Stem Cell Transplantation

Welcome to advanced Immunology Elective says Eli.  This quarter we will be studying the possibility of grafting bone marrow between donors and synergistic recipients in a closed system.  The mice we will be using are Balb/c  inbred mice.  A mouse’s immune system is housed in the spleen which is the murine version of the bursa of Fabricius progenitor organ.  In mammalian systems, the anti-body-producing immune system is the gut-associated lymphoid tissue found in the alimentary tract.  We will irradiate some mice to make them aplastic and then transplant different spleen cells and gauge an immune response by the Ouchterlony technique.  I will need some students to take the mice to the Cobalt 60 facility and irradiate them.  Who would like to go?

The students in the class all point to the Wracks

Beauty before age they say.

I don’t have a car says the Wracks.   I am ineligible

I have a car says Mr. Simms I will drive you

Thank you very much, Mr. Simms, says the Wracks.   You are a scholar and Gentleman.

The Wracks have a large three-foot square cage full of screaming and chiding mice. At least twenty of them.

Put them on your lap says Mr. Simms.   I don’t want   waste on my upholstery.  This is a new car

They are not rats says the Wracks, they are mice.  

They look like rats to me says.

The dark war-green Volkswagen bug plods down the side streets to the Veterans Facility

The Veterans facility at the Big U is a bucolic, idyllic retreat where the men and women who serve the United States military go for housing and medical treatment.  The green expanse of beauty with red brick buildings cast about, almost a forest with park benches and walking paths.   The people who agree to fight for our country deserve the best the nation can offer and it is here, and they offered their lives to inherit it.  So shall it be.  In God we trust.   Then there is building 3C.

Building 3C is a government Cobalt bomb facility with marines, cocked and loaded M16, s and bayonets.  They stand at the ready with their fingers on the rifle safety, on the side, slightly out of sight.  A tall man with goggles and freckles asks, May I see your identification, please?  Wracks and Mr. Simms hand him their student I.D.s.   He looks at the pictures and then hands them back.  You both are on the list he says

Go into the room he asserts.   Put your animals on the stand near the center of the room.  The source is in the middle of the room under ten feet of lead armor.  When you hear the sirens go off, head to the door and exit promptly because when the door closes it locks until the source goes back into the earth.  Turning off the sequence takes time and you will be exposed to the bomb if you hesitate.  Irradiate your animals and come see me before you leave

Cobalt 60 is a man-made alloy of the nuclear age.  Emanating intense Gamma radiation for a half-life of 5000 years, the metal is used by industry to preserve anything because the radiation kills everything.

The Wracks and Mr. Simms bring the mice into the room and Mr. Simms is the first one out.  The Wracks scrambles, a loud siren goes off, flashing lights all around spin around in red and blue, the steel and lead door closes with a loud snap, and heaven comes to the earth.    A person can feel intense gamma radiation even through a four-foot-thick lead wall.   Intense gamma feels like a person is being placed into a huge magnetic field and time stands still, and then the alarm stops after about a minute and the atmosphere smells like chlorine bleach.   Radiation and its parameters must be the key to transposition.  You can feel it. 

Mr. Simms says, Atomic

The Wracks says, Heavy

You go in and get the mice says Mr. Simms.   I will wait here.

The Wracks goes into the room and retrieves the cage.   The mice are stunned and barely breathing and the source is back deep in the floor.  Let’s go back to the lab says the Wracks, these mice need some water and food.   Don’t dirty my upholstery says Mr. Simms.  I won’t says the Wracks.  I promise.

Out of the twenty mice, four died immediately from the intense radiation.  The sixteen now have no immune system.   To transplant an immune system in a mouse, a ground-up spleen, forced through a wire screen and loaded into a syringe is injected into the peritoneum of the mouse.  This action renders them immunocompetent.  In ten of the mice revitalized with spleen cells, only eight survived long enough to be assayed for immunocompetence.  A new graft doesn’t always take.   The rest of the mice display an intact immune system as revealed by a plaque-forming assay in gelatin that probably now is paseo.   Half of the surviving mice show self-rejection of the lupus type with running and eventual death.

Out of ten mice transplanted with identical cells only four survived to assay.

Well students, what do you think?  Are bone marrow transplants viable for human beings?   Eli wants to know what you think.  Even in syngeneic highly inbred litters of mice, there exists enough genetic variability to cause graft versus self-reaction.  Eli looks around and listens.  The students are perplexed.  Eli states transplantation of a related strain CJ157 into the rest of the hosts results in an immediate graft versus host reaction with a mortality of 100 percent.

Is what you are saying, that bone marrow transplants don’t work, asks a senior graduate student.    I didn’t say that says Eli.   We are still working on that issue.   For the rest of the semester, we will study how using extracts of cancer antigens can produce viable IgG production in an appropriate host.  We will be working on immunotherapy of cancer for the rest of the quarter.

What is the carrier for the tumor-specific transplantation antigen going to be asks the Wracks?

We are going to begin with polylysine and peptide linkage says Eli.   Dr. Molinero peers in the door.   He has big horn-rimmed glasses and bushy hair like Samy Hagar.   He is Eli’s partner and cohort.

Class is over.   The Quarter is over.  The Wracks will go on to transplant lymphoma between mice and then be expelled from the program.

I knew it was Eli, exclaims the Wracks to himself.   I knew it all the time.