In high school, my biology class went on a field trip to the Salk Institute, just a 15 minute drive from my hometown of San Diego, CA. At this point in my life, I knew Jonas Salk as the creator of the polio vaccine, but knew little else of him. Moreover, I knew little about the polio virus itself, which is why I decided to read Polio, An American Story by David M. Oshinsky.
Polio: An American Story provides a compelling account of not only the history of polio in the United States, but also the major players that contributed to our knowledge of polio, and the powerful legacy they left behind. Through a close and detailed historical analysis, the book offers a rich trove of factual information, while still preserving an almost narrative feel to it by delving deep into the stories that surround the facts.
Although known today as a debilitating, but largely preventable virus, thanks in part to the efforts of Jonas Salk and Albert Sabin who respectively invented the inactivated and live-attenuated polio vaccines, Polio: An American Story acknowledges that the path towards vaccination was long, arduous, and sometimes downright scandalous. Oshinsky begins by depicting the historical context that allowed polio to come into the public consciousness. Personal hygiene played little role in the lives of the average person at the turn of the 20th century; the majority of people neither used soap nor toothbrushes. The advent of public health campaigns early in the 20th century dramatically changed this, paving the way for one of the largest public health campaigns to come into being when the Salk vaccine was tested in the 1950s. Furthermore, the presidency of Franklin D. Roosevelt, a presumed victim of polio, played a huge part in raising awareness for polio. Under his presidency, the National Foundation for Infantile Paralysis, more commonly known as the March of Dimes, came into existence, dedicated to polio research.
Years of research - on how polio is transmitted, what that route of transmission is, and how many distinct strains of polio existed - finally resulted in an inactivated vaccine by Jonas Salk. This vaccine however, was not without its doubters and its own scandals. Notably, Albert Sabin, who was working on his own polio research at the time was vehemently opposed to the Salk vaccine, though his motives for doing so are questioned. Despite his legacy of success today however, Salk is portrayed as a calculated and sometimes selfish researcher, who, though revered by the people, was not always highly respected among his peers. The development of the Sabin vaccine - and the eventual recommendation that the Sabin vaccine replace the Salk vaccine due to its presumed higher effectiveness, continued the feud between Sabin and Salk even to their deathbed.
In all, Oshinky depicts a vivid landscape of polio research in the early-to-mid 1900s that draws on the many forgotten stories that led to the development of the polio vaccine. Although perhaps warranted, the end seems to be a race to the finish, with much less detail on the history of polio in the United States following the advent of vaccination. As a whole however, Polio: An American Story provides a thought-provoking, detailed, and insightful account of the history of polio in the United States that marries together story and fact into one fascinating read.
--Andrew Duong
Friday, December 26, 2014
Monday, December 15, 2014
Johan Hultin
Remember him? He’s the pathologist who discovered tissues
containing the 1918 influenza virus, which allowed the virus to be sequenced
for the first time. Bob talked about him a bit in class, but Johan Hultin’s
story is so darn cool I thought I’d look into it a little bit more.
Hultin was taking a break from Swedish medical school and
studying microbiology at the University of Iowa and a professor happened to
make a passing remark that intact samples from the 1918 flu still exited in
frozen in bodies in the Artic. Hultin was looking for a dissertation topic and
proposed that he try to find the virus so it could be used to make a vaccine.
(I’m not sure the logic of trying to use an old strain to make a vaccine
against a new strain, but maybe this was before some newfangled techniques and
it was the best they could do.)
In any case, in native groups in the Alaska, death rates
from this outbreak virtually wiped out small villages. Johan Hultin’s
enthusiasm was probably fueled by the fact that he spent a summer in Alaska
with a paleontologist and believed that driving up the newly opened Alaska
Highway, “was itself a great adventure.”
In order to establish
where the mass graves were, he wrote to a few missionaries. They sent him
copies of record books in Norwegian. Being Swedish, he luckily happened to be
able to read Norwegian.
Off Johan went to Alaska, to a village now called Brevig
Mission, to be specific. The villagers let him excavate. Once he got the
samples, he had to quickly get them into the lab. A storm made the bay almost
impassable and dry ice brought to refrigerate the samples had evaporated. Johan
and his small team used carbon dioxide from a fire extinguisher to make dry ice
and with local help, they managed to find an overland route.
Despite this extraordinary effort, Johan’s first attempt was
unsuccessful. He concluded that there was no live virus in the corpses. He
planned to write about the failed attempt for his thesis, but he was accepted
into the medical school at the University of Iowa and never ended up writing
it.
