Science and SF tidbits: middle-aged apes, fantastic cells, and SF genetics

Some recent reading about fictional biology:
• JIM: More Compelling Than GATTACA | DNA Science Blog »

If you are looking for a science fiction film with a scientifically plausible depiction of human genetic enhancement and cloning, you might want to check out JIM. Science writer/geneticist Ricki Lewis reviews the film and says:

"Although Jim, released in late 2010, shares with GATTACA the premise of widespread genetic enhancement, it’s much more subtle and nuanced. The film struck me with its stunning possibility, and the intentional gaps in the glimpse of future history still have me thinking a week later."

And watch a commercial for "Lorigen Engineering", which offers Better Kids, By Design®'

• Author Spotlight: Tom Crosshill 

Tom Crosshill's recent short story "A Well-Adjusted Man" takes a chilling look at the potential repercussions of erasing traumatic memories might have. In his interview with Lightspeed Magazine, talks about the psychology PTSD, the biochemistry of traumatic memories, and his inspiration for the story.

And some fantastic factual biology:

• Great apes go through mid-life crisis » Nature News

Psychologist Alexander Weiss and his colleagues wanted to find out if the human "midlife crisis" that hits somewhere between our mid-30s and 50s could have a biological basis. They decided to survey zookeepers about of the mood of the chimpanzees and orangutans in their charge. They found that our great ape cousins seem to have lower sense of well-being during their late 20s to mid-30s - the equivalent to human middle age.

It would have been nice if the study had included some quantifiable data, such as the level of stress hormones or other physiological measures. It's hard to know how much bias might be introduced by asking zookeepers to try to put themselves in the minds of their charges. But still, an interesting study.

Image: Orangutan Portrait by Chester Zoo on Flickr shared under a CC BY-ND 2.0 license.

• Introduction to Cells (Vimeo)

A dramatic video showing the beauty of cells. The video was created by science teacher Frank Gregorio who makes "introduction" science videos for middle and high school teachers to use in the classroom. I wonder how well it works to capture the imagination of fidgety teenagers?

• Paralyzed dogs walk again (video)

Jasper the dachshund regained some use of his formerly paralyzed hind legs after his spinal cord was injected with cells grown from the lining of his nose. Robin Franklin and his colleagues at the University of Cambridge, used nose cells (or more precisely olfactory ensheathing cells) because, unlike most nerve cells, the nasal nerve fibers continue to grow into adulthood. The injected cells grew new nerve connections restoring function to the dog's damaged spine.

While the treatment appears to have a lot of potential it will take a lot more research before it will be tested on humans. More about the study at the University of Cambridge.

• Chemical biology: DNA's new alphabet

Chemist Eric Kool is reengineering DNA with nucleotide bases not found in nature. He's one of a number of chemists and chemical biologists who are creating new types of DNA and RNA molecules that they hope can be used for studying the function of nucleic acids and that may have new biochemical properties. But Kool explains those aren't the only reasons:

".... researchers are still driven by what Kool calls the “science-fiction appeal” of designing or even improving on living systems. Earth's early life forms may have settled on their genetic alphabet simply because they were constrained by the chemicals available. [snip]
So if nucleic acids arose independently on another planet, would they have the same bases? Benner thinks not, unless the organisms were subjected to the same constraints. Some universal rules might apply, however."

And short of discovering extraterrestrial life, it's only by synthesizing and testing new molecules to see if they might be functional in living systems.

Controlling Our Creations Through Nutritional Requirements: Lessons from Science Fiction

Last week a group of over 100 environmental and watchdog organizations released a report proposing increased government regulation of synthetic biology, which they consider "extreme genetic engineering". The report calls for a moratorium on the release and commercial use of synthetic organisms until such regulations are in place. Their position is a that drastic measures are necessary to protect both the public and the environment.

Not surprisingly, not everyone agrees with that assessment. Representatives of the biotechnology industry have pointed out that synthetic biology is part of the ongoing development of genetic engineering technology that is already covered by rules and regulations. And in 2010 a presidential bioethics commission concluded that no new regulations covering the use of synthetic biology were necessary.

One concern expressed by all parties is that "synthetic" organisms could escape into the environment.Where the disagreement lies is whether current technologies are sufficient for containment.

The presidential commission's report suggests that such organisms could be designed to have limited lifespans or to be dependent on nutrients only available in the laboratory. Such biological barriers to the spread of genetically engineered organisms have been part of the earliest recommendations for safe use of recombinant DNA technology.

The groups calling for a moratorium on the development of synthetic organisms claim that such measures are likely not sufficient and further study is required to ensure that such biological barriers work outside the laboratory.

So what is the lesson that can be learned from science fiction? If creatures are unable to synthesize all the compounds necessary for their growth and sustenance - auxotrophs - can indeed be contained if their nutritional requirements are alien enough.

