The War Against Antibiotic Resistance

           One major advance in modern medicine was the discovery of antibiotics. Penicillin, which was first identified by Sir Alexander Fleming in 1928, was one of the first to be mass-produced for the treatment of bacterial infections. This discovery revolutionized the medical landscape by introducing naturally-synthesized remedies for human illness. Since then, many more antimicrobial agents have been identified and mass-produced for a variety of bacterial infections. However, an emerging issue is antibiotic resistance, which is inevitable due to the rapid evolution of bacterial populations. Another challenge lies in the production of new antimicrobials, since compounds that may have antibacterial properties often face difficulty in penetrating bacterial cell walls.

            A new study published in Nature by Ling and colleagues  may alleviate these challenges for future antimicrobial discovery. They realized that many bacterial species found in nature have not been utilized for antimicrobial production and theorized that these populations can serve as a source for new antibiotics. Thus, they developed a special chip, called an iChip, to grow bacteria from soil samples. Extracts from bacterial colonies were then applied to cultures of Staphylococcus aureus, and those that inhibited S. aureus were classified as antimicrobial candidates. During this screening process, a compound produced by the bacterium Eleftheria terrae was found to have strong antimicrobial activity. This new compound was named teixobactin, and what made it unique was its ability to remain effective against drug-resistant bacterial strains. Ling and colleagues were curious about the efficacy of teixobactin, so they applied teixobactin to S. aureus strains at initial and late stages of growth. Teixobactin was found to kill S. aureus more efficiently than antibiotics currently used for treatment of S. aureus infections, and interestingly, the authors were unable to generate teixobactin-resistant colonies. This finding suggested that teixobactin can potentially be a strong antibacterial compound since bacteria could not develop resistance. Later studies showed that teixobactin prevented the formation of the bacterial cell wall and served as a potent therapeutic in three mouse models of methicillin-resistant S. aureus, or MRSA. Ling et al. concluded their report by highlighting the novelty of their antimicrobial discovery method and setting the precedent for the development of more highly potent antibacterial compounds in the future.

              The growing problem of antibiotic resistance is in need of a solution, and this new finding will be instrumental in the search for novel antibiotics that will not trigger resistance in bacterial populations. This work shed light on the fact that many bacterial species in nature have never been grown in labs. In their natural environment, bacteria must adapt to different conditions and must secrete antibacterial substances to compete with other species and thrive. Therefore, a wide range of antimicrobial compounds must exist that can be utilized to combat bacterial infections, and it is the goal of biologists to identify as many of these substances as possible by creating new methods of cultivating novel bacterial species. I am confident that future endeavors will yield devices besides the iChip that can support the growth of bacteria that have not yet been studied, and we will continue to move one step ahead of pathogenic bacteria.

Antimicrobials are becoming more scarce, but a study by Ling and colleagues suggests that future discoveries of novel antimicrobials may be more common.

Courtesy: http://www.secretnews-compact.com/index.php?option=com_content&view=article&id=13955:heres-the-answer-for-drug-resistant-bacteria&catid=1:latest-news&Itemid=50

Gene Knockouts and Their Relevance to Human Biology

Scientists aim to identify genes that were not previously implicated in human disease with the Human Knockout Project.
Courtesy: http://www.dermamedics.com/science_id35.html

         When scientists aim to uncover the function of a gene, where do they start? They know that genes make up the chromosomes that occupy the nucleus of every cell, but how can this feat be achieved? The classical method for elucidating a gene's function is by "knocking out," or eliminating, the function of the gene. Scientists can prevent a gene from being expressed by introducing mutations, or changes to the genetic sequence, in the gene of interest. They can also introduce a foreign gene into the gene's chromosomal location to prevent it from being converted into messenger RNA, which would in turn prevent protein production. These knockout experiments have been performed in several organisms such as worms, yeast, flies, and mice, and initiatives such as the Knockout Mouse Project (KOMP) venture to collect information detailing the physical effects that result from the ablation of individual genes.

         Due to ethical issues, these initiatives were not implemented in humans. However, Dr. Daniel McArthur at Harvard University has circumvented this roadblock. He is deeply intrigued in the existence of healthy "human knockouts," people that lack function of individual genes without illness, so he began the Human Knockout Project. This endeavor involves the study of naturally occurring mutations in humans that result in the loss of genetic function. This allows Dr. McArthur's group to avoid many of the ethical issues that surround human genetic research. Dr. McArthur stresses that in addition to the necessity for understanding the effects of genetic mutations in essential genes, it is as important to study mutations in genes that lack deleterious effects. This knowledge could lead to the elucidation of genes that are known to improve responses to cancer treatment, for example, and methods to decrease or eliminate the function of these genes can be pursued in humans.