It turns out that the Army was also trying to get the
Spanish flu out of the ice, but found only skeletons in their original
excavation site. Tauenberger, the civilian scientists who heads the
microbiology division of the Armed Forces Institute of Pathology, wondered
whether it’d be possible to get the Spanish flu out. He was able piece together a gene called NS
from 78 soldiers and published a report. Hultin happened to read the report and
offered to bring Tauenberger frozen samples from Alaska with the flu.
Hultin returned to Brevig Mission. The local people were
worried about releasing bad spirits and were relucantat to allow him to dig.
Eventually, someone recalled that they had been given Christian burials, which
was supposed to have sufficiently driven the bad spirits away, so they gave
Hultin the go ahead.
Hultin and his crew found a body he had missed the first
time, a fat woman in her thirties. The fat apparently helped insulate her body
from the brief thaws. In fact, the material that Hultin brought back was more
fragmented than the Tauenberger’s soldiers. However, Hultin gave him all the
material he needed and the virus was sequenced 8 years later.
References:
Epidemiology meets evolutionary ecology
I read an article titled “Epidemiology meets evolutionary
ecology” a few weeks ago, but have not had a chance to fully digest it. I think
it’s potentially useful to think about viruses this way so I’m going to write
down a few points that I find interesting. Probably the most important point that this
paper makes is the definition of virulence, or “the extent of parasite-induced
reduction in host fitness.” (Although it still seems odd to me that virulence
is defined based on the host rather than the parasite itself....)
1. Optimal Virulence
-Viruses face a tradeoff between host survival and
fecundity. Hosts face a tradeoff between the cost of resistance and the risk of
infection.
-Estimates of R0 generally do not take into account vertical
transmission or multiple infections.
2. Transmission
Patterns
-Vertical transmission tends to reduce virulence compared to
horizontal transmission because vertical transmission depends on host survival
and reproduction. But vertical transmission and horizontal transmission are
usually related so it’s difficult to consider these transmission patterns
individually.
3. Spatial structuring
of disease transmission and dispersal mechanism
-Recent models that include spatial structuring tend to
predict lower virulence than those that don’t.
4. Host heterogeneity
-A host parasite that is optimally adapted to get around one
host’s immune system and not another, host heterogeneity selects for lower
virulence.
-The relationship between parasite virulence and host
resistance is more complex than was originally assumed.
5. Competition strains
and within-host dynamics
-Viral strains in the same host are competing to a limited
amount of resources, which leads to selection for greater virulence.
-Kin selection between related strains within one host is
predicted to reduce virulence.
6. Phylogenetic
analysis
-Phylogenetic analysis is useful in providing information
about emerging strains
7. Public Health
Policy
-Evolutionary ecology should be taken into account when
implementing public health interventions.
8. Sex and Virulence
-It is thought
that sex in parasites increases virulence and sex in hosts reduces virulence.
Phew! That just made my brain hurt a little bit more. And I
just discovered that there’s a great table in this article, which distills down
the major points better than I just did. (There’s a screen shot below, but you
should check out the original!) Also, the author makes the point that “the
misconception that parasites will ultimately evolve towards avirulence has only
been dispelled gradually from the medical literature.” (Proof of these “misconceptions” prevalence can be found in the abstract of the paper that Emi sent out on
HIV.)
By Olivia
References:
Galvani, A. “Epidemiology meets evolutionary ecology.” Trends in Ecology and Evolution Mar.
2003. Vol. 18(3): 132-139.
Sunday, December 14, 2014
Prions in the strangest of places
I was doing some research on Huntington’s disease when I
came across the idea that prions, infectious proteins, may be more common than
we previously thought. As we all know, prions are accepted as the
disease-causing agent in transmissible spongiform encephalopathies, such as
Creutzfeldt-Jakob disease. These
infectious proteins form aggregates, and the breakage of the aggregates
represents protein replication.
Amyloid plaques, seen in a variety of neurodegenerative
diseases, are also are created by the misfolding and aggregation of proteins.
Studies on Alzheimer’s and Parkinson’s disease have given some researchers
reason to suspect that the proteins involved in these diseases may exhibit
prion-like behavior. Apparently an early study on Alzheimer’s found that the
disease was transmissible from the white blood cells of people to hamsters.
However, this finding was never reproduced. Another study found that aggregates
of AB peptide from brains of Alzheimer’s patients could be passed to mice
genetically engineered to produce large amounts of the AB precursor protein.
Another study grafted health brain tissue into the brains of Parkinson’s
patients, and the tissue acquired protein aggregates associated with the
disease pathology. Amyloid A amyloidosis can be excreted in feces, and at least
in geese, it can induce amyloidosis if ingested.
The author of the 2005 paper published in Nature voicing this idea makes an
important distinction between prions and what he calls “prionoids.” Prions are
transmissible through populations and can cause epidemics, but “prionoids” can
only affect neighboring molecules or cells. This seems like a very significant distinction
to me, and if this is the case, calling the proteins in these neurodegenerative
diseases prions seems downright confusing.