"Look, we're not fools. We understand these are prehistoric animals. [...]They might have no predators in the contemporary world, no checks on their growth. We don't want them to survive in the wild. So I've made them lysine dependent. I inserted a gene that makes a single faulty enzyme in protein metabolism. As a result, the animals cannot manufacture the amino acid lysine. They must ingest it from the outside. Unless they get a rich dietary source of exogenous lysine - supplied by us, in tablet form - they'll go into a coma within twelve hours and expire. These animals are genetically engineered to be unable to survive in the real world. They can only live here in Jurassic Park...."

Take, for example, the dinosaurs in Jurassic Park. As noted in the quoted text, they were designed to only be able to live on a diet with high levels of the amino acid lysine. Since the local plants and animals in the Park wouldn't be able to supply the necessary nutrients, they could only survive on a diet provided by their handlers. That worked, at least for a while, but the setup had a fatal flaw.

Lysine is an amino acid, one of the twenty standard building blocks of protein. If an organism cannot synthesize one or more of those building blocks in its own cells, then it must eat foods that contain those amino acids to survive.

Humans normally require nine such essential amino acids in their diet, including lysine. That means that a balanced human diet must include foods rich in lysine, such as meat or beans. And that also meant that when a few dinosaurs were able to escape their island in Jurassic Park, they were able to survive on lysine-rich crops and meats on the farms managed by the local human population.

A dietary restriction that can be easily filled by eating the local produce is not a great way to contain your engineered critter. A better approach would use a nutritional requirement that cannot be so easily filled by Earthly plants or animals.

You can find that scenario in science fiction as well. In Michael Flynn's novel Eifelheim alien travelers - Krenk - were stranded in 14th century Germany where they eventually begin to starve. One of the alien scientists explains the problem to the local priest:

"There are certain . . . materials – acids is your alchemic word–which are essential for life. Perhaps four score of these acids befall in nature–and we Krenken need one-and-twenty of them to live. Our bodies produce naturally nine, so we must from our food and drink obtain the others. That food which you have shared with us holds eleven of those twelve. One is lacking, and our alchemist found it nowhere in all the foodstuffs he proofed. Without that particular acid, there is one . . . I must call it a 'firstling', as it is the first building block of the body, though I suppose it shoudl wear one of your Greekish terms."
"Proteios,"Dietrich craoked. "Proteioi."
"So. It puzzles me why you use different 'tongues' to speak of different matters. This Greekish for natural philosophy; the Latinish for matters touching your lord-from-the-sky."
Dietrich seized the Krenk by his forearm. The rough spines that ran its length pricked his hand, drawing blood. "That makes nothing!" he cried. "What of thisprotein?"
"Without this acid, the protein cannot be formed, and lacking it, our bodies slowly corrupt."

Earth foods, it seems, don't contain the full range of amino acids essential to the Krenk diet. They try to sustain themselves by extracting the essential nutrients from their dead companions. And even so they died, because their lives depended on a diet with truly alien components.

So the science fictional lesson is to engineer organisms that require amino acids or other nutritional building blocks that found nowhere in nature if you want to make sure that they are truly unable to live outside the confines of a laboratory. And that may eventually become a reality.

Scientists have successfully been able to engineer microorganisms, animal cells, and even nematode worms  that are able to incorporate several different unnatural amino acids into their proteins. And, more recently, bacteria were engineered to incorporate a normally toxic modified nucleic acid base in their DNA. So the research looks promising.

But scientists are not yet able to create animals or plants that we can be reasonably certain would be unable to live in the wild. And life is so adaptable, there may always be the possibility that biological containment will ultimately fail.

So the question remains whether escaping organisms represent a high enough danger to the environment that current research should be more tightly regulated or put on hold. Or do the potential benefits of synthetic biology - novel sources of energy, more effective drugs, improved crops - outweigh the risks? I'm hoping for the latter.

Background reading:

• "The Principals for the Oversight of Synthetic Biology" (2012) (pdf)
• "New Directions: The Ethics of Synthetic Biology and Emerging Technologies", Presidential Commission for the Study of Bioethical Issues (2010)
• Berg P. et al "Summary Statement of the Asilomar Conference on Recombinant DNA Molecules" PNAS 72;1981-1984 (1975) doi:10.1073/pnas.72.6.1981 (pdf)
• Wang, Q; Parrish, AR; Wang, L. "Expanding the Genetic Code for Biological Studies". Chemistry & Biology 16 (3): 323–36. (2009) doi:10.1016/j.chembiol.2009.03.001.
• Young TS and Schultz PG "Beyond the Canonical 20 Amino Acids: Expanding the Genetic Lexicon" J. Biol. Chem. 285: 11039-11044 doi:10.1074/jbc.R109.091306
• Freie Universitaet Berlin. "Bacterium engineered with DNA in which thymine is replaced by synthetic building block." ScienceDaily, 28 Jun. 2011.

