Monday, March 30, 2009

Horrible Things Happen To Wonderful People

I've been thinking often about the people who receive face transplants, which is understandable since I've been writing about Face/Off these last couple of weeks. The aspect of face transplants that I didn't bring up is a discussion of why anyone might need a transplant in the first place. I'm not going to get into this in great detail, but bear with me since this entry explains my rationale for selecting the next film.

Face transplants carry the risk of infection and/or rejection, as do all transplant surgeries. As I said in my last Face/Off entry, rejection can be immediate, or occur days, weeks, months, or years later even if the patient is on anti-rejection drugs. Those drugs also increase a person's risk of developing certain types of cancers. a person receiving this type of transplant must be prepared to risk their life, and take the risk of having to live without a face at all, if the transplant is rejected.

Who is willing to risk everything on this type of surgery? Someone with incapacitating deformity, that's who. Many of the people who qualify for face transplants are so horribly disfigured that they can't see, talk, smell, or eat properly. What is the quality of life of a person so mutilated or deformed that they have very little, or no, social interactions at all?

This is a link to the site of Jacqueline Saburido, a woman who was severely burned in a car accident. She would likely be a candidate for transplant surgery. Her image puts things in perspective. You are not looking at movie make up when you see her picture. You see her face. Her story is tragic. Jacqueline Saburido

If I had a severe facial disfigurement, how could I live without care free, social physical contact? I'm average looking. I blend in with the crowd. no one stares in shock at my appearance, or is afraid to touch me, or assumes I am mentally retarded due to a speech, hearing, or visual impairment.

I'm not an ethicist or philosopher so I'm going to leave the big investigation of the emotional toll of living with deformity to someone else. That said, I find that if I can ground my intellect in the study of a physical condition, it allows my emotional self to get to work empathizing and putting the unimaginable into some kind of context. Here's a challenge for me as I write this blog - How do I describe severe deformity and still show enthusiasm for the topic and not come off looking like a totally callous jerk? The human body is really amazing and studying even really bad stuff can be (dare I say it?) fun. It's easier to get excited about topics that will kill you, since we all die. But we're not all going to come down with a horrible disfigurement. I face this type of issue when I teach my pathology class, but there I can have a conversation with the students and they can help shape the lesson.

This blog's tagline has a quote on it from Young Frankenstein, so I think you can see my dilemma. i want to talk about movies that are inspired by actual horrible events. I want to be respectful, but I also want to entertain. I'm not quite sure how to address this issue, but I'm going to try to give us some emotional distance from the condition under discussion. We will look at a pathology that is so rare, there is no chance that we or anyone we know will develop it(1). By examining deformity through the context of a movie we can check out make up, acting, and narrative, in addition to exploring the actual condition itself. That should help a little.

What is it like to live with such a Horrible disfigurement? I can't imagine, and I think I have a pretty active imagination. To explore these issues I did what I often do, I read and watched movies. I mad some personal discoveries, and then found myself on the doorstep of David Lynch's 1980 film, The Elephant Man.

I'll leave the script analysis to experts like Todd Alcott, but I do find parts of this film provocative, well presented, and moving. When the elephant man, John Merrick(2) (played by John Hurt) makes his first visit to the home of surgeon Frederick Treves (Anthony Hopkins) and his wife (Hannah Gordon), they sit on a love seat and look at family photos. The wife starts crying, overwhelmed by Merrick's condition, and then I started crying! I cried twice! How embarrassing! I rarely cry at a film. Lynch and the cast really humanize this guy.

It is easy to be flippant talking about face transplants when discussing a film like Face/Off because nothing is at stake. Movies that are "based on a true story" are hard for me to watch because someone was actually subjected to the events of the film. Lynch did a great job with The Elephant Man, but the film would affect me in a very different way if Merrick were a fictitious character.

There is still debate about what caused Merrick's deformity. That's where we'll start next time.

1. There is no chance of adults suddenly developing this congenital condition, and it is so rare that there are only a few hundred people in the entire world who have it. The condition usually manifests between the ages of 6-18 months.
2. According to a couple of sources including Wikipedia, the film mistakenly names Joseph Merrick as John Merrick. Long story. We'll call him John to reduce confusion, I hope.

