Stem cell transplant

This week in class, we did a long game together about stem cell transplantation.  The procedure is also called bone marrow transplantation, because it is the stem cells that normally live in the bone marrow that are transplanted from one person to another.

First, we went over what medical problem would lead to this procedure -- leukemia, which is cancer of the white blood cells.  Normally, white blood cells are part of our immune system, so they protect us from infections.  In leukemia, some type of white blood cell is reproducing out of control and often isn't performing its protective job.  You can see under the microscope that there are way too many of a certain type of cell.  The symptoms of leukemia include fatigue (tiredness), bruising, bleeding, pallor (Pale skin), enlarged organs, and infections.  When a patient first has leukemia, they are usually treated with chemotherapy, which is drug treatments that are supposed to kill off the cancer cells.

Side effects of chemotherapy include losing your hair, because the drugs kill off cells in our body that are dividing and reproducing rapidly.  Hair follicle cells divide frequently, so the cancer drugs kill those cells, resulting in hair loss.  People also get mouth ulcers, fell nauseous and have diarrhea, as well as changes in their blood from chemotherapy.  Our patients in the game had done chemotherapy first and their disease went into remission.  That means their symptoms went away and it seemed like the cancer was gone.  But somehow a cancer cell must have been missed and the leukemia came back.  That's called a relapse, and it means a new treatment is needed.  That's why they might have a stem cell transplant.

The idea is that to get rid of the cancer of the blood cells, you can try killing off all of the patient's bone marrow stem cells (where the cancer cells are living and hiding out), which are the cells that make the blood cells.  Then, you transplant stem cells from someone who doesn't have leukemia, and the patient can then grow a whole new immune system that doesn't have cancer.  It's VERY risky, and that's why chemotherapy is always first.  Only if chemotherapy doesn't work do they try this procedure.  Here are the main risks of the stem cell transplant procedure:

• The drugs they use to kill off the cancer and the patient's bone marrow cells could make the patient extremely sick
• When the patient has no bone marrow stem cells, they have no immune system, so any little infection could kill them
• They could reject the new cells and be left with no immune system, which is very dangerous
• The new immune system could reject them, and attack their healthy cells.  This is called Graft Versus Host Disease, and it's dangerous and uncomfortable.

We walked through all the steps involved in the procedure.  The first thing to do is to confirm that that patient's cancer has returned.  We looked at slides of the patients' blood to see if there are cancer cells in the blood.  The larger cells in these pictures were the cancer cells.  Both of our patients had cancer cells in their blood, and that's how it was decided that they needed a stem cell transplant.



 Next, we actually learned a bit about our patients, Wendy and Michael.  Wendy, our first patient, is a high school student who developed leukemia her freshman year and got better with chemotherapy.  But a year later, the cancer is back.  She has read all the information about the procedure and understands all the risks.  She wants to know if everything will be done in time for her to go to her junior prom.  The doctor says she'll do everything she can to have Wendy well in the next six months, so she can go to the dance.

The next step is to find a donor -- a person who is willing to give their bone marrow stem cells to the patient.  The first thing we do is check full siblings, then close relatives, and then a list of people willing to donate their bone marrow (the registry).  There are 8 million registered donors, but most of them are caucasian (white).  So Wendy's chance is 66% of finding a donor.  Unfortunately, an African American has less than a 25% chance of finding a donor, and a Hispanic/Latino patient has about a 5% chance.
What you're looking for in choosing a donor is something called HLA, Human Leukocyte Antigen.

People have 6 markers on our cells that tell the immune system whether the cells are foreign or part of our own bodies.  It needs to be a pretty good match to avoid the graft attacking the patient's own body because it thinks the cells are foreign.  We looked at all 6 HLAs for Wendy and her two sisters, hoping that one is at least a match for 5 out of 6.  In fact, her sister Hillary is a match for 5/6 and her sister Maggie is a match for all 6, so Maggie is the best donor.

