Saturday, August 30, 2008

How NOT to make "the perfect being": The Fifth Element

If you've ever seen the hit movie The Fifth Element, you may remember this scene from the beginning in which the main character Leeloo (actress/model/designer Milla Jovovich) is brought back to life by scientists.

(Note that all material is copyright Gaumont, Columbia Pictures, and Sony Pictures Entertainment)

Okay, this is a really cool scene and ostensibly sounds very scientific. And I'm happy to see DNA and genetic engineering mentioned in a movie, except this is a really poor example of it. As I mentioned earlier, this scene really bugged my friend Lisa (which admittedly might have something to do with her having a Genetics degree, Summa cum laude. Major overachiever, I know!) So let's revisit that scene for a second:

General: That what you call a survivor?
Scientist: A few cells are still alive. It's more than I need.
General: Have you at least identified it?
Scientist: We tried but the computer went off the charts. You see, normal human beings have 40 DNA memo groups, which is more than enough for any species to perpetuate itself. This one has 200,000 memo groups.
General: Sounds like a freak of nature to me.
Scientist: Yes...can't wait to meet him.
In the lab...
Scientist: Ok General, I want to show you something here. This is a normal human DNA chain, OK? You, me, anybody else, right?
Scientist: Watch this. The compositional elements of his DNA chain are the same as ours; there are simply more of them, tightly packed with infinite genetic knowledge. Almost like this being was...engineered.
General: Is there any danger?
Scientist: No no no...we put it through the cellular hygiene detector. The cell is, for lack of a better word...perfect.

So pretty much every single line in this scene is messed up. Really. The issues at hand are:
  1. How a few cells are "more than [you] need" to reconstruct an entire organism from scratch.
  2. Multiple DNA helices + tightly packed DNA being equated to the perfect being
  3. What are earth are memo groups? And/or how species perpetuate themselves?
  4. Leeloo having "perfect cells"
Problem 1: Reconstructing Life
Okay, I am not going to spend a long time on this as I think it was adequately covered after Jurassic Park was made. Extremely cool concept, but not realistic. DNA is super fragile and extracting and amplifying the entire, 2 meter long, intact DNA sequence from one cell, let alone thousands, is a difficult task, especially with archaeological samples. I mean, we had enough trouble sequencing the human genome in the late '90s before completion in the year 2000, and that was with live donors. Now, of course every cell has a copy of one's entire genetic sequence, and I am happy the writers realized that much. But being able to completely rebuild Leeloo from a few cells is a bit much. Plus, how does she magically get generated at young adult stage? In JP, all of the dinosaurs came out as babies from eggs.

That said, I still think t
he idea of generating a person from a few cells in a gauntlet totally rocks.
(Note: JP photo copyright Universal Pictures)

Problem 2: Superior genetics?
Where to begin with this one....let's start with the easy problem. Saying her DNA is tightly packed and that is one reason she is superior is crap. Everyone's DNA is tightly packed. It's not "highly coiled," it's supercoiled. In fact, that was one of my favorite parts of biochem class. Understanding how a 2m-long string of DNA is wound up into each of your itty bitty cells is awesome stuff. Our bodies are amazing. So she ain't superior for that; she's just an average gal. But b/c I can't resist, I am included an awesome schematic here about the supercoiling of DNA, just b/c it makes me happy. :)

Now let's take a look at Leeloo's DNA structure. The schematic of normal DNA is great--they even show the base pairs, which is nice. However, if you look at Leeloo's DNA there's not two, not three, but eight helices going on there. Count 'em. That is insane! In fact, the miraculous octuple helix design is supposed to give her "infinite genetic knowledge".

  1. Problem A: More DNA does not equal superior organism. Forget about the helices for now. Let's start with how the basic concept of this is just plain wrong. This is like the old misconception that Albert Einstein must have literally had a bigger brain than the rest of us b/c he was so smart. Bigger brains don't make smarter people,. and more DNA does not equal genetic superiority. In fact, yeast (yes, what makes bread) have more genes than you or I. So length of DNA and/or number of genes is meaningless. I mean, if you want to create the premise for a superior life form, do you think saying it has more DNA is the way to go?
  2. Problem B: The helices. Dude, I don't know where to start. As Lisa pointed out, this gal would either have a ton of diseases or just not exist. If her "genetic components are the same as ours" per the movie, how exactly does that work? Currently, one hot area of research is siRNA therapy, in which you stick a short strand of RNA that is complementary to the DNA of your least favorite gene into a cell, and let it stick to that gene. Your RNA transcriptase can't transcribe the dang gene; ergo, no more bad protein is made (in theory, at least.) If she has multiple helices all bound together, how exactly do her polymerases (RNA or DNA) function? B/c there is no way those 8 strands are sticking together in the first place unless they are somehow complementary. If they weren't, you'd only have a bunch of double helices. So by having multiple complementary strands she is sabotaging her own genetic machinery. Not to mention, there is no way on earth that she would even get a helical form out of that. Studies have shown that a triple nucleic acid helix can exist (it happens all the time when you are transcribing DNA to RNA) but 4 together are no longer helical. :(
Alternatives? So then Lisa and I began discussing how on earth you *could* design a being with more genetic information, since this helices thing is wacked out. One way would be to give her a longer genetic code, but as I mentioned, that doesn't mean she is superior. Although at least it is more plausible than an octuple helix. The only other way we could imagine that would give her more genetic information is if Leeloo had more chromosomes. All of her DNA would be a double helix, but there would be more of it.

