Free Friday Flick: Donovan's Brain, Curt Siodmak, and the science of memory

This week's recommended free online movie is the 1953 science fiction horror film Donovan's Brain, starring Nancy Davis (later Nancy Reagan) and Lew Ayres, and directed by Felix Feist.

The basic plot: a multi-millionaire's airplane crashes in the desert, a scientist keeps his brain alive in a tank, and there are unintended consequences (of course)!

The movie is based on Curt Siodmak's best-selling 1942 novel by the same name. While Siodmak is probably best known as a Hollywood screenwriter for horror movies like The Wolf Man, he also wrote a number of science fiction novels. And he wasn't just interested in cheap thrills. In a 1997 interview, Siodmak talks about how took pains to assure scientific accuracy in his novels.

I have a trick with writing sci-fi [. . .] . In all these books there is a tremendous amount of research involved. I pick up the telephone and call the most important scientist I can think of in that field in America. So far they have all worked with me because they all are frustrated writers anyhow. If someone is writing [a book] for them, then they can correct it, which makes them feel they wrote it. I siphon off years of knowledge and research from those people for a small fee, or for a percentage of the book, whatever the case. But at the end, I have a story that is scientifically right. 

Apparently not one to mince words, Siodmak doesn't paint a pretty picture of scientists as wanna-be writers. I suppose it's a small consolation that he compensated them for their time and expertise.

In the novel version of Donovan's Brain, the brain is kept alive in a mixture of "blood serum" and human brain "tissue ash". That does appear to be based on the latest science in organ culture at the time the novel was written.

In the 1930s aviator Charles Lindbergh worked with biologist Alexis Carrel to develop devices to keep organs alive in culture. At the time, blood serum was one of the standard components of organ culture medium. Their work was widely known even outside scientific circles, and even making the cover of Time Magazine in 1935.

Around the same time, Dr. Fenton B. Turck published a book discussing his experiments indicating that tissue ash - tissues baked in an oven, then dissolved in saline solution - was usually toxic when injected into animals, but could stimulate cellular growth in vitro in low doses. He termed the active component "cytost", which appeared to be a species specific. So extracts made from dog tissues would be active more active when injected into dogs, than it would in pigs or monkeys. Taking that to it's logical conclusion, presumably such extracts from human brains would only work to stimulate the growth of other human brains. Unfortunately Turck's results were not reproducible, but that doesn't stop it from being a decent science fictional premise. (Turck also speculated about the possible toxic nature of mummy dust in Egyptian tombs, which is another great science fiction-horror premise.)

I couldn't find any indication that Siodmak had talked to scientists about how to grow a brain in a tank, but it seems that he could have derived inspiration just from the science news in the popular press.

Hauser's Memory, Siodmak's 1968 sequel to Donovan's Brain, likely was inspired by the James McConnell's research into memory transfer in cannibalistic planarians, which seemed at the time to be mediated by RNA. In developing the background for the novel, Siodmak also studied people with memory loss. As he described it:

 In researching that book, I worked at this hospital where they had 2,500 retarded children, insane and old people, too. I remember two old guys asking me, "Tell me, sir, are we going to lunch or coming from lunch?" They didn't know which. But they remembered what they had done when they were eight years old. So we might have a greater amount of RNA—ribonucleic acid—when we are young. As we get older, that substance dries up. That's why we can't learn new languages so easily when we get older, but kids pick it up right away. The growing process of the brain is based on RNA, which is why we learn so fast as kids. Even memory—and also what is right, what is wrong—is information you pick up easily as a child.

So what about the movie version?

There were three mid-20th century movies based on Donovan's Brain. Apparently Siodmak didn't care much for any of them.  He claims he didn't even bother to watch the 1953 Feist-directed version, because in it "God destroys Donovan's brain with a thunderbolt." So be warned that the movie has less scientific plausibility than the novel. Still, it's a decent B-movie for this holiday weekend.

Check it out:

• Watch Donovan's Brain at Hulu.com. Note: this movie may only be available in the US.
• Listen to a 1944 reading of Donovan's Brain, plus a parody by Orson Welles, on the old time radio show "Suspense".

