Accelerated decrepitude due to telomere length in Blade Runner?

Question

PREAMBLE: Before there is debate, let me preface this question by stating that I am indeed aware of the question Why do replicants have a short lifespan? However, none of its answers adequately answer my question below, and I believe the spirit of the question is entirely different. (That question is asking for the motivation behind giving the replicants a short lifespan, not about how the short lifespan is achieved.)

 

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In Blade Runner, Roy, Pris, Leon, and Zhora — replicants manufactured by the Tyrell Corporation — suffer from "accelerated decrepitude", to quote Pris. These particular replicants have a four-year lifespan.

In the Blade Runner universe, replicants are synthetic lifeforms that include genetically-engineered organic components, such as skin, hair, and eyes. These are grown according to custom genetic patterns supplied by the Tyrell Corporation. (In the film, we see that eye production is outsourced, for instance. The character Hannibal Chew grows eyes for replicants in development.)

The conversation between Tyrell and Roy suggests the lifespan problem is biological in nature:

TYRELL: The facts of life. To make an alteration in the evolvment of an organic life system is fatal. A coding sequence cannot be revised once it's been established.

When pressed for more information, Tyrell explains:

Because by the second day of incubation, any cells that have undergone reversion mutations give rise to revertant colonies like rats leaving a sinking ship. Then the ship sinks.

After Batty offers a different possible solution, Tyrell counters with:

...but it does give rise to an error in replication so that the newly-formed DNA strand carries the mutation....

Assuming Tyrell is telling the truth, then there is a natural question:

Is Tyrell's explanation indicative of exceptionally short telomeres in the cells of replicants?

The types of problems regarding life extension put forward by Tyrell would support this. One way to combat the telomere length problem would be to use telomerase to protect nucleotides on chromatids. However, this would theoretically leave the subject open to opportunistic malignancies resulting from mutated cells that form stable colonies due to reduced cell apoptosis.

Is this what Tyrell is describing?

Answer 1

Pretty sure the explanation is just technobabble, with no coherent rationale for why their lifespans couldn't be extended in terms of any real-world science, telomeres or otherwise. Someone asked a question about the science in Tyrell's dialogue on quora.com here, and got one answer from "Joshua Engel" saying "Well... ethyl methyl sulfone is an alkylating agent, and it is mutagenic. ... The rest is gibberish", followed by a much more detailed answer from "Zachary Williams, Graduate Student, Molecular Microbiology, Tufts University" which I'll just quote in full:

As Joshua said, the rest is gibberish, but there are different levels of gibberish, i.e., some parts are just wrong, and other parts could be characterized as "not even wrong."

1: " To make an alteration in the evolvement of an organic life system is fatal. A coding sequence cannot be revised once it's been established."

Common misconception. The vast majority of possible point mutations in the human genome are very close to neutral in their effect on phenotype (i.e., observable changes in organismal form and function). There are a number of reasons for this:

First, most of the human genome is...well, I will not say "non-functional," 'cause that would piss some people off, so, instead, I'll say, rather, that any potential function is not constrained by sequence. Maybe it's a spacer or has some global structural significance (a la centromeres), but it shows no signs of purifying selection. You can google the Encode controversy if you want to get way more reading material than you could ever finish on this topic... Anyway. Also a lot of it is clearly derived from transposons and/or viruses, and while such sequences can be co-opted by evolution to serve some function, most of them are pretty clearly not. For one, all the genes tend to be mutated and deleted all over the place. Also, you see little islands in the genome where a number of unrelated transposons and/or endogenous viruses are crammed together, which I like to think of as "islands of no selection," where any old DNA sequence can jump in with no consequences to the host, leading to an accumulation of junk, over many many generations.

Second, for protein coding sequences, most single point mutations are close to neutral, either because the change in DNA sequence does not change the actual amino acid sequence (google genetic code degeneracy), or the amino acid coded for by the mutation is sufficiently similar chemically and biophysically to the wild type aa, or the amino acid in question is simply not very important to the protein's function. A really interesting paper on this came out recently: http://www.ncbi.nlm.nih.gov/pubmed/23041932 They mutated every amino acid in a certain protein to every other amino acid, and characterized the changes in function. Most mutations had little to no effect.

