There are trade-offs associated with different levels of virulence
Host mobility is critical in the spreading of infectious disease. Example-rhinovirus depends on the mobility of the human host for transmission
Still, because rhinovirus can only reproduce inside the human nose, it has highly restricted reproduction—are the most benign of human infections
So, vector-borne parasites that reproduce very well inside a host vertebrate should be the most successful: they get “fitness benefits and pay little fitness costs” p36
Categorization of pathogens: vectorborne or nonvectorbornestraightforward
Categorization of virulence-much more complicated
Figure 3.1: vectorborne pathogens of humans much more severe than nonvectorborne pathogens. So basically, diseases which humans get from bugs or rodents tend to be more virulent than diseases humans transmit directly between one another
The theory espoused in Figure 3.1 assumes the greater virulence of vectorborne pathogens results from their adaptation to humans
This theory has NOT been addressed in medical literature (at the time this was published)
Comments on Summary Section 1
This first part of the Chapter seemed to be fairly straight-forward. One interesting claim was that the categorization of vectorborne versus non vectorborne pathogens is easy but the categorization of virulence is much harder. This sort of connects with what we have been discussing-that science is just as dependent on narratives as any other discipline. Categorization of virulence is really hard to pin down because the concept itself is insanely complex. How should scientists even measure virulence? Is one way better than another? Does the act of researching virulence have implications for how the concept is transmitted outside of the study? At some point, it seems like theorists just have to pick the definition they think will suit their study best and disregard the others. This is sort of similar to how Dr. Ebersol said that although natural selection is such an important concept in biology, many professional biologists cannot give a good working definition of the concept. Maybe this is because the concept is so complex its definition has to depend on part in how it is being deployed in a particular study and the various motivations of the researchers. Another interesting point was that vectorborne pathogens are generally the most severe. This is actually a “scientific fact” which fits with ordinary intuitions. Most humans seem to have an immediate dislike for insects and rodents. It would be interesting to explore the question-is this capacity sort of hard-wired into us? Do we learn this wariness towards such creatures? If we do learn to feel wary around such creatures, how is this knowledge transmitted? In any case, it is interesting because I think, in general, humans feel more squeamish around creatures like rats than around moderately sick fellow human beings.
McNeil’s theory is discussed: the evolutionary adaption of parasites to their hosts pushes the relationship towards benignness
But, the parasite cannot have a benign relationship with both the vector and the host-this relationships is restricted to one or the other—not both
McNeil concludes that evolution towards benignness occurs in the vector rather than the host because a healthy vector is more important for the transmission of the disease
McNeil’s Theory is termed: restricted adaptation hypothesis
The author goes on to refute McNeil’s theory and argue instead for adaptive severity hypothesis “parasites that cycle primarily between humans and vectors will be more virulent in humans than will parasites that cycle between non-human vertebrates and vectors” pg 39
If ASH theory is to be believed, human should have advantage when fighting against parasites that have adapted to non-human hosts; result should be a benign encounter
RAH predicts that the more a pathogen cycles between humans and vectors, the less virulent it will become in humans
The author then provides evidence that ASH theory is largely correct and RAH theory is wrong
In nearly every parasite, the greater the cycling in humans, the more severe the disease is in humans!!
