The Low Down on Zika

Rebecca Fils-Aime

In the last couple of months it seems as if the hysteria over Zika virus has increased ten-fold. Individuals in South America, Central America and the Caribbean have been advised by public health agencies to avoid pregnancy due to the potential connection between Zika virus infection and birth defects. The potential consequence of Zika that is eliciting the most fear is microcephaly, a condition where babies are born with abnormally small heads that has been associated with infection early in pregnancy. Cases have been reported of traveling Americans returning to the States with Zika, and as a result, American officials are ready to increase mosquito control. Mosquito control is a huge concern, especially in the South, due to the fast approaching spring and summer seasons. But what exactly is the Zika virus and where did it come from?

Zika virus was discovered in 1947 in a monkey that resided in the Zika forest located in Uganda. The virus was first detected in humans in the 1950s. However, the first outbreak of Zika in humans that received international attention was in Micronesia in 2007. A few years later, in 2014, there was another outbreak in French Polynesia. The current outbreak began last year in Brazil and has spread to the Caribbean, South America, Central America and Mexico. Everyone in these areas is at risk and should take all necessary precautions to avoid infection. There are two strains of the Zika virus – the African strain and the Asian strain. The virus that is currently circulating in the Americas is closer to the Asian Strain of the virus.

Daytime-active mosquitoes spread the Zika virus, just like Dengue and Chikungunya are spread. The most common carrier, a type of mosquito called Aedes aegypti, is found all over the world, across all continents. An increasing amount of evidence shows that Zika can be transmitted sexually and from mother to child during pregnancy. Like other sexually transmitted infections, sexual transmission of Zika can be prevented by abstinence or safe-sex practices like condom usage. Zika virus infection in pregnant women has been linked to miscarriage and microcephaly. Microcephaly can cause seizures, developmental delay, feeding problems, hearing loss and vision problems. In very rare instances, Zika has been linked to severe dehydration, neurological diseases like Guillan-Barré and even death. More common effects of Zika are fever, rash, joint pain, conjunctivitis, muscle pain and headaches. The illness caused by the Zika virus is generally mild and people rarely die from it. A large proportion of people do not even show symptoms.

If it is suspected that you or someone you know has Zika, the first step is to go to a doctor for a diagnosis. A history of illness will be recorded and then the doctor will carry out a physical exam and a blood test will be ordered. A blood test is the only way to differentiate Zika virus from related illnesses such as Dengue or Chikungunya. Unfortunately, there is no vaccine or cure for the Zika virus as of now. All current treatment is aimed at reducing symptoms. Treatment includes lots of rest, pain medications for fever and body aches and lots of fluids to prevent dehydration. President Obama and U.S. health officials have requested a large amount of emergency funding – 1.8 billion – in order to combat Zika in the United States and to help protect pregnant women from the terrible effects the virus may have on unborn children.

There are several methods being implemented in attempts to stop the spread of the Zika virus.  Mosquito prevention methods, like window and door screens, insect repellent, insecticides, automatic misting systems, are highly recommended. Even something as small as emptying water from any containers outside can help prevent mosquito breeding. The question of how Zika virus spread so quickly may still be unanswered, but here is to hoping that a cure is discovered before the summer months bring more mosquitoes – and Zika cases – to the United States.

Edited by: Mallory Ellingson

Rebecca is a first year student in the Rollins School of Public Health in the Health Policy and Management program. She can be contacted at: rebecca.fils-aime@emory.edu.

 

Protons for Patients at Emory - Cancer Treatment with a Big Cost?

Tej Mehta

Originally published October 14, 2015

photo by: paula tyler

photo by: paula tyler

In May of 2013, Emory Healthcare and the Winship Cancer Institute (in partnership with a private funding entity) began construction of the Emory Proton Therapy Center. The $200+ million, 107,000 square-foot facility, which is slated to open in January 2017, will be the first of its kind in Georgia. Based on current construction estimates, the Emory facility will be the 17th operating center nationwide, and will prominently feature new “pencil beam scanning” technology, a major development in the field of proton therapy. The technique itself holds significant promise for many patients in the Emory Healthcare system, but is the potential benefit of proton therapy worth its additional price? The Emory facility has partnered with Advanced Particle Therapy LLC, a proton therapy developer, to help fund the construction and operational expenses.

In 1946, Robert R. Wilson at the Harvard Cyclotron Laboratory, first proposed protons as a therapeutic tool, and the first treatment in the United States occurred in 1954 at the Berkeley Radiation Laboratory. Due to major engineering limitations, proton therapy continued to be used sparingly for many years, predominately for research purposes. In 1989, the first hospital-based center was developed at the Clatterbridge Center for Oncology in the UK, followed by the first US hospital-based center in 1990 at Loma Linda University Medical Center. Since that time, proton therapy centers have been developed at a slow but steady pace, currently numbering 15 operating facilities and an additional 20+ centers under construction. This implies a current access rate of 1 facility for approximately every 20 million US citizens. Globally, there is a dramatic upsurge of interest in proton therapy, with nations like Norway developing widespread access by commencing construction on approximately 1 facility for every 1 million inhabitants.

