By Tiago Palmisano
Edited by Bryce Harlan

Xenotransplantation. The first time I heard this word I assumed it was something from a sci-fi show. Technology akin to the faster-than-light hyperdrive or the gravitational tractor beam, perhaps. Little did I know that xenotransplantation is not only very real, but also on the frontier of medicine. But enough introductions, I’ll get to the point. Xenotransplantation refers to any procedure in which the tissues or cells of one species are transplanted into another. For instance, the brain of a dog into a cat or (much more realistically) the use of pig skin on a burn patient. But what is the use of xenotransplantation? After all, we seem to be proficient at transplanting organs between humans.

Well, the importance of developing this technique stems from the lack of available human organs for the overabundance of people in need of a transplant. At the time I am writing this article 121,177 people in the U.S are waiting for a lifesaving organ donation, according to the Department of Health and Human Services. That number shrinks considerably if we can figure out a way to safely put the organs of animals into humans. Pigs, in particular, are the focus of current xenotransplantation research due to their high supply and the fact that their anatomy is relatively similar to ours. Imagine if a cardiac surgeon could simply order up a pig heart every time a patient went into heart failure.

Amazingly, one team of researchers has taken some considerable steps towards that exact goal. They managed to transplant pig hearts into five baboons, and the primates survived for on average 298 days. The remarkable aspect of this experiment is not that the pig hearts were able to effectively pump blood in a baboon body. Rather, the difficult part is preventing the recipient from rejecting the porcine organ. Rejection occurs when the immune system of the host recognizes the new tissue as a foreign and initiates an attack, damaging the transplant and rendering it useless. Organ rejection is a problem even between humans, so the task of getting one species to accept the tissue from another species only complicates the issue.

In this study, published at the beginning of April, the researchers used some clever techniques to increase the chance that the baboons would accept the hearts. First they genetically modified the pigs, decreasing the susceptibility of porcine tissues to immune response. Then, once the xenotransplant was complete the baboons were given a drug regimen to help regulate their immune system. Using this strategy, one of the primates was able to live with a pig heart for over two and a half years. This provides substantial evidence that long-term survival of a heart xenotransplant is possible, and the time may be soon approaching when actual xenotransplant surgeons are in hospitals throughout the world.
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While baboons were used here to serve as approximations for humans, the use of porcine anatomy in humans is not a new idea. The bioartifical liver device (BAL) uses pig liver cells and functions as a temporary dialysis machine for patients with acute liver failure. In this way, the pig liver cells either help the human liver recover or keep the patient alive until a transplant becomes available. Additionally, pig brain cells (neurons) have been used in humans with Parkinson’s disease and Huntington’s disease. It seems as though scientists are slowly finding ways to make the pieces fit. Although the idea of pig parts in human bodies may be off-putting to some, xenotransplants have the potential to make the organ waiting list a thing of the past. And that’s an idea that everyone can enjoy.

Written by Julia Zeh
Edited by Olivia Ghosh

Does homosexuality exist in animals other than humans? Yes, and no.

From the perspective of Darwinian evolution, homosexuality is a puzzling concept. According to Charles Darwin, natural selection works to promote fitness in the sense of increasing reproductive output. In order for certain traits to evolve, they must be adaptive, meaning the benefits to an animal’s reproductive success must outweigh the costs. But from this standpoint, how can homosexuality evolve? By definition homosexuality has no reproductive output and takes away from the reproductive success of the individual and the species, because homosexual sex cannot result in offspring.

Yet, same-sex relationships still exist in nature, and even though they don’t lead directly to an individual passing on its genes, they still must have some adaptive value. In fact, homosexuality is not even a rare trait; so far over 450 species have been identified which exhibit homosexuality. So what is the adaptive value? Why aren’t all relationships heterosexual in the animal kingdom?

The answer lies in the benefits of homosexual relationships, including benefits to social relationships and hierarchies, pleasure, and parental care. These benefits are exhibited in species such as the Laysan albatross, bonobos, bottlenose dolphins, domestic sheep, and humans.

