Author’s Note: I would like to dedicate this piece to the One Billion Rising Bangladesh campaign that is going to culminate on VDay, Feb 14, 2013. While violence against women is much more conspicuous forms of rape, domestic abuse and workplace discrimination, lack of healthcare access, especially in the case of breast cancer given its unique nature and targeted population, serves to show the underlying prejudices held against women in the country.

 

Breast cancer remains the leading cancer type among the global female population with 1.35 million new cases every year (1). It is also a significant contributor to the global cancer burden – in 2008, it accounted for 23% of all new cancer cases and 14% of total cancer deaths (2). The distribution of these cancer cases vary depending on the socioeconomic status of countries, but it is estimated that 69% of breast cancer deaths occurred in developing countries (3). In Bangladesh, the rate of breast cancer occurrence is estimated to be 22.5 per 100,000 females of all ages, compared to 124.8 per 100,000 females worldwide. For Bangladeshi women aged between 15-44 years, breast cancer has the highest rate of occurrence – 19.3 per 100,000, compared to any other type of cancer; cervical cancer comes in second for this age group at 12.4 per 100,000 (4).

However, the incidence rate remains a murky business, largely due to a lack of diagnosis and poor record-keeping infrastructure. Based on cancer registry data from Karachi, Pakistan, and Kolkata, India, Story et al estimates an annual incidence rate of 35-40/100,000, giving an approximate of 30,000 cases in total per year (5). The first-ever national cancer registry (6) that tracked newly diagnosed cases, started in 2005 at the National Institute of Cancer Research and Hospital (NICRH), was published in 2009 and demonstrated a steady increase in incidence rates – 10.3% in 2005 (n= 5,411), 11% in 2006 (n= 6,492) and 12.3% in 2007 (n= 6,926). The Bangladesh maternal mortality survey 2010 (7) cited breast cancer to be responsible for 21% of all women’s deaths between 15 and 49 years of age. Regardless of variations in available data, it is plainly observable that breast cancer is fast becoming a major cause of concern, not only for women, but also as an overall public health concern.

The official fight against cancer in Bangladesh can be attributed to the founding of the NICRH in 1982 as part of Dhaka Medical College, although it did not become a functional treatment unit till 1995 when it first brought in radiotherapy (8). In the last decade or so, non-governmental agencies have joined the initiative, in both rural and urban areas of the country at various scales of operation. Adhunika, a grassroots non-profit focused on empowering women, started its breast cancer awareness programs in Sajida Hospital, Keraniganj in 2011 (9) while the prominent Dhaka Ahsania Mission (DAM) established a cancer detection and treatment hospital back in 2001 and has promised to expand it to a 500 bed hospital by the end of 2013 (10). DAM also hopes to open a cancer center in each division of the country and to that end, has found a 42 bed hospital in Dhaka that supports both diagnostic and treatment facilities (11).

The case of breast cancer in Bangladesh has also attracted the attention of global agencies such as the International Breast Cancer Research Foundation (IBCRF), who partnered up with the local NGO Amader Gram back in 2006 to create four breast problem focused clinics and one specialty treatment center in Bangladesh (12). Amader Gram is an IT non-profit  which focuses on using technology to alleviate the poverty burden of the rural population (13) and has developed an electronic medical record system that provides a data recording infrastructure as well as better treatment and diagnosis for patients and the country’s first free walk-in breast clinic in Bagerhat, Khulna (12). The ultimate goal of this partnership is to establish a model program to improve outcomes from breast cancer, mainly in rural bangladesh (5, 12).

However, even with such great initiatives, the future of this battle against breast cancer remains bleak. Dr. Richard Love, director of the ICBRF, estimated that 80% of all new cases will result in death (14). Field studies done in Khulna from 2007 -2008 show that 87% of new cases are Stage III+ breast cancers (where the cancer has spread to other regions) and are incurable (12, 14). The majority of these tumors were determined to be triple negative in terms of hormone receptor status (estrogen, progesterone and HER2/neu), for which treatment options are rare, inefficient and very expensive, especially in a low resource country such as Bangladesh.

