The past few weeks I’ve been eagerly watching a variety of Japanese television, and I noticed something very peculiar (for an American).
The few Japanese dramas I’ve seen actually end. They build to an end and then just stop. They don’t drag it out for season after season, allowing different seasons to suffer based on actor/actress-negotiations and writers having off-years. They don’t end on ridiculous season cliffhanger-after-season cliffhanger. They have a well-defined endpoint and, by building to it, they keep the story fresh and force it to have a suitable length.
This isn’t to say that the Japanese dramas I’ve seen don’t go on for multiple seasons. But, I would assert that sequels (should) only happen when there is sufficient audience demand for one and when the storytellers think they have another story to tell.
Contrast that with American TV – the seasons are built not for any plot reason, but because a TV studio needs to have sufficient content to fill the months of September to May/June. Seasons are renewed, not because of a deep creative reason or even necessarily because of audience demand, but because of a misguided sense of momentum. This doesn’t always turn into a disaster (I believe House MD, despite its traditional has maintained a reasonable level of quality each season through the quality of its casting and writing), but even series that I thoroughly enjoy like Smallville have had their fair share of “useless filler” episodes and bad seasons.
In my humble opinion, it’d be far better to adopt the miniseries format. It prevents writers from creating ridiculous plot devices to keep a story going way past its prime (and past when its actors begin leaving for greener pastures), and it maintains a quality of production which only a purpose-driven creative process can lead to.
A little over two years ago, I blogged on a very interesting New England Journal of Medicine paper about a bizarre medical case where a young female patient actually took on the blood type of a little boy who’s liver she had taken in a transplant. I had noted then that such an amazing (and not fully-understood) event definitely qualified for being a House MD moment, after one of my favorite TV shows about everyone’s favorite misanthropic genius doctor.
Two years later, a friend of mine from college shows me another case with a similar “signature”, making me dub this “A Case Fit for House MD Part 2”!
The setup (more details in Wikipedia): a 52-year-old woman named Karen Keegan was in need of a kidney transplant and, of course, tested her children for donor compatibility. What she discovered, completely rocked her world. To quote the Damn Interesting page I just linked to:
Imagine if you discovered one day that two of your three children were genetically not yours. Recriminations, marital troubles, perhaps a divorce, right? Now add a twist. What if you were these children’s mother? Suddenly the question becomes not “Who?” but rather “Huh?”
“Huh?” is right.
So, what’s the explanation for how a mother could possibly give birth to children who are genetically not matched to her? The current theory is chimerism.
The type of biological chimerism, named after the mythical chimera which had the parts of a lion, snake, and goat all in one (see image on the right), we usually see involves an organism having DNA from multiple species. This is usually something more mundane and research/medicine-oriented like creating mice that have genes which give them a human being’s immune system. These “humanized” mice are then used to produce human antibodies which can then be used for medicinal purposes.
A more dramatic example in nature would be the parasitic chimerismthat the Ceratioid Anglerfish practices – where the males of the species actually fuse with females to become some sort of chimeric (and immediately fertile) hermaphrodite.
In humans, a common form of chimerism that is observed is in a small proportion of fraternal twins where, because of linkages between their blood supply and blood-producing organs,end up having “shared blood”. They each have and will continue to produce blood cells from their other twin, despite the rest of their body being genetically distinct.
But what about the curious case of our mother who’s kids don’t appear to be hers? What sort of chimerism explains this? A New England Journal of Medicine paper dives into the science, but basically, the theory is that Karen Keegan had a fraternal twin. But, rather than simply share blood cells/blood-producing cells, Keegan and her twin had actually fused in the womb. This theory was supported when they found two sets of DNA in her tissues (one set of which matched her un-matching children).
Interestingly, this paper was cited in the 2002 trial of a British woman named Lydia Fairchild who was denied custody of her children and welfare support because she could not prove with a genetic test that she was the mother of her children. The story was later put into a documentary called “I Am My Own Twin”.
So, anyone want to pitch using this to House MD?
(Edit: It’s been brought to my attention by… pretty much all of my friends who watch House that genetic chimerism was actually the diagnosis for the second episode of season 3 — I suppose I won’t be able to sell this screenplay to the writers after all…)
I’m a bigfan of House, not only because the lead character is someone we all (or maybe just me) wish we could be (someone so brilliant that he can get away with saying and doing just about anything), but because of their use of bizarre medical cases showing off some of the extreme things that one’s body is capable of when sick.
While SUND (Sudden Unexplained Nocturnal Death) will probably never show up on House (given the sudden, inexplicable death of the patient preventing House and company from being able to do or say much of anything), it is definitely one example of an extremely bizarre condition which doctors still don’t have a good handle on.
I first read about it in an article on Forbes covering bizarre sleep disorders. The craziest thing about this “condition” is that it seems the victims die of nightmares!?:
Since 1977, more than a hundred Southeast Asian immigrants in the U.S., primarily ethnic Hmong from Laos, have died from a mysterious disorder known as Sudden Unexpected Nocturnal Death Syndrome, according to reports by the U.S. Center for Disease Control. The victims were mostly men in their 30s or older, who were apparently in good health when they died in their sleep for no apparent reason.
“The victim has no known antecedent illnesses, and there are no factors that might precipitate cardiac arrest,” the Cambridge History of Disease notes. “At autopsy, no cause of death can be identified in the heart, lung or brain. Postmortem toxicologic screening tests reveal no poisons.”
Shelley Adler, a professor of integrative medicine at the University of San Francisco, California School of Medicine, speculates that the cataclysmic psychological stress caused by war, migration and rapid acculturation created such wrenching nightmares among Hmong refugees that they died. In other words, nightmares killed them.
