By Aditya Nair

The United States Government is currently $11.6 trillion in debt. That’s $36,653 per citizen, and represents more than a fifth of the debt held by every government in the entire world combined. Congress and the President constantly struggle to agree to even approve enough funding to prevent default or maintain government operations. This is a crisis, and a solution needs to be found.

In light of this, the following statement may be, for many, difficult to stomach: The United States Government should maintain or expand funding for basic and applied science research.

In 1987, The US Department of Health and Energy submitted a budget involving the initial funding for an ambitious, collaborative, government-sponsored research project that captured the imaginations of both the public and the scientific community: The Human Genome Project (HGP). The goal was to determine the map every gene in the human genome, and determine the base pair sequence of each of those genes.

The project was slated to take 15 years and start in 1990. In 2003, two years ahead of schedule, the sequencing of the human genome was declared essentially complete.

The total cost of the project through its completion was $3.8 billion, with the work being done primarily in US universities and research institutions, but also involving significant scientific collaborations with researchers in the UK, Japan, Australia, France, and other countries.

Scientifically, the project is invaluable, as it presents us with a history of our species’ journey through billions of years of evolution and an indexed encyclopedia for every single biological process in our human bodies. The human impact of this investment can’t be measured. There are simply too many breakthroughs in medicine brought about by this technology to enumerate. Highlights include the ability to test for genetic predispositions to dozens of ailments, the ability to target specific genes in cancer therapies, and the identification of over 4,000 known disease-causing mutations.

As numerous and impactful these human and scientific influences are, some politicians and policy-makers are resistant to the idea of spending taxpayer money on scientific research.

“Sure,” they say, “you’ve demonstrated that funding scientific research can bring real human benefit, but we simply can’t afford to fund everything. A dollar going into science has to come out of defense, Medicaid, medicare, or another very worthy function of government.”

However, that doesn’t have to be the case. According to the non-profit Battelle institute, the HGP has brought about $48.9 billion in federal tax revenue. That’s right – the government has made (as of 2011) an 1186% profit on its investment. This carries with it nearly 4 million job years of employment, nearly $250 million in personal income, and a grand total economic output of $796 billion – all from a $3.8 billion kick-start. Funding science, as shown by the HGP, doesn’t have to be an expensive undertaking. Indeed, it could push the budget-balance equation in the positive direction.

The HGP wasn’t the grand finale of biological research. Our generation has the opportunity to set the stage for the next great biological revolution with the Brain Mapping Initiative, which seeks to map every neural connection in our brains. Much in the spirit of the HGP, it will have ramifications in medicine, pharmaceuticals, and science that don’t necessarily have to hit the taxpayers hard in the pocket.
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Drastic budgetary restructuring is necessary, and both parties will surely have a myriad of difficult decisions to make that will have serious ramifications on our quality of life. However, we as an enlightened society should urge our policy-makers not to throw the proverbial baby out with the bathwater, and maintain public funding for science.

By Erik Schiferle

With the developments of Electron Microscopy, X-ray Crystallography, and Nuclear Magnetic Resonance Spectroscopy, scientists are beginning to determine the sequence and structures of molecules, cells, and proteins. For example, in recent decades, scientists have determined the sequence of scaffolding proteins as well as the sequence and structure of RNA and DNA. The collected data have made countless contributions to the studies of genetics, pathology, and pharmacology, to name a few.  However, the characterizations of molecular structure and sequence are limited in that they fail on some levels to describe the mechanisms of chemical and biological processes.

But luckily, a handful of recent Nobel laureates have found a way to add further insight into how molecules interact. On October 9th, 2013 the Nobel Prize for Chemistry was awarded by the Royal Swedish Academy to Martin Karplus (Université de Strasbourg, France and Harvard University), Michael Levitt (Stanford University School of Medicine), and Arieh Warshel (University of Southern California) for “the development of multiscale models for complex chemical systems.” Multiscale modeling uses models of different levels of complexity or resolution to study one system. In their work, the three scientists were able to use computational techniques to model chemical processes using principles of both Quantum Mechanics and Newtonian Physics (Classical Mechanics). Warshel explains, “In short, what we developed is a way which requires computers to look, to take the structure of the protein and then to eventually understand how exactly it does what it does.”