Friday, March 27, 2009

Face/Off part 5 - Can you handle the rejection?

To wrap up the Face/Off series, a little more exploration of tissue rejection is in order so that we can appreciate the full depth of amazing, entertaining, wackiness serving as a vehicle for this movie.

All the cells in you body have a unique set of protein markers on them called major histocompatibility complex antigens (MHC antigens).

MHC antigens are sometimes called "self antigens." They let the cells of your immune system know what is you (cells with your MHC antigens on them) and what is not you. If cells are not you, they should be inactivated, destroyed, and/or eaten, because they are usually pathogens and about to do you harm, or so your immune system would reason.

There are a number of ways one's body will destroy foreign cells, here are a couple of them. Immune cells (white blood cells) travel to the site of foreign cells to eat them or cells already in the area can release chemicals to destroy them (cell mediated immunity). Or antibodies and other plasma proteins can attack the tissues via the bloodstream (humoral immunity).

What does this mean for our movie? Well, if the blood match is wrong, and/or the graft (or face) for the recipient is of the wrong tissue/blood type, that FACE is coming OFF, all right. It will not be in any shape to return to its original owner, either.

Rejection of a transplant can be dramatic, as in a hyperacute reaction which happens within hours or minutes of revascularization (return of blood flow).

(Dark purple things are stained white blood cells.)

Acute rejection will occur within a week, or months.

Chronic rejections can happen after years, even when the patient is taking anti-rejection drugs(1). With rejection, one's immune system attacks the foreign tissue. In the case of a face, that might make for a good horror movie...

(The slides of tissue rejections are all of kidneys.
I couldn't find pictures of rejected face tissues online.)

Can't you see John Travolta (as Archer) impersonating Nicholas Cage (Troy) with his face all mottled and slipping around? They could fight over the only remaining viable face, which would be Archer's, due to that blood type issue mentioned in Part 4. But I digress.

To prevent rejection, a transplantation patient must take drugs to suppress their immune system for the rest of their life (or as long as they have the transplanted tissue in their body.) These drugs suppress the whole immune system. Death due to secondary infections is very possible with transplant recipients, whether they are using "the new anti-inflammatories" or not because they are not as capable of fighting off pathogenic organisms like bacteria (whose antigenic markers show them to be foreign to one's body.) We don't see it in the film but I'm sure Archer and Troy were scrupulous hand-washers when off camera. Particularly Archer, when he was in prison with Troy's face. I imagine prison is kind of dirty and has lots of bacteria.

Prednisone is a corticosteroid immune suppressant that is commonly used by transplant patients. Dosages of prednisone are much higher immediately following surgery, and can usually be lowered over time, but rarely can the patient stop taking the drug altogether(2).

Prednisone can cause a number of side effects including; increased fat over the face (sometimes called "moon face"), shoulders, and abdomen, although the arms and legs will be unaffected by the new fat distribution; longer healing time for skin; ulcerations of the skin; osteoporosis (thinning of the bones); fatigue; and muscle weakness. In addition, people taking prednisone or other immunosuppressive drugs have a greatly increased risk of developing certain types of cancers, which a healthy immune system would help to keep in check.

In conclusion, it's a great thing for Archer that these procedures were indeed "completely reversible." He got his original tissues (including tummy fat) returned to his body and got rid of the morpho plate inside his face. If Troy's face had damage to it from rejection, it doesn't really matter because (spoiler alert 12 years after the screening of the film) Troy dies, but not from faceless cigarette smoking!

1. Merck. pp. 347-352
2. Merck. pp. 346-354

Monday, March 23, 2009

Face/Off part 4 - Troy Emerges From His Coma!

Troy comes out of his coma without signs of functional or cognitive debility, and unwraps his face. We get some great wet sucking sounds as he pads barefoot through a deserted hospital ward to discover Archer's face-skin floating in a dish.
Troy is initially incoherent and starts screaming when he sees Archer's face, but he's a resilient psychotic terrorist and recovers his wits pretty quickly. Within hours (or less) he's sucking up a cigarette and on the phone to his henchmen.

