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An Ebola Question

Olytico-Question-Mark-1024x576I’ve had a question about Ebola posted on the StackExchange Biology page for some time without getting any answers. Basically, I was wondering about how antibody responses to Ebola can drive either sterilizing immunity (the goal) or actually improve the virus’s entry into host cells (a big problem). The idea that Ebola antibodies may be detrimental to the host was first raised by Baize et al, and my question is how this has impacted efforts to develop an effective vaccine. For background, I’ve written about this topic previously.

If anyone knows what the current thinking is in this area, please point them my way.

 
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Posted by on September 4, 2015 in Uncategorized

 

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CRISPR: Accelerating the pace of molecular biology

CRISPR stands for Clusters of Regularly Interspaced Short Palindromic Repeats. Dr. Jennifer Doudna was one of the first researchers to see these short palindromic repeats in bacteria and archaea where she speculated that they were being used as a form of molecular immune system to protect these organisms from viruses.

Even bacteria get sick, so having a protection against invading viruses is a matter of life and death to a cell. Recall that viruses are essentially genetic material that will reproduce itself again and again after it hijacks a cell. Viruses may have protein coats or membranes to protect them outside of the cell, but inside, they are little more than DNA. If this DNA can be damaged or destroyed, then the virus is rendered harmless.

Screen Shot 2015-07-27 at 9.54.10 PMTo the right is a clip from Dr. Doudna’s video illustrating the repeated elements (in black) flanking a variety of ‘other DNA’. This ‘other DNA’ is what the cell will use to identify  foreign DNA – presumably from retaining the genomic material from an earlier exposure either in the lifetime of the single cell or its parents.

So, how does it actually work?
Two videos do an excellent job of explaining how CRISPR works. A short, simple video from MIT gives a non-technical explanation (a good place to start).

MIT’s McGovern Institute

Jennifer Doudna explains the system in greater detail…

Basically, the natural system uses two RNA molecules to target specific DNA sequences in the genome and recruit a protein that acts as an endonuclease to cleave this target:

crRNA – a ‘targeting’ molecule
tracrRNA – an adaptor RNA that recruits CAS9 to the bound crRNA
CAS9 – an endonuclease enzyme that will bind and cleave DNA once recruited by the RNAs

Doudna’s lab improved the system by combining the two RNA molecules into a single RNA that still effectively recruits CAS9 but is easier for researchers to manipulate in the lab. This last element is essential because manipulating this RNA sequence gives researchers the power to target any DNA sequence in the cell.

As stated above, the system was originally identified in prokaryotic organisms where it appears to allow targeting of the viruses that attack them. CRISPR uses ‘stored’ DNA as the targeting RNA and then brings in CAS9. CAS9 binds to the targeted DNA and cleaves it resulting in one of two possibly outcomes. 1) the virus is destroyed and is no longer a problem, 2) the virus is cut, but then repairs itself – hopefully in a way that introduced fatal mutations.

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How might this translate into clinical medicine?
The possibilities are endless, however a few low-hanging fruit present themselves immediately. Among these are therapies for sickle cell anemia (and a host of other blood disorders). Because sickle cell anemia is caused by a single base pair mutation, it is conceivable that hematopoietic (i.e. blood) stem cells can be isolated, the faulty gene repaired, and then re-introduce the corrected stem cell back into the body (possibly after the faulty stem cells have been ablated).

The newly altered and re-introduced stem cells now do the rest of the work for you by finding their place in the body where they reside while continually producing cells with the desired genetic changes.

The key is that these RNA molecules are quite simple to make exactly and in pure form (i.e. they can be manufactured chemically rather than needing cells to do the job for us and then we have to clean up all the extraneous contaminants). Most labs will design the molecules in-house and then order the constructed molecules from a ‘core lab’ that specializes in doing just that.

Jacob Corn, of UC Berkeley has compiled a simple protocol that anyone with a modicum of molecular biology training could follow. Find that protocol here.

 
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Posted by on July 27, 2015 in Uncategorized

 

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Virus, Vaccine and Passive Antibody Therapy

The immune system is a many-layered construction that protects the body through barrier defences, additional non-specific responses including phagocytosis and chemokines, an antibody-mediated humoral response capable of neutralizing viral particles, and a cellular response for eliminating infected cells.