Like other forms of radiotherapy, proton therapy kills cancer cells by causing direct or indirect DNA strand breaks. In modern external beam radiotherapy, tumor-specificity is achieved by physically shaping the beam to minimize exposure of normal tissue to unnecessary radiation; however, because high energy X-rays continue to travel through tissue, some radiation is always deposited in normal tissues in the exit path of these beams. Protons, like high energy X-rays, can also be shaped to match the shape of the tumor,  but because of their unique physical property of losing energy while traversing tissue and then depositing all of their energy at a pre-defined depth (based on the initial energy of the beam), there is close to zero exit dose. The result is that while other forms of radiation therapy will deliver radiation to healthy tissue beyond the tumor, proton therapy delivers little to no excess radiation to healthy tissue posterior to the entry beam. This special ability of protons is due to a phenomenon called the “Bragg Peak,” which represents the precipitous and sudden loss in energy that stops protons. Modern proton therapy clinics, such as the Emory facility, also use the previously mentioned technique - pencil-beam scanning - which is analogous to 3-D printing. Like 3-D printing, where thin layers of material are repeatedly applied to make a larger 3-D shape, pencil-beam scanning continuously applies thin layers of protons to a tumor until the entire tumor is treated with radiation. This unique capacity not only eliminates radiation damage past the stopping point of the beam, but also reduces radiation damage to normal tissues all around the tumor. These advantages of proton therapy have been lauded by clinicians and the therapy is generally recognized as particularly useful in patients with a likelihood of long-term survivorship, such as children and young adults. These individuals are typically at greater risk of developing organ dysfunction and secondary cancers as a result of radiation to their normal tissues. Additionally, in situations where an adequate dose to control the tumor simply cannot be safely deposited with conventional modalities, proton therapy is often the best recourse.

Despite these apparent advantages, proton therapy has received significant criticism, both with regards to cost and the level of evidence documenting its true effectiveness. Currently, the primary concern about proton therapy is whether the obvious dosimetric advantages result in “cost-effective” clinical advantages. The upfront construction cost of a multi-room proton therapy facility is well over $100 million, and various analyses have projected that treatment with protons is twice as expensive as X-ray radiotherapy. However, other studies have determined proton therapy to be reasonably priced for most cases, particularly given the potential costs of treating adverse effects caused by standard radiotherapy. For example, one study published in the journal Cancer in 2005 found the average cost of treatment for conventional radiation therapy and proton therapy to be $5,622 and $13,552 respectively. However, the same study found the cost of treating adverse events from conventional radiotherapy and proton therapy to be $44,905 and $5,613 respectively, demonstrating that while the upfront cost of proton therapy may be high, the total costs are significantly reduced.

The other primary criticism against proton therapy is whether or not it is truly as effective as its proponents claim it to be. Thus far, there have been few controlled, randomized clinical trials to demonstrate improved survival or quality of life with proton therapy over other forms of external beam radiotherapy. One such trial randomized patients with ocular melanoma to particle therapy with Helium (similar to proton therapy) against a localized form of radiation known as plaque brachytherapy, and reported superior clinical results for patients on the Helium therapy arm. Several non-randomized trials have supported the clinical benefits of proton therapy. Conversely, detractors of proton therapy point to the lack of randomized clinical trial data as cause for concern with proton therapy, while proponents argue that no clinician has true equipoise to conduct such a randomized trial, stating that to knowingly withhold proton therapy from patients who could benefit from the treatment is unethical. Other critics of proton therapy raise concern over the potential inaccuracy of the exact placement of the Bragg Peak within the tumor. Because of the sudden deposition of energy caused by the Bragg Peak, small errors in measurement or slight movements of the patient could cause a dose-shift. Most modern proton systems deal with this by reducing error through a series of technical refinements, and by performing what is known as “robustness evaluation,” as well as accounting for this uncertainty through a process known as “robustness optimization”. 

Emory Healthcare and its affiliates have weighed the costs and benefits of proton therapy and elected to build the facility. The construction of a proton therapy center in Atlanta by Emory Healthcare demonstrates Emory’s conviction to patient care and treatment options and aims to improve the survival and quality of life outcomes of many patients. As the first proton therapy center in Georgia and one of only a handful of treatment centers in the country, Emory has again distinguished itself as a nationwide leader in healthcare.

Edited by: Carson Powers

Tej Mehta is a student in the Rollins School of Public Health and can be contacted at tej.ishaan.mehta@emory.edu.

Baby Crazy: The Mind Control of Motherhood

Amielle Moreno

Originally published August 13, 2015

Photo by: jadiel wasson

Photo by: jadiel wasson

Any wilderness expert will tell you the most dangerous animal to see in the wild is a baby bear. Accidently stumbling between a mother bear and her cubs is a sure way to get mauled. And none of us would be here today if it wasn’t for the selflessness of our ancestors, putting the survival of their offspring sometimes before themselves.

So apparently, the most basic drive for self-preservation can be trumped by babies. While we can’t live forever, we can pass on our genes. Thus, what Richard Dawkins termed “selfish genes” have created animals built for their own survival, and that drive for self-preservation can be redirected to reproduction and then parental care.