Troy also talks on the phone pretty well. We see a bit later in a reflection of his faceless face that he's still got a lot of lip and cheek left, which explains why he is so coherent when speaking. It also explains how he can get that smoke out of his cigarette. Yes, smoking without a face, nice touch! It reminds me of the old films like Double Indemnity where Fred Mc Murray has been mortally wounded, is oozing blood everywhere, and wants a cigarette from Edward G. Robinson, which he smokes as he slips into unconsciousness(1).

My colleague Bill reports that the whole smoking without skin on your face thing had been done already. Hellraiser III apparently has a woman, with no skin at all, calmly smoking a cigarette.

We don't see Dr. Walsh and his team perform Troy's surgery as he takes on the face and body of Archer, but one again, the procedure is a success. surgery is performed and Troy is recovered before people come in to work the next morning.

An allograft is a tissue graft between genetically dissimilar members of the same species(2). An autograft is a transfer of one's own tissues from one site to another(3). Transplantation is the transfer of living tissues or cells from a donor to a recipient(4).

So when Archer gets Troy's face the first time, it's transplantation/allograft. The question is, is it autograft when he gets his face back at the end of the film? Is there a name for a procedure where one has living tissue removed, and then re-attached to the same place after hanging out on someone else for awhile?

Allografts may be rejected by the recipient's immune system. this is a major danger for most types of transplants.
Image from Dailymail

As a plot point in the film, Troy's AB blood gives him away to Archer's doctor wife, which Archer's O- blood confirms that he is who he claims to be. I assume that both men are Rh negative(5), just for the sake of argument. If we only look at blood typing, people with type AB blood can receive type O, but people with type O blood cannot receive type AB (long story). So Archer's face might go onto Troy's body (assuming tissue compatibility for a moment) without major trouble, but Archer will probably reject Troy's face tissue that minute his blood vessels get his blood into Troy's tissues. CLOT CITY!

Next time: The final episode of Face/Off - Tissue rejection!

1. Chandler, Raymond, Billy Wilder, et al. Double Indemnity. Universal legacy series. Universal City, CA: Universal Studios Home entertainment, 2006. One of the bes love stories about two men in the insurance business.
2, 3, 4. Berkow, Robert. The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 1992 p. 347
5. In the most basic of nutshells, Rh factor is a blood group discovered on the surface of erythrocytes (red blood cells, to you and me) of rhesus monkeys. Some people have this group (RH+) and some do not (Rh-). If you inject an Rh- person with Rh+ factor, their body will become sensitized to it. If injected with it again later on, perhaps via a transfusion, the Rh- person's body will have a transfusion reaction, which is an allergic reaction (cytotoxic hypersensitivity reaction for you trivia buffs). Red blood cell destruction and huge amounts of clotting are the result. Gues what "Rh" stands for...Yup! Rhesus!

Friday, March 20, 2009

Face/Off part 3 - The Surgery

Troy and Archer are in surgery at the same time so that Troy's face will be plenty fresh for Archer's skull. Surgeons cut through the dermal layers of Archer's face with another laser that looks very similar to the laser that was building Loomis' ear. There is very little blood. I assume that laser is cauterizing as it slices. these people have red and blue lasers for everything!

After cutting around the perimeter of his face, the surgeon (presumably Walsh) applies a clear plastic face-suctioning device that seems to work pneumatically, pulling Archer's skin, fat, and a a few muscles, away from the deeper structures with a light, wet, sucking sound.

Because there was no incredibly wet ripping-noise foley, we must assume that they didn't show the hours of surgery it would take to free Archer's face from the fascia, muscle, and bone below, without tearing chunks of tissue or creating geysers of blood.

After all that, one of the surgeons decides to save time by cutting and dying Archer's hair DURING THE SURGERY. Cutting hair during surgery is so unhygienic! You could see those little bits of hair flying away from those scissors, and no matter how carful you were, eve with "laser sheers," some bacteria laden bits of hair would find their way into the wound site and contribute to a drippy infection later. Brrr!

As they place and manipulate Troy's facial skin over Archer's skull, you get a nice sense of the texture the the skin would have. They really got the right limp, leathery, fatty texture for that type of tissue. I was impressed!

The surgery is quick and bloodless, whereas the woman who had the partial face transplant last December was operated on for 23 hours, and I'm inclined to think there was more bleeding, even with cautery, for her procedure.

The saga of Face/Off continues, when Troy emerges from his coma!

