Instructor: Mr. Jack Moen

Today was my first seminar of YYGS and my second day of the program!

Yesterday was when I had family time (kind of like advisory)! Our mentor is Maddy from Dartmouth ( a neuroscience major) who is extremely affable and so relatable and just really warm-hearted. Then we had the lecture from Dr. P.E.

I chose this seminar because it just seemed really interesting that our technology has now advanced to an era where we can practice such intricate procedures, like how exactly do we precisely cut out the thousands of nerves in the spinal cords?

Sorry for the very messy and unorganized notes, but these were my notes for today:

Guiding Questions:

1. What science needs to be advanced for head transplants to happen in humans?
2. When is it okay to acquire another body for transplantation?

__________________________________________________________________________________

• What’s in a brain?
  • Broken down into lobes (different areas associated with different activities)
    • Frontal Lobe – Decision making and problem solving (higher order thinking)
    • Temporal Lobe – Holding onto memories
    • Occipital Lobe – Associated with Vision
    • Breathing, hearing, all the way to memory and emotions
  • Our brains are most highly developed compared to other species
    • Higher mass and lots of convulusions
      • Increase in surface area is also essential to having higher intelligence
• What else is in our head?
  • Eyes, Sense of smell, taste, ears, all small little tings important for head that we don’t really think often but as important to brain function
    • Everything from neck up is most important in our body
  • Nose helps enhance taste 
  • Most interested in transplanting
• Ability to have another body but have our own thoughts

Rather move the head vs move the brain?

• Rather easier moving the head cuz it’s connected to muscles
• Essential to consider the patient’s perspective as they may be unsatisfied with their physical appearance

Why would we want head transplants?

• Prevent aging, disease, injury, death
  • Aging
    • Although body ages, brain still is alive and young
  • Injury
    • Spinal cord damage —> restore having a body through a head transplant
  • Death
    • Avoid death in some situations

Aging:

• Your body starts to deteriorate gradually as you age
  • Heart stiffen/decompensate , high/low blood pressure, muscles get weaker, bone density drops —> harder to hold onto muscle —> joints get weaker too, skin starts to thin and sag (elastic nature of proteins in body fades with time)
    • As you lose the elasticity —> develop wrinkles, age spots
• Process as part of living is part of dying

Head transplants can help with certain diseases

• But may be difficult as they’re multifactorial, may be difficult to fix
• Illnesses that control movement and lead to physical disabilities, caused by variety of bacteria, still idiopathic
• Congenital (physical disabilities possibly) when genetically inherited
  • Mother doesn’t have nutrients )spinevitifia —> note enough follae , the spin doesn’t form, and bulges out of it
    • Won’t have use of lower half of body

Treating disabled or injuries from accidents

• Every year around 2 million people will be involved in car accidents that leave them injured or dialed
• C4 injury (cervical/neck) injuries, head is still going to be perfectly fine
  • Grievance where body doesn’t work —> psosible option: head transplant

Can’t do a transplant to a brain dead person

Sudden damage to the body can cause failure of vital organ systems like the heart or lungs which the brain needs to survive

• Brain can’t store enough oxygen —> hypoxeda/hypoglycemia
  • Can’t survive without enough sugar, consumes about 25% of sugar in body
    • Dependent to have High levels of sugar
  • Cells die quickly without oxygen —> can’t survive a few minutes

History of head transplants

• Vladmir Demikhov (Soviet Russia, 1954)
  • Joined two dogs together(upper part of one dog  + limbs attached to other dog)
    • Dog lived for a few weeks
  • Jarring experiment that dog underwent suffer
  • Did demonstrate the feasibility of transplanting between two similar species
• Robert White (1970)
  • When transplantation surgery was coming into its own 
  • Experimented on monkeys, successfully transplant one monkey’s head to another monkey body
    • Monkey’s head was still functioning, could see, hear, taste, swallow
  • Stayed alive for a few days but unable to move any part of body
    • Didn’t have enough technology to connect/preserve nerves
• Xiao-Ping Ren (2015)
  • Used mice (common model organism as they grow fast)
  • Found a way to cut the head at the right angle to preserve the motor functions while keeping the donor body in tact with more organ functions of the body
    • Robert white – depending where you cut on the brain/neck determines how well the rest of the body will function
    • Donor was separated at brain stem, blood vessels connected with silicon tubes to reach asap and successfully
    • Polyethylene glycol
    • Fixed to donor buy with pins and switches before removing stitches
      • Lives for a day

Valery Spirididonov 

• Werdnig Hoffman disease, muscles spine and brain waste away slowly
• Signed up for first head transplant in 2015, but decided to pursue less aggressive treatment options in 2019 even though his body was going to essentially fail
  • Head transplant could be only permanent cure, but he would be the first one to do this

Poll 1:

Debate from poll:

Able to physically move heads but functionally make it work is still uncertain

• The closer he is to death, would make sense to undergo the surgery since the likelihood is
• quite high 

Poll2:

HEAVEN process (= Head Anastomosis Venture)

• Team work together simultaneously

1. Cool down person’s head to minimize any harm
2. Cuts to neck
3. Muscles are color coated so they can know which muscle is attached to which 
4. Arteries and esophagus are cut
5. Blood is drained
6. Cut Nerve fibers using a diamondd edged blade
7. Head hangs freely from crane 
8. Spinal cord is connected first, not fully sucessful
   1. How?
      1. Use a “glue” – polyethylene glycol, found in skin creams and printers
      2. Able to mend and fuse delicate cell membranes, fuse it into blood —> fuse the spinal cords together
9. Esophagus and neck sewn together
   1. Where does cutting through the neck begin?
      1. Head controls so much stuff that even the structure port is essential
         1. Thyroid (body’s ability to produce energy)
         2. Esophagus
         3. Vocal cords
10. Sew together to minimize scarring

Protect the brain stem!