It would have been easy to just put majority of the blame on lack of awareness and early detection and part of it on lack of public health infrastructure, but that is not necessarily the case, especially in the rural areas of Bangladesh. The much-heralded Westernized notion of “Awareness and early detection” does not fit the cultural context of Bangladesh where women, especially in rural areas, face more than just organizational barriers (complex healthcare system, understanding of the disease, communicating with medical staff) to healthcare (5, 15). They face psychological barriers such as fear of cancer, denial of fatality, conscious choice of not seeking care, and sociocultural barriers such as religious barriers to screening, structural violence and oppression, financial constraints and gender discrimination (5, 15, 16). Anecdotal evidence shows lack of support from male partners and family, avoidance of diagnosis and treatment due to financial burdens, widespread superstitious beliefs about cancer and its origins and sometimes ineffective treatments such as homeopathy, spiritual healing and ayurvedic medicine (5):

It’s a curse from God for wrong doings.“; “It is evil. Once it visits your house it kills.” – Focus group participants in Rampal, Khulna

When I told my husband I had breast cancer he said I don’t want anything to do with you, you can go die.” – 45-year-old divorced and homeless interviewee, Jessore

The homeopath prescribed me many drugs and gave me some injections…but my breast lumps [“chakas”] didn’t go away” – 28-year-old interviewee from Rampal, Khulna

It’s true men are not always supportive… cancer is costly, so they won’t take us to the hospital [for treatment].” – Focus group participant, Sreefaltola, Khulna

The costs add up in people’s minds. My wife had a caesarian section and then a thyroid nodule. Even when you are a good person these thoughts cross your mind…if the costs are too much, maybe I should separate?” – Male community group discussion participant in Rampal, Khulna

Added to this mix are lack of access to healthcare, discontinuous treatment regimens that may give rise to resistant cancers, lack of female doctors (since 1971, a total of 23% of all medical graduates are female) and doctor absenteeism and malpractice (reported to be around 70% in rural clinics) (5, 17), all of which point towards unfavorable outcomes for Bangladeshi women at risk of breast cancer.

Even with such adverse conditions, all hope is not lost. Progress is being made, albeit slowly, in improving such outcomes. Reports show that the hormone receptor status, which is essential in determining treatment, has been affected by improper handling of patient breast tissue sample (5). When handled properly, 72% of samples were found to be positive, which drastically expands treatment options for such patients and increases survival rates for them (5, 18). Studies are already underway to test the effectiveness of both hormonal and non-hormonal therapy for breast cancer in Bangladeshi samples, through the international collaborative project setup by IBCRF (19). Besides clinical advances, public health approaches have been taken in terms of self-screening and palliative care, such as easy to use pain chart as developed by Dr. Rumana Dowla (20). On the social side, female health care workers are being trained (21), a more detailed registry is being built (12), awareness is being spread through fundraising, folk songs and other culturally suitable media (23, 24, 25, 26).  All of these initiatives are in accordance with the recommendations developed by the Breast Health Global Initiative for low-resource and middle-resource countries (27) and the guidelines of the cancer control continuum.

Breast cancer is not only a public health issue in Bangladesh, it is also an issue of human rights and social development.  A potentially fatal disease that is intertwined with the multisymbolic organ of femininity, and whose origins are shrouded in superstition and fear and connotations that reach far beyond its biological understanding, breast cancer has taken the form of the metaphorical illness as described by Susan Sontag (15, 28). In order to reduce mortality rate, improve available treatment options and outcomes of breast cancer, there needs to be dispelling of myths surrounding cancer and its origins [“as long as a particular disease is treated as an evil, invincible predator, not just as a disease, most people with cancer will indeed be demoralized by learning what disease they have” – Susan Sontag, (28)], better healthcare infrastructure, more social accountability by both the people and the government and collaborative research between international organizations, local institutes and pharmaceutical companies. But before all of that can happen, the social status of women in Bangladesh must be elevated to the level of any other male as equals, violence against women and gender discrimination must be ended, and women should be given the equal priority for their lives as any other human being. For “women are not dying because of untreatable diseases. They are dying because societies have yet to make the decision that their lives are worth saving” (29). And it is high time we step up to give the proper respect to women that they deserve.

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The recent success of PETA’s protests against overseas shipping of primates for laboratory research in the US highlights the less talked about issues of using animal controls. Whereas primates were the focus of the protests at hand, the PETA has also been actively engaged in raising awareness about treatment of other lab animals including mice. Their investigations at the University of Chapel Hill labs show the need for increased awareness about such issues, especially when they are the most commonly used mammalian animal model, but lab mice are not protected under the Animal Welfare Act administered by USDA APHIS. However, the Public Health Service Act administered by the National Institutes of Health do provide a guideline for the care and use of such animals. This standard of care is maintained by the Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC), but strangely enough, this accreditation is voluntary, although most academic research institutes do ask for it, and not a prerequisite for US federal funding. Regardless of the upcoming and proposed alternatives to animal testing (ref), the need for such use of animals remain somewhat indisputable as 93% of researchers (as of 2009) still supported it and the US federal law requires animal testing for all drugs and some chemicals (ref).