Historically, Newtonian Physics and Quantum Mechanics were treated as mutually exclusive models. Newtonian Physics is extremely accurate in its application to large objects that do not have speeds which approach the speed of light. However, as the size of the object shrinks down to a certain threshold and/or approaches speeds close to the speed of light, the rules of Quantum Mechanics are applied to take into account the wave-particle characteristics of the object.

However, Karplus, Levitt, and Warshel were able to combine aspects of both Quantum Mechanics and Newtonian Physics beginning with their work of the molecule 1,6-Diphenyl-1,3,5-hexatriene. But, the ability to combine the aspects of both models was limited to planar molecules as there is a natural separation between the π-electrons found in pi bonds, which are described by quantum mechanics, and the σ-electrons of sigma bonds, which are handled by Classical Mechanics. Later, their work was developed for structures more complex than planar molecules. In their study of the folding mechanism of the Bovine Pancreatic Trypsin Inhibitor protein, it was shown that it was possible to group atoms of the protein into units. These units retained certain properties and could be described using classical mechanics. Clustering atoms into units made it possible to create quicker simulations of the mechanisms as simulations that are described using quantum mechanics require an exceptional amount of computing time. Ultimately, these advances led to work that won the three scientists the Nobel Prize.
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In practical terms, the theoretical approach of computational chemistry creates less ‘wet lab work’ for chemists and biochemists. The approach can be used to predict molecular structure of molecules, identify relationships between chemical structure and properties, and even pre-screen compounds for medicinal purposes. The work that won Karplus, Levitt, and Warshel the Nobel Prize illustrates the great value of the ever-growing field of computational chemistry.

By Alexander Bernstein

For years, one of the greatest drawbacks to chemotherapy has been its potentially devastating side effects. Indeed, many individuals are unable to complete their treatment, or even be treated with a potentially more effective drug because of severe side effects that the body cannot bear.
Finally, a group of researchers at the University of California San Diego School of medicine may have a solution. Their break through idea? Real time MRI (magnetic resonance imaging) guided gene therapy. While chemotherapy typically affects and exposes nearly every human cell to potential side effects, Dr. Clark Chen, the vice chairman of neurosurgery at UC San Diego Health System, explains that with the help of the real time MRI, it is possible to “limit the presence of the active drug to just the brain tumor and nowhere else in the body.”

Concentrating their efforts on the treatment of brain tumors, Dr. Chen and his team have pioneered the use of MRI navigational technology to directly inject novel gene therapy right into the actual tumors themselves. The premise behind the technique is that the MRI illuminates the tumors while leaving the rest of the brain untouched, allowing doctors to hone in specifically on the area of interest. The cancer cells are then further pegged down through injection of Toca 511, a bioengineered retrovirus with the capacity to infect solely cancer cells, thereby labeling them. The truly incredible thing about Toca 511, however, is that it has been modified in such a way as to secrete a triple mutant of an enzyme called ytidine deaminase (yCD), which then transforms the typically anti-fungal drug flucytosine (5-FC) into the cancer-killing drug 5-fluorouracil (5-FU). Thus, the drug introduction is very specific as cell killing can only occur where an introduced 5-FC drug comes in contact with the yCD enzyme. In other words, cell killing only occurs in the tumors themselves.
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Brain tumors, especially glioblastomas, are some of the most deadly forms of cancer, with barely more than a third of all people diagnosed with a malignant tumor living over a year after diagnosis. Dr. Santosh Kesari, director of Neuro-oncology at the Moores Cancer Center, explains that the biggest problem with current treatments is likely that the drugs are unable to effectively enter the brain due to the blood-brain barrier and other natural protection mechanisms that actually work against the brain in this particular case. Dr. Kesari explains that the premise behind this technique is that “this MRI-guided approach will help us deliver this drug into the tumor directly to see if the drug is working.” Since 5-FC is able to travel past the brain blood barrier, and Toca 511 is injected directly into the tumors, this treatment should yield exciting information regarding the effectiveness of current drugs used for treatment and potentially improve treatment for various other cancers as well.