The only case which contradicts this: less virulent Gambian form of sleeping sickness; but one exception was clamped onto by scientists
This one exception shaped the view of scientists—it was repeatedly offered as evidence that parasites evolve toward benignness with humans
Important note on scientific process: host-parasite relationships must be sampled without bias to test GENERAL VALIDITY of theories, not selected to support certain hypothesis
Comments on Summary Section 2
This section has a lot of extremely important concepts. Most interestingly, McNeil’s hypothesis of disease evolving towards benignness is supposedly disproved. It seems on the face of it that the author’s refutation of McNeil’s theory is convincing, though I don’t understand parts of the scientific lingo. In a sense, McNeil’s whole book depends on the idea that disease evolves towards benignness-that the horrible diseases of complex civilizations evolved towards being childhood diseases which were not nearly so debilitating as before. If McNeil is wrong, are we just living a period in which terrible disease is “lying low”-that it will eventually emerge again more virulent than before? Maybe this is not the correct projection of the argument, but it seems that McNeil has sort of propagated a false sense of security. That humans and parasites can live in relative harmony if given enough time to adapt to one another. This is a very nice theory-it has sort of a peace-loving vibe-everything can exist in harmony once different species learn a process of give and take. Maybe this has something to do with the period in which McNeil was doing his research-the early 1970s would have encouraged this sort of harmonious thinking. World peace, environmentalist movements, social progressive values were becoming increasingly popular so maybe McNeil was influenced by those values. The rejection of McNeil’s theory seems to think that this is a fanciful world view-that parasites are selfish. The only purpose of parasites is to thrive and their virulence or lack thereof is not dependent on any notion of evolved harmonious relationship with humans. In a way though, could it be possible that the author’s refutation of McNeil is based partly on the prevailing philosophy of his time? The book would have been researched in the early 1990s; is it possible that the values of nihilism pervaded Edwald’s thinking? Of course, this quickly becomes very, very messy. Can scientific findings ever be immune from other pressures? Are scientific findings ever factually conclusive or does their truth vary by decade?
Another interesting point made by Edwald lambasted other theorists for having pet theories and designing experiments for the purpose of advancing these theories. This obviously happens in all disciplines but I feel as though we often forget this happens in science. Quite rightly in my opinion, Edwald advocates for more studies which look to support or deny the general validity of theories, not a certain hypothesis. As we discussed in our debate about whether to destroy smallpox, science works best when it is not preoccupied with a particular hypothesis which dictates all modes of study. One of the insights put forth by Professor Foster was that smallpox should not be destroyed because it could be useful in the future. Even if we think we have enough understanding about this disease presently, the virus could be useful in the far future if another terrible virus appeared. This seems to be the sort of approach Edwald is advocating; science should work by going from the general to the specific not generating the general from the specific. Certain theories become beloved and put forth as the truth for centuries-even if there seem to be little empirical evidence for it. So, it is important not to write off conflicting studies or general data because we may have great use for such knowledge in the future.
People advocating for pet theory that disease evolves towards benignness in humans
These theorists overlooked historical patterns in death rates from particular disease agents: the diseases in which virulence has declined over time are nonvectorborne!
Pathogens transmitted by vectors continue to cause very severe illness even if they have been around a very long time
A new theory: insufficient time hypothesis seems to argue that all highly lethal infections of humans have only recently become human diseases
Author then attempts to refute ITS: clinical descriptions of patients prior to 16th century make the mere absence of clear documentation of a disease extremely weak evidence for saying the disease did not exist at all!
Example: typhus was not officially differentiated from typhoid until the early 19th century
Also, high virulence can tell very little about the previous duration of a parasite’s relationship with humans
Another example: ITS theory says that “rat typhus” and “louse typhus” are basically the same. But mortality in humans caused by “louse typhus” is 10x greater than “rat typhus”. Agents of “rat typhus” and “louse typhus” should be considered separate species that diverged from each other a very long time ago-so “louse typhus” probably isn’t a very recent disease.
Another example: ITS theorists say that the parasite P. Falciparum has had only 10,000 years to evolve in humans and this relatively recent origin explains why it is very severe.
Author responds by saying 10,000 years is plenty of time for a protozoal parasite to adapt. Also, other human malarias may have had even less time to adapt in humans but remain extremely lethal.
Author puts forth his own theory: Virulence Niche Hypothesis
P. Falciparum’s high rates of reproduction would be most beneficial when there are large numbers of susceptible humans available year-round
Simultaneous infection of many in a population should increase virulence if susceptible hosts always available
But, in some regions, mosquitoes are lacking for part of year. P. Falciparum’s aggressive strategy would work very poorly in such an environment
Other more mild parasites are more successful because they can survive in a person for a long time; they have a delayed incubation period
Final example disproving ITH: rabbits in Australia, lethality of a virus decreased because of increased resistance in the rabbits and reduced virulence of the virus
This seems to prove an evolution towards benignness but decreased virulence was not found to continue after the first decade. The virulence of the virus has actually increased.
Also, you won’t find a severely sick wild rabbit because it will have died.