Ebola: Disease and Response

mapEbola is a viral disease first identified during a first appeared in 1976 in two simultaneous outbreaks, one in Nzara, Sudan, and the other in Yambuku, Democratic Republic of Congo.  It is reasonable to suspect that Ebola has infected humans prior to this time without being identified specifically. This is a reasonable assertion because, like the first, all subsequent outbreaks have occurred in remote areas of Western African countries that are largely isolated. Although infamous for its lethality, this remoteness has proved self-limiting in terms spread.

The current epidemic has defied these rules resulting in escape from the remote areas of West African villages to larger population centers, and for the first time ever, even resulting in at least one case presenting in the United States. (citation)

In general, although viral infections are not treatable by classical antibiotics, vaccines against these types of organisms have been largely successful. Although it is impossible to know exactly why a specific vaccine works, it is reasonable to assume that a humoral response (i.e. mediated by antibodies) is involved in most cases as antibody titer correlates well with protection.

I the case of Ebola, there is data regarding the type of immune responses mounted by patients who have survived the disease compared to those who have not. Baize et al report that “early and increasing levels of IgG, directed mainly against the nucleoprotein and the 40-kDa viral protein, were followed by clearance of circulating viral antigen and activation of cytotoxic T cells” in survivors of disease. While “fatal infection was characterized by impaired humoral responses, with absent specific IgG and barely detectable IgM.” Again, this supports the idea that an effective humoral response is key to protection.

More evidence of the centrality of the humoral response comes from data published by Villinger, et al (citation) showing that “IL-6 levels are unusually low among fatal cases.” They suggest that this points to a deficiency of the endothelial cells that produce this cytokine leading to failure to protect. An alternative explanation may be that macrophages, which are key targets of ebola infection – and are producers of IL-6, are also failing to respond appropriately due to their involvement as targets. This leads to an obvious defect in immune response as IL-6 supports the growth of B cells and is antagonistic to regulatory responses (i.e. regulatory T cells).

If antibodies are so important to response, what are the targets of these antibodies and what issues are there related to this response?

Ebola Virus:

Eboal5Ebola has only one known surface protein found on virions and infected cells. It is presumed that this protein, a ‘sugar-coated’ glycoprotein (GP), is what enables virions to adhere to target cells, a vital first step in the infection of host cells by animal viruses. As neutralizing immunity against viruses is presumed to be a result of the opsinization of viral particles by antibody, the Ebola GP is the obvious target of these antibodies. However, there are still a number of epitopes (regions of the protein to which immune reactions develop) on the GP protein to which antibodies bind. And, furthermore, two versions of GP are made, one in the viral envelope (membrane) and one that is secreted from infected cells. Together, this means that there are a lot of different spots for antibodies to bind, and some spots may be better for protective immunity, while others have no protective effect at all.

Vaccines against ebola are currently being developed with the hope of bringing these to affected areas to either prevent – or at least control- outbreaks at their source. The benefits of developing an effective vaccine include actively inducing life-long immunity.

A second method of fighting disease is to treat with previously generated antibodies in a way that the virus is neutralized, but life-long protection is not induced. One way of accomplishing this treatment is by harvesting serum from patients who were infected, but survived the disease. This has obvious limitations logistically and there is insufficient data on these treatments to know whether they were actually helpful in treating patients. Another way to transfer this sort of ‘passive’ immunity is by making large amounts of a single antibody in cell culture. These ‘monoclonal’ antibodies are highly standardized and can be produced in very large quantities.

A number of monoclonal antibodies targeting different epitopes on the Ebola GP have been developed and show protective effects when administered after viral exposure (i.e. therapeutically). One example of this kind of therapy is ZMapp  from Mapp biopharmaceutical. In studies with animals, they found that “a combination of monoclonal antibodies (ZMapp), optimized from two previous antibody cocktails, is able to rescue 100% of rhesus macaques when treatment is initiated up to 5 days post-challenge.”