 Further reading for the technically inclined:

• Backstory 2: Interviews with Screenwriters of the 1940s and 1950s, ed. Patrick McGilligan (1997) 
• Turck FB "The Action of the Living Cell: Experimental Researches in Biology" (1933) 
•  Lindbergh CA "An apparatus for the culture of whole organs" J Exp Med 62(3): 409-431 (1935) (Note that the text abstract is for the wrong article. Click on the Full Text link for the correct abstract) 
•  Carrel A "The culture of whole organs" J Exp Med 65(4): 515-526 (1937)

Image: The quintessential brain in a jar, by Flickr user Kaushik Narasimhan, licensed under Creative Commons Attribution 2.0 Generic

Erasing Memory

"What is your name?"

[...] Norman Kent's name leaped into his mind, in response to the question - and vanished.

It was not simply the name itself tha t vanished. with it went eh associations and mnemonics keyed to it in his memory. Jokes from childhood about Superman, jokes from adolescence about the Norman Conquest, jokes from he jungle about the Norman DeINvastion. An old Simon Templar novel he had read many eyars ago, and remembered all his life because it featured a hero named Nroaml Kent, who laid down his life for his friends. Certain times when the speaking of his name had been a memorable event. The sight of his dogtags. The nameplate on the desk in his office at the University. His face in the mirror.

If you take a hologram of the word "love" and try to read a page of print through it, you will see only a blur. But if the word "love" is printed anywhere on that page, in any typeface, you will see a very bright light at that spot on the page. In much the same way, one of the finest computers in the world riffled through the "pages" of Norman Kent's memory, scanning holographs with a reference standard consisting of the sound of his name. Each one that responded strongly was taken from him.

All this took place at computer speed. Without perceptible hesitation the man on the table answered honestly and happily, a puppy fetching a stick. "I don't know."
~ Mindkiller, Spider Robinson

The ability to erase specific memories is an old one in science fiction. While not the first to use it as a plot device, Robinson's 1982 novel Mindkiller goes into detail about how the erasure of something as simple as a name from the mind requires the removal of many different associated memories. And unlike the characters in Eternal Sunshine Of The Spotless Mind, the man who is given the treatment is well-aware of the holes in his memory.

In this week's issue of Neuron, scientists at the Shanghai Institute of Brain Functional Genomics and the Brain and Behavior Discovery Institute at the Medical College of Georgia in Augusta reported the first step in developing such technology: they successfully erased specific fearful memories in mice while those memories were being retreived. The specific method the neuroscientists used won't be easily transferred to humans because it involved specially constructed transgenic mice that allow induction ofexpression of high levels of an enzyme involved in the memory process (CaMKII) while the memory to be erased was being recalled. Even so, the study's principal investigator, Joe Z. Tsien, has speculated about the method's usefulness to treat people suffering from traumatic memories:

"While memories are great teachers and obviously crucial for survival and adaptation, selectively removing incapacitating memories, such as traumatic war memories or an unwanted fear, could help many people live better lives," Tsien said.

It's not clear, however, whether even selective removal of such memories would leave the patient with the feeling that some important part of them was missing.

Original article: Cao X, et al. "Inducible and Selective Erasure of memories in the Mouse Brain via Chemical-Genetic Manipulation" Neuron 60(2): 353-366 (2008) doi:10.1016/j.neuron.2008.08.027

Tags:memory, neuroscience

Stephen Nottingham: Screening DNA

In 2000, agricultural biologist and writer Stephen Nottingham published a book about genetic engineering technology in the movies, Screening DNA: Exploring the Cinema-Genetics Interface. While print copies aren't available in the US*, he has kindly provided the full text on his web site. With chapters on cloning, resurrecting dinosaurs, designer babies, alien DNA, scientist biopics he takes a look a wide range of films with genetic themes. He concludes that, while biotechnology is often portrayed negatively (and inaccurately) in the movies, he believes that they have little influence on the politics surrounding use of genetic engineering, cloning and other technology.