Friday, March 13, 2009

Face/Off part 2 - new anti-inflammatories

Walsh and Miller pitch the face transplant idea to Archer.  While trying to convince him that this cosmetic/transplantation procedure will be a snap, Walsh tells Archer, "with the new anti-inflammatories, healing takes days, not weeks."

Inflammation gets a bad reputation, but actually helps to stimulate acute wound healing.  The problem is that inflammatory reactions can get out of hand and secondary tissue death and/or delayed healing can be the result.  I'm curious what "new anti-inflammatory" might make it possible to heal from major surgery in "days, not weeks."  One interesting anti-inflammatory mediator I cam across is called Activated Protein C, or APC for short.  This stuff is great at healing rat skin(1) and seems like a very promising therapeutic agent for the healing of chronic wounds.  Even though the research I found dates from 2005 instead of 1997, kudos to screenwriters Mike Werb and Michael Colleary for hopping on the research train.

Image from

Walsh also tells Archer that they'll use "laser sheers" and micro plugs to alter his head and body hair.  Did you know that about 80% of all transplanted hair falls out within three weeks, then starts growing again(2)?  I love the idea of John Travolta and Nicholas Cage going about this movie with many looking bald patches on their heads and torsos.  Did they transplant leg hair too?  How many hours would that take?  A head can take hours.

Image from Wikipedia

This is a great line: "Your blood types won't match, but Pollux won't know that." But Pollux might get suspicious when Archer's face, which would actually be Troy's face, started turning black and sliding around.  The problem here is that blood typing is really important to transplanting.  Tissue rejection can happen within minutes to hours (acute rejection) from blood coagulation, if the donor and recipient don't have compatible blood types.  Tissue typing would also be a good idea if you were doing a transplant.  More on this in later posts.

Walsh also explains to Archer that abdominoplasty can be performed for his "love handles."  Abdominoplasy is often called a "tummy tuck."  The procedure involves "tightening" the abdominal musculature and fascia with sutures, repositioning the navel, cutting away redundant skin, and a little liposuction to get those extra areas of fat.  Does Troy get Archer's fat squirted into his abdominal fascia when he takes Archer's place?  Ew!  He might need some of that cut away skin to accommodate the extra fat.  Ick!  If he's on prednisone (an immune suppressive drug to prevent tissue refection) for long enough, he may develop a layer of abdominal fat caused by the drug, and not have to get Archer's fat squirted in there after all.

Walsh has been taking Archer around his facility, showing him the great strides he's made in surgery, tissue regeneration, and transplantation.  After talking about anti-inflammatory drugs and love handles, Walsh says "but here's the real science."

To give Archer Troy's face, Walsh is going to use a "state of the art Morphogenetic Template" which looks like a clear hard plastic facemask with blobs of putty inside it.  The inside is modeled on Archer's skull, the outside on Troy's skull, although the external surface is shaped like soft tissue and not bone.  The morpho plate (my nickname for it) doesn't have a separate jaw hinge, which should make speaking difficult, but we don't notice any speech impediments or inability to chew, post operation, so what do I know?

That the template is "morphogenetic" implies all sorts of things, and nothing at all.  Morphogenesis means the formation of an organism.  It can refer to cell formation, tissue formation, and also the organization of cells and tissues in a larger structure or organism.

So if I was the writer trying to justify the science, I might say that the morpho plate was impregnated (by lasers, of course) with some type of, I don't know... polymer?.... enzyme?... protein?... I'm trying to recall substance that previous movies have relied on for this kind of thing.  Ultimately the plate would be impregnated with something that promotes organized cell growth, as dictated by the DNA(3) of the cells in the donor tissue that has been laid over it.
Image from Wikipedia

Now, this part is unclear to me:  The remove Archer's skin, put the mask on him, and put Troy's skin over the mask to "fit the face on top."  Walsh will "simply connect the muscles, tear ducts, and nerve endings" and voila!  My confusion arises because some facial muscle run from bone to bone(4), some run from skin to skin(5), and some from bone to skin(6).  If they want to attach zygomaticus minor, how do they get the muscle from Archer's face through the mask to Troy's mouth-skin?  Or, how do they get Troy's muscle through the mask to the bone below?  Apparently they can do this because both men smile after their transplants.  Of course Archer (as Troy) is smiling ironically at the cruelty of his position, but it's still a smile.