          The Human Knockout Project is a creative way to address the relevance of individual genes to human disease. Oftentimes, scientists tend to have a linear methodology for studying the role of genes in disease, usually focusing on genes that confer harmful effects upon elimination. But as Dr. McArthur eloquently described, we forget that the loss of a subset of genes can bestow beneficial effects on an organism, and ultimately this may revolutionize the current mode of thinking when treating disorders such as Alzheimer's and diabetes. With the implementation of the Human Knockout Project, it is possible that additional efforts to understand the function of human genes can be formulated and carried out in an ethical manner.

I'm a Scientist and I Still Won't Eat Cultured Meat!

         In August 2013, the world marveled at a discovery made by Dr. Mark Post's lab at Maasstricht University in the Netherlands. His lab cultured meat in the laboratory with the use of stem cells obtained from a cow's shoulder. These stem cells were stimulated to differentiate, or convert themselves, into muscle cells. Upon differentiation, the newly generated muscle cells formed a strand, and 20,000 muscle strands were assembled to make a meat patty. This meat patty was cooked and sampled by individuals at an event in London, and while the reviews were not negative, its taste-testers did note that it lacked the flavor associated with the conventional burger.

          Dr. Post manufactured this patty to demonstrate that meat could in fact be made in a laboratory setting, and he hoped that this would be a starting point for ending world hunger in an environmentally conscious manner. Poverty is prevalent in many countries, and the current methods of meat production are believed to be leaving a large carbon footprint. However, is this really the answer? One caveat of the "lab burger" is that it was made with fetal calf serum, so as of now the patty cannot be made without pre-existing animal products. Another drawback is that stem cells have not been successfully isolated from other meat sources such as chickens and pigs, meaning that the types of meat that can be made in the laboratory may be limited.

          Besides the methods utilize to make the meat patty, another important factor to consider is the taste. Does the lab-made patty taste like that from a grass-fed cow? One of the taste testers noted that the texture of the patty was reminiscent of meat, but the taste was bland. Scientists noted that the stem cells utilized to produce the meat were not able to differentiate into fat cells, which may be the reason for the decreased taste of the patty.

          I think that it is amazing that meat can indeed be made in a laboratory, and it is a testament to the advancements that have been made in understanding the differentiation process of stem cells. However, I would not feel comfortable eating a beef patty made in a lab because I love juicy burgers. Dr. Post's group as well as others may encounter great difficulties in recapitulating the taste of farm-raised beef, so the taste is definitely a deterrent. Also, the idea of my food being cultured in a lab is not very pleasant. I've dealt with many chemicals and animal samples in my thesis lab, and I do not want my food being anywhere near that vicinity. I can appreciate the advances being made in the field of stem cell biology, but I rather keep those and my dietary sources separate.

The first lab burger at its grand debut in London.
Courtesy: Natt Garun, http://www.digitaltrends.com/cool-tech/unsurprisingly-300k-lab-grown-burger-tastes-horrible-heres-what-to-eat-instead/#!Qij7k 

The Difficult Plight of the Bee

        What often comes to mind when we think of spring? Usually, it's the cessation of frigid temperatures, the increasing amount of daylight, and of course, the flowers! Flowers have had a longstanding association with the re-emergence of life after a long winter. This relationship evolved from the knowledge that flowers can give rise to fruit and other crops, which are harvested later in the calendar year. Due to this fact, flowers hold great significance in societies around the globe. Since the pollination of flowers triggers fruit formation, the bee is integral for the maintenance of the world's food basket. In addition, bees produce honey, a common flavor enhancer of teas and other confections that we enjoy. Therefore, bees infiltrate many aspects of everyday life.

         Unfortunately, bees have been facing major hardships in the past few years. They have been dying in large numbers with each passing winter, but scientists were unable to pinpoint the cause for this phenomenon. Bees have increasingly been experiencing colony collapse disorder (CCD), in which many worker bees abandon a colony and are found dead elsewhere. This leads to a significant decrease in the number of worker bees maintaining the colony, which often leads to its extinction. Some possible reasons for high death rates among bees were increasing bacterial infection, pesticide use, and even a virus. Nevertheless, the cause of the bees' demise remained unknown.