The problem with this is that most higher organisms with additional chromosomes are toast. Extra chromosomes can be broken down into aneuploidy and polyploidy. Aneuploidy refers to having an extra copy of a particular chromosome; polyploidy is an extra copy of your entire genome. A good example of aneuploidy is trisomy 23, in which a person has an extra copy of their 23rd chromosome, resulting in the condition known as Down's Syndrome. But if Leeloo wanted to have the equivalent of 8 DNA strands or 4 double helices, she would want extra copies of her entire genome. 1 set of chromosomes = 23 = "haploid"; humans are diploid (46 chromosomes). If Leeloo wanted 4 times the amount of DNA of the rest of us, she would have to be octoploid (I don't even know if I spelled that right or if that even exists in nature, even with synthetic nanotubes.) Some plants are tetraploid, which means 4 sets of chromosomes. But for most humans, that is a bad thing. In order to better understand the cause of miscarriages, doctors have karyotyped babies after stillbirth. Many cases of early term miscarriage are due to triploidy in the baby--most likely, when two sperm fertilize one egg. Even rarer is tetraploidy. So if Leeloo were to have even one more copy of each chromosome, she would not be in good shape.

As an aside, I am not even getting into the "greasy solar atoms" that force skin to grow thing. Like skin cells are programmed by your DNA? Duh. Or is she genetically inferior in that aspect??

Problem 3: What are memo groups? And how do they help species "perpetuate themselves"? Ok, right off the bat, let's get this straight. No one genetic element helps you perpetuate your species. Reproduction does that. Saying she has genetic elements that allow her to regenerate from a few cells in a glove does not equate to perpetuating her species. Especially if she is the only member of her species. I don't even get where that came from.

As far the memo groups, I am totally excited about the mention of this. I might be wrong, but I think they are referring (intentionally or not) to telomeres. Every cell in the body has regions at the end of their chromosomes called telomeres. In a nutshell, these regions protect the chromosomes and also limit the number of divisions each cell goes through. The telomere region gets shorter with every cell division, until eventually the cell dies. Telomere research gets attention from the media from time to time as it is related to cell aging and/or lifespan. So the media dub telomerase research work on the "fountain of youth."

Now, I don't know how many telomere repeats humans have. There are a given number of repeats per chromosome, and the number of the repeats vary with cell age. I doubt the 4,000 and 20,000 numbers have any basis in fact. However, my guess is that maybe the screen writer read something about telomeres in the news and turned that into "memo groups" which affect lifespan and aging--allowing Leeloo to extend her life as an ancient organism, if not "perpetuate her species." That is just a hunch, but I think it would be cool if that was their intent.

Problem 4: How does Leeloo have "perfect cells"?
Okay, this just bothered me. Like, how does any scientist define a perfect cell? The general just wanted to know if she had a disease or weird abnormality or something. Does being currently disease-free mean perfect cells? Or does it mean you have super duper DNA polymerases that never, ever make an error in transcription? Does it mean you are impervious to all infection via some awesome genetic mutations of some sort? (For example, there are people who cannot contract HIV because they have a mutated, nonfunctional CCR5 receptor, which HIV needs to enter cells.) Or is physical beauty all you need to have perfect cells? I just thought this line was kind of lame. And, ever since our team did that whole eugenics project in college, the idea of "perfect" genetic anything bothers me. I know that's not what they meant in the movie, but still.

So all this made me think: How do you define a perfect being? In the movie, having more genetic material and more regenerative/healing ability made Leeloo perfect. If you were going to describe a perfect being, are those the criteria you would choose?

Coming soon: X-Men: Genetic mutations, Radiation, and Yellow Spandex

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