Ends with a great metaphor: “Epidemiologists who came into an area and made a snapshot study…missed the conflict. A photographer coming into a war-torn country months after a major battle may photograph injuries, scars and rubble but little of the death that results from the combat. How wrong it would be to conclude from the pictures that warfare is not lethal” pg. 46
Comments on Summary Section 3
This section offers more support for Edwald’s theories. He offers specific examples of studies in which vectorborne disease does not evolve towards benignness. He dismisses insufficient time hypothesis which basically states that if a disease is severely debilitating, it simply has not had enough time to adapt to humans. Once it has had sufficient time, it will not be as lethal because, presumably, this mortality is as bad for the parasite. Edwald clearly demonstrates that this is usually not the case. Instead, he proposes that a parasite does not adapt to humans but to environmental conditions. If it is convenient for a parasite to kill large numbers of humans to keep up transmission, it will evolve to do just that. If it is detrimental for a parasite to kill large numbers of humans, it will evolve to be less aggressive in its transmission. In either case, humans are secondary. McNeil’s theory was so nice because it assumed that humans were the standard to which parasites had to adapt their behavior. This new theory is more troubling because it implies that parasites have no interest in maintaining a harmonious relationship-their only interest is in survival and transmission. In a way, McNeil included parasites within the realm of morality while Edwald take them out again. Also important is Edwald’s point that disease does not follow linear patterns. Even is a disease appears to decrease in virulence, it will most likely increase once again. Diseases do not “stop” being virulent at a particular point-they follow a cycle of being more or less virulent depending on numerous conditions. I think this is a challenging idea for a lot of people, myself included, because it goes against our way of structuring the world. We are taught a lot of beginning and end-points- i.e. The Civil War began on April 12, 1861 and ended on April 9, 1865. Obviously we understand intellectually that the Civil War began long before that date and in some ways never ended. But we still talk about beginning and ending dates to just about every event. Parasites seem to prove that this way of thinking about the world is misleading-that events are cyclical more often than they are linear.
On a final note, Edwald provides a really brilliant metaphor for describing the ways in which epidemiologists go wrong. But this metaphor applies equally to all disciplines. The problem is that often, we miss the conflict and all we have to go on are the remnants. I wonder if there is a way in which we can interpret the leftovers of a conflict and get an accurate understanding of it. Does a true, holistic understanding of a conflict necessitate your presence while the conflict is actually occurring? If not, how can we really understand something from its vestiges? Is this where primary sources become so important?
Infections in the Vectors: Pages 46-55 Here Ewald investigates the following hypothesis: “that parasites tend to evolve to benignness in vectors.” (p.46) This theory appeals to intuition: we have seen that a microbe which is so virulent in its host species so as to immobilize it will jeopardize its own transmission and therefore its survival.
This principle might even hold particularly in vector species for a number of other reasons:
One: “Because vectors are smaller than vertebrate hosts… The benefits of extensive reproduction in the vector should also be relatively low.” (p.47)
Two: A single individual of the vector species will tend to transmit contagion only once or twice (via, say, bites) to a given vertebrate, whereas a significant number of vector species will generally converge on this given vertebrate, meaning that for a contagion to spread from one individual of a vector species to multiple vertebrates is less likely than transmission from one vertebrate into a number of individuals of the vector species. Therefore: “Vectorborne parasites should specialize on their vertebrate hosts as resource bases for amplifying their numbers and on their vector hosts as agents of dispersal.” (p.47)
Having argued that common sense suggests the hypothesis that a contagion will be much less virulent in a vector than in a host, Ewald now states that actual evidence does indeed support this conclusion. However, he cautions against too hastily attributing this lack of virulence to adaptive severity specifically, and raises another hypothesis. “There is an alternative explanation for the mildness of vectorborne parasites in their vectors. Many of these… can be transmitted from mother to offspring, [which]… should favor evolution toward benignness.” (p.47) Then he again cites evidence to suggest that the adaptation to take advantage of vertical transmission, in which a virus will have more reproductive success if it does not kill a potential mother, so that she may transmit it to her offspring, is an important consideration in understanding why diseases are relatively benign in their vectors.