Conditioning is the procedure of using drugs and radiation to kill off the leukemia and the bone marrow stem cells.  Wendy has to stay in the hospital with special air flow conditions to keep germs and bacteria away from her while she has no immune system.  At the right time, Maggie is given drugs that make the bone marrow stem cells go into the blood, and then her blood is collected to gather the stem cells to transplant.

The cells are put into Wendy's body through her central line, right into her blood.  She stays in the protective area in the hospital, and the doctors keep checking her blood to see when she has enough of an immune system to go home.  We counted neutrophils on this slide to see if she has at least 500 neutrophils per microliter.  She did, so now she can go home, if her temperature and blood pressure are ok.  She has a fever, so she has to stay in the hospital until it's gone.  3 days later, she's fine and can go home.  3 weeks later, her transplant still seems to be ok, but she has a rash all over, diarrhea, and is swollen.  It's Graft Versus Host Disease, her new immune system is attacking various parts of her body.  She has to come back into the hospital and go onto steroids, which reduce the swelling and diarrhea, but she still has some symptoms.  They decide to do an experimental procedure that might help with her symptoms.  They don't know that it will work, don't know what side effects might happen, and it might cause an allergic reaction or some other problem.  She decides to try the experimental therapy, and it works.  I pointed out that this part is not necessarily realistic.  Experimental treatments do not always work.  In fact, most of the time they don't work, but it's important to try them because that helps us learn more so we can find treatments that do work.
We moved on to the next patient, Michael, who has the same disease but a different situation.  He is an older, African American gentleman, and he cannot find a suitable donor.  So, he has a cord blood stem cell transplant, which is when they take stem cells from the umbilical cord of a newborn baby that have been stored and use them for the transplant.  It often takes longer for the new immune system to start working.  I encourage you to explore this part of the game.

Blood Typing

This week, we learned about how blood types work.  This follows our genetics unit because blood types are determined by your DNA.  There are three possible versions of the blood type gene you could get:  A, B, or i.  Each person gets one from their mother and one from their father, and the combination you get determines your blood type.  Here's a chart to illustrate:

Got from mother	Got from father	Blood Type	Notice
A	A	A
A	i	A	A is dominant over i
B	B	B
B	i	B	B is dominant over i
A	B	AB	No dominance A or B
i	i	O	i is recessive

So, if you have one parent who is type A and one who is type B, it would be possible to get any of the blood types (A, B, AB, or O) if both parents are carrying the i gene (which is recessive).  But if one parent is type AB and the other is type O, then the children could only be type A (carrying the recessive i) or type B (also carrying the recessive i).  And if both parents are type O, then all children will be type O.    As this image shows, A is an antigen like a horn or flag on the blood cell, and so is B.  Blood type O means there are no antigens on the cell surface for antibodies to recognize.  When you mix antibodies to A with type A blood or type AB blood, it clumps together, but if you mix antibodies to A with type O blood, nothing happens.  

Then, there is the Rh factor, which is a dominant gene.  If you have one or two copies of it, then you are Rh+.  And if you mix antibodies to the Rh factor with blood that is Rh+, it will clump together.  A person who is negative for Rh factor cannot receive blood from a person who is positive for it.  But a person who is positive can receive either Rh+ or Rh- blood.  As we described it in class, you get freaked out if you see an antigen you don't normally see (like an A, a B, or the Rh factor).  That is incompatible and could kill the person.  But if you normally see an antigen (A, B, Rh factor or all of them), you don't have a problem receiving blood without it.
To illustrate, we first played the Nobel Prize website blood typing game (the discovery of blood types has saved millions of lives and earned a Nobel Prize).  

 First, you need to determine the emergency room patient's blood type.  To do this, there are three tubes:  one with an antibody for A, one with an antibody for B, and one with an antibody for Rh factor.  You add the patient's blood to each tube and see what happens.  Either the blood reacts with the antibody, forming a clump in the bottom of the tube, or it doesn't react and the tube remains red throughout the liquid.  From these results, you know the patient's blood type.  If all three react, the blood type is AB+, if none react, it's O-, if the first and third react, it's A+, and so on.  Now that you know the blood type, you can determine which blood bags you could give the patient without endangering them.  

