Download About Disease Detectives

Overview ..........................................................................................1
What is the Outreach Program? ......................................................1
Concepts...........................................................................................2
Objectives.........................................................................................2
Arizona Science Standards ...............................................................2
College and Career Ready ELA Standards ........................................3
Next Generation Science Standards ................................................3
Learning Progressions ......................................................................4
Brief Background Information .........................................................4
Extended Background Information for Teachers.............................5
Vocabulary .....................................................................................11
Links and References .....................................................................13
6th – 8th grade
Disease Detectives is a 50-minute, facilitator-led outreach
laboratory activity during which students learn about antibodies
and antibody recognition and process a sensor array to determine
the disease a patient may have based on the biosignature defined
on the array.
Pre- and post- activities help prepare for the Disease Detectives
program and also reinforce or extend key concepts of the lab.
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Students discuss and learn about current methods health
professionals use to diagnose disease. They discuss what
molecules are and what is meant by nanotechnology. They learn
that lab-on-a-chip (array) is a type of nanotechnology that can be
used to diagnose diseases in patients by observing the
interactions between antibodies and invaders (antigens), which
behave similar to a lock and key.
Students are given antibody models of various microbes with
different “locks,” which are called surface proteins, on them and
must find the proper “key” (antibody) that fits their specific
microbe model.
They then learn that different microbes have different surface
proteins (locks) on their surface, which can be stuck to a glass
slide (array) to act as sensors, and that doctors can apply a drop of
blood or saliva, filled with antibodies (keys), to the array and
determine if a patient has a particular disease, by searching for
patterns called biosignatures.
Students model this array technology by performing antibody
model activity. They perform a sensor array simulation to
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determine a biosignature and diagnose a disease. They also
discuss how microarrays differ from current diagnostic methods.
Finally, students are shown a real world example of how sensor
arrays are used to study and diagnose Valley Fever and discuss
possible ways sensor arrays may be used in the future.
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Doctors perform many tests but standard methods of diagnosis
are costly in terms of time, dollars and discomfort.
Molecules associated with disease can be measured and can
communicate important information about someone’s health.
Scientists are working at the nanoscale to engineer technologies,
like the “lab on a chip,” for non-invasive measuring of multiple
health indicators at once.
Students may confuse atoms, molecules, and cells.
They are not well-informed about chemical processes and
feedback loops in the body.
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Students will learn about antibodies and antibody recognition
using a model.
Students will process a sensor array to determine the disease a
patient may have based on the biosignature defined on the array.
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Basic Functions (6-8)
Defense
 Specialized cells and the molecules they produce identify and
destroy microbes that get inside the body.
 Thinking about things as systems means looking for how every
part relates to the others. The output from one part of a
system (which can include material, energy, or information)
can become the input to other parts. Such feedback can serve
to control what goes in the system as a whole.
Coordination
 Interactions among the senses, nerves, and brain make
possible the learning that enables human beings to predict,
analyze, and respond to changes in their environment.
Particle Model of Matter
Grades 6 – 8 (one 8-10 week unit at Middle School Level)
 Structure and behavior of Atoms and Molecules (includes
particle concept, movement, and conservation principles).
Nature of matter (Nanoscience literacy)
Across grades 7 – 14
 Structure of matter, periodic table, and ionic forces (i.e.
interatomic forces)
Laboratory experiences in life sciences
Grades 1 – 13
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Patients sure can be subjected to a lot of poking, prodding, and
anxiety waiting for test results to come back. Whew! The Mystery
Disease presented at the beginning of the Disease Detectives
outreach program is notoriously difficult to diagnose using
conventional methods. It is often misdiagnosed.
Wouldn’t it be great if there was a way that doctors could
perform many tests at one time with only a little bit of blood,
urine, saliva, or other body tissue or fluid?