The Power of Hormones

I’m sorry to be the one to tell you this, but the areas of your brain responsible for decision-making can be overpowered by hormone-driven signals from deeper brain regions. During development, hormones influence the structure of our bodies, including our brains. During puberty, the same hormones can act again on these existing systems to make you feel awkward during gym class. But perhaps the largest natural shift in hormone concentrations is during pregnancy.

The milieu of hormones pregnant women experience can make long-lasting structural changes to the neurons in our brain. The neurons in deep brain regions responsible for maternal behavior can grow in size when exposed to pregnancy hormones such as estrogens. So, the same time motherhood occurs, the brain is experiencing significant changes. The growing neurons start to communicate with areas of the brain that make the signaling molecule dopamine.

Dopamine rules what neuroscientists call “the reward pathway” and it’s the reason you like anything… ever… in your entire life. Your body releases this magical molecule when you perform activities that will keep you and your genes alive and spreading. Dopamine is released while consuming food or having sex, and because your genes want to be passed on, the drive for parental care relies on this reward pathway too. Large doses of estrogen, such as those occurring during late stages of pregnancy and labor trigger the release of dopamine, stimulating the reward system. This makes new mothers primed and ready to love that 7 pound 5 ounce screaming, floppy pile of responsibility, you named “Aden.”  

Hormones lead to new and permanent changes in brain circuitry, which is how areas of the brain interact and respond to one another’s activity. Perhaps surprisingly, animals that haven’t been around babies are not initially fond of infants. Virgin, pup-inexperienced female mice have a natural avoidance to infant stimuli, which is not completely unreasonable. Think about what a baby would seem like if you didn’t know what it was: they cry for seemingly no reason, smell, and demand a lot of time, money and attention.  In mice, researchers have explored a natural avoidance and defensive response associated with animals that are new to infant care. There are defined circuits in the brain responsible for this avoidance response. The hormones of pregnancy, silence this circuit, and neural circuits responsible for maternal responses can then be more active.

Changes in Behavior

You might have heard from your friendly neighborhood neuroscientist you don’t have free will. Let me reassure you that yes, you’re a slave to the power of babies. The immediate changes in a mom’s behavior after childbirth suggest major changes are occurring in brain circuitry. This new baby addiction or “sensitization” is caused by changes in the reward system’s dopamine release. Cocaine and other addictive drugs trigger the reward system and release dopamine throughout the brain. Like a drug, the allure of babies is so strong that when given the choice, rats with maternal experience prefer to press a lever that delivers infant pups over one that delivers cocaine. Using this knowledge, let’s take care of two societal problems at once: “Orphanages: The New Methadone Clinic!”

Sensitization causes mothers to act differently. Mother rodents show increases in risk-taking behavior. For example, mother mice on an elevated maze with enclosed and open arms, will spend more time exploring the potentially dangerous open arms than virgin mice. On the up side, new mothers display increases in memory. In a maze, mother rats were better than virgins at remembering where the food was and were faster to retrieve it. The researchers concluded that improved foraging memory increases the chance of survival for a mother’s pups.  If this held true in humans, the concept of “baby brain” might be unfounded. However, funding cuts have halted the construction of the human-sized maze stocked with baby supplies.

Even abstaining from motherhood won’t save you from becoming a slave to baby overlords. Mere exposure to infants can activate changes in the brain regions responsible for maternal behavior, and start the process of sensitization in rodents. The process does take more exposure time than in natural mothers, without the surge of hormones to speed things along. This suggests that women become “baby crazy” by exposure to infant stimuli. While we all might inherently be ambivalent or avoidant of infants, through exposure to babies, they become conditioned and highly rewarding stimuli. Do you want kids? Then it might already be too late.

Not being female won’t save you either. A study looking at brain activity using an fMRI machine found that when fathers are shown images of their children, they display similar brain activity as mothers. Recent research out of Emory made headlines when it found this increase in activity in the reward pathway was inversely correlated with testes size, and blood testosterone concentration. The conclusion: more parental care equals less testosterone and smaller balls, fellas!

Against Logic

The combination of a higher consciousness and a desire to reproduce means, unlike other animals, humans are presented with the question of if we should reproduce. However, the reason they instruct you on airplanes to put the air mask on yourself before you assist young children is because the human drive to protect our genes, I mean, children, sometimes overrides logic. There’s also an illogical drive to have our own children. In a planet with millions of orphan children, you would assume that the baby-loving masses (and cocaine addicts) would decrease the supply of foster kids overnight. However, our biological nature has a way of convincing humans that we don’t just want a child, but we want our child.

In a modern environment where motherhood is a choice, it’s illogical for anyone to be pressured to give birth to an eighteen-year commitment. Because not all people (or laboratory animals) naturally become sensitized to infants, it might be better for everyone if people who don’t want children aren’t pressured to have them. By simply understanding the literally mind-altering process of parenthood, individuals can make decisions that benefit everyone, including our baby overlords.

Edited by: Bethany Wilson

Towards Precision Medicine: Promises and Hurdles

Hyerim Kim

Originally published April 13, 2015

Photo by: Jadiel Wasson

Photo by: Jadiel Wasson

If you’ve ever seen an ad on the internet that seemed as if it was intentionally catered to your interests, you’ve probably been subject to customization in marketing. While mass customization has become commonplace in fields such as marketing and manufacturing, its scope is extending further than just business. Advances in genetics are allowing doctors to start customizing medical treatments for individuals through a new field being called ‘Precision medicine.’