Treatment of Ebola patients with Convalescent Serum

Treatment of Ebola patients with Convalescent Serum

I’ve written before in this space about one of the challenges that antibody treatment against ebola. Because ebola infects macrophages as one of its targets, and because one of the jobs of macrophages is to clear opsonized (antibody-coated) particles, ebola appears to have co-opted this function as a mechanism for penetrating and infecting cells. This characteristic is termed Antibody-Dependent Enhancement (ADE) of infection and has been shown to increase the infectivity of the embryonic kidney cell line, HEK-293, in vitro (Takeda et al 2003). Reportedly, the mechanism for this enhancement is via the complement protein, C1q, and receptors on the host cells.

Together, these data beg the question of whether antibody treatments, such as ZMapp, or vaccines leading to humoral responses will be helpful or harmful in the treatment and protection of patients.

“On 11 August, a group of experts convened by WHO reached consensus that the use of experimental medicines and vaccines under the exceptional circumstances of the Ebola epidemic is ethically acceptable.” So, we may find out the answers to these questions much sooner than we would otherwise expect.

 
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Posted by on November 5, 2014 in Uncategorized

 

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Working Overtime to Prevent Sudden Death

Do you have Ebola? If you're reading this, then probably not.

Do you have Ebola?
If you’re reading this, then probably not.

My cousin, in Philadelphia, tipped me off that I should write a blog article about the current Ebola outbreak that has occurred this year in Western Africa. One of the reasons that this interested him was that the story of the outbreak was being shadowed by another story of a ‘secret’ serum that was being used to treat some of the American victims of the disease. I think ‘Secret’ was the operative word. I had definitely heard about the outbreak, but this was actually the first time that I heard about this serum – and it immediately tipped of my BS / Conspiracy theory detector because of the suggestion that America actually had a secret ‘cure’ for Ebola. It almost begs for allegations by people wearing tinfoil anti-alien hats that America was engineering some Apocalypse Bringing Disease a la I am Legend or Dawn of the Planet of the Apes.

So, I was interested to hear that there actually is a serum to treat Ebola – it’s just not secret, and it’s not an approved treatment, but an experimental one. Ebola VirusFirst, something about the virus…

There is currently no vaccine available for Ebola virus infection and the standard of care remains supportive therapy aimed at maintaining the body’s electrolytes, blood pressure and to prevent / treat additional infections that may otherwise complicate care(1). Coupled with an extraordinarily high fatality rate (up to 90%) and horrifying symptoms including internal and external bleeding, fever and

Western Africa

Western Africa

intense weakness, it remains one of the most feared diseases in the world (2). Ebola is so debilitating and deadly, in fact, that its severity has actually functioned to keep it contained within a relatively small area of western Africa. Most cases tend to occur in and around poor, unsanitary hospitals where virus spreads from a contaminated individual or cadaver to a person (often serving as a healthcare worker). Often cases present with symptoms similar to more common, less lethal diseases and are not quarantined away from other patients leading to a rapid accumulation of nosocomial infections (3). One reason for the high mortality rate associated with Ebola infections may be due to a curious condition in which antibodies against the virus may, ironically, worsen the infection. The mechanism of this behavior appears to operate through the binding of antibody to viral glycoproteins, followed by antibody-mediated phagocytosis of virus by immune cells. This is confounding because it is this process that is utilized by immune cells to destroy viruses and may further impair the ability of researchers to develop an effective vaccine as most vaccines work by promoting antibody development (4). With Ebola, the interaction of a protein on the virus’ surface is bound by antibody, which is then bound by an immune cell that internalizes the virus, but instead of destroying the virus, it manages to escape destruction and infect the cell.

Rather than making you better, antibodies against Ebola may make you worse off.

Rather than making you better, antibodies against Ebola may make you worse off.

To make matters worse, this time around many more people are contracting the disease, so concern is elevated around the world, even some US Congressmen have been making hay about the possibility that undocumented immigrants from Central America may introduce Ebola into the US. Which brings me back to the conspiracy angle. What’s this about a secret serum again?