Choosing which blood types the patient could safely receive

As we learned, you can't give a patient blood that has an antigen their blood doesn't have.  They can always receive their own exact blood type, and any type that has fewer antigens than theirs has.  So our A+ patient can receive A+, A-, O+, and O-.  In fact, the reason you hear in movies and tv shows, "Two units of O negative, STAT!" is because everyone in the world can receive O negative blood.  It has no antigens, so you don't need to take the time to check someone's blood type to know that you can transfuse it in.  O negative blood type is called the "universal donor" for that reason -- they can donate their blood to anyone.  However, people with O negative blood cannot safely receive blood from any blood type other than their own -- O negative.  Since their blood has no antigens, their immune system will "freak out" if it sees any antigens on blood that is transfused, and the reaction could be dangerous.  People with AB+ blood, on the other hand, can receive anyone else's blood (A, B, AB or O, Rh + or Rh -).  They are called the "universal recipient" because their blood has all the common antigens so all the different blood types are safe to transfuse into them.  But their blood can only be given to AB+ patients.

Next, we played the American Red Cross blood typing game.  You have one person at the bottom, the transfusion recipient, and you have five people above to choose from who could be the donor.  You need to remember the same basic rules of blood compatibility to correctly choose whose blood could be transfused.  What threw us off a little was that sometimes there wasn't a match -- none of the donors on the screen could safely give blood to the recipient.  It was a little nerve-wracking.  

Finally, we each made a chart of the matching blood types for transfusion, essentially the same as this chart below.  

DNA -- the secret code!

Since last class was focused on genetics, I decided this week's class would be about the secret code in genetics -- DNA!  DNA is the blueprint for an organism.  My DNA contains the instructions for making a complete copy of me, and there is one blueprint inside each of my billions of cells (with a few exceptions).  We talked about how exactly cells use their blueprints, using students in the class.

Aaron was the DNA in the cell, so he was located in the nucleus and is the information that is needed to make proteins.  Jakob was the RNA, specifically the messenger RNA, or mRNA, and he is a transcription of the message for a protein.  Inside the nucleus, the DNA gets copied carefully into RNA, which then travels to the ribosome to be translated.  In the ribosome, the RNA, which was Jakob gets made into the protein that is needed, which was Jaedan.  This is called the central dogma (that DNA is transcribed into RNA, which is then translated into protein).

Our games this week focused on the codes that are used for this.  DNA is a code that is made of only four different bases.  We name them using four letters -- A, C, G, and T.  In the first game, DNA workshop, we saw that the structure of DNA is a double helix, and for replicating DNA, first the DNA is unzipped, then the complementary (matching) bases get added on until there are two strands of DNA instead of one. There is a pattern for matching -- A always matches with T and C always matches with G.  For the "Protein Synthesis" part of the game, we saw that first the DNA is unzipped and RNA is made.  RNA uses the same bases as DNA except that instead of T, there is a U.  From the RNA, proteins are made, which are chains of amino acids.  For every three RNA bases, it specifies one amino acid.

We then played the Nobel Prize DNA game, which also had us matching up the base pairs of a DNA double helix.  From this game, we also learned about how much DNA various organisms have.  Humans have 23 pairs of chromosomes, a total of 46 chromosomes, and about 3 billion bases that are a secret code for about 34,000 genes.  Mice have about 22,000 genes, and about 80% of our genes have a matching mouse gene.  We're really not that different from mice, which is why we study them so much!  Students also seemed surprised to learn that yeast is a living organism, and it has plenty of DNA too -- 16 chromosomes.  Two organisms we talked about were the malaria mosquito and the malaria parasite.  The parasite lives in the blood of people who have malaria, and when mosquitoes bite them, they get the parasite and then pass it on to the next person they bite.  This is how malaria spreads.

Lastly, we played the Ribosome Game, in which we take the RNA code, which was copied from the DNA code, and make it into proteins.  You have to remember that A goes with U (in RNA) and C goes with G.  Then we group them into sets of three and find out what amino acids are represented by the code.  We made a short polypeptide chain.

