Optograms: images from the eyes of the dead

On a cloudy fall morning in 1880, Willy Kuhne, a distinguished professor of physiology at the University of Heidelberg, waited impatiently for 31-year-old Erhard Reif to die. Reif had been found guilty of the reprehensible act of drowning his own children in the Rhine, and condemned to die by guillotine. Kuhne’s eagerness for Reif’s death, however, had nothing to do with his desire to see justice served. Instead, his impatience was mostly selfish—he had been promised the dead man’s eyes, and he planned to use them to quell a bit of scientific curiosity that had been needling him for years.

For the several years prior, Kuhne had been obsessed with eyes, and especially with the mechanism underlying the eye’s ability to create an image of the outside world. As part of this obsession, Kuhne wanted to determine once and for all the veracity of a popular belief that the human eye stores away an image of the last scene it observed before death—and that this image could then be retrieved from the retina of the deceased. Kuhne had given these images a name: optograms. He had seen evidence of them in frogs and rabbits, but had yet to verify their existence in people.

Optograms had become something of an urban legend by the time Kuhne started experimenting with them. Like most urban legends, it’s difficult to determine where this one began, but one of the earliest accounts of it can be found in an anonymous article published in London in 1857. The article claimed that an oculist in Chicago had successfully retrieved an image from the eye of a murdered man. According to the story, although the image had deteriorated in the process of separating the eye from the brain, one could still make out in it the figure of a man wearing a light coat. The reader was left to wonder whether or not the man depicted was, in fact, the murderer—and whether further refinements to the procedure could lead to a foolproof method of identifying killers by examining the eyes of their victims.

Optograms remained an intrigue in the latter half of the 19th century, but they became especially interesting to Kuhne when physiologist Franz Boll discovered a biochemical mechanism that made them plausible. Boll identified a pigmented molecule (later named rhodopsin by Kuhne) in the rod cells of the retina that was transformed from a reddish-purple color to pale and colorless upon exposure to light. At the time, much of the biology underlying visual perception was still a mystery, but we now know that the absorption of light by rhodopsin is the first step in the visual process in rod cells. It also results in something known as “bleaching,” where a change in the configuration of rhodopsin causes it to stop absorbing light until more of the original rhodopsin molecule can be produced.

In studying this effect, Boll found that the bleaching of rhodopsin could produce crude images of the environment on the retina itself. He demonstrated as much with a frog. He put the animal into a dark room, cracked the windows’ shutters just enough to allow a sliver of light in, and let the frog’s eyes focus on this thin stream of light for about ten minutes. Afterwards, Boll found an analogous streak of bleached rhodopsin running along the frog’s retina.

An optogram Kuhne retrieved from the retina of a rabbit, showing light entering the room through a seven-paned window.

Kuhne was intrigued by Boll’s research, and soon after reading about it he started his own studies on the retina. He too was able to observe optograms in the eyes of frogs, and he saw an even more detailed optogram in the eye of a rabbit. It preserved an image of light coming into the room from a seven-paned window (see picture to the right).

Kuhne worked diligently to refine his technique for obtaining optograms, but eventually decided that—despite the folklore—the procedure didn’t have any forensic potential (or even much practical use) at all. He found that the preservation of an optogram required intensive work and a great deal of luck. First, the eye had to be fixated on something and prevented from looking away from it (even after death), or else the original image would rapidly be intermingled with others and become indecipherable. Then, after death the eye had to be quickly removed from the skull and the retina chemically treated with hardening and fixing agents. This all had to be done in a race against the clock, for if the rhodopsin was able to regenerate (which could even happen soon after death) then the image would be erased and the whole effort for naught. Even if everything went exactly as planned and an optogram was successfully retrieved, it’s unclear if the level of detail within it could be enhanced enough to make the resultant image anything more than a coarse outline—and only a very rough approximation of the outside world.

Regardless, Kuhne couldn’t overlook the opportunity to examine Reif’s eyes. After all, he never did have the opportunity to see if optograms might persist in a human eye after death and—who knew—perhaps optograms in the human eye would be qualitatively different from those made in the eyes of frogs and rabbits. Maybe human optograms would be more accessible and finely detailed than he expected. Perhaps they might even be scientifically valuable.