The power of genetic engineers to radically modify organisms is usually exaggerated, while misconceptions about scientists' ability to regenerate life from DNA abound. The benefits of genetic engineering are often acknowledged, particularly advances toward curing diseases such as Alzheimer's. (55) However, whatever the benefits, the risks always tend to outweigh them, because narrative conventions require a crisis. The potential threats posed by genetically modified ("alien") organisms are consistently exaggerated. Misconceptions about cloning are everywhere in the movies. Clones have often been portrayed as exact instant copies of adults, whereas clones arise from embryos. In the movies, clones are derived from originals, who have precedence, unlike real clones who are equals. Clones are also either erroneously seen as inferior copies, or as the child rather than twin of a cell donor. No cloning movie can be said to further advance the public understanding of science. Meanwhile, human genetic enhancement is represented as a highly predictive science, which overemphasises the role of genes in determining complex human behaviours. Movies therefore reiterate a key, but politically-loaded, assumption of the genetic determinism. Artificially assisted reproduction technology, from artificial insemination, through IVF, ICSI, PGD, to the uses of human cell cloning, continues to be branded with the label "unnatural practice" in the movies. The nature of the scientific method and the motives of scientists, corporations and governments are typically misconstrued. To cap it all, genes have been given a mythic or spiritual aura, a genetic essentialism that conveys the impression that DNA is somehow in god's realm and not something for man to meddle with. Despite all this though, movies have tended to reflect society's anxiety about biotechnology, rather than creating that anxiety.

In the long-run, it will not be movies that stop technological progress by influencing public attitudes, but well-informed considerations of the benefits and risks of the technology. An important debate is now taking place, with the messages of multinational corporations, politicians, environment and consumer groups, and the media reaching a large proportion of the population. If human cloning, transgenic crops, or any other application of biotechnology is stopped, then it will not have been movies that were responsible, but a concerned citizenry worried about the type of world their children will grow up in. Important technological developments that affect everyone within a democracy, for example, those that affect the food supply, should not proceed without a popular consensus approving them. It is up to politicians, scientists and corporate biotechnologists to put the case for each application of biotechnology to the public. If the public do not buy it, then so be it.

I have to disagree with his final conclusion. The debate surrounding the use of biotechnology is driven not only by "concerned citizenry" but by politicians, and religious and corporate groups that have their own agendas. There is a ton of misinformation (and outright lies) promoted by lobbyists for those groups, and, not surprisingly, members of the public who are largely informed on scientific topics by popular culture are likely to have opinions about biotechnology that are based on emotional appeals and its sensationalist depiction in the movies than on careful analysis of the facts. I hate to think that our public policy is being set by the special interest groups that are best able to spin an entertaining tale.

In addition to Screening DNA, Nottingham's web site includes his "Biologist at the Cinema" series of essays and reviews that look at some popular science fiction films from a biologist's perspective:

• A.I. Artificial Intelligence (intelligence and consciousness)
• Blade Runner (clones, DNA and memory)
• Jurassic Park 3 (genetic engineering and ecology)
• Planet of the Apes (animal experimentation and evolution)
• The 6th Day (clones)
  
• Solaris (clones)
  

* You can order a hard-cover copy of Screening DNA from Amazon.co.uk
Tags:Stephen Nottingham, movies, science fiction, biotechnology, genetic engineering, cloning

Amy Sterling Casil: Perfect Strangers

Denny was born with HLHS. That's an acronym for hypoplastic left heart syndrome. Hypoplastic left heart syndrome is universally fatal, if left untreated. Even now, there are babies that do not survive, even with full-lenght clone DNA therapy administered in-utero.
When at five months of pregnancy, Carolyn went for a high-level ultrasound that determined Denny had HLHS, it seemed like the most natural thing in the world to try gene therapy. The doctors explained how the heart healed itself as the baby grew.
~ "Perfect Strangers", Amy Sterling Casil

Amy Sterling Casil's "Perfect Strangers" is a touching story of a father and his genetically engineered son. Her preface notes that the story was inspired by her own experience, which makes it all the more moving for me:

My son Anthony died in 2005. He was born with Down Syndrome. I began thinking about what this story became when the genetic counselor discussed chromosomal abnormalities with me, saying that a cure for them was a long way off, but other genetic illnesses would soon be cured. Every therapy mentioned in the story is currently being developed. The story is fiction; the feelings are real.