Doing some additional research on Wikipedia reveals that the current operating hypothesis appears to be cardiovascular – mainly that SUNDS victims could all have potentially died of ventricular fibrillation (a lethal heart arrhythmia where the heart ceases to pump normally). There’s even a syndrome named for this – Brugada syndrome – with 6 associated genes which show a higher risk for the condition.
Now, in all honesty, I’m not sure how you diagnose a patient who’s already dead (esp. when autopsies and histories reveal nothing significant), but that leads us to the prognosis:
If no one you know died suddenly in their sleep, you probably won’t either (it’s at least partially genetic)
If someone you know did die suddenly in their sleep, go bulk up on Thiamine (Vitamin B-1), get routine heart monitoring, and maybe get a cardiac defibrillator implanted into your chest.
I’m a huge fan of the show House MD. In particular, I love the show’s use of incredibly bizarre, but true medical cases. For example, in one of the earlier shows, House and his team make a diagnosis based on the fact that sleeping sickness can be transmitted by sexual contact. That may sound like nothing extraordinary, until it becomes emphasized that this medical “fact” is actually one reported case in a foreign medical journal. Probable? No. But, fake? Not really.
Unfortunately, consulting does not leave much time in my day for keeping up with scientific papers. I end up accumulating a pile of papers to read which just never seems to shrink. However, I was recently shook from my paper-reading stupor when A. Phan pointed me to one particularly interesting study published in the most recent issue of the New England Journal of Medicine. The AFP article which summarizes the study is simply jaw-dropping:
Girl switches blood type after liver transplant
The medical study details the struggles of a 9 year old Australian girl who needed a liver transplant due to a case of “non-A-to-G hepatitis” (translation: doctors know that something serious is hitting the liver, but they have no clear idea what it is). She is given a liver transplant from a 12 year old boy who died of hypoxia (lack of oxygen to the brain) and is positive for a normally innocuous virus called CMV (cytomegalovirus). The match is nowhere near perfect, so the girl is treated with immunosuppressants to prevent rejection.
Unfortunately, while CMV is normally harmless, it can cause problems in patients with weakened immune systems. Sure enough, the girl had to be re-admitted to the hospital 2 weeks after being discharged. Her doctors noted that the severe lymphopenia (a shortage of the blood cells needed to fight infection) that was ailing the girl prior to the transplant had persisted even 5 weeks after the transplant. The doctors had simply thought this was a combination of infection and the immunosuppressants they were giving her, so they adjusted the medication they gave her.
7-8 months after that (9 months post-liver transplant), the girl was re-admitted to the hospital for surgery due to a bowel obstruction, and it was then that they noticed that the patient’s blood, which had previously been type O-negative, had tested O-positive! This was especially incredible given that both parents were homozygous O-negative, meaning that there was no way, genetically, that the girl could produce O-positive blood. Typically, the only way a blood type switch happen is through a bone marrow transplant, which replaces the blood-making cells of our bodies with the blood-making cells from a donor — and even then, it’s accompanied by something which the girl did not suffer from called GVHD (Graft-Versus-Host Disease), where the new donor immune system thinks that the recipient’s entire body is foreign, and should thus be attacked.
A month after that (10 months post-liver transplant), after a mild respiratory tract infection (a cold or cough), the girl started showing signs of hemolytic anemia. Literally, her blood cells were bursting — something you would expect in blood type mismatch problems. Heavy immunosuppressive therapy and constant transfusions seemed only to alleviate the problem slightly. A careful examination of her blood showed that her immune cells were more than 90% from the donor, something which was verified not only by blood type, but also by the fact that these cells had Y chromosomes (results from fluorescence in-situ hybridization to the right; red dot is a Y chromosome; green dot is a X chromosome; the cell at the top is thus XX — female — and the cell at the bottom right is XY — female).
In words that President George W. Bush might understand, the donor’s new blood cells are US forces in Iraq. The remaining blood cells from the girl are scared Iraqi’s who see strangers everywhere and are prone to using guns. The hemolytic anemia is the result of the ensuing fighting. And the immunosuppresants are some magical way (maybe supplying both sides with alcohol?) to reduce the ability of both sides to fight.
The doctors had a choice. Do they:
Give her a drug to wipe out a big chunk of the immune cells from both donor and recipient (nuke Iraq to kill enough people, on both sides, to stop the war)
Stop all immunosuppressants and just let the immune cells duke it out (take off all the handcuffs on US forces and let them wipe out the remaining Iraqi insurgents and hope that Iraq is still in one piece when it’s all over)
They went with the second strategy.
It is now about 5 years after the transplant. The girl is healthy, and no longer on immunosuppressants. Her blood is now completely from the donor, despite the lack of bone marrow transplant. There has been no sign of the GVHD which typically accompanies the sorts of bone marrow transplants which could lead to blood type switching, and it would appear that the girl’s new immune system has been “re-trained” to not recognize the liver or the girl’s body as foreign.
So, the big question in my mind is how? How could a non-bone marrow transplant lead to blood type switching? The only two things I can think of are:
A virus caused liver cells from the transplant to fuse with the girl’s blood-making bone marrow cells. Why it may be possible:
In biology labs, forcing cells to fuse is oftentimes done with viruses
It is known that stem cells like the blood-making bone marrow cells are prone to fusing (a result which confused many early researchers who were positive they found examples of blood stem cells turning into non-blood cells)
Because the boy was so young, it is possible that the transplanted liver still contained blood-making stem cells which were re-activated. Why it may be possible:
The fetal blood supply is produced, at least in part, by cells in the liver
Stem cells which are dormant (e.g. the cells in your skin that can produce new skin) can be activated with the appropriate stimuli (e.g. burn)
This is all just speculation on my part, and I doubt we will ever find the answer in the case of this patient (who is no doubt sick of doctors and hospitals), but things like this are reasons why I love House and why I love science.