Ewald then complicates the equation: “The relative benignness of vectorborne parasites in their hosts does not mean that their associations will evolve toward commensalism or mutualism… If evolution can generate flexible parasite strategies that are responsive to changing costs and benefits, then we might see indications of moderate virulence at very specific times in otherwise benign relationships.” (p.49) He gives the following example of such changing costs and benefits: It is in the interest of both the mosquito and its hosted parasite that the mosquito successfully bite a vertebrate. Once the bite has been made however, if the mosquito is killed while dining, the consequences are much more severe for the mosquito than for the parasites, many of which have already passed into the vertebrate. Thus a parasite which is virulent enough in the mosquito to “hinder its feeding time” may have an evolutionary advantage.
Clearly the “balance sheet” for coevolution of parasite, vector, and host is extremely complicated and one must be careful of making hasty assumptions. But given that we do have strong evidence in support of a relatively complete theory of parasite-vector-host coadaptation, how can we put this to use in order to:
Control Vectorborne Diseases
Genetic Control Ewald first discusses the attempt to genetically engineer populations of vectors (specifically, mosquitoes) which are unsuitable to hosting and transmitting pathogens. This seems to be a foolish phrasing. Which pathogens? Certainly it is not realistic that we could by some mechanism prevent all conceivably virulent microbes from adapting to mosquitos as a vector. Ewald must be referring to those pathogens currently known to be transmitted through the mosquito, especially those most common or virulent in the human being. But how long could such an intervention forestall the inevitable actionof evolution, the principle of which is adaptation?
Ewald concurs in being suspicious of this idea: “The potential for the pathogens to overcome the engineered resistance may be great because the pathogens transmitted by the remaining unengineered mosquitoes will provide a continuing pool of pathogens under great evolutionary pressure to break through into the engineered... population.” (p.50) However he notes that given a pathogen with a low rate of mutation (which would adapt only slowly) and a possible method of “decimating” the unengineered mosquito population, its success might not be inconceivable.
This is a short section in which Ewald illustrates his (rather dismissive) assessment of the role of drugs in combatting vector-borne pathogens. He focuses on malaria and the history of its resistance to the quinine derivatives used to treat it. Essentially, the mechanism of resistance is the evolution of more transport proteins in the parasites’ cells which “pump out” the quinine faster than it can get in. Even as the drug is made more potent, the malaria parasite adapts with sufficient speed to remain a serious, deadly disease in those regions where it is endemic.
I think Ewald might be revealing his heritage here as an evolutionary biologist prejudiced in assuming the triumph of evolution over medical technology, because he neglects to note the extraordinary successes in developing drugs which combat microbial infection. Resistance may be a serious issue and one which will always be “with us” but it is pessimistic to write off resistance in any given pathogen as insurmountable especially so long as we are diligent about the proper methods of using antibiotics.
Interesting: a method informed exactly by that theory that “vectorborne diseases are more virulent than nonvectorborne diseases... [because] vectors can transmit the pathogens from immobilized hosts.” (p.52) Ewald wonders whether we could not modify pathogens so that they could no longer be transmitted from such ill hosts. My first thought: This idea seems both brilliant and impossible.
But his method is simple. Using mosquito-borne disease as an example:Mosquito-proof houses and hospitals. First, these reduces transmissionin general: “In Thailand, residents of houses with full screening and doors that opened outward suffered dengue at one-fifth the rate of people living in unscreened houses.” (p.53) But secondly and, according to Ewald, more importantly, persons so ill as to be immobilized within a house or hospital would not transmit the disease. Thus, theoretically, less virulent strains would be at an evolutionary advantage.
Ewald considers whether, in his day of such advanced medicine and medical technologies, it is too modest a goal to aim only to reduce the virulence of diseases like malaria and yellow fever. It is his contention that history suggests our efforts to entirely eradicate these diseases will be always unsuccessful and “our efforts will at best restrict yellow fever to regional flareups.”
I am reminded of the scientists who eradicated smallpox explaining that their superhuman efforts would still have been unsuccessful if the disease had had a natural reservoir to retreat into when driven out of the human population.
