Edgar Allen Poe is often credited with the origin of the modern detective story. His first such was The Murders in the Rue Morgue. The idea of murders in a place where dead bodies might be expected gives some insight into his thinking, though he did not capitalize on that at once. (He must certainly have been aware that the Paris morgue was something of a public attraction where the general public could examine unidentified bodies, even if there was no street with the name he used.) He used the idea that we ignore what is ubiquitous explicitly in his third detective story The Purloined Letter. The letter in question was hidden in plain sight by making it resemble an entirely different, and ordinary, letter stored openly.
I will now consider one possible similar problem, a retrovirus which has been ignored because it is ubiquitous. As in earlier posts in this series I will assume the replication and transmission of this virus is adapted to human life cycles, as described before. For most people, most of the time, it would be held latent. This is only a thought experiment, but I found the idea so compelling that I felt a need to insert material about research in areas where we know very little (blank spots on the map) to balance a perceived bias in research literature.
For comparison I'm going to explore changes in research on another delta retrovirus. This has more of the flavor of "looking for your keys under the lamppost", but that is unavoidable if I want to reference widely accepted research. The first confirmed human retrovirus, HTLV-1, was a delta retrovirus, and related research therefore has the longest history. As I have said, I think historical and geographical contingency played a large role in that discovery. We might easily have missed it. With the count of this group of human retroviruses now standing at four, most resulting from separate jumps to a new host, I don't think there is any question such transmission is possible, and even likely on ordinary human time scales.
What do we know about a delta retrovirus in a common domesticated animal? I quote from the Wikipedia article on bovine leukemia virus, used simply because it is up to date and easy to access:
Is there any reason to assume this percentage is lower in non-dairy cattle? I think I can make a pretty strong case that huge numbers of humans are currently exposed to this virus, directly from cattle, meat and milk, and there were likely many more opportunities for similar viruses to be transmitted to humans prior to the introduction of pasteurization. We now know most infected animals are largely asymptomatic, so inspection alone would not prevent spread.
The next question which arises is the host range of this virus. Here's the pertinent quote:
Now, consider the normal behavior of this virus in a host to which it is well-adapted.
Do any people out there suffer from a "benign mononucleosis-like disease"? Are there clusters of leukemias near them? Are B-cells involved?
Early tests for antibodies to this virus in humans said we were free of these. More recent tests show that such antibodies are widespread.
Antibodies could result from consumption of food with viral fragments which are not replication competent in any host. They could also result from slow infections which are below limits of detection. Antibody tests are currently used to screen donated blood for HTLV. If blood with antibodies to BLV were rejected blood banks would have an immediate supply shortage.
Limits to detection are a problem in all efforts at surveillance. This includes those studies looking for the virus in wildlife. It is entirely possible for a marginal infection in an intermediate host to provide an evolutionary stepping stone to yet another host species. This allows an evolving pathogen to undergo some changes in a new host which would not take place in the original host. Domestication of animals has introduced many new opportunities for this process in that last few thousand years. The modified pathogen may evade tests designed to find the original pathogen in the original host species.
There is one other way that humans depart from "natural" processes. It is virtually unknown for mammals to suckle young of other species in the wild. Since this infection is typically transmitted via milk, (and probably via infected cells in that milk rather than free virions,) feeding unpasteurized milk to infants with immature immune systems offers a novel method of transmission. This is one way around the normal limitations of experimental infection. I have only been able to find one paper on infection of chimpanzee's by this route, and it is not encouraging about what might happen with human infants.
I'm not going to sound an alarm about a possible human retrovirus derived from BLV in the future. What I want people to think about is the possibility this took place in the past, before modern medicine was around to notice. In addition to feeding infants unpasteurized cow's milk, people have even consumed raw cow's blood. My introduction to the practice referred to an African tribe safely removed from my environment. Only later did I understand that our European ancestors were mostly peasants who were very short of protein in their diets, and far too poor to slaughter cattle often. (The nobility were under no such constraints, nor were they subject to laws forbidding them to poach game on land they owned, or to fish.) The result was a craving for many things at which we now turn up our noses, including blood pudding. Whatever official assurances were given about transmission of pathogens during the "mad cow" disease scare would not have been true a few centuries ago. We should assume our ancestors were infected with many things. Vertical transmission of a retrovirus via breastfeeding, as with HTLV-1, would then carry the infection forward in time. There are plenty of people alive today who regularly consumed unpasteurized milk as children.