While the technology is certainly being discussed and developed, I don't think we are anywhere near to routine human genetic engineering. It's not just that there are technical difficulties (and there are), but serious ethical concerns. Take, for example, this week's report of the first genetically modified human embryo. The scientists didn't attempt to make any changes to human genes; instead they inserted DNA that encodes a fluorescent protein allowing the modified cells could be tracked. The embryo that was used was abnormal and nonviable, and was never intended to implanted or even develop beyond five days. Even so, there research provoked intense debate and discussion. I do believe that genetic engineering technology will eventually improve to the point that it can be used safely in humans, but the ethical concerns that arise from the technology will be harder to overcome.

"Perfect Strangers" was originally published in the September 2006 issue of Fantasy & Science Fiction. You can read it free online (pdf).

Tags:science fiction, genetic engineering

Science in the Movies: Science Fiction that Gets it Right?

Michael Marshall at New Scientist has picked out five science fiction movies that "contain some accurate, plausible science. They may not be completely realistic, but they get it right when it matters most." Three of their five choices are based on the biological sciences:

Eternal Sunshine of the Spotless Mind (2004) makes the list for its depiction of how memory is stored.

Sensibly, the film depicts memory as essentially a network of links. In its frenetic second half, Joel is asleep while the technicians "operate" on his mind. We follow as he careens from recent memories of his relationship to those of his earliest childhood.

Alien (1979) gets a thumb up for its depiction of the alien's life cycle, despite it's fantastic growth rate.

Every element of the life cycle can be found in nature, variously in parasites, robber wasps and social insects. Much of the film's suspense comes from the filmmakers' decision to let events unfold without too much explanation – the viewer has to piece the life cycle together for themselves.

Perennial favorite Gattaca (1997) is included for its "grimly plausible vision of a society dominated by genetic prejudice."

The other two on the list are 2001: A Space Odyssey (1968), for its depiction of space travel and Solaris (1972, 2002) for its "portrayal of the limits of science and of human understanding."

The great thing about all these movies is not just that (at least some) of the science they depict is plausible, but that they are entertaining. There is no reason why the science has to be awful to make a good movie.

Tags:science fiction, biology, Eternal Sunshine of the Spotless Mind, Alien, Gattaca, movies

Repressed Memories

On a hygenic bed Douglas Quail lay breathing slowly an regularly, eyes half-shut, dimly conscious of those around him.
"We started interrogating him," Lowe said, whit-face. "To find out exactly when to place the fantasy-memory of him single-handedly having saved Earth. And strangely enough --"
"They told me not to tell," Douglas Quail mumbled in a dull drug-saturated void. "That was the agreement. I wasn't even supposed to remember. But how could I forget an event like that?"
I guess it would be hard, McClane reflected. But you did -- until now.
-- "We Can Remember it For You Wholesale", by Phillip K. Dick

The plot is a familiar one. Our heroine always felt a little uncomfortable, like something was a bit "off" in her life. Then, out of the blue, a familiar face or a smell or a song triggers a rush of memory. Something terrible happened to our heroine, so terrible that that specific memory was completely suppressed. What happens next depends on the genre: she'll crumble, or investigate, or seek revenge. Of course, in science fiction it can be more complicated. Perhaps the repressed memory was physically erased, or may actually turn out to be a virus masquerading as a memory engram.*

It's used so often it's a cliché, but I've never considered whether it's something that happens in real life. Researchers at the Biological Psychiatry Laboratory argue that repressed memories, AKA dissociative amnesia, is actually a "romantic notion dating from the 1800s, rather than a scientifically valid phenomenon." Interestingly, they base their hypothesis on the absence of descriptions of repressed (and regained) memories in fiction and non-fiction prior to the 19th century (pdf). Most psychological phenomena - depression, anxiety, delusions, hallucinations, dementia, and regular amnesia - are documented in literature throughout the ages.