Reif was beheaded in the town of Bruschal, a few towns over from Kuhne’s laboratory. After Reif’s death, Kuhne quickly took the decapitated head into a dimly-lit room and extracted the left eye. He prepared it using the process he had refined himself, and within 10 minutes he was looking at what he had set out to see: a human optogram.

Kuhne’s drawing of The image he saw when he examined Erhard Reif’s retina.

So was this the revolutionary discovery that would change ophthalmic and forensic science forever? Clearly not, or murder investigations would look much different today. Kuhne made a simple sketch of what he saw on Reif’s retina (reprinted to the right in the middle of the text from one of Kuhne’s papers). As you can see, it’s a bit underwhelming—certainly not the type of image that would solve any murder mysteries. It confirmed that the level of detail in a human optogram didn’t really make it worth the trouble of retrieval. Kuhne didn’t provide any explanation as to what the image might be. Of course any attempt to characterize it would amount to pure speculation, and perhaps the esteemed Heidelberg physiologist was not comfortable adding this sort of conjecture to a scientific paper.

This experience was enough to deter Kuhne from continuing to pursue the recovery of human optograms, and it seems like it would be a logical end to the fascination with optograms in general. The idea of using them to solve murders, however, reappeared periodically well into the 1900s. In the 1920s, for instance, an editorial in the New York Times critiqued a medical examiner who had neglected to take photographs of a high-profile murder victim’s eyes, suggesting that an important opportunity to retrieve an image of the murderer had been lost.

But as the 20th century wore on and our understanding of the biochemistry of visual perception became clearer, interest in optograms finally dwindled. Those who studied the eye were not convinced of their utility, and that opinion eventually persuaded the public of the same. It’s intriguing to think, though, how different our world would have been if optograms really had lived up to the hype. It certainly would have simplified some episodes of CSI.


Lanska DJ. Optograms and criminology: science, news reporting, and fanciful novels. Prog Brain Res. 2013;205:55-84. doi: 10.1016/B978-0-444-63273-9.00004-6.

2-Minute Neuroscience: Concussions

A concussion is a type of mild traumatic brain injury that occurs when rapid movement of the head or an impact to the head causes the brain to move within the skull, potentially stretching axons and damaging cell membranes of neurons. In this video, I discuss the biochemical and structural changes in the brain that are associated with the symptoms of a concussion.

2-Minute Neuroscience: Trigeminal Nerve (Cranial Nerve V)

The trigeminal nerve (cranial nerve V) is the main sensory nerve of the head, and carries information about touch, pain, temperature, and proprioception from the face and head. It also has motor functions, which involve controlling the muscles of mastication (chewing). In this video, I discuss the anatomy and function of the trigeminal nerve, as well as describe what can happen when the nerve is damaged.

Know Your Brain: Alzheimer's Disease

Background

Auguste Deter, the subject of Alois Alzheimer’s case study describing what would come to be known as Alzheimer’s disease.

In 1906, at a meeting of psychiatrists in Germany, Alois Alzheimer gave a lecture in which he detailed the unusual case of Auguste Deter. Alzheimer had encountered Deter about five years prior, when he was working as an assistant physician at a psychiatric institution in Frankfurt am Main in Germany. Deter had made an impression on Alzheimer because she was relatively young, but was suffering from a unique constellation of severe, dementia-like symptoms.

Deter was 51 years old when Alzheimer met her. Her most noticeable symptoms had begun in the previous year, when her behavior became alarmingly erratic. First, she began displaying uncharacteristic jealousy of her husband. Then, her memory started to deteriorate rapidly. She would easily become disoriented, and often lose touch with reality, consumed with paranoid delusions. As Alzheimer described it:

“…sometimes she thought somebody was trying to kill her and started to cry loudly… Sometimes she greets the attending physician like company…sometimes she protests loudly that he intends to cut her…Then again she is completely delirious, drags around her bedding, calls her husband and daughter and seems to suffer from auditory hallucinations. Often she screamed for many hours.”

Alzheimer was intrigued by the case. Deter seemed to be afflicted with a form of senile psychosis, which was probably a symptom of dementia. But it was rare to see dementia this severe in someone so young.