Is his method without serious obstacles? No, according even to Ewald himself. First, given an epidemic where houses and homes have not yet all been mosquito-proofed, the sick have less of an incentive to screen themselves off than the healthy. The former would only be doing so for the benefit of others. To me this suggests the importance of instituting protective measures long before an epidemic flares up. Secondly, it would constitute a significant barrier to adaptation toward benignness if infected individuals before becoming extremely ill remained out and about in society transmitting their virulent disease. Ewald says that there is a need for policies forcing those who feel even “slightly ill” to essentially head into quarantine and notes that this is unlikely given “current socioeconomic conditions.” (p.55)
Moreover, my question regarding his second concern is that if everyone who felt “mildly ill” was immediately sent to a screened-off home, wouldn’t this defeat the purpose of increasing the likelihood of less virulent strains being transmitted compared to virulent strains? That only the latter incapacitate the host inside a quarantined area was supposed to be the mechanism by which the former gained an advantage.
Paul Ebersold’s Lecture
During Darwin’s time most intellectuals and scientists believed in the biblical accounts of Creation.
It was a relatively new discovery that many fossils were clearly not remnants of any creature still living, and to explain this phenomenon many subscribed to a theory called “catastrophism.” Delineated by the scientist Comte de Buffon, it essentially elaborated on themes in the bible of successive catastrophes (which wiped out most of the living creatures at a given time) followed by a round of new creations.
Nevertheless, even before Darwin there was some consideration of the theory that life-forms change over time, given the similiarity in a given region of certain fossils to creatures living there. Jean-Baptiste de Lamarck, for instance, espoused a theory by which creatures inherited “acquired characteristics.” For instance, a prey animal which is often forced to run in order to avoid becoming dinner will pass on its aerobic fitness to its offspring.
Interestingly, Lemarck’s theory did account for the content of natural selection (a species which is required to run far and fast will adapt over time to run far and fast) but not its mechanism. Characteristics acquired over a lifetime are not inherited. Only genetic material is inherited, and thus the composition of a species’ characteristics changes only very slowly over many generations. How?
Sailed as a naturalist on the HMS Beagle in 1931, sent mainly to accompany the captain and prevent his nervous breakdown under pressure of youth and his father’s recent suicide. On the extensive voyage he made the following important observations:
In any given place fossils resemble the creatures living there but with slight changes
Species composition changes gradually with latitude on a given landmass
Species composition changes dramatically when isolated on different landmasses
Species composition indeed reflects demands of the local environment (Here Darwin especially relied on his observations in the Galapagos islands, home to a group of birds which varied from island to island only essentially by the shape of their beak which reflected the local variety of vegetation.)
By the time he left the Galapagos his journals show that Darwin had mostly worked out the theory of natural selection, but he didn’t publish until over twenty years later upon receiving an excited letter from a younger naturalist named Alfred Wallace who had independently reached the same conclusions.
They co-authored a paper in the 1850s but it was not well received given that the ideas it contained were so revolutionary. Not until Darwin published On the Origin of Species in 1860 did he convince his contemporaries.
Ebersold explained that the argument laid out in The Origin is based on 5 facts and 3 inferences.
Fact 3: (inspired by Malthius) Resources are limited
Inference 1: All living creatures are involved in an ongoing struggle for existence defined by limited resources
Fact 4: In any species, individuals vary from one another
Fact 5: The features of individuals are heritable
Inference 2: There is differential survival and reproduction of individuals within a species
Inference 3: These differences reflect the process of favorable features accumulating, favorable features being those which are at an advantage at reproducing themselves. This creates microevolution (As distinct from macroevolution which is the process of a single species diverging into two)
The problem with this theory is that it does not account for how the variation so necessary for evolution is maintained over time when common sense would suggest that with each generation it is reduced as the characteristics of two parents blend “like paint” in their offspring
Darwin died without satisfactorily resolving this problem, which was solved by later scientists (around 1900) who resurrected the discoveries of Gregor Mendel regarding characteristics of genetic material
-1 that they are particulate and are not mixed through the generations like paint but rather recombine to form new characteristics and
-2 that mutations arise spontaneously in the genetic material
Together these facts account for the indefinite preservation of variation
Darwin’s inductive reasoning seems airtight. The general opinion today is that evolution is a “fact” because the evidence against it is indisputable, but without an understanding of the principles which order and explain that evidence (And a certain degree of faith in reason) the “evidence” would be meaningless. In this light the faith of creationists in an alternative kind of reasoning seems less ridiculous.