Even with the "new anti-inflammatories," it takes time to build movement skills with parts that have undergone major surgery, or parts that were moved from one area to another, or parts that aren't originally yours.  As an example of the time it takes for this type of recovery, the woman who received the first face transplant in the United States in December of 2008 has a good prognosis.  she should have feeling return to her face in six months, and with physical therapy to retrain her muscles, she should be able to smile and have most function (speaking, eating, expression) return in about a year(7).  Archer has six days to have transplant surgery, recover full function, fool Pollux into revealing the location of the bomb, find it, and neutralize it.  That's a lot of pressure for his physical therapist.

One of my favorite things about this film is that everyone keeps saying, "this procedure is completely reversible."

Next time, the surgery!

1.  Jackson, Christopher J., et al. "Activated Protein C Prevents Inflammation Yet Stimulates Angiogenesis to Promote Cutaneous Wound Healing." Wound Repair & Regeneration 13.3 (2005): 284-94.
2.  "Hair Today, More Hair Tomorrow?" Harvard Health Letter 33.10 (2008): 1-3
3.  Yes, I know DNA is so 90s but this is a 90s film, so it would fit if they'd used it.
4.  E.g., the masseter which closes the jaw, attaches at the cheekbone and onto the jawbone.
5.  Obicularis oculi makes a sphincter around teh eye, just under the skin.  It is a blinker and a squinter.
6.  Zygomaticus minor runs fromt he cheekbone to tissue of the upper lip.  This muscle contributes to smiling and sneering derisively.
7.  Altman, Lawrence K.  "First U.S. Face Transplant Described."  The New York Times, December 18, 2008.  

Wednesday, March 11, 2009

Face/Off part 1

Here's the first post for a multiple installment analysis of John Woo's Face/Off.  

For six years FBI agent Sean Archer (John Travolta) has been pursuing terrorist Castor Troy (Nicholas Cage), the murderer of Archer's young son.  Troy is finally captured, albeit in a comatose state.  Archer discovers that Troy and his brother, Pollux (Alessandro Nivola) have planted a bomb containing a nerve gas and a biological payload somewhere in LA.  Archer takes on Troy's identity by borrowing the skin and superficial fascia of his (Troy's) face in a hefty surgical procedure that also transforms his voice and body into a replica of Troy.  He heads off to prison as Troy, to trick Pollux, whose central nervous system is intact, into revealing the location of the bomb.  Troy awakens from his coma faceless, and insists on making use of Archer's face and looks.  He then murders the surgeons and agents who know about this top-secret project.  Now things get complicated.  No one but Troy and Archer knows that they are not themselves. Archer (posing as Troy) escapes from prison, to recover his face and his family. There is a lot of great action.  Archer reveals himself to his wife (Joan Allen) who types the men's blood (O- and AB) to discover the truth.  After more great action, Troy dies and Archer is restored "just the way he was."  He also gets a new adopted son, the offspring of Troy.  Balance is restored.

A friend of mine in med school couldn't stand this film.  She hated it!  It was so idiotic!  That surgery could never happen!  She took the whole thing very personally, which is too bad.  She missed a great film.

The key to the success of this movie is that everyone knows the premise is impossible and nobody cares.  I'd say the film even leans into that impossibility as hard as it can, mixing heavy doses of the preposterous with touches of accuracy and new directions in medical research.  Woo uses special effects and snappy dialogue to ignore or gloss over gargantuan obstacles to the success of a super-secret cosmetic alteration and transplantation project.

Let's look at some of the ideas this film invokes regarding transplantation surgery and healing from this type of operation.

