Archives for posts with tag: Synthetic Biology

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.


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?