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Many scientists are actually working on such a technology, right
now! They call it a lab-on-a-chip and that is what the Disease
Detectives outreach program will demonstrate. Scientists are
designing chips that have special sensors attached to them. Each
sensor is capable of sticking to a different type of tiny molecule in
the blood, urine, saliva or other body fluids or cells, and tells a
story about someone’s health; even before the story becomes
clear. These chips are called sensor arrays. More about sensor
arrays, later.
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As science progresses, we learn where to look for clues about
health and healing. Before people understood the scientific
causes of disease, they often relied on mythological and practical
remedies to discern the causes and solutions to medical
problems.
For example, in 1792 Dr. Benjamin Rush believed people were
getting sick with Yellow Fever by breathing in something in the air
caused by the filth around Philadelphia. To rid the city of illness,
he believed that lighting bon fires in the streets and pouring
vinegar around the buildings would cleanse the city. Treatments
for Yellow Fever included bloodletting using leaches and mercury
tinctures (now known to be a toxin). At the time, they didn’t know
any better!
Nowadays, we do know better; Yellow Fever is caused by a virus
transmitted by mosquitos. Scientists have developed tes ts and
procedures that doctors can use to assist diagnosis in order to
figure out what might be wrong with patients. We now have
vaccinations to prevent diseases and medications to control them
when people become infected.
Today, there are hundreds of tests that doctors can order to
determine what might be wrong with someone. Physicians have
to act like disease detectives by matching physical symptoms and
patient histories to the proper diagnostic tests that they can
order.
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For example, if someone is having trouble breathing, a doctor will
not order a colonoscopy, but rather listen to their lungs and
heartbeat and perhaps order a chest x-ray or breathing test.
Physicians gather clues after determining the appropriate tests to
perform and then use the clues to link cause and effect. They
track the data over time and consider the data as a whole to make
a diagnosis and prescribe a treatment.
Physician: does not perform diagnostic tests but takes the
samples and receives the results; describes information needed
and then scientists and engineers invent and operate the tests
and instruments to make it possible.
Nurse: collects, labels, prepares samples and sends them to
laboratories for testing; collects and manages data, observations,
and records; provides treatments and medications. A nurse often
carries out the tests required by the physician.
Medical Technologist: Also known as a clinical laboratory
scientist, conducts diagnostic laboratory tests that are important
in detecting, analyzing, and treating a wide variety of diseases and
medical conditions. Microscopes, chemicals, precision tools, and
computer equipment are used by this medical professional to
perform tests that give doctors and patients detailed information
about various conditions, including the progress and prognosis of
the patient.
Scientist: A scientist is a person who is an expert in one of the
sciences: biology, physics, chemistry, history, etc. Scientists study
the world, do experiments, create theories, and write about them
in papers. The research scientists do often help create new forms
of health care to help physicians treat illness/disease.
Engineer: Builders, adventurers and problem solvers. An engineer
uses the forces and materials of nature to help people with
laborsaving devices such as engines and computers. They also
help design and build health-enhancing devices such as artificial
kidneys and heart-lung machines, which help provide tools for
physicians to treat patients.
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Clinical laboratory technician: Highly skilled scientists who
discover the presence or absence of disease and provide data that
helps physicians determine the best treatment for the patient.
Although they are not often personally involved with patients,
laboratory technologists and technicians play a crucial role in the
process of providing personalized care. They generate vitally
important data for identifying and treating cancer, heart disease,
diabetes, and many other health conditions.
Clinical laboratory director: Primary responsibility includes
planning, organizing and directing the overall operation of the
Laboratory Department. Activities included are performance of
chemical, microscopic and bacteriologic tests performed in the
laboratory to obtain data for use in diagnosis and treatment of
diseases. They manage the people, procedures and finances of
the department and make sure that the department following the
regulatory laws, standards and protocols.
There are thousands of tests available for doctors to choose from
and the process of diagnosis can get really complicated, painful,
and costly in terms of time and money. Patients and doctors can
easily become frustrated as more and more tests have to be
ordered, more time passes, and more money is spent as they try
and figure out what is wrong – sometimes, they might not find
anything wrong, and they have to start all over again!