The serum is actually just an experimental treatment – one that is extremely early in the development process, called ZMapp. This is a product produced by Mapp Biopharmaceutical Inc. that is a combination of three monoclonal antibodies made in tobacco plants (this is a more common method than you might think). The idea being that these antibodies will provide passive protection against Ebola, much like the antibodies produced by a typical vaccine, but -hopefully – without the adverse effects associated with the antibodies that enhance infectivity. Reading the article describing the manufacture of these antibodies does not provide an explanation of how the antibody-mediated enhancement of infection will be evaded, but one may imagine the construction of neutralizing antibodies that lack the constant regions associated with FcR or C1q binding as the binding of these two proteins have been proposed as causing the adverse effect. As this drug lends passive immunity, it may (if effective) prevent infection of an exposed person – or at least lesson the severity of the infection, however it will NOT lead to the accumulation of antibodies by the patient as would a vaccine. Rather, this form of immunity is more akin to treatment with an anti-serum following a snake bite. With luck, a silver lining to this major outbreak may be the opportunity to test an early-stage treatment, possibly resulting in the first ray of hope in improving Ebola survival.

Can I catch this?

Can I catch this?

References:

  1. http://www.vox.com/2014/7/29/5945515/ebola-outbreak-virus-disease-symptoms-africa-facts-guinea-nigeria
  2. http://www.who.int/mediacentre/factsheets/fs103/en/
  3. https://microbewiki.kenyon.edu/index.php/Infection_Mechanism_of_Genus_Ebolavirus
  4. http://jid.oxfordjournals.org/content/196/Supplement_2/S347.full.pdf
 
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Posted by on August 7, 2014 in Uncategorized

 

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Antigen Presentation #3: MHC Class I

Antigen Presentation

Presentation by Epithelial Cells

Consider: Under what circumstances would any cell in the body need to initiate an immune response?

Here, I’m using epithelial cells as an example, however, every cell in the body has the ability to present antigens on MHC Class I. In fact, it is a normal, continuous process that the cells cannot fail in without consequence.

While professional APCs process and present antigens that they have phagocytized, other cells divert a small amount of the total protein they make towards MHC I presentation. This allows the immune system to constantly observe these cells and ensure that they are not suffering gross mutations or infections. Most of the time, cells produce normal, ‘self’ proteins against which there are no T Cells (due to negative selection – see Lymphocyte Development).

In the event that MHC I expression is subverted, these cells are presumed to be infected and will be targeted for killing by special cells called Natural Killers, or NK Cells.

If a Non-Self antigen is presented by MHC I, these are recognized by CD8 T Cells. Like the reactions between APCs and CD4 T Cells, cells expressing MHC I + Non-Self Ag engage T Cells via their unique TCRs. The only difference is that these T Cell : Presenting-cell complexes are stabilized by CD8 molecules on CD8+ Killer T Cells.

ImageThe result of this binding is the activation and proliferation of Killer T Cells that will turn upon and kill the presenting cells by releasing perforin and granzymes that perforate target cells and trigger apoptosis (cellular suicide).

Keep in Mind the Big Picture!

To summarize with an example:

  1. Host cells are infected with a virus
  2. The virus replicates within the host cell, producing viral proteins in the process
  3. Some of these proteins are diverted to proteases that digest them and load the antigen fragments onto MHC I molecules
  4. The MHC I +Ag is transported to the plasma membrane to ‘present’ Ag
  5. MHC I +Ag is recognized by a T Cell bearing an TCR specific for the MHC+Ag complex. This interaction is stabilized by CD8 binding to MHC I.
  6. If a stable interaction is formed, the T Cell will become activated, meaning it will proliferate and secrete perforin and granzyme toward the presenting cell
  7. Perforin and Granzyme will lead to the apoptotic death of the presenting cell
  8. By killing the infected cells, the infection can be stopped before spreading farther in the body.

A CD8 T Cell (the smaller cell) killing a virally infected host cell:

Image

 
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Posted by on December 8, 2013 in Uncategorized

 

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Paul Offit’s Vaccine class

ImageIn my microbiology class, students read Paul Offit’s ‘Vaccinated’, an excellent account of the life and work of Maurice Hilleman, creator of many vaccines in common use today. I don’t know how many of my students are aware of it, but Coursera.org is a free online university offering courses in a number of subjects taught by senior faculty from many distinguished universities. Today marked the first day of Paul Offit’s Vaccine course, which covers topics related to the history, development, use and misinformation surrounding vaccines. From the course website:

1) History of Vaccines – Viruses

2) History of Vaccines – Bacteria

3) Current and ‘Alternate’ Schedule

4) Common Questions About Vaccines

5) Vaccines in the media

6) Creation of a Vaccine – Case Study: The Rotavirus Vaccine

7) Vaccine Exemptions

I can’t promise that this course is still open, but I expect it is – and best of all it’s FREE.