Before precision medicine, diagnosis and treatment of disease was determined by categorization without consideration of individual diversity. These procedures, albeit leading to a huge improvement compared to non-scientific treatment, have brought concerns about diagnostic accuracy and side effects of prescribed medicine.

Some of these concerns can be resolved by studies on the variation between the genes of different people. Scientists have launched international projects in order to illustrate the common patterns of human genetic variation. These ongoing efforts have helped in understanding why a certain population of people would be susceptible to a particular disease and what their responses would be to certain types of drugs.

A medical movement applying individual genetic data into medical practice is considered as a milestone in the journey toward precision medicine. The movement is gaining momentum, with the President’s 2016 Budget allocating it a $215 million investment. In particular, the system is expected to reap enormous benefits in cancer treatment.

Hence, we can now ask ourselves: What’s the success story for precision medicine we’re looking for, and what are current challenges faced by this medical movement?

Back in the 60s, chronic myeloid leukemia (CML) was a devastating disease and the average lifespan of patients was 3-7 years after diagnosis. However, a new genetic technique in 1970 enabled scientists to identify what caused the deadly disease, an abnormal molecule called Bcr-Abl. The elucidation of this abnormal molecule promoted the development of a new target therapy, “Gleevec” for CML patients. Since nearly all CML patients carry the fusion molecule, a therapeutic outcome was outstanding with higher efficacy and lower side effects compared to conventional chemotherapy.

The success of Gleevec brought to the field a concept of targeted therapy in cancer treatment, resulting in the development of many similar therapies. A wider breakthrough in targeted therapy, however, could not be accomplished without further technological innovation.

As technologies did develop, they were unfortunately too costly. However, newer sequencing platforms have led to the rapid reduction in DNA sequencing costs, and in the near future, $100 genome sequencing will be open to most people. As such, one can imagine genomic mutation profiling becoming routine in determining the best therapeutic regimens for individual cancer patients.   

Despite the mapping of a personal genome being expensive, the extraction of biological information from complex human genomes is a major obstacle to the start a precision medicine era.

To illustrate, the detailed biological functions of protein-coding genes (1 % of human genome) still needs to be explored, although the ENCODE Project launched to identify all functional elements of genome after the completion of the Human Genome Project has brought about substantial understanding about the genome. In addition, most genomic regions outside of what codes for proteins (99 % of human genome), such as promoters, enhancers, and insulator regions that regulate gene expression, remain to be elucidated. In particular, intergenic regions considered as “junk” DNA before are now thought to play regulatory roles in gene expression yet most of them remain uncategorized..

In other words, current genomic data is incomplete. In addition, there are no standard informatic programs to analyze raw sequencing data, and data storage and sharing are practical issues to be discussed. In order to overcome these limitations, international collaborations for breakthrough efforts are necessary.

In the case of cancer research, The Cancer Genome Atlas in the US, the Cancer Genome Project in the UK, and the International Cancer Genome Consortium have been launched to aim for a deeper understanding of individual cancer patients by managing and sharing the data from these projects. Such combined efforts to elucidate the human genome, standardize data processing, and generate publicly available datasets will pave the way for precision medicine.

Precision medicine is not a void dream. Along with technological innovation in genome research, individual diseases will be minutely categorized depending on an individual’s genetic makeup, and treatments will be carefully chosen based off of that information. In addition, patients will be able to access their own genomes so that they are able to play an active role in prevention of predisposed disease and treatment. Moreover, the pharmaceutical industry will have to restructure itself toward a more patient-oriented outlook. In terms of medical costs, we can save money from unnecessary examination to identify the cause of disease. As such, precision medicine is expected not only to realize optimal medical services to patients but also to transform medicinal industry in future. This realization, nevertheless, cannot be done by only an institute or a country. Collaborative research across the world to clarify undermined and undiscovered genomic data is essential.

Edited by: Anzar Abbas

What We Talk About When We Talk About Sex

Edward Quach

Originally published April 12, 2015

Photo by: Jadiel Wasson

Photo by: Jadiel Wasson

The manner in which societies and cultures have constructed gender and gender identity has been changing for ages. Although an academic or philosophical dichotomy was not acknowledged for several thousand years, the separation of physiology and gender identity has existed perhaps since the dawn of man. It may have its origins in the very moment early hominids forewent stark individualism and entered into John Locke’s social contract. A couple days ago, I had the opportunity to chat with the John L. Loeb Associate Professor of the Social Sciences at Harvard University, Sarah Richardson. Dr. Richardson is a historian and philosopher of science with an impressive collection of research concerning gender and the social dimensions of science. According to Dr. Richardson, the academic sex/gender distinction is traced to the 1960s and sexologists dealing with gender identity disorders or feminist theorists of the same era. Nonetheless, she goes on to trace less specific philosophical sparks of this distinction to the 19th century and earlier.