In addition to being a physician, Alzheimer was also an industrious researcher. He was intensely interested in pathological changes in the nervous system that accompanied psychiatric and neurological illnesses. Thus, when Deter died at the age of 55, Alzheimer requested her brain be sent to him for study. Upon examination, Alzheimer found the brain had suffered widespread neuronal loss and was riddled with abnormal structures (later learned to be the protein deposits discussed below).

Deter’s age, symptom profile, and neural deterioration convinced Alzheimer that she was a unique case. The psychiatrists present at his lecture on the topic didn’t seem to feel the same way, however, as there were no questions, comments, or other indications of interest following his presentation (the attendees seemed much more intrigued by the next presentation on compulsive masturbation). But little did Alzheimer know that his lecture would mark a historic moment, as only a few years later the renowned psychiatrist (and Alzheimer’s colleague) Emil Kraepelin introduced the term Alzheimer’s disease (AD) to describe an early-onset form of senile dementia.

It wasn’t until the late 1970s that researchers began to recognize that most cases of AD are not early-onset, and occur in patients over the age of 65. Today, AD is one of the greatest health concerns for people in this age group, and due to the fact that this population continues to increase in number (which is, ironically, a result of our improved ability to keep people alive longer), it is a rapidly growing problem. Today, about 1 in every 10 people over the age of 65 suffers from AD, and the number of people with AD in the United States is expected to nearly triple by the year 2050.

What are the symptoms of Alzheimer’s disease?

AD is a type of dementia, a term used to describe a condition that involves memory loss and other cognitive difficulties. There are a number of different types of dementia, however—each with its own causes and specific symptom profile. AD is just one variation.

The best-recognized sign of mental decline in AD is problems with memory. In the early stages of the disease, this often manifests as difficulties creating new memories, and problems are especially noticeable with declarative memories, or memories about information and events (as opposed to memories for how to do routine things like tie your shoes or eat with utensils, which are known as non-declarative memories). Early on, patients are typically able to maintain older memories and non-declarative memories. Over time, however, all memory can be affected, and even the most enduring memories may deteriorate.

But memory deficits are just one aspect of AD symptomatology. Patients can also experience problems with communication, and the ability to read and write may be impaired. Unpredictable mood disturbances, ranging from apathy and depression to angry outbursts, can occur. Thinking often becomes delusional, and a substantial subset of patients (up to 20%) even experience visual hallucinations.

It’s not just cognition that’s affected, though. Movement is hindered, causing patients to begin to lose mobility and have trouble performing even the simplest acts of self-care. Basic motor functions like chewing and swallowing become faulty, and incontinence eventually occurs.

In the end (if a patient survives this long), there aren’t many brain functions that haven’t been affected in some way, and patients become completely dependent on caregivers to help with even the most basic daily activities like eating and going to the bathroom. The disease is always fatal.

What happens in the brain in Alzheimer’s disease?

When Alois Alzheimer examined the brain of Auguste Deter, he noted a few distinct pathological changes. The first was that the brain had undergone significant atrophy. It appeared somewhat shrunken compared to a healthy brain.

This atrophying of the AD brain is due to the death of brain cells that occurs in the disease. AD is what is known as a neurodegenerative disease, which is a classification used to refer to diseases that cause the degeneration and death of neurons. A number of diseases fall into this category (e.g. Parkinson’s disease, amyotrophic lateral sclerosis), but AD is the most common of the group.

Alzheimer also noted unusual formations both within and surrounding neurons. He remarked that “distributed all over the cortex…there are…foci which are caused by the deposition of a special substance,” and he also mentioned “many fibrils located next to each other…they appear one by one at the surface of the cell.” Alzheimer was describing what today are the two hallmark neurological signs of AD: amyloid plaques and neurofibrillary tangles.

The first of these structures, amyloid plaques, consist of collections of small peptides (essentially a smaller version of a protein) known as amyloid beta, or Aβ, that form large clusters outside of neurons. Normally, enzymes called proteases can help to get rid of unwanted peptides and proteins in the brain. But amyloid plaques are especially resistant to degradation by proteases. Thus, they build up in the brain as the disease progresses; their presence is a defining feature of an AD brain.

Watch this 2-Minute Neuroscience video for a summary of the way Alzheimer’s disease affects the brain.