As mainstream researchers adhere more and more strictly to the “Three Rs” guideline (Replacement, Reduction, Refinement) for animal experimentation, the use of lab mice as animal controls have come in question. The lab mouse has come a long way from the cheese-loving corner-dwelling innocent-but-cute animal to being the animal model of choice to study complex diseases such as cancer (ref). The advent of Genetically Engineered Mice (GEM) and their subsequent commercial successors, the JAX mice, has allowed the biomedical research field to make great advances in not only the study of diseases and treatment options, but also in related public health issues such as obesity. Such success has even earned lab mouse the accolade of “Best supporting role in a medical drama“. But this success comes with its limitations – how far can the mouse model tell us about diseases and drugs?

In terms of cancer research, the focus has narrowed from the large scope of how population dynamics affect cancer incidence to the molecular mechanisms of the disease, thus leading to modelling of individual mutations. The GEM models used are inbred for such purposes and ironically, has come to represent a single individual in a population rather than the population as a whole (ref). Because of the process of generating such mice, their genetic history gets murkier and thus polymorphisms are introduced back into the genetic mix, which may not always show up in the phenotype (example here). The lack of control over the genetic background and testing for it may produce unreliable results as the introduced variability will not have been considered for a measure of control. The single variable inbred system may shed light on the workings of a particular mutation, but with such inherited variability involved, it becomes difficult to pinpoint the cause of cancer incidence even in such models.

It is not quite possible to able to strictly control all variables involved in the incidence of a multi-faceted disease such as cancer. The aim of the control group in any scientific experiment is to provide a means of comparison of the concept being tested. This may reduce the problem of untested variability in mice used as control subjects, but as the study by Martin et al (2010)  shows, a large majority of such animals are “metabolically morbid”. Lab mice are usually sedentary and overweight, mainly due to the large intake of food and lack of movement. The standard lab conditions result in such mice becoming overweight, insulin resistant, hypertensive and may experience premature death (ref). The same study also shows that cutting daily food intake by 20-40% of the usual standard, or providing food intermittently, results in significant decrease in the likelihood of incidences of cancer, type 2 diabetes, renal failure and can even extend the lifespan up to 40%.  These findings raise the concern that the pathologies associated with obesity and cancer may not have been properly controlled in the control group and thus, the cause of incidence may not be accurately pinpointed (ref).

The problems of using the lab mouse as animal model highlighted above are, of course, solvable. Suggestions have already been made in the studies mentioned above and a recent study shows that mice, which are allowed to build nests to keep themselves thermally stable (30-32 degree Celsius), provide a better model for studying humans compared to the mice housed under standard lab conditions (20-24 degree Celsius). While the colder temperature suppress aggression and allow female mice to lactate better, if kept towards the lower end, the mice show decreased immunity and growth retardation. The study also showed that the nest-building mice actually ate less compared to their inactive counterparts, since their metabolic demand to keep themselves warm had been reduced by higher temperature and nest building (ref). In addition to such research, the NIH has already proposed revised guidelines for animal care which includes increased housing space for a breeding female mouse, among others (ref, ref). Researchers have also been questioning the undisputed position of the mouse species as the lab animal of choice, since not all physiological processes in the mice are translatable to humans (ref). Other researchers, instead of inducing a disease in the rodents, try to use healthy rodents as models for how human health could be improved to fend off cancer and other deadly diseases. One such animal is the naked mole rat, which as Dr. Rochelle Buffenstein at the Barshop Institute, Texas, pointed out, do not develop cancer even when irradiated, chemically treated or even through xenograft transplantation (ref).  [On a side note, Daniel Engber has a fantastic series of articles in Slate where he explores the ubiquitous use of lab mice as test subjects]

The utilitarian and reductionist approach to science may not allow researchers to provide the best treatment to mice, but the guidelines in place ensure that the most humane approach is taken when working with such animals. Although cases as seen in the PETA’s investigations of the UNC labs do occur, it is a misunderstanding that such phenomena constitute the norm. But because it is only such news that gets out to the general public, the scientists themselves must come forward and dispel accusations of performing atrocious acts on animals. For let us not forget that such experimentation is undertaken to feed the constant consumption of humans, arising from endless craving for a materialistic life.