Top image: The bacteria Shewanella putrefaciens use chemical signals to coordinate biofilm formation and other community-level behaviors. [Credit: DOE Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory.]

(Bio)Chemistry in the Movies

At ScriptPhD Doug Fowler interviews University of Nebraska chemistry professor Mark Griep and artist Marjorie Mikasen, husband and wife co-authors of ReAction!: Chemistry in the Movies.

When Mark taught General Chemistry for the first time, he gave the students a 600-word writing assignment. They were supposed to write about the chemistry in a recent newspaper or news magazine. Such an exercise promotes deep learning because the student has to process the issues and decide what is important. Mark was surprised that only 60% of the students completed the assignment and disappointed that some of them wrote about topics such as vaccines, supernovas, etc. without mentioning their chemical aspects. [...]  The next two times Mark taught General Chemistry, he projected two of these movies and had the students write about one of them. It was a great success; 95% of the students completed the assignment and the quality of writing was vastly superior.

Griep and Mikasen published that finding along with a list of movies with a focus on chemistry in the Journal of Chemical Education*, and that was ultimately expanded into the ReAction!

One of the things that struck me in reading the interview is how many of the chemistry-based movies could also be considered bioscience or at least biochemistry movies as well. Take, for example, Dr. Jekyll and Mr. Hyde, which Griep spent some time analyzing and is one of the major themes of ReAction!:

Even though Jekyll is shown mixing chemicals, Mark was intrigued that the transformative formula was not described in enough detail to know what it was supposed to represent. Stevenson’s original story describes a contaminant in a white powder that changes color when it is added to a blood-red solution but it doesn’t name the powder or the contaminant. Seeking other avenues to pursue, Mark contacted Stevenson scholar Richard Dury to find out whether any scholarship had been done on this topic. Dury told him that Stevenson’s wife Fanny had written a letter immediately before Stevenson wrote the novella in which she says he suffered from hallucinations after being treated with an ergot extract. This episode appears to have inspired Stevenson to write the story. Mark then discovered that ergot fungus is a pharmacological toolbox containing compounds to constrict arteries but also compounds to cause hallucinations. It seems that Stevenson’s doctor had treated him with the ergot extract to stop the bleeding in his lungs. The hallucinogenic side effect was caused by a minor component of the extract. This led Mark to conclude what Jekyll’s compound might be.

I love technical geekery like that! What Griep discovered was that the story's chemistry was based on a compound found in a fungus extract that has a physiological effect on the human nervous system - so both chemistry and biology.

And as Doug Fowler points out, at least part of the book tackles movie biochemistry even more directly:

And what about the chemistry of the alien microorganism in Andromeda Strain? I’m sad to report that ReAction! reveals that the mass spectral analysis in the film reports an elemental composition that can’t exist. After a bit of tweaking, the authors suggest that perhaps the alien life form could be alkaloid-like, and that the rock-like substance the life form arrived on could be a siloxane. 

It's not surprising that the biological and chemical sciences overlap in the movies, since they do in real life too - there is a lot of specialized chemistry that's required for living organisms to function.

Read the whole interview,  which includes an interesting discussion of the changing depiction of chemists in the movies,  public perception of science, and scientific literacy.

For additional information check out the companion Chemical Movies Blog. It isn't actually very blog-like, considering that each of the ten "posts" are downloadable pdf files, but it does include a list of all the movies discussed in ReAction! and a bit more discussion of some movie chemistry.

* Griep MA and Mikasen ML "Based on a True Story: Using Movies as Source Material for General Chemistry Reports" J. Chem. Educ. 2005 82(10):1501 DOI: 10.1021/ed082p1501

Image: Fredric March as Doctor Jekyll in the 1931 version of Dr. Jekyll and Mr. Hyde

Cum Grano Salis

Imagine you and the rest of your expedition are stranded on a distant planet. Food stores are running low, but the local trees produce a lovely chartreuse fruit. It's tasty and full of nutrients, but has the unfortunate side-effect of killing the experimental animals you've tested it on (as illustrated above). So what can you do?