          Interestingly, a new study from the University of Maryland is providing more insight into the underlying cause of colony collapse disorder during the winter. Dennis vanEngelsdorp and his entomology lab have found that bees are dying from the Varroa mite, a parasite which prefers worker bees as its host. The Varroa mite is opportunistic in that it invades eggs newly laid by the queen bee, before worker bees are able to seal them for their protection. The mites then feast on the blood of the developing bees as well as the worker bees caring for them, which leads to deformities in young bees and the death of their caretakers. With this finding, scientists are hopeful that the death rate of bees can be controlled with pesticide applications.

           Nevertheless, several questions remain. Increased bee death has been observed during the summer months as well, leading scientists to believe that other environmental causes may exist. vanEngelsdorp postulates that pesticide applications and the loss of plants may be contributing to bee death. Because bee pollination is responsible for producing most of the world's food, the increasing rate of bee death is problematic. With time, due diligence in recognizing Varroa mite infestation should allow bee populations to retain their colonies and continue to provide us with the many fruits and vegetables we need to survive.

Bees have been dying from an unknown cause.
Courtesy: www.britishscienceassociation.org

Synthetic Biology: Innovation or Mad Science?

   

The four bases that make up DNA may not be the only ones with the ability to support life.
Courtesy: http://plus.maths.org/content/dna

           Every introductory course in biology teaches students about the building blocks of deoxyribonucleic acid, or DNA. DNA holds the key to life because it holds the instructions needed to make proteins, which facilitate and carry out chemical reactions necessary for life. DNA is composed of units called nucleotides, which consist of three phosphate groups, a 5-carbon sugar, and a nitrogen-containing base. Four nitrogen-containing bases comprise the genetic code: adenine, guanine, cytosine, and thymine. These bases pair with each other, adenine to thymine (A-T) and guanine to cytosine (G-C), to form the characteristic double helix structure of the DNA molecule. These bases have remain fixed for the entire course of evolution, meaning no additional bases have been found in any existing organism. Due to this observation, scientists have been in concordance that only these four bases can support life.

          However, this long-standing dogma may not necessarily be true. A recent report in Nature describes the generation of Escherichia coli (E. coli) cells that carry a third pair of bases in its DNA. Romesburg and colleagues at the Scripps Research Institute in La Jolla, California, have incorporated an unnatural base pair that can be replicated effectively in bacterial cells without compromising their growth. The Romesburg group utilized two compounds, d5SICS and dNaM, to form a new pair of bases, and they were able to introduce these bases into E. coli cells by expressing a gene that encodes a special nucleotide transporter found in algae. Once these synthetic bases were in bacterial cells, they were observed to contribute to the propagation of a plasmid (a circular piece of DNA) containing the unnatural base pair formed by d5SICS and dNaM. Bacteria carrying this modified plasmid were able to divide normally, suggesting that the introduction of the d5SICS and dNaM base pair was not toxic to bacterial cells. These results indicated to the Romesburg group that it was possible to introduce an unnatural nucleotide base pair into an organism without deleterious effects.

          This newest breakthrough in the field of synthetic biology is a step forward for scientists looking to re-engineer cells for various purposes. Some researchers have praised this study as a stepping stone for one day enabling cells to produce biofuels or medicines that have been historically expensive to produce. It is the hope that one day scientists will be able to produce environmentally safe energy alternatives and other necessary products from organisms, eliminating the need to spend millions to obtain these materials utilizing conventional methods.

          On the other hand, another faction believes that these studies may be used for malicious or unnecessary purposes. Some people believe that scientists are going too far in creating organisms that produce substances that they would not normally produce. In their eyes, scientists are "trying to play God" and are engaging in "mad science." However, these individuals often forget that scientists are far removed from re-engineering animals, or even humans, with foreign DNA, and that many ethical safeguards exist to prevent the misuse and abuse of these new technologies. The aim of synthetic biology is not to employ animals and humans as guinea pigs for radical experiments, but the aim is to formulate novel methods for generating biological materials that are scarce or costly to manufacture. This newest advancement in the synthetic biology field should make this goal more attainable in the near future.

MERS: The Next Global Epidemic?