Furthermore, if you sign up and only decide to watch one or two class lectures, there’s no risk: just drop out or simply stop signing in. So, if you have any interest in the subject, or would simply like to see what it’s like, go onto Coursera.org and type ‘vaccines’ in the search bar.

 
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Posted by on September 3, 2013 in Uncategorized

 

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Another Measles Outbreak puts 2013 on course for another peak year

ImageA new Measles outbreak erupted in Tarrant County, TX when a visitor to the Eagle Mountain International Church infected members of the congregation, staff and the daycare. Although the church’s pastor, Terri Pearsons, has been critical of vaccines in the past, she has fortunately changed her outlook and is now urging her congregation to get immunized now to prevent further spread of the disease.

ImageMeasles is a highly contagious virus, that infects ~90% of those who are exposed (and unimmunized). Since the introduction of the vaccine in 1963, cases have fallen from the hundreds of thousands per year to near eradication levels. However, global travel and the recent rise in anti-vaccine rhetoric has allowed for the past several years to see higher numbers of cases in the ‘post-vaccine era’.

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2013 Measles Map

Although it is imperfect (due to incomplete and sometimes redundant data), I put together this map of the 2013 outbreaks in the US, presently amounting to ~135 cases (using data from  Vincent Iannelli, M.D.’s report to About.com.) With four and a half months remaining in the year, 2013 stands a chance of reaching or surpassing the 2011 (modern) record of 220 cases.

This map helps to highlight that Measles is considered to be eradicated in the United States, however the disease continues to be introduced by travelers and spread in short bursts amongst unimmunized individuals.

“The majority of measles cases were unvaccinated (65%) or had unknown vaccination status (20%). Of the 911 reported measles cases, 372 (40%) were importations (on average 34 importations/year), 239 (26%) were epidemiologically linked to these importations, 190 (21%) either had virologic evidence of importation or had been linked to those cases with virologic evidence of importation” says the CDC.

The CDC encourages parents (and all Citizens) to remain vigilant and follow these recommendations to help maintain herd immunity and prevent introduced cases from becoming endemic:

  • vaccinating children at age 12-15 months with a first dose of MMR vaccine,
  • ensuring that school-age children receive a second dose of MMR vaccine,
  • vaccinating high-risk groups, such as health care personnel and international travelers including infants aged 6 to 11 months,
  • maintaining measles awareness among health care personnel and the public, and
  • working with US Government agencies and international agencies, including World Health Organization (WHO), on global measles mortality reduction and elimination goals.

 

 
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Posted by on August 26, 2013 in Uncategorized

 

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There’s a new Coronavirus in town, and it’s kickin’ ass and taking names

ImageThe most frequent coronaviruses we encounter are those that cause common colds, although other, more severe viruses occur within this family including the virus that causes SARS.

The current newsmaker, MERS-CoV, is a newly described coronavirus noteworthy for its high mortality (approximately 50% of patients diagnosed with the virus have died). Aside from high mortality, the name of the virus (MERS-CoV stands for Middle East Respiratory System Coronavirus) has drawn controversy because of its identity with the ‘Middle East’. Beyond that, this provides an opportune time to describe and discuss the coronavirus family in terms of structure and other characteristics, which might be a good place to begin.

The Coronavirus Family

Coronaviruses are a group of viruses with a plasma membrane envelope surrounding a helical nucleocapsid, which, in turn, surrounds the genetic material – in this case a positive strand RNA.

ImageCoronavirus genomes an extraordinarily large positive strand RNAs encoding a spike protein (S), and Envelope protein (E), a membrane protein (M) and a nucleocapsid protein (N). Additionally, the virus also encodes an RNA polymerase required for the copying of its RNA genome (a function unlike any naturally occurring in the host cell and therefore requiring a specialized viral protein).

The Envelope is derived from the intracellular membrane of previously infected cells that is taken during the process of viral ‘budding’. Coronaviruses are named for the corona-like appearance (by electron microscopy) of these envelopes and the distinctive viral proteins (E and S) radiating out from the surface. These proteins are essential for the virus’ ability to bind to, and enter, uninfected cells through specific protein:protein interactions.