 By Ian MacArthur
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Consuming a meal when hungry is often accompanied by a profound sense of satisfaction. This state of feeling full and satisfied is induced by the release of glucagon-like peptide-1 (GLP-1), a hormone that binds to receptors when a particular craving is quenched. Now, researchers believe that GLP-1 and other compounds that mimic its effects can be used in the treatment of tobacco addiction. By blocking the receptors involved in gratification, GLP-1 and similar molecules might reduce the satisfaction obtained from smoking and aid in reducing nicotine dependence.

To demonstrate the regulatory effect of GLP-1 on satisfaction, scientists at the University of Gothenburg in Sweden performed studies on mice that had been given doses of nicotine. The nicotine induced an increase in activity as evidenced by the mice’s movement patterns. Some mice were then given a dose of Exendin-4 (Ex4), a compound that mimics GLP-1’s interaction with receptors. It was observed that the mice treated with Ex4 were afterwards less active and displayed lower levels of dopamine compared to the untreated mice.  From this the researchers concluded that Ex4 had reduced the reward associated with nicotine consumption. Another important result of the study was that no decrease in activity was observed in mice that hadn’t been given nicotine before Ex4 treatment. This suggests that GLP-1 and related compounds only reduces satisfaction associated with particular activities, such as nicotine and food consumption, but does not affect normal behavior.

The scientists believe that drugs designed to mimic GLP-1 and Ex4 in their effects on gratification can be used to help treat nicotine and other addictions. Analogous studies performed on mice that had been given alcohol, cocaine, and amphetamines produced similar results. By inhibiting the sense of reward produced by ingesting these substances, these drugs could help addicts kick the worst of habits.

While these studies show the potential for drugs that mimic the behavior of GLP-1 to treat addiction, their effect on behavior as a whole must be cautiously investigated. An obvious danger of using such drugs would be the suppression of gratification produced by behaviors other than the ones that are desirable to suppress. GLP-1 is not specifically associated with nicotine and substance-induced gratification, so the potential for an analogous drug to affect gratification associated with other activities, such as exercise and creative endeavors, is very high.
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As previously mentioned, no reduction in activity or dopamine levels were observed in mice that had not been given nicotine before being treated with Ex4. While this seems to indicate that the compound does not affect normal behavior, the qualifications of this claim, based solely on dopamine and motor activity, are quite narrow. Until further studies are performed to identify how these compounds affect behavioral brain chemistry in a more comprehensive way, their potential use as treatments for addiction should be taken lightly.

By Alexandra DeCandia

With an ever-increasing frequency, one pudgy little macropod marsupial is making headlines. Proclaimed the “Happiest Animal in the World” by Huffington Post some ten months ago, the quokka has since bundled into millions of hearts with its teddy-bear frame, cheeky grin, and characteristically social nature. Despite its near constant appearance on internet forums such as BuzzFeed and Reddit’s r/Aww, though, public awareness of the modern risks to quokka populations remains low.

Quokkas are one of the many species listed as vulnerable on IUCN’s Redlist (a wildlife conservation database). Due to their extreme endemism in the southwest corner of Australia and its two abutting islands (Rottnest and Bald), quokkas are particularly sensitive to habitat fragmentation, destruction, and climatic alteration. Unfortunately, as a result of human activities, quokka populations now face all three such threats. In fact, in a study conducted by Lesley Gibson et al. (2010), extinction is estimated to occur as early as 2070 if steps aren’t taken to drastically mitigate the species’  decline.

In order to combat threats afflicting native species, it is crucial for scientists to understand the exact causes of projected population declines. For quokkas, these causes are directly linked to their preferred habitats. In Australia, a continent marked by deserts and aridity, quokkas thrive as vegetative specialists. Nocturnal foragers, these herbivorous wallaby-relatives seek dense, shrubbery-laden habitats near swamps to permanently lodge their societies of 25-150 individuals. Historically, these habitats occurred in regions with 700 mm of annual rainfall. However, recent quokka populations have shifted to reside in areas receiving over 1000 mm of rain per annum as a defense mechanism. Small and ill-equipped to fend off predators with their chubby cheeks and tiny paws, quokkas rely on rain-fed vegetation for protection as well as nutrition. Seeking ample rainfall in an arid locale may not seem a winning strategy, but it is one that has obscured quokkas from dingoes, foxes, cats, and even large birds for millions of years. As humans alter the environment in unprecedented ways, though, the quokka’s strategy may no longer apply.