Mendelian Genetics -- Pea plants, Crazy Plant Shops, Lemmings, and Dragons!

This week, we went further into genetics, using several games.

This game was a second game about Mendel's pea experiments.

We looked at seven traits that Gregor Mendel observed in his pea plants, and did breedings of various plants to see what happened.  Mendel was the Swiss monk whose experiments with pea plants formed the foundation of genetics.  Genetics is the study of how traits and diseases are passed from one generation to the next.

We discussed the difference between a trait that can be inherited and a disease that can be inherited.  A trait is a characteristic of an individual that we can notice (like Aaron O.'s ginger colored hair), is caused by something in his DNA, but doesn't appear to cause death, disease, or other harm (such as an enzyme not being able to function normally).  An inherited disease is when something in your DNA, often just in one gene (specific part of your DNA) is different in a way that causes a disease, usually because a protein doesn't work properly.

An example we talked about was sickle cell anemia.

There is a gene that for some people doesn't work properly because it has a mutation (a change in the DNA compared to most other people).  People who have the mutation have blood cells that don't quite look normal, they are squished and shaped like a sickle.  This makes it so their blood doesn't carry oxygen as well, and sometimes the people with this disease have episodes where they have to be hospitalized.  This disease is more common in certain parts of Africa than it
is here, specifically in areas where malaria is common.

We all have two copies of every gene, one from our mother and one from our father.  People who have sickle cell anemia got two copies of the mutated gene, and that's why they're sick.  People who have one copy of the mutated gene and one normal gene don't have the disease and are called carriers (because they carry the mutated gene).  What researchers have discovered is that carriers of sickle cell anemia are protected from malaria.  They get much less sick from malaria than people with normal red blood cells.  They think that's why the mutated gene (which can cause sickle cell anemia) is common in parts of Africa.

Next, we moved onto a game called Crazy Plant Shop,

and you can play the free version even though it's part of a paid service called BrainPop.  In the game, you own a plant shop, and Gregor Mendel talks you through buying plants from a catalog, breeeding them together to get the plants that people order, and then fulfilling the orders.  You get new plants and traits and see how Punnett squares work.  We could see from the Punnett squares what the chances were of getting the plants we wanted, and could choose to let probability decide or use our machine to get what we wanted for sure.  We saw that even when the chances were 75% for getting the one we wanted, sometimes we didn't get it.

Then, we looked at a game called Phylo, which is a game

that uses the players to further scientific research.  Humans are actually better at recognizing patterns than computers, so the computers take DNA sequences from different species and turn them into sets of colored boxes for us humans to line up.  When we line up all the colored boxes so they match as best we can figure, we have helped come up with information about how the different species are related for the particular gene.  We could see that work is being done with several important cancer genes, and playing the game generates valuable scientific data that is actually used!

Lastly, we played a genetic game about lemmings, to
better understand Punnett squares.  In this game, we looked at the gene for albinism, which is a lack of pigment (coloration) in the hair, eyes, and skin.  It is a recessive gene, which means it could hide out.  An animal could have one normal gene and one albinism gene, and they would look normal.  Two animals with the recessive albinism gene would look normal but could have an albino baby.  We saw that when looking at genetic crosses, we name a gene with a letter, and the capital letter is the dominant form while the lowercase letter is the recessive form.  Albino animals are called "aa" because albinism is recessive.  Animals that are "AA" or "Aa" are not albino, they have normal pigmentation.  In the game, we had to figure out how to breed a lemming baby that had albinism and also a long tail.  We could use Punnett squares to check for each pair of lemmings what the possible babies were and what the chances were for getting each baby.  Finally, we got a long-tailed albino baby lemming.  Then they all jumped off a cliff!

The Cell Cycle, Cloning, and Plant Genetics

In this class, we started by playing the homework computer game together.  It was a game from NobelPrize.org (an excellent site for games about Nobel prize discoveries) about the cell cycle.

Most importantly,
1.  Cells use the cell cycle to reproduce
2.  The cell cycle is very well controlled.  Cells are not allowed to reproduce if they can't pass through the checkpoints.
3.  When something goes wrong and cells can reproduce out of control, that is called cancer.
4.  There are several steps of the cycle:  growth, synthesis, growth, separation, division

Here is the link to the game we played.