Within the envelope is the nucleocapsid, a helical structure that self-assembles from capsid proteins in the host cell’s cytoplasm. As this structure assembles, it binds and takes up a viral genome that contains all the genetic information to infect and reproduce in subsequent host cells.

MERS-CoV by the numbers

300px-CampFunstonKS-InfluenzaHospital

I had a little bird,
Its name was Enza.
I opened the window,
And in-flu-enza.

So far, of the 55 cases the CDC recognizes as testing positively for the virus, 31 have died. That’s 56% of infected persons dying of the disease. The majority of these cases remain in the middle east, however a small number have also appeared in western Europe, but with identifiable ties to the middle east. Compare this to the 2.5% mortality rate from the devastating 1918 swine flue epidemic.

Naming Convention

Although the name has accepted been adopted (as well as ‘Saudi SARS’), it goes against a tradition opposing the use of locations in the name of the virus. There are two reasons for this convention – first, it may easily become inaccurate as the virus spreads and second, it can lead to stereotyping and persecution of a group of people. A previous example of this sort of mistake occurred when a new autoimmune disease was becoming prevalent amongst homosexual men in the US. Instead of using a more generically descriptive name, this virus was initially referred to as GRID (gay-related immunodeficiency virus). The virus, itself, had no idea it was supposed to stick to the gay population and before long it was discovered that everyone was potentially vulnerable. The name was then switched (or, more accurately, it finally got an official name, ‘HIV’, for human immunodeficiency virus). However, the damage was already done and many people adopted the belief that the virus only affected gay men, so straight people were not as likely to practice ‘safe sex’, and practitioners of hate speech added another arrow to their quiver: ‘Gay plague was sent by God, who was upset at homosexuals.’

Going Forward

Last week Novavax, Inc. announced the production of a nanoparticle vaccine candidate using the spike protein of MERS-CoV, a strategy that the company previously used in making a SARS vaccine.

Regardless of the method (vaccination, quarantine, etc.) it remains a vital priority to establish a protocol for maintaining public health prior to the Hajj, which is expected to fall between October 13-18, 2013. In 2011 the hajj saw An estimated 2.5 million pilgrims gathered in Mecca, most traveling from (and then returning to) countries outside the Arabian peninsula.

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Posted by on June 11, 2013 in Uncategorized

 

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Rubella (AKA German Measles or three-day Measles)

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Appearance of Rubella Rash

A student in one of my classes brought up a recent case of a baby being born with a lethal heart defect that had been linked by the physician to a viral infection. In class, it did not occur to me what virus might be linked to a malformation of this type, but we did actually just read about a virus capable of doing just that in Vaccinated, by Paul Offit.  

It seems reasonable then, to discuss a disease that has faded from our cultural memory due to an effective vaccine campaign here in the US and abroad.

The virus discussed in that book is Rubella, or German Measles. In Vaccinated, the virus was referred to as the ‘Monster-Maker’- due to its teratogenic effects on developing fetus’. In fact, heart defects very much like the kind described have been attributed to Rubella infections of the mother between the third and tenth week of pregnancy.

ImageThe classic triad of symptoms associated with congenital rubella syndrome (CRS) is: 1) Deafness, 2) Eye abnormalities including cataracts and 3) Congenital heart disease, especially patent ductus arteriosus. Rubella also can cause miscarriages and stillbirths if the mother is infected early in the pregnancy. The CDC describes CRS and its symptoms in its Manual for the Surveillance of Vaccine-Preventable Diseases (5th Edition, 2012) by McLean et al.

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Patent Ductus Arteriosis

The push for an effective vaccine was driven, in part, by a devastating global pandemic in the early 1960s during which more than 12 million cases of rubella presented in the United States alone, resulting in 10,000+ therapeutic or spontaneous abortions and 20,000 cases of CRS.

Since the development of the vaccine, Rubella infection has been drastically reduced and in 2004 it was determined that Rubella had been eliminated in the US (so, it is unlikely that the case brought up in class was due to rubella). As of 2011, this elimination has been maintained and surveillance measures are in place to ensure immediate reporting of suspected cases to prevent recurrence of disease in the US. 