The discovery of the DNA was certainly one of the biggest breakthroughs in science history. But in my humble opinion, the paradigm shift in research methodology was caused by molecular biology techniques. With the use of such techniques, perfected and advanced over time, the field has produced major discoveries regarding regulation of our activities. During this period of biological research, there was a rush to discover the genetic cause of any anomaly observed biologically, or even sometimes, stretched to more abstract concepts of personality, even probing political ideology (ref). But this change in the course of research also resulted in accumulation tons of data, a lot of the times overlapping. Every single bio-molecule was being carefully studied, and as naturally happens, scientists got too lost in the molecules they were studying. Similarly, the sequencing and bioinformatics field has suffered the same problem – there were just tons of genomic data that needed to be documented (ref). The solution seems to lie in the field of systems biology, since it became “a movement of its own” since 2000 (ref).

 

A perfect example of the use of this concept is reflected in the works of Dr. Salil Lachke (Univ. of Delaware). Dr. Lachke studies the genetic and molecular cause of cataract formation using bioinformatics and animal models. How does he bridge the gap between these seemingly far-away fields? His lab has developed a systems biology tool called iSyTE (integrated Systems Tool for Eye gene discovery) to identify candidate genes based on patient-derived data on cataract formation and to elucidate regulatory gene networks (RGNs) behind eye development. Because his work is extensive (Pubmed), it will not be possible for me to describe all of it. So I would like to talk about two key projects that he did, which in my humble opinion, speak out for the significance of his work. In regards to eye development, he has used iSyTE to build an information network known as the “Developmental Oculome“. Based on the published literature on dynamic RGNs and protein networks interacting during eye development, this project aims to accumulate all the relevant information on molecular interplay and create the big picture. Similarly, his work in cataract formation has resulted in the identification of the Tdrd7 gene, a mutation in which results in glaucoma and cataracts (ref). TDRD7 is a RNA binding protein that are critical for the cytoplasmic RNA granules to properly regulate mRNAs post-transciptionally for organogenesis. He showed that null mutations in this gene results in glaucoma and cataract formation in mice models and even causes arrest of spermatogenesis (ref). He has also shown that targeted RNA sequences can be used to reverse this mutation and restore eyesight lost due to cataract formation (unpublished*).  In the course of this research, he has also identified other genes that have been seen to cause congenital cataract formation (ref, unpublished*). Interestingly enough, he has also identified the skin to be facilitating the mating of Candida albicans,   a causal agent of oral and genital infection in humans (ref). It is rather amazing to observe how he brought together fibroblasts present in the skin, and the opaqueness of C. albicans cells to shed light on the opacification of the lens, due to genetic mutations in lens fiber formation. He literally “cleared up the big picture” on eye disease and development.

 

Just as Dr. Lachke is trying to provide a more dynamic landscape of the numerous molecular interactions behind development, a recent study has provided the background for studying such interactions in multiple conditions, rather than a single condition used so far. Large-scale changes in gene-gene, gene-protein and protein-protein interactions can be studied, in the future, using this approach. As stated in the paper, the researchers’ approach was to investigate the parts of the system to be most affected due to a disturbance. This study essentially bridges the nature vs. nurture duality by pointing out differences within protein-protein and protein-gene interactions, resulting from an environmental stimulus, and also the differences in the gene-gene interactions resulting from a mutation in the same context. With increasing developments in both high-throughput data production, the field of differential network biology is a rapidly expanding tool aiding in studying DNA damage response, different disease states, and even on a macro scale, relationships between organisms based on genetic data.

 

Thus it is of no surprise that systems biology is a vital driving force in the paradigm shift observed in current biological research, just as molecular biology had done in the previous century. It will be through systems biology that we understand ourselves and our surroundings in a bigger picture, for as Linas Pauling said “Life is a relationship among molecules and not a property of any molecule”.

 

*The unpublished data was taken from a lecture by Dr. Lachke at Thomas Jefferson University on Feb 8, 2012 that I attended in person. 

The recurring pattern of “back-to-nature” movement has taken on a new meaning in the current time. While there is the usual rise in environmental awareness among populations, there is also the growing interest in using plants as sustainable industrial tools. There is no doubt that plants have played a vital role in human existence by producing oxygen and thus, it is of not much surprise that after much ignorance, we are finally looking for sustainable solutions to problems that industrialization has led to.