Thirdly, other reasons but I'm tired of this.

2. "Because by the second day of incubation, any cells that have undergone reversion mutations give rise to revertant colonies like rats leaving a sinking ship. Then the ship sinks."

Um...no idea. Those are all sciencey words, yes. Reversion mutations are a real thing. Revertant colonies are a real thing. Incubation is a real thing. But the sentences convey no meaning to me.

3. "EMS recombination"

Not a real thing AFAIK. EMS causes point mutations, not recombination.

4."It created a virus so lethal the subject was dead before he left the table."

No. Maaaaybe they were thinking of DNA methylation, rather than alkylation. Methylation of certain sites on DNA is a very important form of genetic regulation. The virus angle comes in because methylation can silence gene expression, and it appears that one important role of this is silencing viruses that have inserted their DNA into ours (google endogenous retroviruses, my favorite things in the whole world). So, theoretically, a de-methylating agent of some sort could reactivate a dormant provirus, causing Bad Things. Or good things; people are currently trying to use this as a way to cure HIV, by reactivating latent HIV in cells so that anti-HIV drugs can kill it.

5. "Then a repressive protein that blocks the operating cells."

Repressor proteins are a thing, yes. Not sure what they have to do with...whatever the topic is, which I'm not really clear on. Operating cells: no idea.

6. "Wouldn't obstruct replication, but it does give rise to an error in replication so that the newly formed DNA strand carries the mutation and you've got a virus again."

Hrm. Yeah, no clear meaning to me. Not even wrong.

The end.

Answer 2

The Tyrell speech about replication errors and viruses was invented for the Blade Runner film. The novel Do Androids Dream of Electric Sheep simply points out that android metabolism is faster than human metabolism and that androids die because of poor to nonexistent cell replacement. Basically, like any machine with moving parts that aren't replaced, they wear out.

RACHAEL:“They never could solve that problem. I mean cell replacement. Perpetual or anyhow semi-perpetual renewal. Well, so it goes.”

Answer 3

The exact mechanism for limiting lifespan is never revealed in the film. However, it would not seem to be something as "simple" as telomere length since that would lead to some variability in lifespan and presumably signs of aging (e.g., like Sebastian). However, not only does Roy die looking exactly as he did at incept, when he dies he really just seems to "switch off." Certainly, it wasn't as abrupt as a switch. He obviously knew it was coming, as the film made clear by his use of a nail through the hand to delay onset of death. But it was only a matter of minutes from the earliest such signs conveyed by the film until his death.

EDIT: I've rearranged my answer to place the answer to the OP's question at the top. The remainder of my answer remains below and serve less to answer the OP's question, and more to rebut other answers/comments.

Regarding motivation, the movie itself answers this question directly:

Deckard: Well I don't get it. What do they risk coming back to earth for? That's unusual. Why--what do they want out of the Tyrell Corporation?

Bryant: Well you tell me pal, that's what you're here for.

Deckard: [funny look]. [pause] What's this?

Bryant: Nexus 6. Roy Batty. Incept date 2016. Combat model. Optimum self-sufficiency. Probably the leader. This is Zhora. She's trained for an off-world kick-murder squad. Talk about beauty and the beast, she's both. The fourth skin job is Pris. A basic pleasure model. The standard item for military clubs in the outer colonies. They were designed to copy human beings in every way except their emotions. The designers reckoned that after a few years they might develop their own emotional responses. You know, hate, love, fear, anger, envy. So they built in a fail-safe device.

Deckard: Which is what?

Bryant: Four year life span.

That explanation in the film is straightforward and to set it aside means you have to disbelieve Bryant. Leaving aside his obvious "charm", I see no evidence in the film that Bryant shouldn't be trusted on this seemingly benign bit of background information established early in the film, particularly where he's never established as being an unreliable narrator in other ways.

I take it that Tyrell's proclamation that "[t]o make an alteration in the evolvement of an organic life system is fatal" and "[a] coding sequence cannot be revised once it's been established" is intended to convey the idea that Tyrell could have given them some other lifespan, but cannot do so after the fact. Though not established as fact per se, I believe Deckard is a replicant which if true also establishes that 4 year life span is not an artifact of being a replicant (due to, e.g., a lack of "cell replacement"), but a design choice.