 

“Other Infections that can cause birth defects include rubella (German measles),cytomegalovirus (CMV), syphilis, toxoplasmosis, Venezuelan equine encephalitis, parvovirus, and, rarely,chickenpox.”, a discussion of these can be found at kids health.org.

 
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Posted by on April 5, 2013 in Uncategorized

 

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Life Revisited: We’re speaking different languages

I know I’ve talked about this before on this blog, but I can’t get my hands on any essays I’ve written about how life is defined and how this question remains a longstanding topic of discussion between me and my wife on what makes something alive.

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bacteriophage

I feel fairly confident that we both have a pretty good grasp on what the arguments for and against something being called ‘alive’ are. It’s not the characteristics of life that we dispute, but how much weight each of them should carry.

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pooch

As a bit of background, it should be stated that even biologists have a fairly difficult time defining life formally. Many of us can point to a rock and declare ‘not alive’, to a dog and declare it ‘alive’, etc. But these are simple examples. The things that really challenge the definitions are where details and technicalities become sticking points.

The two standard tests of life can be summarized as:

1. The Cell Theory – The cell is the basic unit of life and therefore all life must be cellular.

2. Defining life as things that have ‘The Characteristics of Life’:

a. Life must be ordered

b. Life must reproduce

c. Life must metabolize

d. Life must be homeostatic

e. Life is evolving

f. Life responds to stimuli

g. Life must grow/ develop

My wife has a much more comprehensive view of what it takes to be called alive. She would like to see most, if not all of the seven characteristics of life fulfilled and also holds to all life being cellular. When pressed, I think that she finds the most value in defining life as those things that can metabolize for themselves. They may require certain environmental support (waters, food, etc.) but when given these things, they can meet all the characteristics of life… but metabolism seems to be one of the most defining of these characteristics.

I’m not sure if holding to this definition represents any specific school of thought, but I suspect it reflects an organismal approach to life informed by her history as a clinician.

I, on the other hand, have a much more minimalistic definition of life that elevates the importance of reproduction over most other characteristics. If a thing has genetic material of some sort and can reproduce this material resulting in new life, that is sufficient for me – even in the absence of many other characteristics from the list above.

Why is this so important to me that reproduction trumps all else? I wasn’t sure what it was until I got to thinking while listening to Richard Dawkins’ newest book, The Magic of Reality. I’m listening to it for a number of reasons, perhaps primarily because I am developing a new course for the Summer semester that examines the philosophy of science. However, Dawkins hits upon many of his standard points in this book, one of which is, ‘we are all simply machines built by our genes, for the sole purpose of perpetuating those genes.’

There it is, a molecular definition of life. A definition, which although I was not always consciously aware of it, was critical to the way I approached biology. In my head, all living things are just self-replicating molecules wrapped in complicated shells (bodies). It’s really just the DNA that is alive.

This is exactly the opposite definition as that held by my wife. She views the organism as a whole as the primary unit, that thing which is really alive. One comment that she made that clarified her perspective to me the most was that it’s really not as important to talk about what is alive and what is not, as it is to talk about what has consciousness and what does not. I think this is really cool, it’s almost like an eighth characteristic: awareness. This is not to say that things cannot be alive just because they are not self-aware, but to add something new and elevate the definition from mere life to something more. Something relatable.

I think it’s important to remember that this is really a philosophical point. As such, the answers are not as easily classified as right or wrong, but merely as points of view.

We have also talked a lot about how language shapes the way people think. We both agree that this is possibly one of the major differences amongst people of various cultures. Some people speak languages that place more or less importance on things (one example we discussed recently was that some languages do not have a future tense that distinguishes it from talk of the present tense. This may impact how certain cultures value the future more or less than others … think saving for retirement). Some people benefit from being multi-lingual and therefore having many frames of reference, or lenses that they can view current events through.

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ATGCATGCATGC

I bring this up because she started her professional career as a veterinarian, caring for animals, curing disease, controlling chronic problems, managing pain. The animal was the focus. I, on the other hand, began my professional career as a molecular biologist, snipping out genes, cloning them and expressing them in different organisms. The genetic material was the focus.

Just like language, our careers shaped our approach to life and allowed us to define it from very different perspectives.

People are funny that way.

 
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Posted by on February 27, 2013 in Uncategorized

 

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