model, to even introducing me to a fellow anesthesiologist who is an expert on this matter. Ms. Chalupny reached out to her friend who knows an anesthesiologist named Jannette Hogshire who was able to tell me firsthand about the complications that have arisen when the volatile anesthesia mixes with dried out components of the carbon dioxide scrubber. Hearing this from an actual anesthesiologist was extremely important to me because as I have said before, this is a current problem in the medical world that has many solutions in the workings and is still trying to be solved. My biotechnology teacher Mr. Cooke introduced me to the 3D modeling program Cn3D through the NCBI (National Center for Biotechnology Information) database. Hemoglobin is a fairly large molecule so this website was able to put its

complicated structure into something I could view, play around with, and understand. This software is actually what really helped me execute my model. I wasn’t entirely sure what materials to use at first, but the Cn3D was able to in a way simplify the hemoglobin molecule in a way that I could be able to reproduce something similar to it on my own. It put into perspective the sizes of the alpha and beta helices compared to the hemes and atoms. The way Cn3D portrayed hemoglobin is what inspired me to use dowels and wire, which would provide structure yet mobility at the same time. My teacher Mr. Cooke suggested using either magnets of velcro to showcase the different bond strengths. So in the end, after collaborating with Ms. Chalupny, Ms. Hogshire, Mr. Cooke, the Cn3D software, and many other sources listed in my bibliography, I was able to achieve the final end product of my science paper and hemoglobin molecular model. Part V

Annotated Bibliography

Copy and paste your annotated bibliography in the gray square below: "A Possible Fix for Post-Operative Cognitive Decline." A Possible Fix for Post-Operative Cognitive Decline. 17 Jan. 2014. Web. 26 Nov. 2014. This source covers basically every single aspect of my project except for the molecular modeling part. The source was extremely helpful because it was basically an outline of everything that I need to research. It touched on post-operative cognitive decline (POCD), the carbon dioxide that accumulates in people's bodies due to anesthesia, and a prototype that was developed to remove the carbon dioxide and prevent POCD. It's overall a reliable source because it was published recently - 3 years ago - and it talks about how this prototype will go into clinical trials in 2014 which means that hopefully there's some more information about this prototype now. This source made me ask myself certain questions that pointed me towards the right track for my project.

"Carbon Monoxide Exposures during Inhalation Anesthesia: The Interaction between Halogenated Anesthetic Agents and Carbon Dioxide Absorbents." Carbon Monoxide Exposures during Inhalation Anesthesia: The Interaction between Halogenated Anesthetic Agents and Carbon Dioxide Absorbents. 1 Nov. 1998. Web. 26 Nov. 2014. . This article was extremely helpful in that it described step by step exactly how the accumulation of carbon dioxide in the body occurs during surgery and methods that were unfortunately ineffective in removing the carbon dioxide from the patient's bodies mid-surgery. It talked about the flaws in methods used to remove carbon dioxide, but it also talked about how to avoid these flaws and in the future what modifications should be made to these methods so they are more effective. It was a great source in that it made this complicated topic easy to read about and easy to understand. It was also very descriptive so it was able to paint a picture about what's going on in the body during this carbon dioxide accumulation and how exactly it is a problem. This source answered all of my questions regarding this subtopic of my project. Chevalier, Fanny. "1865 – Hofmann’s Croquet Ball Models." List of Physical Visualizations. 28 Nov. 2014. Web. 10 Dec. 2014. . This website provided me with specific facts regarding the first ever molecular model created by August Hofmann in 1860. This information provided a great transition into why physical molecules are inferior to and inaccurate compared to computer models which are mainly used today. Gosper, Jeffrey. "Introduction to Molecular Modelling." Molecular Modelling. St. Edwards University. 7 Apr. 2003. Web. 24 Nov. 2014. .

This website covers the history of molecular modeling by showing the transition from physical to computer generated models. It also describes and gives examples of the advantages and applications of molecular modeling. The information is pretty basic and straightforward which is good because it gives me a solid base for this general topic of molecular modeling. Overall, it was pretty helpful, but I'm definitely going to have to find another source that will be more descriptive and less general. I didn't like that this source went really in depth on Computer Aided Molecular Design (CAMD) because that doesn't really apply to my project. Hehre, Warren, and Alan Shusterman. "Molecular Modeling In Undergraduate Chemistry Education." 1 Jan. 2007. Web. 18 Dec. 2014. . This article was extremely useful because it really gave me the basis of molecular modeling I needed to start on my science background paper. My other source on molecular modeling was very specific so it was helpful to have a broad, simple overview on such a complex matter. Luebbehusen, Michael. "Technology Today: Bispectral Index Monitoring." Modern Medicine. 1 Jan. 2005. Web. 26 Nov. 2014. . One of my other sources mentions a bispectral index and I was curious as to what that is and how exactly it helps decrease post-operative cognitive decline. A bispectral index (BIS) only measures how sedated a patient is so it prevents POCD by preventing over-sedation. BIS does not directly remove carbon dioxide from the body. This article was written about nine years ago so it was interesting to me to see the progression scientists and doctors have made with anesthesia and preventing POCD. BIS is safe way to monitor the anesthesia, but today