We read through everything together, and learned these facts (and more):

• Cells in our bodies are going through the cell cycle, reproducing themselves, every second
• Skin cells and blood cells are dividing all the time, but other cell types, like liver cells and brain cells, do not divide very often.  
• In order to divide, a cell needs to receive a signal that it's ok to proceed.  Sometimes this signal is the death of a nearby cell.
• Once the cell has received the signal, it grows by 20%, which is called the Gap 1 phase.
• Then it reaches Checkpoint 1, where the cell is checked to confirm that it has grown enough and that its DNA (the blueprint for creating the entire organism) is not damaged.
• If it passes the checkpoint, it goes into Synthesis phase, where it duplicates its DNA
• Note:  each cell needs to have exactly the right amount of DNA, which in humans and most other organisms is two complete copies of every chromosome.  Any more or less could be disaster for the organism.
• Plants, however, often have 4 or even 8 copies of each chromosome, and end up being larger.
• Humans who have one extra chromosome 21 (a small chromosome without many genes on it) have Down syndrome.  Humans who have an extra X chromosome are ok because every cell inactivates one copy of the chromosome, and humans who have an extra Y chromosome are ok because there are not many genes on it.  But an extra copy of any other chromosome usually leads to death before birth and is a very severe problem.  
• So it is essential for cells to make sure they have exactly the right amount of DNA before they start duplicating it, and they need to make sure they copy it perfectly.
• We have enzymes whose job is to proofread the DNA.
• Once the DNA has been duplicated, the cell needs to grow again, so it enters Gap 2 phase.
  
• Then is Checkpoint 2, when the cell is checked to confirm that it has made enough DNA, that there are no DNA errors, and that the cell has grown large enough.
• If damaged DNA is detected, the cell can either repair the damage, or the cell can commit suicide.
• If it passes this checkpoint, then the chromosomes all line up in the center of the cell, attach to spindles, and separate apart so that each half of the cell has one complete set of chromosomes.
• Checkpoint 3 is to make sure that each chromosome is attached to spindles.  
• If it passes, then the cell can divide and there are now 2 cells, identical to the first.

The next game we played illustrated exactly how to clone a mouse using a procedure called Somatic Cell Nuclear Transfer.

• The idea is to create a genetic clone of Mimi, a brown mouse.
• First, we discussed the difference between clones, siblings, and identical twins.
  
• To clone Mimi, we will take a body cell (somatic cell) from Mimi, probably a skin cell, an egg cell from Megdo (a brown mouse), and have Momi be the surrogate mother (a white mouse who will let the embryo grow into a baby mouse in her womb.
• We will know if it worked by the color of the baby mouse.
• The steps are:

1. Take the somatic cell from Mimi and a fertilized egg from Megdo.
2. Remove the nucleus from the fertilized egg. (this is called enucleation)
3. Transfer the nucleus from the somatic cell into the enucleated egg.
4. Wait a little while for the nucleus to adjust to its new home, then add a chemical to tell the cell to begin dividing so it can create an embryo.
5. Put the embryo into the surrogate mouse (Momi).
6. After 19 days, the baby mouse will be born -- what color will it be (if the procedure worked)?

I mis-spoke to the class by telling them that there is currently an international ban on human cloning and research focused on cloning humans.  This is controversial, and only a few countries actually have a ban.  The United States does not have a ban on human cloning.

Lastly, we began a game focused on plant genetics.  It started with an introduction to what Gregor Mendel did.  We saw that with his pea plants he was able to observe a pattern in how characteristics showed up in baby plants when he chose who the parents would be.

The traits (characteristics) we worked with were:

• pea color -- green or yellow
• flower color -- pink or white
• stem length -- long or short

There were many other traits he looked at, and most of them had two possible versions (like green or yellow peas, as described above).  By observing what happened, Mendel figured out that each plant has two copies of a gene, which is the part of the DNA that determines that particular trait.  They get one copy from the mom and one copy from the dad.  One version always seems to "win" over the other, so that if a plant has one copy of the green pea gene and one copy of the yellow pea gene, their peas are not greenish yellow, but instead are yellow.  The green pea gene is "hiding" within the plant.