 

The case of treatment of malaria hopefully will shed more light to what I am trying to get at. Quinine, found in the bark of the cinchoa tree, have been used to treat malaria since the 17th century. But as we progressed technologically, the active ingredient, quinoline, was no more extracted from the plants, but rather synthesized in lab and soon after, synthetic analogues with higher potency were available in the market. But with the rise of multidrug-resistant strain of Plasmodium falciparum, the race to develop a novel anti-malarial agent led to the discovery of Artemisinin, found in the leaves of  the herb Artemisia annua in the 1970s from a Chinese medical book from the middle of the 4th century. But given our “need” for efficiency and circumstantial demand, the highly expensive process of naturally extracting it or chemically synthesizing it failed to make it a highly accessible drug in the market. With the advent of synthetic biology, we seemed to have cleared this hurdle too, when researchers found a way to produce a precursor, Amorpha-4,11-Diene in both E. coli (ref, ref) and yeast (ref). This was taken a step further when  the biotechnology company, Amyris Biotechnologies, announced that they had successfully produced a semisynthetic artemisinin precursor in yeast and were moving it to the production stage (ref).  Despite all these developments, the production of actual artemisinin was not possible in engineered microbial and plant systems till Vainstein et al (2011) reported the synthesis of Artemisinin in an engineered tobacco plants. Once cannot help but notice the recurring pattern of consistently looking into the Plant kingdom for answers that we have followed in developing anti-malarial treatments.

 

And it is not only diseases that plants are providing the answers for. Although ethanol-based biofuels have not been quite the success they had been imagined to be, it was our narrow “vision” of producing energy in liquefied form (probably stemming from our oil addiction) that led to the failure. A recent study showed  on average, converting plants that are sources of ethanol for biofuels, to bioelectricity led to 56% more energy for transportation per acre, even considering that the same biomass was also used to produce ethanol for cattle feed. When concerns were raised about CO2 emissions from production of ethanol, the researchers suggested modifying the power plant to actually capture and store CO2, resulting in a carbon-negative production process. While this is still in the works, the research for greener biofuels have led to the use of halophytes for producing the next generation of biofuels by the GreenLab at NASA. The researchers have developed an “extremely green” sustainable ecosystem for producing biofuels that do not need fresh water or fertile land that could be used for crop production. Outside the biofuel field, researchers are now looking into the process of artificial photosynthesis, the signature energy and food producing mechanism of plants till cyanobacteria came into the picture, as a sustainable renewable energy source through solar-driven generation of hydrogen (ref). The freshest step in this project comes with the development of the artificial leaf, which exhibited twice the efficiency compared to the natural photosynthetic efficiency of bacterial species, and the development of photovoltaic cells that can store solar energy like plants do, by splitting water. The research page of the Joint Center for Artificial Photosynthesis shows how this technology is inherently based the design of photosystems existing in both plants and cyanobacteria (more here).

 

Plants have also long served as indicators of changes in environmental quality resulting from anthropogenic activity (1, 2, 3, 4). Given the current decline in the environmental quality, there is an increasing need to monitor introduction of the plethora of synthetic substances that we use in our daily lives. Since these synthetic compounds usually do not have naturally occurring receptors in plants, research into fine-tuning plants to sense such foreign substances have resulted in the design of a completely synthetic detection system using periplasmic binding proteins (PBPs). These proteins, usually involved in bacterial chemotaxis, had been previously engineered to detect toxic agents. Because it is not possible to spread the engineered bacteria all around the globe, the researchers looked towards developing an easily readable system with fast detection methods. And thus, using a synthetic “de-greening” gene circuitry, where there is rapid loss of chlorophyll as response to a particular input, the engineered evolutionary conserved (between bacteria and plants) histidine kinase pathway of signal transduction and gene expression regulation, and the engineered PBPs and their receptors, the researchers effectively created a synthetic detection system that can be used for monitoring environmental contaminants. And not only as environmental indicators, but plants could be also used to study genetic variation in humans, as this recent study suggests. The analysis of 250,000 single nucleotide polymorphisms (SNPs) present in 1,307 global variants of Arabidopsis thaliana showed that the historical pattern of recombination in this plant is similar to the one observed in humans, but very different from the ones observed in other plant species.

 

On a more molecular scale, we are beginning to understand the profound impact plants have had throughout our evolution. A recent study showed that 5% of all small RNAs present in the human sera were plant microRNAs (miRNA). MicroRNAs are involved in the post-transcriptional regulation of gene expression through the RNA interference system and has entered the our bodies through the plant contents of our diets. Because they can survive the process of cooking, and given their ability to affect gene expression in our cells (eg – plant miR168, found in rice, inhibited LDLRA production, a protein involved in the removal of LDL from blood), a new alarm about genetically modified crops have been raised (ref). But as Charlie Petit of the Knight Science Journalism Tracker pointed out, the risks involved in ingesting GM plant miRNAs are not restricted only within GM crops, but are also packaged along with miRNAs from all the other food that we eat (a more detailed critique of that article can be found here). On the topic of eating, it seems that plants can also act as modes for horizontal gene transfer from bacteria to humans, as seen in Japanese populations who have received sea-weed digesting genes from the sea-dwelling bacterium Zobellia galactanivorans (ref).