           The Severe Acute Respiratory Syndrome, or SARS virus, made headlines as a formidable public health threat in 2003. According to the Center for Disease Control and Prevention (CDC), the SARS virus was initially discovered in Asia when several individuals were experiencing severe cases of pneumonia. Unfortunately, this illness was observed to be highly contagious, and it was later attributed to a new viral strain that was subsequently called SARS. This virus spread across four continents and killed 775 people until it was contained several months later. Since the SARS outbreak, public health officials and scientists have worked tirelessly to prevent another viral outbreak.

           These efforts have now been put to the test. A SARS-like virus was identified in late 2012 when a Qatari man exhibited severe respiratory illness in an English hospital. This virus noticeably affected many individuals in Saudi Arabia and other Middle Eastern countries, leading to its name "Middle Eastern Respiratory Syndrome," or MERS, virus. Many comparisons have been drawn between MERS and SARS, mainly due to the similarities in symptoms. However, scientists studying MERS have noticed that it does not spread as easily as SARS because it has not resulted in as many cases. This may be due to a reduced ability of the virus to spread from human to human, but the virus is known to infect humans through animal contact since camels have been characterized as the main vehicle for MERS in the Arabian Peninsula. Scientists studying the genetic makeup of MERS have not been able to detect significant genetic changes that would shed light on the increasing number of MERS cases, but they are hoping that increasing awareness will drive individuals to become more cognizant of possible sources of infection.

             Due to the sharp increase in cases, the general public does not know whether MERS should be raising alarms. Because this virus is contagious, people should adhere to stringent hygienic practices. Simple efforts like covering the face after a sneeze, hand washing, and taking a sick day may curb the spread of viruses such as MERS. At this point in time, an effective vaccine cannot be developed due to the MERS virus belonging to the coronavirus family, a notoriously difficult virus subtype to target. Furthermore, we will have to rely on old-fashioned sanitary measures to protect ourselves and others from another potentially devastating virus.
           

The recent series of MERS infections closely resemble those of 2003's SARS virus.
Courtesy: Reuters

Biomedical Research and the Male Scientist

Mouse behavior in a study may depend greatly on the sex of the researcher.
Courtesy: http://www.allaboutvision.com/conditions/amd_news.htm

           Many scientific fields focus on disease studies in order to develop effective therapies. Before potential remedies are supplied to human subjects, their efficacy and safety must first be tested on animals. Mice have served as suitable subjects for new drugs and treatment options that may potentially alleviate or eradicate human disease; thus, an overwhelming majority of biomedical research projects utilize mice. In these studies, variables need to be considered in order to accurately assess whether the experimental group is truly responding to the administered treatment. Such variables may include the health of the mice, the time of day that the treatment is administered, and the treatment dosage.

            Nevertheless, there may be an additional factor that biomedical researchers are not considering: the sex of the researcher. A report in Nature Methods details this discovery. Jeffrey Mogil's lab specializes in projects relating to pain perception in mice at McGill University in Canada. Interestingly, Mogil noticed that something was amiss with the recent set of experiments done by his students.  A pain-inducing agent was injected into the hind paws of mice, and facial grimaces were measured post-treatment. However, mice showed a significant reduction in facial grimaces in the presence of male researchers compared to that of no researcher, and the number of facial grimaces was not affected by the presence of female researchers. It was hypothesized that the smell of males influence this trend because placing a male's shirt in close proximity to a cage was able to exert this same effect, and surprisingly, this effect was nullified by the placement of a female's shirt nearby. Upon further analysis, the scent of male researchers and males of other species increased the levels of corticosterone, a stress-related hormone, in the blood of mice. This revelation led Mogil's group to postulate that the male scent induces a stress response in mice, which can alter the outcome of administered treatments.

             Though the idea that mice behavior exhibits a sex bias can be comical, this possibility raises a number of concerns. For example, some people wonder whether all past biomedical experiments employing mice are now invalidated. This finding does not necessarily prove this notion for a number of reasons. First, this set of experiments was done solely to measure pain responses; this study does not address sex bias in other types of mouse studies, such as those involving drug responses. Also, some physical characteristics of mice are known to be dependent on genetic background. This means that a particular stimulus may elicit a different behavior in a mouse with brown coat color compared to one with black coat color. Mouse behavior may also exhibit a more pronounced sex bias in response to pain versus other stimuli. Furthermore, we are reminded that there are subtle aspects of scientific studies that may influence their outcome, and we should identify and consider these factors more heavily when evaluating the data of future experiments.