Our job in the game was to try to create plants with a specific set of target characteristics, as quickly as possible.  You can see both what the plants look like and what their genes are.  Try it out, and see how far you get!!!

Science Fields and Cell Biology

This class started with an activity I had planned for the previous class but we ran out of time.  We talked about the many fields of science and basically who studies what.  Here is a page that summarizes a few science fields we discussed.

We played a quiz show about these types of scientists:

1.  Biologist -- studies life

2.  Physicist -- studies matter, its movement and properties

3.  Astronomer -- studies outer space and what's out there

4.  Geologist -- studies the earth, including volcanoes and rocks

5.  Archaeologist -- studies ancient humans and what they did

6.  Botanist -- studies plants

7.  Meteorologist -- studies the weather

8.  Chemist -- studies chemicals and how they interact and change

9.  Ecologist -- studies systems of living things and non-living things

10.  Psychologist -- studies the human mind and how people think, behave, and perceive

11.  Sociologist -- studies groups of people and what they do as small or large groups, including government

12.  Entomologist -- studies insects (bugs)

13.  Limnologist -- studies freshwater bodies, like lakes, rivers, and streams

14.  Zoologist -- studies animals

15.  Anthropologist -- studies humans and human ancestors

16.  Paleontologist -- studies ancient life forms and fossils, including dinosaurs

17.  Cosmologist -- studies how the universe began

18.  Oceanographer -- studies the oceans

Then, we moved on to cell biology.  We are made of cells, and there are organisms such as bacteria that are just one cell.  We discussed the parts of a cell:

Plasma membrane - like skin, keeps insides in

Cytoplasm -- like jelly, everything floats in it

Nucleus -- contains DNA, the blueprint for the organism

Endoplasmic reticulum -- near the nucleus, when new proteins get made

Golgi -- holds and packages new proteins

Ribosome -- makes new proteins by reading the blueprint

Lysosome -- like a garbage can, breaks down waste

Mitochondria -- powerhouse, makes ATP energy for the cell from sugar

Vacuole -- only in plant cells, empty space that holds water

Cell wall -- only in plant cells, rigid wall around the cell

Nucleolus -- inside the nucleus, contains the DNA

The games we played were:

1.  Cell Craft, an excellent free game that teaches cell biology by having you navigate as a cell and collect what you need.

2.  Cell Explorer, another good game about cell organelles.  Both of these can take a little while to load at first.

Here are two sites with games for testing cell biology knowledge:

Biology Junction
The Biological Cell

I encourage kids who like the topic and want to learn more to try these quizzes.

First class

For the first week, we learned about the scientific method.  The steps we discussed were:

• Observe Something That Interests You
• Ask a Question
• Do Background Research
• Construct a Hypothesis
• Test Your Hypothesis by Doing an Experiment
• Analyze Your Data and Draw a Conclusion
• Communicate Your Results

The games we played about the scientific method were:

1. A detective game that had two parts.  Here is the page describing the scientific method and how this game demonstrates it.
1. Here is the first detective game.
2. Here is the second detective game.
3. These games showed that when you weren't sure what was going on, you observed the room, asked a question like "should I press this button?", had a guess about what might happen, tried it, noticed what happened or didn't happen, and made a conclusion about what was going on.  That's the scientific method, and we use it all the time in our daily lives.
2. A more advanced scientific method game (involves a lot of reading)

1. This is an interactive lab that teaches what the scientific method is, how scientists and others follow this method. The second part of the lab shows how the scientific method applies to the history of astronomy.

   This game starts with a detective story to illustrate the scientific method, then goes into each step of the method.  
2. It really is geared towards kids,  but the amount of reading involved means it would be great for confident readers to do on their own and for less confident readers to do with a parent.

Some kids also were able to play this game about laboratory devices.  It reviews the functions of various lab equipment, particularly equipment used by environmental scientists.