 

As we frantically search for solutions to our existential crisis (literally), we are constantly looking towards the Plant kingdom for salvation where our technology has failed, essentially treating plants as Plan B. It is essential for humans to acknowledge their symbiotic relationship with plants and other components of their ecosystem for the continued survival of the species. And it looks like there is still hope.

Disclaimer: I do not work with influenza on an empirical basis. However, I have authored a chapter on the genetic origins of the 2009 H1N1 pandemic strain that has been published in a book by the Pennsylvania Academy of Sciences. 

 

For the first time ever, the US government has asked scientific journals not to publish certain details of the methodology used in a study to create a highly transmissible strain of the H5N1 bird flu virus. The study in question was a joint venture between researchers at University of Wisconsin-Madison and Erasmus Medical Center at Rotterdam, Netherlands, and it showed that the virus spread among ferret populations just through airborne transmission alone without the need for direct contact (ref). This has caused the bioterrorism alarm to go off in the government administration and the purpose of this study has been called into question, regardless of the reassurance by Dr. Ron Fouchier (leader of the Erasmus team) that security was one of the top priorities in the study performed. In an interview, Dr. Fouchier has informed us that the experimental design was carried out over a period of 10 years and that throughout the hands-on work (2 year period), there were no security breaches. Of course, the specific mutations performed were not disclosed, but he did point out that carrying out the mutation pattern for developing such a virus requires highly sophisticated facility. While many biosecurity experts have called on the need for such a “dangerous” study, Dr. Fouchier has claimed that such studies will help prepare us for possible flu pandemics in the future and allow for better vaccine and drug development. And such a claim is not unfounded, to say the least, when our preventive measures against flu in general are scrutinized.

The H5N1 flu virus does not usually transmit to humans because of different sialic acid binding receptors present in the airways of mammals and birds. In total, 501 cases of humans affected by H5N1 have been reported by the World Health Organization (WHO) and 297 of these cases were found to be fatal (Imai et al, 2010). The problem, as a public policy expert points out, is not the transmissibility of the virus, but rather the lack of surveillance and political issues regarding this virus. The same has been vocalized by scientists who complained against the indifference of the National Science Advisory Board for Biosecurity (NSABB) towards taking proper precautions against possible flu pandemics through better surveillance.

Regardless of the surveillance problem, there is another issue that must be discussed in regards to the virulence of this new H5N1 virus. Researchers argue that increased rates of transmission will actually reduce the virulence of the strain, a prime example being the most recent flu pandemic in 2009. A followup study performed in 2010 showed that the pandemic H1N1 was no more severe than the seasonal flu. This goes on to show that although the 2009 H1N1 was highly contagious, it was not as virulent. Another question that rises from this study is the use of ferrets as models for studying flu in humans. As this great blog post notes, although the ferrets have proved to be the good models so far as they display human-like symptoms of flu infection, they do not always represent the effect of flu on humans, as in the case of the 2009 H1N1. Also, ferrets have shown to be a much more sensitive system to study flu compared to humans (ref) as they display neurological symptoms, even when exposed to the seasonal strains. With all this information, is it really worth freaking out over this mutant H5N1 strain as the “Flu of Doom“, when the 1918 pandemic flu strain could be created in lab (ref) or even polio has been created from scratch?

While this debate still rages on, the question of who can have access to such a publication (censored or not) comes into mind. As Dr. Fouchier put it in his interview, the whole study should be made accessible to the flu research community for better understanding of the H5N1 virus. The US govt is reviewing the option of only allowing flu researchers to view the data and on top of that, it seems that it may also be against open access to scientific data. The new “Research Works Act“, introduced in the House of Representatives last month and sponsored by Rep. Carolyn B. Maloney (D-NY) and Rep. Darrell Issa (R-CA) and backed by the Association of American Publishers, will be “ensuring the continued publication and integrity of peer-reviewed research works by the private sector”. What it actually means is that the National Institutes of Health will NOT require its grantees anymore to submit their publications to its library, thus essentially requiring taxpayers to pay more to read the results of the studies that they had already paid for (ref)! What is even more ironic is that the same Rep. Issa has been a vocal proponent against the controversial SOPA bill (ref), but as Dr. Michael Eisen points out, clearly such actions come from a financial interest on both representatives’ parts.

How does the flu freakout tie in with restricting open access to research data? It’s pretty simple actually – restricting access to such sensitive data would actually promote “terrorists” to hack into the data and make it more widely available in conspiring circles (ref). This goes hand in hand with the fact that restricting open access to any research data for that matter will considerably slow down progress of Science itself, as shown by the examples here. And as a recent study showed, collaboration between scientists and open access to data, not only ensure, but also increase the rate at which progress is made in the scientific community.