If there were such an endemic infection in humans, as there is in cattle, would we see much different in public health data than we have actually seen?
I will now consider one possible similar problem, a retrovirus which has been ignored because it is ubiquitous. As in earlier posts in this series I will assume the replication and transmission of this virus is adapted to human life cycles, as described before. For most people, most of the time, it would be held latent. This is only a thought experiment, but I found the idea so compelling that I felt a need to insert material about research in areas where we know very little (blank spots on the map) to balance a perceived bias in research literature.
For comparison I'm going to explore changes in research on another delta retrovirus. This has more of the flavor of "looking for your keys under the lamppost", but that is unavoidable if I want to reference widely accepted research. The first confirmed human retrovirus, HTLV-1, was a delta retrovirus, and related research therefore has the longest history. As I have said, I think historical and geographical contingency played a large role in that discovery. We might easily have missed it. With the count of this group of human retroviruses now standing at four, most resulting from separate jumps to a new host, I don't think there is any question such transmission is possible, and even likely on ordinary human time scales.
What do we know about a delta retrovirus in a common domesticated animal? I quote from the Wikipedia article on bovine leukemia virus, used simply because it is up to date and easy to access:
Is there any reason to assume this percentage is lower in non-dairy cattle? I think I can make a pretty strong case that huge numbers of humans are currently exposed to this virus, directly from cattle, meat and milk, and there were likely many more opportunities for similar viruses to be transmitted to humans prior to the introduction of pasteurization. We now know most infected animals are largely asymptomatic, so inspection alone would not prevent spread.
The next question which arises is the host range of this virus. Here's the pertinent quote:
Now, consider the normal behavior of this virus in a host to which it is well-adapted.
Do any people out there suffer from a "benign mononucleosis-like disease"? Are there clusters of leukemias near them? Are B-cells involved?
Early tests for antibodies to this virus in humans said we were free of these. More recent tests show that such antibodies are widespread.
Antibodies could result from consumption of food with viral fragments which are not replication competent in any host. They could also result from slow infections which are below limits of detection. Antibody tests are currently used to screen donated blood for HTLV. If blood with antibodies to BLV were rejected blood banks would have an immediate supply shortage.
Limits to detection are a problem in all efforts at surveillance. This includes those studies looking for the virus in wildlife. It is entirely possible for a marginal infection in an intermediate host to provide an evolutionary stepping stone to yet another host species. This allows an evolving pathogen to undergo some changes in a new host which would not take place in the original host. Domestication of animals has introduced many new opportunities for this process in that last few thousand years. The modified pathogen may evade tests designed to find the original pathogen in the original host species.
There is one other way that humans depart from "natural" processes. It is virtually unknown for mammals to suckle young of other species in the wild. Since this infection is typically transmitted via milk, (and probably via infected cells in that milk rather than free virions,) feeding unpasteurized milk to infants with immature immune systems offers a novel method of transmission. This is one way around the normal limitations of experimental infection. I have only been able to find one paper on infection of chimpanzee's by this route, and it is not encouraging about what might happen with human infants.
I'm not going to sound an alarm about a possible human retrovirus derived from BLV in the future. What I want people to think about is the possibility this took place in the past, before modern medicine was around to notice. In addition to feeding infants unpasteurized cow's milk, people have even consumed raw cow's blood. My introduction to the practice referred to an African tribe safely removed from my environment. Only later did I understand that our European ancestors were mostly peasants who were very short of protein in their diets, and far too poor to slaughter cattle often. (The nobility were under no such constraints, nor were they subject to laws forbidding them to poach game on land they owned, or to fish.) The result was a craving for many things at which we now turn up our noses, including blood pudding. Whatever official assurances were given about transmission of pathogens during the "mad cow" disease scare would not have been true a few centuries ago. We should assume our ancestors were infected with many things. Vertical transmission of a retrovirus via breastfeeding, as with HTLV-1, would then carry the infection forward in time. There are plenty of people alive today who regularly consumed unpasteurized milk as children.
If there were such an endemic infection in humans, as there is in cattle, would we see much different in public health data than we have actually seen?