As we can see, for several decades now, social scientists have been studying countless aspects of gender. The sociology, psychology, history, politics, and performance of gender have been under scrutiny in humanities classrooms around the world. However, one thing that has seemed to remain relatively static is the biological understanding of “sex”, a steadfast counterpart to the fluid and constructed idea of gender. Or so it was presumed. Growing up in the in the fairly progressive time period that I did, my childhood had been at least minimally shaped by the idea that a person’s gender may not actually match up with what they have between their legs. That being said, it was fairly well established that your sex was your sex, and that the distinction was primarily binary (male or female). However, a recent Nature News feature published by Claire Ainsworth examines several studies both new and old, which may complicate the issue of biological sex in the way that the social sciences have unpacked and examined gender. According to Ainsworth, the binary male vs female distinction is antiquated, and biology requires a more comprehensive spectrum.

When I asked Dr. Richardson about this, she elaborated on the concept, explaining how a hard-line distinction between the biological sexes was often an underpinning of more traditionalist ideologies which use this dimorphism to reinforce restrictive gender roles. She feels it is “important to really allow the scientific data to speak for itself and to learn from the great degree of variation…”

But what are these data and wherein lies the variation? We have all heard about individuals born without physiologically distinct male and female parts. In the medical field they are referred to as individuals suffering from Disorders of Sex Development, or DSD, but you might have heard the term “intersex”. These individuals, while not entirely uncommon (some form of DSD occurs in approximately 1% of individuals), are likely not going to rewrite government and medical forms or completely change the way we understand sex. Besides, the fact that many of you will recognize the term “intersex” implies that this condition (or set of conditions) is something that isn’t outside the realm of general knowledge. A lot of us are already aware of intersex individuals, but we’ve yet to adjust our concept of biological sex.

A more broad-scale change in our attitudes toward biological sex may require a more radical challenge. Coincidentally, there are some interesting cellular and molecular events that may give us a little more food for thought. Take, for example, the axiom that human males have one X and one Y sex chromosome in their cells while females have two X chromosomes. This is one of the most universally accepted facts about biological sex, especially among non-scientists. You don’t have to have a degree in a life science to know that this difference in our chromosomes makes us male or female. In the case of this guiding principle of biological sex, there is a good basis for it. It is true in general that if you snatch a single cell from anywhere in my body and look at the chromosomes, you’ll see one X and one Y. However, in the case of the merging of twin embryos, there can be individuals born with some cells bearing an XX and some bearing an XY. Indeed, given certain circumstances of this chimerism as we call it, one may not even notice that they are living with two distinct groups of cells in their body.

Certainly in the case of would-be twins that fuse in the womb, this is an interesting phenomenon. However, chimerism in humans is not so rare. There are a number of much more common processes by which we can acquire the cells of another genetically distinct individual and grow with that person’s cells becoming, quite literally, a part of us. Consider the significant interchanges that can occur between mother and fetus during gestation. These exchanges of materials can and often do include cells, specifically stem cells which are multipotent or pluripotent, a term we use to mean that they can turn into many different kinds of cells. We call this phenomenon microchimerism, and it means that you can have cells from your mother inside of your body right now. In fact, if you have any older siblings, it is possible that their cells continued to grow in your mother’s body, and were subsequently transferred to your body during your growth. I can sense the outcry from younger siblings already. These cells are not just mooching off your energy, either. In many cases, they are earning their keep by working. Cells from your mother or siblings may mature into cardiac tissue, neurons, immune cells, and the like, lending a whole new meaning to the term “you’ve got your mother’s eyes”.

In addition to actually having cells in your body from another person of a different sex, there are instances where the sex differences may be even sneakier. For decades, scientists believed that sex development was a pretty clean switch from female to male, with female being the default program. It was thought that the female programming had to be suppressed by the male programming in order for genes responsible for testes, male sex hormones, and other sex characteristics to win out. However, more recent studies have identified a signal for testicular development which female programming must suppress in order for feminine characteristics to develop. Development of one sex over the other (although expressing them in a binary appears to be getting harder and harder) is not one program overriding the default program. Rather, it is a constant competition of factors. There isn’t just one “yes” or “no”, but rather a chorus of “yes” and “no” shouting in a cacophony that may well come out sounding like a “maybe”.

When I first began researching this issue, these phenomena all seemed like fun or intriguing biological quirks. I thought it was fascinating that some people could be born with genitals not matching their chromosomes or with a cellular makeup that was a mosaic of male and female. However, I began to wonder what these new understandings meant for us as a country, a society, and a species.

One issue, which Ainsworth and many before her have highlighted, is the common practice of genital “normalization” procedures that occur quite frequently. They allow intersex babies to go on and develop as one sex or the other. We have come a long way in our societal treatment of gender. Many people no longer care what pronouns you use to refer to yourself, your choice of sexual partner, and the way you choose to dress. If I am being too optimistic about this, then there are at least signs of progress in that direction. On the other hand, there are no such advances being made in the world of medicine and biological sex. Babies are too young to be able to consent to this change in their genitals, often occurring just days or hours after birth. Do parents have the rights to decide which sex their intersex child continues down the path of? Is this in the same vein as trying to change someone’s sexuality or gender identity? Richards was quick to emphasize that there are clear differences between gential normalization procedures and something like gay conversion therapy. Nevertheless, she underscored that a healthier way to approach this kind of surgery would be to ensure it is coming from a place of informed and empirical science, perhaps for individuals who are old enough to understand what is unique about their bodies, and not out of our sense of panic that intersex does not conform to the binary.