Thankfully enough, majority of scientists have spoken out against this new bill being pushed by AAP-funded representatives and I urge you to do the same. It is only through collaboration and open access will we be able to solve scientific and social problems, old and new.

OPEN ACCESS FTW!

There has been much speculation about the future of human procreation in both the literary and scientific world. Science fictions, in print and film, portray a bleak, post-apocalyptic scenario where babies are designed by an institution and “farmed” in large quantities. In contrast, the scientific community is not so far behind, especially with the advent of genetic engineering. As the synthetic biologist and futurist Andrew Hessel claimed at the Techonomy 2011, we will be able to create and edit synthetic genomes for babies in the future, thus essentially engineering our babies. (Christina Agapakis has an awesome piece debating the humane component of such engineering)

Perhaps synthetic genomes are a bit too much of a stretch with the current technology, but this brings up the question of selective breeding. Selective breeding has been employed by farmers and breeders over the ages to gather the best of the gene pool of a particular species and manipulate the genes according to their need, which did not always correspond to environmental adaptive pressure. Essentially, it is this selective breeding that marked the beginnings of genetically modified organisms. While it is true that recombinant DNA technology has become pretty recently available for commercial use, one cannot deny that what the farmers were doing before the discovery of genes and DNA was  genetic modification, albeit a lot slower and clumsier than what current technology allows. The animosity towards GMOs then is somewhat misplaced, especially on the basis of biodiversity and gene flow. The accusations that GMOs are disrupting the natural gene flow then should have probably made centuries ago, but this recent rise in animosity could be a reaction to the increasingly negative impacts humans are making on Nature.

Selective breeding in humans, especially through genetic modifications, can most probably be labeled as blasphemous. But if looked deeper into the matter, one can see that in case of humans, we are actually restricting our gene pools through intraracial marriages. Insitutions such as religion and ethnicity govern much of the gene flow within our populations by dictating our reproductive behavior. One could even argue that we are reducing the adaptibility of the future generations by compartmentalizing the gene flow. Fortunately, there has been a steady increase in interracial marriages over the 20th century which has allowed for abundant gene recombinations resulting in the variety of appearances and mixed ethnicities we see today.

What is interesting is that in both interracial and intraracial marriages, selective breeding is taking place, but in a more sophisticated and complex way. The courtship ritual or the pairing of mates among humans involves more than expression of sexual intent or secretion of pheromones and so, selective breeding is not really apparent. But considering the facts that mating decisions are also largely based on social factors of the mates, it could be said that these social factors are what is driving our selective breeding. With in vitro fertilization coming into the picture, selective breeding has been more exposed, especially when it involves appearance and inheritable diseases. Choosing among thousands of sperm and egg donors does allow a lot more choices available for interested couples, thus essentially humanizing the process of selective breeding. Because of the genetic information available to us, it is relatively easier for us to predict the design of an offspring, which really is not much different from predicting and then creating GMOs. Because our reproductive behavior is intermingled with the social dynamics, it cannot be denied that such selective breeding is also affecting our social evolution.

The rise of the middle class, throughout world economy, can be represented by a stabilizing selection model, which indicates a certain change in the biological interactions humans have. Although it is not apparent, the different economic classes do exist within different biological environments and have different interactions with the environment around them. As for example, a poor individual would be more exposed to harmful chemicals and less access to healthcare, whereas a rich individual will have more access to healthcare and medical technology and less exposed to toxic agents. Thus the changes in the genomes of these two distinct economic classes over time can be attributed to their living environments.

What would Jane Austen say about all this? The author, who portrayed poor governesses pairing up with rich gentlemen, was perhaps indicating to this particular stabilizing selection as shown by the growing middle class. This social evolution, combined with plummeting cost of genome sequencing and rapidly progressing field of genetic engineering, could result in the bleak picture of human reproduction that is still confined within fiction and fantasy. Or is it really confined within just fiction?

Recently there has been a rise in ecological awareness throughout the globe. The reason being that mankind is essentially destroying Nature with the toxicity of progress. Thus, understandably, it is a positive realization among us that we are in a mutual relationship with the environment and that we should be preserving it as well.

But, what if the motive behind such awareness and actions is not that pure to begin with? Why should we be trying so hard to keep Nature the way it is? Does Nature really need us to nurture it back to its previous state?