"Cum Grano Salis" is a good old-fashioned science fiction problem story that was originally published in a 1959 issue of Astounding Science Fiction. Since figuring out the scientific solution to the problem is the whole point of the story, I won't give it away. But if you want a few hints, you can follow the links below (mousing over the links will probably give it all away):

• chartreuse is the same color as this pigment with this structure, which can have this property.
• Cum Grano Salis means this
  

Read "Cum Grano Salis" by David Gordon

(Edited to make the links clearer)
Illustration by Emsh (Ed Emshwiller) for "Cum Grano Salis", originally published in Astounding Science Fiction, May 1959, currently at Project Gutenberg. Colored by me.
Tags:science fiction, biochemistry

Science Fictional Ribosomes

"What you want is to add and subtract lengths of input DNA easily, and the feedback enzyme arrangement does this. When the feedback arrangement is in place, the molecule will open itself up for transcription much more easily, and more rapidly. Your program will be transcribed onto two strings of RNA. One of the RNA strings will go to a reader - a ribosome - for translation into a protein. Initially, the first RNA will carry a simple start-up code ––

~ Blood Music by Greg Bear, 1985

This year's Nobel Prize in Chemistry went to three scientists - Venkatraman Ramakrishnan, Thomas Steitz, and Ada Yonath - for their study of the structure and function of the ribosome", the organelle assembles proteins from amino acids based on nucleic acid sequences. Since ribosomes are essential part of the cellular machinery, it's no surprise that writers who incorporate genetics and biotechnology into their fiction include it in their fiction. They even provided the name for the bioscience-based science fiction subgenre called "ribofunk".

This classic 1971 human reenactment of protein synthesis, made by the Department of Chemistry at Stanford, can give you a pretty good idea of how ribosomes work¹. (Click for bigger video)
The much abbreviated version:

• DNA sequences that encode proteins are used as a template for the transcription of messenger RNA (mRNA)
• a ribosome attaches to the mRNA
  
• protein synthesis begins at a specific sequence of three nucleotides - the AUG start codon - within the mRNA
• a transfer RNA (tRNA) that has a sequence complementary to the start codon sequence (the anticodon) carries the amino acid methonine to the ribosome.
  
• a tRNA with an anticodon complementary to the next three nucleotides in the mRNA - the next codon - also binds the ribosome, and the amino acid it carries added to the initial methionine
• this process continues along the length of the mRNA until a stop codon is reached and the newly synthesized protein is released from the ribosome
  

Greg Bear's mention of ribosomes in Blood Music gets the process right. Other science fiction writers have used ribosomes much more fancifully in their stories. Take, for example, the 2003 short story "Junk DNA" by Rudy Rucker and Bruce Sterling:

"You’re about to tell me that Alan Turing anticipated the notion of DNA as a program tape that’s read by ribosomes. And I’m not gonna be surprised."

"One step further," coaxed Veruschka. "Since the human body uses one kind of ribosome, why not replace that with another? The Universal Ribosome–it reads in its program as well as its data before it begins to act. All from that good junk DNA, yes Janna? And what is junk? Your bottom drawer? My garbage can? Your capitalist attic, and my start-up garage!"

"Normal ribosomes skip right over the junk DNA," said Janna. "It’s supposed to be meaningless to the modern genome. Junk DNA is just scribbled-over things. Like the crossed-out numbers in an address book. A palimpsest. Junk DNA is the half-erased traces of the original codes–from long before humanity."

While they use lots of sciency terminology, the description of ribosome function doesn't make much sense. Of course ribosomes skip over "junk DNA" - they don't interact with DNA at all. And while some "junk DNA" may be transcribed into "junk mRNA", it appears that those sequences are degraded before they can be used to encode protein. I'm just not grokking how "junk DNA" that is primarily made up degenerate coding sequences², could be translated into proteins that do anything more than muck up cells, even given an Universal Ribosome Turing-like machine.³

And I should say that "Junk DNA" is an entertaining story if you can gloss over the nonsensical biology details - read it for yourself for free at Asimov's Science Fiction.

I'm hoping that science fiction writers will embrace recent research exploring complex biochemistry of our cells to come up with some interesting variations on life as we know it. I just wish they would get their terms straight (of course, that's probably just me).

Oh, and if you know other SF that uses ribosomes as a plot device, mention them in the comments. I know there is an episode of Star Trek:TNG that does, but I couldn't come up with any other examples.

1. Note that the ribosomal components are not depicted to scale. They are also a bit more colorfully dressed than you find in your typical cell.

2. What most biologists call "junk DNA" is primarily made up of repetitive DNA sequences from transposable elements, not interesteringly "scribbled over" ancient genes.

3. While DNA-based Turing machines have been proposed (and even shown to work in rudimentary form), the "computations" are not performed by protein synthesis, which is the function of ribosomes I don't think that's the case, anyway. My understanding of Turing machines is a little fuzzy. Mark Chu-Carroll has posts about them here and here and here that I'm still thinking about.

My related posts:

• Gregor Mendel Died for Your Sins! Biopunk and Ribofunk
  
• Another Day, Another Woman Wins a Nobel Prize for Nucleic Acid Biochemistry (at Women in Science)
  

Animation: "Animation of the small subunit of the Thermus thermophilus ribosome. RNA shown in orange, protein in blue." Taken from PDB 1FKA and animated by David S. Goodsell
Tags:science fiction, ribosomes