Foremost among risks to quokkas lies climate change. With the continued outpouring of anthropogenic greenhouse gases into the atmosphere, the overall temperature of our planet is increasing. For some areas, such as the northeastern United States, climate change will bring wetter conditions and more frequent occurrences of super-storms. For others, such as the entire continent of Australia, climate change spells increased heat-indices and ultimate desertification. Even the mildest models examining these rainfall alterations and projected quokka distributions predict ultimate range restriction. The most extreme models foresee extinction within our lifetime. Without dense vegetation afforded by ample rainfall, quokkas will be unable to defend against natural and introduced predators. Ultimately, they will be hunted to extinction as desert and suburbia afford little protection.

However, despite the gloom-and-doom nature of this Holocene Extinction, there exists hope for the quokka moving forward. In the best-case scenario, mankind can halt climate change, eradicate introduced predators, reconnect fragmented habitats, and expand the quokka’s current range to encompass greater (and wetter) regions. In a more realistic scenario, man can limit further greenhouse gas emissions, control invasive predator populations, conserve existing habitat, and design an action plan for species relocation should their current range ultimately disappear. The bottom line is that quokkas do not have to die. Steps can be taken towards their protection.
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The quokka is just one species currently staring at the face of extinction. As human populations continue to grow at astronomical rates, it becomes our duty protect those we have harmed in our meteoric rise. Studying the effects of climate change on endemic species and managing their recovery programs before their necessary institution is and should be our present reality. Otherwise, we risk the loss of those species that make this planet worth the fight. Otherwise, we risk the loss of that contagious smile of the world’s happiest animal.

By Kellie Lu

With Syria’s not-so-clandestine arsenal of chemical weapons debated over the table of the UN Security Council, chemical weapons, particularly nerve gases, have once again been thrust into the global attention. The power of these macroscopically undetectable molecules is not to be underestimated; within seconds, a mere milligram dose of sarin can kill a human being. And these gas attacks aren’t quite like Heisenburg’s (Walter White) nifty explosive chemical stunts on Breaking Bad.These unnatural, man-made chemical fiends are transparent, odorless, and colorless; they are undetectable by any of our five senses. As a hydrophilic species, nerve gases also easily mix with water, rendering their transmission through human bodies devastatingly rapid.

So how do these killers operate? Nerve gases function similarly to common insecticides, or organophosphates, when in contact with a human body. These nerve agents kill by inhibiting the acetylcholinerase enzyme in the neuromuscular junction between muscle fibers and nerve fibers. The nerve agent inhabits the serine esteric site of the acetylcholinase enzyme, where acetylcholine normally binds, breaks down into acetic acid and choline, and becomes inactive.
However, by preventing this chemical decomposition, sarin allows the acetylcholine neurotransmitters to remain in the synapse of the neuromuscular junction long after a signal has been transmitted from a nerve fiber to a muscle fiber. As a result, acetylcholine continues to trigger muscle reactions repeatedly, generating hyperstimulation of all muscles in the body. Imagine the experience as a massive seizure involving the stomach, lungs, and pretty much every smooth muscle and skeletal muscle in the body. Within minutes, victims violently convulse, fall stricken in paralysis, and perish.

So what can we make of the new rise of these deadly weapons? Over the last few weeks, the Norwegian Nobel Peace Prize committee unveiled their 2013 recipient, the Organization for the Prevention of Chemical Weapons, in an effort to encourage “progress” in the elimination of chemical weapons in Syria.

Yet while the Nobel Peace Prize and the highly publicized Syria conflict have elevated public consciousness of chemical mass weapons of destruction, complete dissolution of chemical weapons, like nuclear weapons, still remains a stagnant issue. Less publicized in mass media are the countries who clench yet-to-be-destroyed stockpiles of chemical weapons tightly in their hands behind their backs: the United States and Russia. Indeed, while the (feeble) anticipatory gesture of the Nobel Peace Prize redirected public spotlight back to the Syrian crisis, “peace” is still a long ways off.