Laysan albatrosses usually mate for life, but these mating pairs are not always male-female pairings. One third of pair bonds are between two females and these females try to mate with each other and care for their offspring together. Males do still mate with females, so offspring are produced, but males don’t usually stick around. This is where the female-female pair bond is useful; the females take care of their babies together with equal responsibility. Males provide no parental care, so having two female parents is actually adaptive and beneficial because it helps with parental care and offspring fitness.

As opposed to the albatross, both bonobos and bottlenose dolphins use sex as a strategy for social communication. Both of these species are social mammals with complex social relationships and, as with many other species, sex is used in maintaining these complex relationships. In bottlenose dolphins, homosexual sex is exhibited in both males and females and it is used to form strong social bonds. Bonobos are similar. One of the most peaceful species on the planet, these animals use sex as a peacekeeping strategy, and the groups with more instances of homosexual sex are more peaceful. Bonobos establish matriarchal societies in which social status is established through sexual relations, both for the dominant females as well as for subordinate males. In addition, this species replaces aggression with sex, and mating behaviors are observed in individuals both very young and old, as well as between male-female pairs, male-male pairs, and female-female pairs.

In domestic sheep, on the other hand, some individuals never form female-male pairs. Certain males mate with another male for life, showing no interest in females, even when they are ready to breed. This behavior likely evolved because the gene that promotes homosexuality in males also benefits reproductive output in females. For example, this same gene could increase fertility in females, thus making the reproductive benefits to the species greater than the costs of a few males who never reproduce. This link between genes that increase fertility in females and homosexuality in males has been proposed, but the specifics are still unclear.

But there is also a reason to say that no species of wild animal is truly homosexual other than humans. Although there are male domestic sheep who never mate with females, spending their entire lives only interested in males, this is likely due to artificial selection by humans. This behavior has only been observed in domestic sheep, not wild sheep, and it is likely that humans bred their sheep to be more fertile. This increased the frequency of homosexuality, so it is not necessarily a natural occurrence. All of the examples described previously, other than domestic sheep, are technically bisexual. They all have one main thing in common: despite the presence of homosexuality, all individuals still mate with the opposite sex at some point and produce offspring.
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So why are humans the only wild animal species with truly homosexual individuals? The answer is we don’t know. Research has been done on how hormones and brain circuitry may cause homosexuality, but as for its evolution and the reason why it hasn’t evolved in other animals, the answer is not yet clear. But what is clear is that homosexual sex and pair bonds are both natural and actually quite common, and there are a huge number of species which, although they do not exhibit true homosexuality, do exhibit bisexuality.

By Tiago Palmisano
Edited By Bryce Harlan

One reason I love biology is that despite centuries of research and discovery, we are continuously gaining new insight into the machinations of the human body. Even today our understanding of medicine is expanding as biotechnology and pharmaceutical companies strive to develop more sophisticated strategies for combating disease. In this article I want to discuss two potentially game-changing advances in medicine.
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PCSK9 Inhibitors

The PCSK9 protein binds to the LDL-receptor on the surface of liver cells. This causes the LDL-receptor to be degraded, which prevents the uptake of LDL cholesterol from the blood. The PCSK9 inhibitors stop this process. (via The British Journal of Cardiology)

In order to understand the significance of PCSK9 inhibitors, it is first necessary to understand the physiology of cholesterol. Cholesterol is a modified steroid that serves an essential role in all animals. Among other things, cholesterol is required to maintain the integrity of cell membranes and to synthesize hormones and bile acids. This important molecule does not travel in the body independently, but rather is carried through the bloodstream in capsules known as lipoproteins. Two types of lipoproteins exist in the human body, known as HDL (high-density lipoprotein) and LDL (low-density lipoprotein).

Although cholesterol is a crucial component of bodily functions, elevated concentrations (known as high cholesterol) are problematic. Specifically, a high level of LDL can result in coronary heart disease, which in turn may lead to a heart attack. Typical treatment of this condition involves a class of drugs known as statins, which lower LDL levels by inhibiting an enzyme necessary for the production of cholesterol. Various statins are available on the pharmaceutical market, accounting for billions of dollars in sales. However, a new class of drugs known as PCSK9 inhibitors may soon give statins a run for their money.