However, it’s a very interesting idea and once again blurs the distinction
of what we consider life.
By Olivia
Aguzzi, Adriano. “Cell biology: Beyond the prion principle.”
Nature 18 Jun. 2009; 459:924-925.
Herpes and your telomeres
What’s the secret behind that cold sore that pops up on your
face at the most stressful of times? According
to a soon-to-be published study by a group of researchers at the Wistar
Institute, Herpes Simplex Virus 1 manipulates telomeres, the protective tips of
chromosomes. HSV-1 causes the cell to transcribe telomere repeat-containing
RNA. The virus then degrades a telomere protein called TPP1, which is involved
a protein complex that helps protect telomeres. By disabling this protection,
HSV-1 is able to replicate more efficiently. The virus also uses a replication
protein, ICP8, which helps promote viral genomic replication.
HSV-1 is not the first herpes virus to manipulate its host’s
genome. A review published in the Annual
Review of Virology (2014) states that telomeric repeats have also been
described for HHV-6, HHV-7, and several other members of Herpesviridae. This
new finding for Herpes Simplex 1 is of particular interest because according to
the CDC, the virus infects 776,00 new Americans every year.
As a side note, I noticed that the press release for this
new study was published well in advance of the December 24th edition
of the journal Cell Reports. Is
having a press release first normal?
By Olivia
References:
Osterrieder, N., Wallaschek N., and Benedikt B. Kaufer.
“Herpesvirus Genome Integration into Telomeric Repeats of Host Cell
Chromosomes.” Annual Review of Virology
2014. 1:215-35.
HIV becoming less virulent
I read the article that Emi sent
along about decreasing HIV virulence. In HIV infections the HIV virus faces a
tradeoff between high virulence (increasing the likelihood of transmission), and
reduced lifespan of the host (decreasing the likelihood of transmission). This
study looked at the HLA molecules in Botswana and South African populations and
used models to assess ART’s ability to accelerate the effects of HLA-mediated
viral adaptation.
HLA genes are an important factor
in immune control of HIV-1 infection, as they direct cytotoxic T lymphocytes
against virus-infected cells. HIV can only evade this immune response by
selecting for mutants that reduce the viral replicative capacity. The authors also hypothesized that increasing
the use of ART would likely remove viruses with the highest replicative
capacity from the population, and also lead to a decrease in virulence
overtime.
The study examined two populations
of ART-naive antenatal mothers in Botswana and another in South Africa. They
tested the adaptation of all HIV sequences in the populations against each
individuals HLA molecules. To assess whether the frequency of cytotoxic T
lymphocyte mutants would increase over a decade, the researchers looked at a
second cohort enrolled ten years later at the same site in South Africa. The authors also created a mathematical model
to assess the effects of ART.
This study suggests that even
within a decade, the population-wide effects of HIV evolution are evident. The
findings show that there is a lack of HLA-B*57 associated protective effect in
the Botswana population. This suggests that HLA B and HLA-B*57 are important
drivers in the HIV selection, with predictable losses in immune protection.
Consistent with the author’s hypothesis, they found a lower viral replicative
capacity in the Botswana population compared to the South African population.
Although there was an increase in the number of HLA-B*57 mutants in the
Botswana subset for which viral replicative capacity measurements were taken,
the number of these mutants did not correlate significantly with the viral
replicative capacity, which suggests that additional factors are in play.
The authors believe that one factor
is the increased diversity of HLA-associated mutations in the Botswana
population compared to the South African population.
Another factor to consider is the
effect of ART. The study hypothesizes that giving ART to people with low CD4
counts tends to accelerate the evolution of variants with lower viral
replicative capacity. The authors’ model suggests increased use of ART also aids
in lowering the virulence of HIV.
The study’s findings have important
implications and extrapolated to an individual level, it may mean that more
people’s immune system will be able to control disease for longer. If
scientists can understand what is required to control the virus, it may help
with development of better antivirals or a vaccine. In the very long run, this could
help us eradicate the infection.
Remaining questions include what
made the North American population that demonstrated a contrary finding to this
study different from the Botswana and South African populations these
researchers studied? Are these two populations in Botswana and South Africa
representative of what is happening worldwide? The authors state, “epidemics in
new hosts diminish in virulence over time?” Is this true for other epidemics?
Thanks to Emi for passing this
article on and for an interesting read!
By Olivia
References:
Payne, Rebecca et al. “Impact of
HLA-driven HIV adaptation on virulence in populations of high HIV
seroprevalence.” PNAS Early Ed.,
received for review July 15, 2014, approved Oct. 31, 2014.
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