In this scene Troy is comatose, I assume due to head trauma incurred in the great action sequence during his arrest.  Archer visits Troy in the hospital ward where he lies in a stupor, sporting what looks like an oxygen feed up his nose.  Another FBI agent, Dr. Hollis Miller (played by CCH Pounder - lover her!) tells Archer that Troy isn't dead after all.  He's in a coma and "he's a turnip."  She then puts her cigarette out on Troy's arm.  Troy doesn't twitch.  His monitors blink regularly and don't alter tempos in the least.  This moment clearly demonstrates that, "In deep coma primitive avoidance reflexes may be absent"(1).  This means that you could put a giant glowing coal on Troy's arm and, if the damage to his brain were severe enough, he wouldn't respond.  I believe we were meant to understand that Troy was in a coma, not a vegetative state, even though he was called a "turnip"(2).  I'm no doctor, but I watch one on TV, and I suspect someone unresponsive to cigarette burns will core pretty low (below an 8 out of a possible 15) on the Glasgow coma scale(3).  That's not good in terms of prognosis of spontaneous recovery, even though this is a plot point later.

In order to impress Archer, and get him to agree to a risky and preposterous mission, the head surgeon, Dr. Malcolm Walsh (Colm Feore) leads him to a glass wall, behind which we see a team of surgeons building a new ear, from scratech, with red and blue lasers.  the ear is for an agent Loomis, injured during Troy's capture.

In order to build and ear, these lasers would have to be able to organize a number of different types of cells into a super organized arrangement of skin layers, superficial fascia, elastic cartilage, blood vessels, and a number of nervous structures.  the surgeons then attach the ear to Loomis, and seal the tissue with another laser. Later a laser is used as a cutting tool to perform surgery.

In the real world, lasers are being used to perform a number of different tasks from skin tightening to tumor removal(4).  When researching to see what has been done in the area of lasers and tissue regeneration, I found an abstract describing the use of lasers to stimulate cartilage cells to grow(5), and since one's ear is elastic cartilage, that's a big part of the wounded agent's ear graft.  The abstract was a little vague as to whether or not this approach will pan out in terms of its usefulness, or even if it really worked at all.  But, assuming it worked, I suspect that the cartilage cells stimulated by laster activity would grow in one big, undifferentiated lump.  Still, the way the film used lasers to generate and destroy tissues wasn't quite as far-fetched as one might think.  Well, okay.  It's pretty out there but I could find evidence of research (regardless of outcome) in this area, so you have to give the movie a little credit here.

Next time, we look at the "new anti-inflammatories!"

1.  Berkow, Robert.  "The Merck Manual of Diagnosis and Therapy."  Whitehouse Station, NJ: Merck Research Laboratories, 1992 p.1398
2. Wikipedia classifies turnips as true "root vegetables" as opposed to modified stems such as tubers or other root-like structures such as bulbs.
3.  "Merck" p. 1463  Yes, they have a point scale for comas.  you can score between 3 and 15.  The lower the score, the worse the prognosis.  3-5 means you will probably die.  Over 8 and your chances of recovery are good.  Troy must have been somewhere between 5-8 and had the help of a miracle.
4. Galewitz, Phil. "Multi-use Lasers Cast doctors in New Light." USA Today
5. Baumann, Marcus, et al.  "Influence of Wavelength, Power Density and Exposure Time of Laser Radiation on chondrocyte Cultures - an in-Vitro Investigaion."  Medical Laser Application 21.3 (2006): 191-8. Abstract.

Monday, March 9, 2009

First Post Ever

The more I learn about the body, medicine, and disease, the more I enjoy a film for its treatment of those topics.  The next time you watch a film with a "medical" perspective, appreciate the research that went into the portrayal of a surgical procedure.  Check out the make up artists' techniques for building scars.  Ask yourself if the blood coughed up by Nicole Kidman really has the color and consistency of pulmonary blood sputum.

I love it when a film gets it right.  I love it when the film gets it wrong.  Why would I like a film that got the science wrong? Because it's entertaining.  I admire the way the script (or director) diverts attention from a big hole in medical theory.  It brings up questions:  Is everything wrong?  Do they get something right?  Do they know they're wrong?  Do they care? Can they sustain the plot with this bottomless chasm of a mistake lying there, waiting for one false step, slip, and plummet to doom?  We may never know the answers to all of these questions, but exploring the possibilities will be a lot of fun!

These pictures are from some medical film classics: Young Frankenstein (a personal favorite), Outbreak, Mr. Sardonicus, and The Fantastic Voyage.  All are delightful films that I will look at in the future. 

My next post will be a movie-science analysis of the film that has the distinction of launching this blog - Face/Off, John Woo's gem of a film from the Archives of Ludicrous Science.