• Xiao-Ping Ran was concerned about preserving brain stem in donor body – control heart rate, breathing, blood pressure , swallowing, digestion
  • Preserve brain stem from donor so that the body is still functioning when you attach the head..?
• Proposal 1: Since the brain stem sits at the bottom of the head, you might have an extra few inches of your neck  because if spinal cords don’t reattach, body won’t be able to regulate breathing

The biggest question: How will fusogens(polyethenel glycol, “glue) work?

• Been using this technology since 20-30 years ago, works easily with cells
  • Why can’t we use stem cells
    • Induced pluripotent cells —> stem cells to create new tissue and nerves
    • Stem cells with another tissue, takes property of tissue, or sometimes the metabaloids and cells don’t match, fluids and spinal fluid and bone and support structures

Why is blood important for the body?

• Clotting, replenishes cells with oxygen, 
  • Drain host head of blood while transplant them onto the body (presumably same type of blood)

Protecting against blood loss and related damage

• Several arteries and veins must be severed —> may cause massive loss of blood 
  • Blood in donor body and head needs to be continuously oxygenated and artificially circulated
• Ischemia – when cells die from lack of oxygen  (probable idea)
  • Ischemia conditioning – heart muscle, deprive it of blood and oxygen enough to where it’s not damaged, do a few times —> heart is more resistant to full blood ischemia when it’s starved of blood and oxygen

Perflurochemical Droplets (PFC) —> biologically inert (x react with anything in body), 1/40th size of red blood els, and 50 times better dissolve oxygen than blood (helps hydroxygenate blood)

So hyper oxygenated liquid (tissue in there during transplantation)

• Would’n’t disturb the regulation of nutrient balance, thermoregulation, but would help enhance things like oxygenated heads

When hypothermia might save your life.

How can we minimize damage to the brain during surgery?

• Cool body down (core temperature down) using ice to 10˚C

1. Hypothermia
   1. When the body is losing heat faster than it can produce and gets below 35˚C
2. Everything in our cells that function at 37˚C, but drop temperature, cell stops functioning —> basically stop all cells from functioning —> won’t be producing reactive oxygen or prequire oxygen, keeping body at cold temperature, things usually losing oxygen wouldn’t since the cells would stop functioning

Justin Smith (ex)

• Drinking, 26yrs, walking home in a winter storm, blacked out
  • Fell into snow, as core temperature got down to 10˚C, they saw him and brought him in (heart stopped working and was dead for a few hours)
    • Raised body temperature slowly, able to recover just fine (technically dead for several hours but thanks to hypothermia, able to survive)

Staying alive after the surgery

• Immunosuprression,
  • host vs graft(donor) or  graft vs host diseases (attack each other)
    • Host vs graft:
      • Liver from another person and put in into another body, your body attack the liver because it has different antigens from your body
    • Graft vs host(rare):
      • Grafted tissue has immune cells that attack the host (more dangerous)
        • Lungs have a lot of T cells (immune cell that attack pathogens), may see new host cells infiltrating the lungs. The graft sends inflammatory molecules , but because the host has more tissue, may cause more danger
      • More of an issue since the whole body: graft, host: head
  • Need to be under very heavy immunosuppressive drugs when getting head transplant
• Blood clots, major vasculature has just opened and suture closed, very high chance for blood clots (esp in brain, stroke)
  • Blood clots form any where open
    • Blood thinners can help but not for long durations
      • Harder for vascular areas to heal
      • Might form at the neck since that’s where the neck is cut —> stroke as no blood passed to brain
• Potential for pain (Idiopathic pain= pain of an unknown origin)
  • Lack of long lived animal and subjects —> do not know how pain will be received tolerated in transplant
    • Different pain tolerance levels for each person, know no idea how people will respond
    • You could be experiencing extreme pain for unknown reasons

• Psychological effects?
  • Phantom limb syndrome – when one loses a limb, they’ll still feel like a limb is present
    • Possible with head transplant?
  • Since brain has a specific map that is linked to every part of body
    • 5 feet tall —> 6 feet tall (limbs are longer and bigger) —> inappropriately mapped in brain since you’re not used
      • Intact is only neck up, so we don’t know how the body will accept these things 
  • Apotemnophilia: body integrity identity disorder
    • Very rare, person doesn’t identify a part of their body as their own
      • Neural map that says this is my hand, but patients of this disorder will say that even this hand is attached, it’s uncomfortable and foreign and isn’t my hand
    • Seek out surgical amputation/self mutilation to have limb removed to feel better
      • Unsure of what the causes of this are
    • Could be very prevalent to someone with a body transplant (may feel horrible in your own skin after the surgery)

Questions: What would happen if the brain itself would physically deteriorate? Even after numerous head transplant procedures?

How would circadian rhythm cycles work?

• Would take some time to adjust, but wouldn’t be a limitation

(This seminar continues on until tomorrow, and I’m going to add more to this page!)

I have my first simulation today too, and an Opportunities Across Yale lecture too!

– Joanna Kim, July 6th 2021, 10:50PM KST –