Another issue may arise in individuals with chimerisms, which may describe many of us. There are certain diseases, both genetic and acquired, which affect one sex (or perhaps I should say “chromosomal profile”?) more severely than the other. Let’s say that certain cells in my brain developed from my mother’s cells which I acquired in the womb. If I were suffering from a brain disease affecting XX individuals more severely than XY individuals, doctors might not necessarily diagnose me correctly until they had exhausted many other options, simply because I’d checked M on the form in the waiting room.

It would appear that the issue of sex development and biological sex has not quite reached a critical mass, but this growing body of work certainly complicates sex in ways we could not have anticipated during the development of our medical system and our societal opinions on sex. While pressure to adhere to a given gender is beginning to alleviate, pressure to conform to a single, specific sex is alive and well. It can be a little discomforting to think so differently about a concept we often consider black and white, but understanding the intricacies which govern sex development can help us to appreciate the beauty of gray.

Edited by: Brindar Sandhu

What missing link? Filling the 'holes' in the theory of evolution

Kristen Blanchard

Originally published March 4, 2015

Photo by: Kristen Thomas

Photo by: Kristen Thomas

When Georgia Congressman Paul Broun was asked about his views on evolution, he claimed it was an idea “straight from the pit of hell.” However, despite being framed as a conflict between religion and science, the basic tenets of evolution do not preclude faith or religion. Unfortunately, the topic of evolution still evokes passionate debate from both supporters and detractors, such as the one that occurred between Ken Ham and Bill Nye earlier this year. Sadly, in many of these debates, those who disagree with so-called Darwinian evolution disseminate information that simply isn’t true. Such misinformation hinders the public’s conception of evolution and obscures the true questions that still remain in our understanding of how organisms change over time. What follows are some of the common misconceptions held by opponents of evolution and the reasons these talking points are false.

The fallacy: It’s possible to believe in both evolution and Intelligent Design.

Some proponents of Intelligent Design, Creationism, or other “alternatives” to the theory of evolution will argue that their views can coexist with those of evolution. They might argue, for instance, that there is no disagreement. They agree that organisms change over time, hence, they accept that evolution occurs. They just believe it occurs as part of a directed and pre-planned course.

The facts: The theory of evolution is directly antithetical to pre-planned, “directed” series of changes.

Evolution occurs through a series of random changes. In a large enough population, mutations will occur, leading to genetic diversity. The genes that are best at propagating (i.e., the “fittest”) will propagate the most and become the largest portion of the population. On an individual level, the organisms that are thus best at reproducing will reproduce the fastest, and overtake the population. To argue that these genetic mutations are not random, but rather preordained, runs directly counter to the definition of evolution. This distinction may seem like an issue of semantics – if both sides agree that organisms change over time through genetic mutations, why does it matter whether these changes are random or planned? The answer is because the latter runs contrary to what scientists see in the lab. As scientists monitor organismal changes over time, mutations are random. Populations experience both beneficial and deleterious mutations, not merely preordained changes according to a design. This observation forms the foundation how we understand genes, proteins, and whole organisms to change over time. Applications of evolutionary science, such as tracking infectious disease transmission, would be impossible without this framework for understanding how changes occur. Thus, to argue that evolution and Intelligent Design are synergistic theories is simply disingenuous.

The fallacy: Entropy disproves evolution – the natural tendency is for things to become more disordered, not more complex.

The second law of thermodynamics states that in a closed system, entropy can never decrease. Technical jargon aside, this immutable postulate means that absent outside influence, things cannot become spontaneously more ordered. An unordered set of molecules cannot suddenly become ordered without external force. For opponents of evolution, this argument means that the development of complex biological structures (i.e., living organisms) requires a designer in order to be consistent with this law of thermodynamics.

The facts: The energy provided by the sun powers the creation of ordered molecules.

The important caveat in the second law of thermodynamics is that it holds true for a closed system. With external input, entropy (or disorderedness) can decrease. This input can take many forms, without necessitating the existence of a designer. For example, we know that plants can utilize energy from the sun to form sugars from smaller molecules. Entropy decreases due to the addition of energy to the plant. Our natural environment is not a closed system. Energy is constantly added to the system and no external designing force is needed to explain the decrease in entropy as life forms evolved.

The fallacy: Scientists have never observed speciation, or seen the evolution of new or separate species.

Some opponents of evolution also make the distinction between “microevolution” and “macroevolution.” They might concede, for instance, that bacterial populations can develop antibiotic resistance over time, but argue that bacteria can’t evolve into separate species. Implicit in this claim is that such evolution, the development of offspring into separate or new species, has never been directly observed.

The facts: Large-scale organismal changes have been observed both in the lab and in nature.