There are a few tests that physicians might order for a patient
who has respiratory signs and symptoms:
1) Complete Blood Count (CBC) abnormalities – A complete
blood count includes a tally of each cell type but is extremely
nonspecific. A blood sample is removed from the patient and
viewed under the microscope. One CBC result could indicate
hundreds of diseases, including a healthy patient mounting a
normal response to an infection. For the mystery disease
described in the Disease Detectives scenario, one would expect to
see an elevated white blood cell count. In particular, the number
of eosinophils, a type of grainy-looking white blood cell, would be
elevated. As a work of the U.S. federal government, this image i s in the public
doma in.
2) Antibody Studies – The body makes antibodies in response to
disease. There are five major types of antibodies whose body
fluid concentrations change over time as a disease progresses.
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Antibodies can be collected from the blood at various time points
and analyzed in the lab. This is a very specific and sensitive blood
test often used in conjunction with other test results to make a
diagnosis. The Mystery Disease causes an elevation in IgM
antibodies during the early phases of infection and, later, an
elevation in IgG antibodies.
In humans and other mammals, IgM antibodies exist linked in
clusters of five. They are the first to be produced during an
immune response to most antigens. Because they are clustered in
groups of five, IgM antibodies work together to crosslink invading
microorganisms; pulling them into clumps that then get eaten up
by other white blood cells called macrophages.
IgG antibodies are singular. They are produced after IgM
antibodies during an immune response. They make up 75% of all
the antibodies in the blood.
3) Imaging (x-rays, MRI, etc.) – Imaging is good for identifying a
general infection or a mass in the lungs. Diagnostically speaking,
imaging is kind of like trying to identify the make of a car from the
top of a skyscraper. It is not very specific and cannot discriminate
the cause of disease. It can only let you know if physical
abnormalities are present. Other tests are required to determine
exactly what is causing them. Ima ge courtesy of Ai dan Jones from Oxford,
UK, http://commons.wikimedia.org/wiki/File:Chest_x-ray.jpg
4) Skin Tests - A unique piece of protein from a disease-causing
organism is purified and injected just beneath the skin. White
blood cells that usually fight body invaders travel to the site and
respond by releasing chemicals that cause swelling at the
injection site. If bumps develop, the patient has either been
exposed to the disease or is currently suffering from infection.
This test is only effective two to twelve weeks following exposure
and has a poor diagnostic value in someone severely ill, but great
for screening individuals not yet showing symptoms (because it’s
cheap). Ima ge courtesy of Nancy, Fl ickr:
http://commons.wikimedia.org/wiki/File:Allergies_-_When_nature_attacks.jpg
5) Lung biopsy – A small needle is inserted through the chest wall
or into the lung through the air passages using a bronchoscope to
collect a small piece of tissue and look at its stained cells under a
microscope. This is a definitive test but not done to diagnose the
Mystery Disease due to patient risk. It is more often performed to
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rule out lung cancer in a patient that has had a nodule discovered
via a screening exam or random chance. Lung bi opsy guided by computer
tomogra phy. Image courtesy of Hellerhoff,
http://commons.wikimedia.org/wiki/File:Biopsie_Lunge_Computertomographie_BC.png
6) Cell Staining – Staining requires a tissue sample (or clump of
cells) from the suspicious site. Different cell parts and types
absorb dyes in different ways. Specially-trained microscopists can
use these differences to discriminate between bacterial or fungal
infections and cancer.* Cel l s have light staining mucus rich cytoplasm a nd
fl a ttened dark s taining nuclei. Image courtesy of Pa tho,
http://commons.wikimedia.org/wiki/File:Chronic_recurrent_cholecystitis,_HE_5.JPG
7) Culture – Culturing cells means growing them in nutrient broth
under conditions that they specifically prefer. This is the “gold
standard” of diagnosis (along with biopsy) but not always helpful,
as the microbes that cause the Mystery Disease grow slowly (~
week) so the value to someone who is acutely ill is low.* Ima ge
courtes y of Pöllö,
http://commons .wikimedia.org/wi ki/File:Columbia_blood_a ga r_pla te_to_tes t_betahem
ol yti c_streptococci.jpg
*These methods are rarely performed because those ill with the
Mystery Disease rarely have a cough that produces excess mucous
containing cells or microbes. Therefore, to get a sample you need
a bronchoscopy and that would only likely be done in a
hospitalized patient that was severely ill.