This may seem a blasphemous question to ask, but if given more thought, it would show a perverse paternalistic approach to Nature, not that much different from the Catholic Church’s extinct belief of a geocentric universe. In some twisted way, we have convinced ourselves that without our intervention, Nature will not exist the same way and will become extinct. What we forget in our anthropocentric perspective of the salvation of Nature, is that Nature is not centered around us, as Darwin stated (Ref). But time and again, it has been shown that nature flourishes or restores itself (if you prefer) better WITHOUT human intervention. There is no better example than the case of coral reefs, where researchers showed that damaged coral reefs, without human intervention, grew healthier compared to the “reefs with people”.

If looked deeper into this matter, could it be that our fear of change is holding us back? Slavoj Zizek argues that our idea of ecological preservation deriving from the idea that us, humans, have disturbed it, is what is wrong with our understanding of “Nature”. His perspective is an echo of Timothy Morton‘s theory on ecology that this delusion of saving nature is actually driving us away from Nature itself. Perhaps this is a manifestation of our fear of letting go of “Nature”, or as we understand it. Are we really that scared of a future with a hybrid form of nature with organisms with synthetically engineered genomes, in vitro meat, printed out organs and structures held together by complex chemicals that act like biological units?

The restoration of natural flow, if we have disturbed it, can only be fully performed if we come to understand that Nature does not revolve around us, rather we are “embedded” in it. Let us remember the closest approximation to the origin of our existence – self-assembly and evolution.

“ORGANIC LIFE beneath the shoreless waves
Was born and nurs’d in Ocean’s pearly caves;
First, forms minute, unseen by spheric glass,
Move on the mud, or pierce the watery mass;
These, as successive generations bloom,
New powers acquire, and larger limbs assume;
Whence countless groups of vegetation spring,
And breathing realms of fin, and feet, and wing.
Thus the tall Oak, the giant of the wood,
Which bears Britannia’s thunders on the flood;
The Whale, unmeasured monster of the main,
The lordly Lion, monarch of the plain,
The Eagle soaring in the realms of air,
Whose eye undazzled drinks the solar glare,
Imperious man, who rules the bestial crowd,
Of language, reason, and reflection proud,
With brow erect, who scorns this earthy sod,
And styles himself the image of his God;
Arose from rudiments of form and sense,
An embryon point, or microscopic ens!”
Erasmus Darwin, The Temple of Nature, 1803

Have you ever looked into your reflection in the mirror and felt you are staring at a completely different and separate entity? If so, then an out-of-body experience would probably be the closest explanation of your mental state at that point of time. An out-of-body experience (OBE) is an experience that  that typically involves a sensation of floating outside of one’s body and, in some cases, perceiving one’s physical body from a place outside one’s body, as says Wikipedia.

OBEs are not a new phenomenon, or a rare one. For thousands of years, individuals delving deep into spirituality, such as monks and gurus from the East mainly, have been able to separate themselves from their “ego” as they put it. After years and years of meditation and searching within themselves for the truth to existence, such individuals have arrived at a fatalistic conclusion of the non-existence of the Self in this reality.

A recent study published in Nature shows that it is possible to separate one’s Self from one’s body, thus providing an OBE. The quality of the OBE is prone to fluctuation depending on the expectation of the individual, but the test subjects in this study have consistently shown awe, anxiety and in some cases, fear, even. The researchers, led by Dr. Henrik Ehrsson at Karolinska Institute, Sweden, created these OBEs for the test subjects using nothing more than a video camera, sticks and goggles. The test subjects experienced emotions when they saw their virtual bodies being subject to different treatments. As for example, one test subject exhibited fear when a knife was plunged into his virtual chest.

In a very different study, Dr. Miguel Nicolelis and colleagues showed that a monkey was able to control a robotic arm and feel virtual objects just using its brain. Besides the clear possibilities in prosthetic development, the study also indicates the question about the ownership of the body. It is an age-old question of Cartesian dualism – are the mind and the body the same entity? Both these studies show that the mind and the body merge to manifest as the brain and are not exclusive of the brain, as Dr. Thomas Metzinger puts it.

What does Gertrude Stein have to do with all of this? Perhaps the book “Autobiography of Alice B. Toklas” may shed some light on this matter. Although titled as such, the book is not written about Alice B. Toklas, but rather, focuses more on the life of Ms. Stein herself, as “observed” from the perspective of Ms. Toklas. This brings out the question – was Ms. Stein inducing an OBE on herself as she wrote this literary piece?

On that note, it must be said that the book itself is not a narcissistic ego trip, but rather a wonderful description of the artist and literary circles of Paris during the Cubist period. This book also serves as an introduction to Gertrude Stein’s writing style, which definitely would not be tolerated in the modern writing structure bound by the rules of MLA, APA, and what not…