The Cohan laboratory at Wesleyan University studied adaption over time in communities of Bacillus subtilis, a type of bacteria. In this experiment, not only did they observe B. subtilis descendants develop into unique ecological subtypes (“macroevolution”), they observed that these drastic changes occurred on a similar frequency as changes within an ecological subtype (“microevolution.”) In fact, most scientists do not make a distinction between microevolution and macroevolution. As the work of the Cohan laboratory shows, both small-scale changes and large-scale changes happen concurrently as organisms reproduce; microevolution and macroevolution are occurring through the same process.

Despite our certainty that evolution can and does occur, there are plenty of exciting questions that remain. Research is constantly underway to refine our understanding of evolution. In fact, labs here at Emory are currently investigating diverse topics ranging from evolution of antibiotic resistance to host parasite interactions. The question of how organisms evolve is still a rich and exciting mystery – but that they evolved, and continue to do so both in nature and in the laboratory, is simply not up for debate.

You Can Handle The Truth: What You Can Learn From Your Own DNA

Zachary Ende

Originally published March 2, 2015

photo by: jadiel wasson

photo by: jadiel wasson

Samuel L. Jackson is known for a plethora of apoplectic soliloquies, but you’ve probably never heard him say, "Wow, get out of here! I have to Google Gabon immediately, and see what’s there!" If you thought this was hyperbole-laden acting, you would be surprised to learn that he was reacting genuinely. All it took was the science of DNA. On the television show "Finding Your Roots," Samuel L. Jackson learned his DNA matched that of the Benga tribe of modern day Gabon, sparking his interest in the Central African nation.

The connection was made possible by Africanancestry.com, one of nearly a dozen personal genome sequencing companies that have sprouted up to decipher your DNA. Why now? DNA sequencing costs have plummeted precipitously as technology has rapidly evolved. Decoding an entire human genome went from over $100,000,000, in the year 2000, to $1,000,000 in 2007, to under $10,000 today. Most personal genome sequencing companies probe short informative regions of your DNA. These private companies can tell you amazing things about yourself. What kinds of things are hidden in our DNA?

All of humanity originated in East Africa roughly 150,000 years ago subsequently spreading throughout the world. For about $200, the National Genographic Project traces your ancestors' migration to the present day solely from skin cells on the inside of your mouth. They decode small portions of your skin cell derived DNA known to differ between people (single nucleotide polymorphisms or SNPs, pronounced "snips").

At most times during human evolution, more than one hominin species lived concurrently. Our habitually besmearched cousins, the Neanderthals, lived alongside modern humans up to about 30,000 years ago. In a landmark study published in 2010, Green et al. examined Neanderthal DNA in modern humans and showed that "non-African haplotypes match Neanderthal at an unexpected rate." Since then, other publications have suggested mixing probably occurred in the Middle East about 50,000 to 60,000 years ago. For non-Africans the average match to Neanderthal DNA is ~2%. You may find out you are part Neanderthal, literally.

I am admittedly a bit of a Neanderthal. How do I know? I tried 23andMe for $100. I also learned much more relevant information about my genetic predispositions. Some of the propensities they test for may surprise you: drug side effects (i.e. statins for cholesterol), diseases (i.e. various cancers, asthma and dementias) and, physical and metabolic traits (i.e. height, food preference, and aging).

These tests also surprised the Federal Drug Administration (FDA) of the United States government. The FDA told 23andMe to "immediately discontinue marketing" in an official warning letter on November 22, 2013, until approval is granted for the health risk assessments (though they still give you the raw data). Why would the government block us from potentially valuable health information found in our own DNA?  

The warning letter cited concerns "about the public health consequences of inaccurate results." The FDA categorized the DNA service as a medical device and thus expressed concern about false negatives, false positives, and misinterpretations by consumers that could lead to bad healthcare decisions.

Not everyone supports the FDA's decision. Robert Green is one formidable dissenter if there ever was one. He is an M.D., M.P.H. in the Division of Genetics at Harvard Medical School and is also part of "The Impact of Personal Genomics Study." In a comment in the journal Nature, Green and Nita Farahany, a law professor at the Duke Institute for Genome Sciences and Policy, said that "a US drug-agency clampdown is unwarranted without evidence of harm," and, " we urge the FDA to let consumer genomics testing proceed." Most people (~60%) do nothing when learning of their genetic risk factors, while over a quarter of people change exercising and eating habits for the better. Other articles in the Journal of the American Medical Association and the New England Journal of Medicine support the FDA's decision, though Green and Farahany's arguments are the most convincing since they have actually studied the issues in play.

Putting aside the argument about the paternalistic stance of the FDA, maybe this information is too heavy for many of us to consider knowing on an emotional level. After all, besides the disease risks, we could find unknown half siblings (search "With genetic testing, I gave my parents the gift of divorce" for an interesting story about an anonymous 23andMe customer who reported just that). On the other hand, knowledge is power, and perhaps you will discover important facts about your genetic risk factors for you and your children.

Of utmost concern is privacy and data security. The Genetic Information Nondiscrimination Act of 2008 protects those in the United States from discrimination based on genetic information in the realm of insurance and employment. That information alone is not enough to allay most people's fears. Most would-be consumers I have spoken with said privacy is paramount in their minds and the top reason for not participating in personal genome sequencing.