When things that don’t belong get into your body, like bacteria
and viruses, white blood cells in your blood, called B-cells, identify
these invaders and make unique antibodies against each different
kind. Antibodies that are made against different invaders have
different shapes and chemical features; their shapes match the
shapes present on each invader. The shapes on the surfaces of
invaders and other cells are called antigens.
For example, if I get strep throat and you don’t, then I develop
antibodies against the strep throat bacteria and you don’t. The
strep-throat antibodies in my blood trap invading microorganisms
in large clumps. This makes it easy for other white blood cells,
called macrophages, to eat them.
Antibodies in body fluid:
Ima ge courtes y of http://a s ka bi ol ogi s t.a s u.edu/b -cel l
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A biosignature is any phenomenon (molecule, gene,
characteristic) produced by life that is characteristic of a particular
state. So, a very powerful biosignature is found in peoples’
antibodies. Your body can produce an almost infinite number of
antibodies because every time it experiences something foreign,
antibodies are created and kept around, like memories.
Antibodies also help deactivate invaders by sticking to the
antigens on their surfaces and preventing them from attaching to
body cells.
Your body has other ways of fighting off invaders, too. For
example, fevers are thought to create an unfavorable
environment for the invaders, preventing them from surviving
and/or replicating, and fevers may also help to speed up immune
system functions, so your own disease-fighting players act more
quickly.
In the lab, scientists put pieces of microbial antigen molecules
onto the surface of silicon or glass chips to act as sensors. Since
these pieces are found on their cell surfaces and are very specific
to each type of disease-causing organism, they can be called
disease sensors.
These sensors can capture antibodies out of blood or saliva
samples by sticking to them. After washing off any molecules that
do not stick to the sensors during sample incubation, the captured
antibodies can be made to light up. Since they know what sensors
are located in each position on the array, scientists can catalogue
particular lighted patterns and relate them with specific diseases.
They are still working on what sort of molecules make the best
sensors, like bits of DNA or protein, but they know a lot already.
Here is what a sensor would look like on the surface of a chip if
you could see it up close. There would be a piece from the
bacterium or virus, called an antigen, attached to the surface of
the chip. Then, antibodies that the body made against the
antigen will be present in the blood if the person was exposed to
or infected by the antigen sources. If they are present, the
antibodies will stick to their specific and corresponding sensors
(antigens). Then, a chemical dye is added to light up the
antibodies that stick to the array.
Sl i de i mage courtesy, Arra yit Corp. a nd Dr. Ma rk Schena, copyri ght 2012
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Al l ri ghts reserved, worldwide, www.arrayit.com,
http://www.euro-bionet.net/network/index.php?option=com_content&view=article&id=10&Itemid=60
A picture of the array is then taken and computer software codes
the spots according to how much the chemical dyes light up.
Those spots that have many antibodies stuck to them turn red.
Blue and black spots indicate low or no binding. The other colors
represent intermediate amounts of binding.
Courtes y of Pa phrag, http://commons.wikimedia.org/wiki/File:Microarray2.gif
All communication and chemistry between cells is made possible
when molecules recognize and respond to each other. The “rules”
of the nano-scale define the way that matter sticks together and
behaves. Atoms are attracted to each other based on electric
charge and bind to form molecules. Molecules then stick together
based on electrical charge and three-dimensional shape. When
they match, molecules snap together like magnetic locks and
keys. This is known as molecular recognition.