PCSK9 is a naturally occurring protein that binds to the receptor for LDL cholesterol on liver cells. When LDL cholesterol binds to this receptor, it is taken up by the liver cell and removed from the blood. However, the PCSK9 protein can bind to the LDL-receptor and initiate breakdown, preventing the receptor from taking up cholesterol. Put simply, the PCSK9 protein prevents the removal of LDL from the blood. And this is where the brilliance of pharmaceutical advancement comes into play. The newly developed PCSK9 inhibitors are monoclonal antibodies that do exactly what they say – they bind to PCSK9 and inhibit its normal function. If PCSK9 cannot attach to the LDL-receptor, then more receptors are available to take up LDL and the levels of cholesterol in the blood decrease significantly.

Currently, the Food and Drug Administration has approved two PCSK9 inhibitors for use in the United States (alirocumab and evolocumab). Research has demonstrated that PCSK9 inhibitors are much more effective than statins at lowering LDL levels. For example, one study found that PCSK9 inhibitors lower LDL levels by approximately 60% in patients already taking a statin! Furthermore, PCSK9 inhibitors are given via injection every 2-4 weeks, whereas statins are taken as a daily pill. Such an improvement in efficiency suggests that it is only a matter of time before they replace statins as the go-to prescription for treatment of high cholesterol.

WATCHMAN Left Atrial Appendage Closure Device
The WATCHMAN device is inserted into the heart via a catheter, and it sits in the left atrial appendage. This prevents blood clots in the left atrial appendage from escaping into the bloodstream and causing a stroke. It is vital to note that drugs are not the only form of modern medical advancement. Large-scale medical devices are also becoming increasingly sophisticated, and the WATCHMAN device is the latest example. As its name suggests, the WATCHMAN closes the left atrial appendage. But what does this mean? Well, the heart is composed of four chambers, two atria and two ventricles. In this case, we are looking at the left atrium in particular. Electrical signaling in your body causes the heart to contract, which pushes blood out of the left atrium and into the left ventricle.

For an unknown reason, there is a small pouch (an “appendage”) on the wall of the left atrium. Normally this is not a problem, as the contraction of the heart pushes all of the blood out of this appendage. However, the left atrial appendage becomes an issue if the contractions are abnormal. Coronary heart disease, high blood pressure, and age can all result in atrial fibrillation (AF), a condition in which the electrical signals in the heart fire irregularly. AF disrupts the heart’s contractions and allows blood to collect in the left atrial appendage, since effective transfer of blood to the left ventricle does not occur. Over time this collected blood can clot, and these clots can result in a stroke if they are pumped out of the heart. If AF occurs, then the left atrial appendage becomes a problem.
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The typical method for preventing stroke in patients with AF is warfarin, a blood thinner that inhibits the formation of clots. However, since the left atrial appendage is not actually necessary, Boston Scientific has developed an interesting way to prevent strokes in patients with AF. The WATCHMAN device is a net-like implant that is designed to sit in the left atrial appendage. This device is delivered to the heart via a catheter, and once in place it expands to fill the appendage. By effectively closing off the left atrial appendage, the WATCHMAN device prevents potential clots from escaping, decreasing the risk of a stroke. The major benefit of this alternative treatment is that warfarin, the typical treatment, has numerous adverse side effects. For example, blood thinners such as warfarin can lead to excessive bleeding, known as hemorrhage. The WATCHMAN solves the issue of stroke risk without thinning the blood, and therefore many doctors may begin to view this new device as the safer and preferable option.

Written by Julia Zeh 
Edited by Olivia Ghosh

The animal kingdom is chock-full of weird, crazy, mixed-up gender roles and sexualities. From sex-changing fish to homosexual birds, and everything in between, evolution has created an immense diversity among animals when it comes to the behavioral and morphological aspects of gender and sex.