23andMe may as well be considered a side project of Google given that 23andMe CEO Anne Wojcicki is the wife of Google Co-Founder Sergey Brin (it is not just gossip, it is also a $3.9 million investment in 2007). Google's connection is unsettling on the one hand given the fear that our own DNA could end up being "Googled" or worse yet added to the ungodly amounts of data Google has on us.  On the other hand, Google is a technological mammoth that one would imagine has resources and know-how to protect private information—if anyone can.

I shared my 23andMe results with any of my family members that would listen—both ancestry and health-related analyses. My own experience was a journey of self-discovery and personal empowerment; friends who have tried the service have echoed that sentiment on the whole. Nevertheless, improved sequencing methods leading to lower costs and a better understanding of the results will enable a more complete DNA decoding experience than the "snips" currently offer. That is why, for those considering paying for DNA sequencing services, like those considering purchasing the newest computer or smart phone, you will likely be rewarded for your hesitation and indecision. As soon as you buy the new version, the newer improved version comes out a day later. But hey, like DNA, to each his own.

Ebola: From Science to Treatment

Erica Bizzell

Originally published October 31, 2014

ebola.jpg

Ebola… this is the word on everyone’s lips over the past few months, and rightly so. Since its discovery in the late ‘70s, there have been five species of the Ebola virus in circulation, which up until recently caused a little over 2,300 total cases of human infections.  With close to 9,000 cases of Ebola in West Africa just since March of this year, and a mortality rate of at least 50%, this is by far the most widespread Ebola outbreak in recorded history. The Zaire strain of Ebola (EBOV) has been the culprit behind the majority of major human outbreaks throughout the past four decades, and is the strain currently in circulation.  However, two major questions remain: (1) What makes this Ebola outbreak so different than all the previous ones, and (2) What steps are currently and should be taken to combat this deadly virus?

So what is it that makes this particular outbreak so unique?  Your first response may be to “blame the virus”.  Some viruses, such as HIV, are known to have rapid mutation rates that alter the course of disease over time, which leads many to wonder if this is what underlies this particular outbreak.  However, mutations do not appear to be responsible for the current spread of Ebola. The first Ebola case study, reported in the New England Journal of Medicine by Dr. Sylvain Baize et al., revealed that the virus is 97% identical to EBOV strains from the DRC and Gabon.  With viral mutations not being the driving force behind the outbreak, we must turn our attention to something besides the virus.  The unprecedented magnitude of this outbreak is mostly due to a host of social factors, including inadequate basic hygienic tools during treatment (such as private bathrooms), distrust of government due to continued civil unrest, as well as porous borders allowing for unchecked travel between affected areas.  All of this has contributed to the formation of a “perfect storm” scenario for the spread of this virus.  

Considering that the current Ebola species in circulation has been around since the discovery of the virus, one can’t help but wonder what advances have been made to contribute to treatment or prevention.  Many people have now heard of the experimental drug ZMapp, which was used during treatment of the first two Ebola patients in the United States.   Through research conducted in the lab of Dr. Gary Kobinger, this drug, consisting of a cocktail of antibodies against Ebola, was shown to be effective in primates when administered early (up to five days post-infection) during viral infection.  While no studies have been published to determine the effectiveness of the drug further into disease progression, this is a significant step in the right direction for treatment of Ebola.  

Measures are currently being taken to address prevention of Ebola.  At the WHO Consultation on Ebola Vaccines on September 29-30 of this year, it was decided that the testing and production of the two most promising Ebola vaccines be expedited.   Both vaccines are currently ready for phase I trials, meaning that they have already shown adequate safety and efficacy in at least two different animal models.  One of these vaccines, now being produced by GSK in collaboration with the US National Institute of Allergy and Infectious Diseases, has had very promising results in initial studies with primates.  In a publication from the NIH Vaccine Research Center lab of Dr. Nancy J. Sullivan this September, the ChAd3(Z) vaccine conferred 100% protection to animals challenged with a lethal dose of Ebola. These along with various other studies provide some hope for the future of Ebola treatment and prevention.  

Here at Emory, much is already being done at the clinical level to fight Ebola.  At the Emory University Public Health Sciences Grand Rounds on September 19th, the Emory community was given a peek into the treatment regimen of the first two United States citizens infected with Ebola treated here at Emory.  Dr. Marshall Lyons explained the many considerations that had to be addressed in order to treat these patients here in the U.S.  One can only imagine the logistics behind coordinating a team of over 120 people for the care of these two patients.  While the experimental drug ZMapp was included in the patients’ treatment regimen, there was a host of supportive therapy that was critical for the survival of these two patients including but certainly not limited to administration and monitoring of fluids, electrolytes, ventilation, life support, and blood transfusions. The use of adequate sanitation, full isolation of the patients during treatment, and the work of professionals in proper personal protective equipment made it possible for both patients to walk out of the hospital completely healthy. Through the panel discussion at this event, we learned that collaborative efforts are now being made by the CDC along with other health groups around the world to bring some of the more basic medical standards, which we have in the US, to the West African countries most affected by the current epidemic.  It is clear, however, that in order for there to truly be a long-term resolution to the issue of Ebola in this region, more efforts will need to be made both to restore public trust in government and to build an adequate infrastructure for health care in the countries affected.