For example, if an antibody fits an antigen three-dimensionally
and electrically, they will snap together like a key fits only one
lock. Only perfect matches permit a response. Biochemical
matching is exact which is why the body can carry out so many
complex reactions at once and also why nanomedicine has the
power to distinguish between diseases.
Each antibody binds to a specific antigen; similar to a lock and key.
Ima ge courtes y of Fva s concel l os ,
http://en.wi ki pedi a .org/wi ki /Anti body
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Antibody (ˈantiˌbädē/): proteins generally found in the blood that
detect and destroy invaders
Antigen: (ˈantijən/): a harmful substance which enters the body
which causes the body to make antibodies as a response to fight
off disease.
Atom (/ˈatəm/): the basic unit of matter, sometimes described as
building blocks.
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Bacteria (bakˈti(ə)rēə/): the simplest of creatures that are
considered alive. Bacteria are small single cells whose whole
purpose in life is to replicate.
Biosignature (bio|signa¦ture):A naturally occurring molecule,
gene, or characteristic by which a particular pathological or
physiological process, disease, etc. can be identified.
Blood Test (bləd/ test/): a scientific examination of a sample of
blood, typically for the diagnosis of illness or for the detection and
measurement of drugs or other substances.
Contagious (kənˈtājəs/): (of disease) capable of being transmitted
by infection.
Disease (diˈzēz/): an illness that affects a person, animal, or plant :
a condition that prevents the body or mind from working
normally
Lab-on-a-chip: (LOC) is a device that integrates one or several
laboratory functions on a single chip of only millimeters to a few
square centimeters in size. LOCs deal with the handling of
extremely small fluid volumes.
Lung Biopsy (ləNG/ ˈbīˌäpsē/ ): a medical procedure performed to
obtain a small piece of lung tissue for examination under a
microscope
Microarray (/ˈmīkrō-əˌrā/): a collection of microscopic DNA spots
attached to a solid surface. A grid of DNA segments of known
sequence that is used to test and map DNA fragments, antibodies,
or proteins.
Microbe (ˈmīˌkrōb/): very small organisms that cannot be seen by
the human eye ... Bacteria, fungi, and some plants such as algae
are examples of microbes.
Microorganism (ˌmīkrōˈôrgəˌnizəm/): Another word for microbe.
Very small organisms that cannot be seen by the human eye ...
Bacteria, fungi, and some plants such as algae are examples of
microorganisms.
Molecule (/ˈmäləˌkyool/): a group of two or more atoms that stick
together.
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Nanotechnology (ˌnanəˌtekˈnäləjē): the science of working with
atoms and molecules to build devices that are extremely small.
Receptor (/riˈseptər/): specialized proteins in the cell membrane
that take part in communication between the cell and the outside
world.
Sputum Culture (ˈspyootəm/ ˈkəlCHər/): a test to detect and
identify bacteria or fungi that infect the lungs or breathing
passages. Sputum is a thick fluid produced in the lungs and in the
adjacent airways.
Surface Protein (ˈsərfis/ ˈprōˌtē(ə)n/): protein that is embedded
in the layer of cell and is responsible for the way in which a cell
interacts.
Virus (ˈvīrəs/): Viruses are tiny bundles of chemicals covered with
protein. They need to be inside living cells to grow and reproduce.
Some common viruses you are probably familiar with (and may
have even been infected by) are chicken pox, the common cold,
measles, and mumps.
X-Ray (ˈeks ˌrā/): particles of electromagnetic radiation. They are
used to show doctors what is going on inside your body. An x-ray
machine sends out invisible x-ray particles, which pass through
your bones. A computer or special film records this and produces
pictures of what is happening inside you for your doctor to see.
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http://mw.concord.org/modeler/
http://www.youtube.com/watch?v=4f_khh6paJI
http://pbskids.org/dragonflytv/show/selfassembly.html
http://www.ted.com/talks/skylar_tibbits_can_we_make_things_that_make_themselves.html
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