The spotted hyena is an animal lacking a trait that belongs to most other mammals: sexual dimorphism, which is the difference between the ways males and females look and act. The males and females of this hyena species, the largest of three species, look so similar that even trained scientists have a lot trouble telling them apart in the wild. For centuries, people even believed that this was a hermaphroditic species of hyena. However, this species of large, brown, furry scavengers does in fact have both sexes, but they are easily mistaken for one another because the two sexes have almost identical genitalia. That’s right, the females of these animals, well known for their eerie laugh and their appearance in a well-known Disney movie about lions, do in fact have what is known as a “pseudopenis.”

Another interesting thing about this species is their complex social structure, dominated by aggressive females who also tend to be larger than the males. The weird anatomy of the females is a Darwinian puzzle, or an evolutionary mystery, thanks to the danger to hyena offspring that comes from the existence of the pseudopenis. These females urinate, copulate, and give birth with this organ. Yes, the cringe worthy truth is that these hyena moms give birth through the pseudopenis, which results in a 60% death rate of first-born cubs and 10% death rate of new moms. So if this experience, which not only sounds painful, is also detrimental to the health of offspring, why hasn’t natural selection gotten rid of it?

The answer lies in the complex social structure of the species. Determining a social hierarchy is vital to the way the social structures of these hyenas works, and that’s why these pseudopenises exist. As a greeting ceremony, individuals sniff each other’s genitals, and this greeting allows them to determine superiority and dominance. In a species in which females are incredibly aggressive towards both each other and towards males, it is actually an evolutionary advantage to have this structure, despite its costs in reproduction. Females are so aggressive that it is actually dangerous for males to try and mate with them. Males are incredibly submissive and must be very careful around females, especially when trying to mate, so that they are not attacked or even killed. All of this aggression and social hierarchy is important because these hyenas live where food is very scarce. More dominant females are allowed to stay with the clan, and higher ranking females have larger pseudopenises, higher survival rate, and greater access to food.

Outside of the world of mammals lies another well-known group of animals, which, unlike the spotted hyenas, have extreme sexual dimorphism. But like the hyenas, this group has socially dominant females. This animal is the anglerfish, the epitome of alien deep-sea fish known for its bioluminescent, glowing lure that hangs from the top of its head. These fish look terrifying with their large jaws filled with huge teeth that can be used to swallow prey twice their size. But what most people don’t know is that the image that comes to mind when you think “anglerfish” or even the one that comes up when you google it is actually the female, and the male looks drastically different.

Females are, in fact, the only anglerfish with a lure on top of their head and giant jaws and teeth. Males are tiny and lack all of the monster-movie features that the females possess. It would even be easy to call these little guys pathetic, given their life history as parasites of the females. When the male anglerfish is born, in most species, he cannot provide for himself at all and is immediately hungry. But without the ability to eat or catch food, he is totally helpless. The one skill he does possess is a highly specialized sense of smell that he uses to search out his one purpose in life: the female anglerfish. He uses smell to seek out his larger, scarier counterpart, eventually biting into her side in an attempt to finally provide himself with a form of nutrition. But even after finding food and a female, the little guy doesn’t get a happy ending.
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The male anglerfish fuses with the female after he bites into her, and this is how reproduction occurs. Eventually, all of his internal organs and eyes atrophy and dissolve until he becomes merely a pair of testes attached to the female’s side. His body becomes one with hers and he shares her bloodstream, becoming even more helpless than he was at birth, if what he becomes can even be considered existence. Even weirder, the females can have six or more males attached to her body. Like the female hyenas, these females are large and dominant, while the males are smaller, submissive, and in the case of the anglerfish, even helpless. But this is not to say that this more masculine version of the female is the “correct gender role.” Just as with humans, spotted hyenas and anglerfish illustrate how individuals cannot be put into categories and labeled. In the animal kingdom, gender roles are not easily defined, especially considering hermaphrodites and sex-changing individuals exist. What is natural is weird and varying and even in the animal kingdom, outside of the realm of the human, there is no universal definition of male and female.