The other structure observed by Alzheimer, neurofibrillary tangles, also consist of abnormal deposits of proteins. In this case, the protein culprit is called tau. Tau normally plays an important role in helping to transport materials throughout the cell, but in AD it loses its normal function and clusters together in the tangles Alzheimer described. Like amyloid plaques, normal mechanisms the brain uses to remove unwanted protein deposits fail to effectively clear away neurofibrillary tangles. In fact, even after an affected neuron dies, the tangles found within it remain like a reminder of the neuron that was.

As the disease progresses, amyloid plaques and neurofibrillary tangles accumulate more and more in the brain. Thus, the appearance of these abnormal structures is correlated with the severity of the symptoms of AD. At the same time, exactly what role these structures play in the development of the disease remains unclear. For example, researchers are still unsure if amyloid plaques themselves are damaging to neurons, or if they represent an effort by the brain to sequester toxic Aβ peptides to protect neurons from their detrimental effects. There are similar questions about neurofibrillary tangles. Their appearance seems to be disruptive to neuronal function, and their spread throughout the brain correlates even better with neurodegeneration and symptoms than the proliferation of amyloid plaques. Nevertheless, their specific contribution to the progression of AD remains uncertain.

Causes and treatments

Thus, there are a lot of questions still surrounding the disease process of AD. Similarly, uncertainty surrounds why the disease affects some people but not others. In a small fraction of AD cases, the disease can be linked to mutations in a handful of identified genes whose protein products are involved in the production of the Aβ peptides mentioned above. But for most patients, there is no clear genetic or environmental cause of the disease.

There are, however, some known risk factors. For example, a variant of a gene called Apolipoprotein E, or ApoE, is known to increase the risk of AD by 10 to 20 times. ApoE encodes for a protein that is involved with the transport of cholesterol and other lipids in the blood, but it’s not yet clear why it might be involved with AD risk. High lipid and cholesterol levels, however, have also been identified as possible risk factors for the disease.

There are a number of other potential risk factors, like smoking, repetitive head injuries, poor cardiovascular health, and diabetes. Researchers are still unsure, however, just how these factors might increase the chances of developing AD. And by far the greatest risk factor remains one that we can’t avoid: old age.

Thus, the causes of AD remain somewhat obscure, which perhaps makes it unsurprising that our treatments are similarly unsatisfying. The most common treatment for the disease involves drugs that raise levels of the neurotransmitter acetylcholine in the brain. Acetylcholine is thought to play important roles in learning and memory, and large repositories of acetylcholine neurons (e.g. the nucleus basalis) are decimated during AD—likely contributing to memory loss.

Drugs called acetylcholinesterase inhibitors (AChEIs) suppress the activity of an enzyme called acetylcholinesterase, whose normal function is to remove acetylcholine from the synapse—in effect reducing the effect the neurotransmitter can have at that synapse. By inhibiting acetylcholinesterase activity, AChEIs cause acetylcholine levels to increase. In the process, these drugs can lead to modest improvements in memory. Because the effects are modest, however, AChEIs are often not very useful in the later stages of the disease. In fact, clear improvement in cognitive symptoms is only seen in less than 10% of patients taking the drugs. Additionally, AChEIs can only treat the symptoms of AD—they don’t do anything to stop the disease from progressing.

There are a handful of other treatments, and many others being explored, but at this point we don’t have any means of halting the neurodegeneration that underlies the symptoms of AD. Thus, we remain somewhat limited in our ability to treat the disease. Hopefully, continued neuroscience research allows us to one day develop better methods of addressing the pathological changes that occur in the AD brain.

References (in addition to linked text above):

Alzheimer A, Stelzmann RA, Schnitzlein HN, Murtagh FR. An English translation of Alzheimer's 1907 paper, "Uber eine eigenartige Erkankung der Hirnrinde". Clin Anat. 1995;8(6):429-31.

Cipriani G, Dolciotti C, Picchi L, Bonuccelli U. Alzheimer and his disease: a brief history. Neurol Sci. 2011 Apr;32(2):275-9. doi: 10.1007/s10072-010-0454-7.

Sanes JR, Jessell TM. The Aging Brain. In: Kandel ER, Schwartz JH, Jessell TM, eds. Principles of Neural Science, 5th ed. New York: McGraw-Hill.