They turned to the wisdom of the masses, offering $1000 for any example of dissociative amnesia written before 1800. Their Repression Challenge was won by the person who submitted the libretto of the opera Nina (pdf), written by Marsollier in 1786, so just barely before the turn of the 19th century. Their conclusion is that

". . . dissociative amnesia may seem very real, and even commonplace, to contemporary clinicians an their patients, just a s pseuo-paralysis was commonplace at the Salpetriere of Charcot in the 1890s, or pseudo-seizures at the Salem witch trials in the 1690s's. But each of these syndromes appears to have represented a cultural product of its time, rather than an actual neurological disorder of the brain. Viewed in this light, dissociative amnesia is best characterize as a 'culture-bound' form of conversion disorder, a phenomenon pecular to our modern Wsestern culture.

I find it amazing that our psychological condition may be influenced by literature, just as literature is built on our psyches. I wonder what else we may take for granted that is just a figment of our collective imaginations.

* In addition to the stories I linked to – Dick's "We Can Remember it For You Wholesale" which inspired the movie Total Recall, Spider Robinson's Mindkiller, the Star Trek Voyager Episode "Flashback," and the Enterprise episode "The Seventh" – check out this discussion at Lexicon Harlot for lots of other science fictional examples.

(Information on the Repression Challenge via Mind Hacks)

Tags:science fiction, repressed memory, psychology

Reading Memories

In the trade, the legitimate trade - I've never done porno - we call the raw product dry dreams. Dry dreams are neural output from levels of consciousness that most people can only access in sleep. But artists, the kind I work with at the Autonomic Pilot, are able to break the surface tension, dive down deep, down and out, out into Jung's sea, and bring back - well, dreams. Keep it simple. I guess some artists have always done that, in whatever medium, but neuroelectronics lets us access the experience, and the net gets it all out on the wire, so we can package it, sell it, watch how it moves in the market.
- William Gibson "The Winter Market" (1986)

In science fiction it's not uncommon for memories to be uploaded into computers, either to create a facsimile of a living person, or to create marketable "experience" downloads. Gibson wasn't the first - Dick's "We can remember it for you wholesale" (the inspiration for Total Recall) described implanted memories for sale back in 1966. While it's a seemingly easy process in fiction, the fact is that we are only just starting to understand how the brain organizes and stores memories.

The July issue of Scientific American (available as a free pdf) takes a look at the how memories are stored in mice. The article is written by Boston University professor Joe Tsien, whose claim to fame is the generation of a mouse strain that could learn faster and remember longer, which he aptly named Doogie*. His recent research has been to understand how memories form in mice. It appears that memories are stored in groups of neurons that relate to different aspects of the recorded event:

The brain relies on memory-coding cliques [of neurons] to record and extract different features of the same event, and it essentially arranges the information relating to a given event into a pyramid whose levels are arranged hierarchically, from the most general, abstract features to the most specific aspects. We believe, as well, that each such pyramid can be thought of as a component of a polyhedron that represents all events falling into a shared category, such as "all startling events."

Each specific memory involves a unique set of these "neuronal cliques," which makes up what Tsien calls the "memory code." A stored memory could be read, at least in theory, by determining which of the groups of neurons are associated with it. Such information could be uploaded into computers that are designed along the same hierarchical principals, although Tsien doesn't anticipate us having that ability any time soon.

If all our memories, emotions, knowledge and imagination can be translated into 1s and 0s, who knows what that would mean for who we are and how well we will operate in the future. Could it be that 5,0000 years from now, we will be able to download our minds onto computers, travel to distant worlds and live forever in the network?

For more on the current state of the art in brain scanning, check out the ABC (Australian, not American) radio called "All in the Mind" that looks at the use brain scans in the courtroom (via Mind Hacks).

If you are interested in offloading some your own memories, the Braintec web site claims to have developed a way to perform "human uploads." You can even donate your extra computer processing cycles to their distributed analysis system (a la SETI@Home) to process the uploaded memories. Install the .exe file at your own risk**.

* For young readers (or those who didn't watch TV in the late 80s), "Doogie" is a reference to Doogie Howser, M.D.

** Just to be clear, SETI@Home is a legitimate project which you can install on your home computer to help the Search for Extraterrestrial Intelligence. Similarly Folding@Home uses your computer to work on protein folding problems. In contrast, the Braintec program is an unknown quantity.

Tags:memory code, intelligence