doctors are working on a way to remove all carbon dioxide from the body regardless of the amount of anesthesia intake. This was a very helpful source in that it answered all of my questions about the BIS and also showed me the history of anesthesia monitoring technology. MT, Chan. "BIS Guided Anesthesia Decreases Postoperative Delirium and Cognitive Decline." National Center for Biotechnology Information. U.S. National Library of Medicine, 1 Jan. 2013. Web. 21 Nov. 2014. . This source was extremely helpful because it was an actual experiment conducted that proved that general anesthesia can result in postoperative cognitive decline, but by titrating the anesthesia first you eliminate some of risk of this happening. However, it does show that this method is not 100% effective showing the need for improvements to make general anesthesia safe for all. This is a very reliable source because it was conducted by very prestigious institutions and hospitals and the conclusion is entirely backed up by actual data. Perkins, Bill. "How Does Anesthesia Work?" Scientific American 7 Feb. 2005. Print. This was a very helpful article because it made the concept of anesthesia and how it works very easy to understand. It was great at explaining why local anesthesia works, but unfortunately not so much regarding general anesthesia. It gave me many hypotheses as to how it works but at the same time it informed me that scientists don't really truly understand its workings yet either. Sheridan, Mark, and Neil A. Campbell. Instructor's Guide for Biology, Campbell, Reece, Mitchell, Fifth Edition. San Francisco, Calif.: Benjamin/Cummings Pub., 1999. Print. This is a fantastic textbook. It explains the entire central nervous system and then dives into specific and very detailed information on all of the workings of the nervous system: nerve cells,

axons, action potentials, etc. It was extremely helpful and very informative even though it was a bit difficult to understand the first time through. OSHA. "Carbon Monoxide Poisoning Fact Sheet." Carbon Monoxide Poisoning. Washington, D.C.: U.S. Dept. of Labor, Occupational Safety and Health Administration, 2002. Print. This was a short, informatory book written by OSHA (Occupational Safety and Health Administration) that gave m the basic facts behind carbon monoxide and how dangerous carbon monoxide poisoning can be. Only two pages out of the book were useful for me and it was written over ten years ago which makes it a bit outdated, but the basic facts were still relevant and it gave me a solid background on the gas carbon monoxide. "How Your Body Detects When It's Low On or Has Too Much Oxygen." Today I Found Out RSS. Vacca Foeda Media, 30 May 2013. Web. 14 Jan. 2015. . This website gave me a thorough description of how your brain can detect the levels of carbon dioxide and also that the brain is unable to detect the levels of oxygen or carbon monoxide which is why carbon monoxide poisoning can go so easily unnoticed. "Air We Breathe: Air Composition." Air We Breathe: Air Composition. 4 Mar. 2013. Web. 15 Jan. 2015. . This website helped me begin my sketch for my actual molecular model. It described in detail the hemoglobin molecule and all of the 500 amino acids the make it up and the "heme" part of the molecule which is where either oxygen, carbon dioxide, or carbon monoxide attach to an iron atom. There was also an extremely helpful picture which I will add in my

essay to help my readers visualize. Boundless. “Transport of Oxygen in the Blood.” Boundless Biology. Boundless, 14 Nov. 2014. Retrieved 22 Jan. 2015 This website explained to me more about the hemoglobin and how it changes shape when oxygen binds to it and the transport of oxygen through the blood. It was very similar to another resource I am using, but it’s helpful to hear the same information in a different way so I can understand it better. Dosch, Michael. "Carbon Dioxide Absorption." Anesthesia Gas Machine-. University of Detroit, 1 July 2012. Web. 22 Jan. 2015. . This website was recommended to me by Janette Hogshire who is an anesthesiologist herself. It gives a thorough description of the compounds that go in to making a carbon dioxide absorber and also describes the pros and cons of using one of these devices during surgery. It was overall very helpful, but it is written in very technical, scientific terms making it difficult to understand. Biswal, BK. "Deoxy Hemoglobin (90% Humidity)." NCBI. U.S. National Library of Medicine, 1 Jan. 2002. Web. 9 Feb. 2015. . This website allowed me to view the deoxy hemoglobin 3-dimensionally from many different angles. I will use this pre-made 3D molecule as the basis of my molecular model by 3D printing it and then I will attach the oxygen to one and the carbon monoxide to the other using magnets to show the differing strengths of the bonds.

Davidson. (2005, June 23). Hemoglobin. Retrieved March 19, 2015. This website was created as an undergraduate project by a student at Davidson College making it a fairly reliable source. The pictures provided were extremely useful in helping me visualize the alpha and beta helices of the hemoglobin molecule and it also explained those helices in very deep detail. Most of the other information it provided was not very useful to my topic, but it was still extremely interesting to read and learn about. Part VI

Any Additional Information (optional)

If there is anything else you would like to include with your project, describe it or insert it in the gray square:

After completion, use the “save as” function to save this document as a PDF, if possible.

Project Labeling Information

The electronic submission form should be labeled the following way:

2-Letter Category Abbreviation_2-Letter School Abbreviation_LastName For example, Lucy Lopez from Eastlake High School submitting a Multimedia project would label her file: ML_EL_Lopez

CODES: Category Art Career Pathways Creative Writing Drama & Dance Journalism Lab Research Molecular Modeling Multimedia Music SeaVuria SMART Team

Category Abbreviation AR CP CW DD JN LR MO ML MU SV SM

Teaching Website

TE WB

School

School Abbreviation AL BA CL CH EL EC FO HMJ IH JU LY ME RO RC SH SN WFW WO

Attic School Ballard HS Cleveland HS The Chrysalis Eastlake HS Eastside Catholic Foster High School HM Jackson Ingraham HS Juanita HS Lynnwood HS Meadowdale HS Roosevelt HS Royal City Shorecrest HS Snohomish HS WF West Chehalis Woodinville HS