In San Jose's Santa Clara Valley Medical Center, psychiatrists insisted that their medical mystery patient had a neurological disorder. However, neurologists were adamant that the patient was undergoing a psychiatric episode. Amidst the arguments, Director of Neurology, William Langston, noticed a striking resemblance of the patient's condition to that of Parkinson's disease (PD). They were alert, but their body was rigid – with an arm involuntarily raised for long periods of time. PD is the second most common neurodegenerative disorder (behind Alzheimer's disease), and the most common neurodegenerative movement disorder worldwide, but it is typically associated with old age, and symptoms develop over a period of years – not weeks.

The doctors used news media alerts and police assistance to see if their medical mystery patient was an isolated incident. Soon, they discovered six other similar cases across the state. The patients did not know each other, but all had one thing in common: they had recently taken the same recreational drug. It was described as a "synthetic heroin" and, after police raids and cooperation from local dealers, chemical analyses of the drug revealed that one batch was near pure 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP is a byproduct of the synthesis of an opioid, with effects similar to morphine. Our bodies metabolize MPTP into a toxin that selectively kills neurons in the substantia nigra, the same area of the brain affected in PD.

A nearly identical case of synthetic opioid-induced Parkinsonism had actually been identified a few years previously but had gone unnoticed by much of the scientific community. It wasn't until Langston's team published their findings, reporting that MPTP consumption led to their patients' Parkinsonism before PD researchers took notice. 

Within hours of the publication of Langston's paper, all of Aldrich Chemical's (one of the largest retailers of chemical supplies) commercial stock of MPTP had sold out. The cost of MPTP increased almost 100-fold once it was restocked. The doctors had not realized it at the time, but they had just informed the world of a valuable new research model of PD. 

Human diseases like PD are often difficult to model in a laboratory setting. Before new drugs are eligible for human trials, they must first be tested on cells or animals. However, in order to evaluate the effectiveness of a drug, a disease-like state must be induced in these cells or animals first. Therefore, the striking clinical and pathological similarities of the effects of MPTP consumption to PD, though tragic for the patients, was a silver lining for research. Just a year after publishing their findings, other scientists had reported the remarkable effects of MPTP in non-human primates. Like in humans, MPTP induced motor symptoms in monkeys and these symptoms were alleviated with levodopa – the precursor to dopamine and a common PD treatment. Levodopa-responsiveness is usually used in the clinical diagnosis of PD.

In the near-forty years since its discovery, over six thousand MPTP-related PD studies have been published. The majority of these have been performed in mice – interestingly, rats, a common neuroscience lab model, are resistant to the effects of MPTP. The MPTP mouse model has been useful in picking apart the mechanisms of disease, especially the effects of mitochondrial dysfunction in PD. 

These animal models have also informed the development of potential therapeutics. Substances that could prevent MPTP-induced neurodegeneration and movement symptoms in animals could also be protective in human PD. For example, one study found inhibitors of an enzyme called monoamine oxidase (MAO) B, were protective against the toxic effects of MPTP in mice. This discovery inspired the first clinical trials for MAO B inhibitors for treating PD, known as selegiline and rasagiline. Both of these drugs are prescribed to PD patients today, however, like all PD treatments, they unfortunately only improve symptoms rather than modify the severity or progression of the disease.  

In addition to helping scientists develop PD drugs, MPTP animal models have also been useful in understanding the environmental risk factors of PD. The toxic metabolite of MPTP, MPP+, has a very similar structure to a herbicide called paraquat. Paraquat is used worldwide, under the brand name Gramoxone. However, many studies have now demonstrated an association between paraquat use and PD development. While some countries, including the EU nations, have now banned its use due to this link with PD, paraquat remains one of the most widely used herbicides today. 

The unfortunate case of the "Frozen Addicts" has been an enormous breakthrough for the PD field in countless ways. Their misfortune has led to the development of multiple therapies and increased our understanding of the disease, undoubtedly aiding the lives of millions of PD patients across the world and will continue to do so.

"We hypothesize that the patterns we observed are an innate adaptation that allowed our ancestors to take advantage of this natural source of evening light that occurred at a specific time during the lunar cycle," said Leandro Casiraghi, lead author of a new study, published in Science Advances.

The research, a collaboration between the University of Washington, Yale University, and the National University of Quilmes in Argentina, assessed the activity patterns of 562 participants across an urban-rural gradient. Participants included members of three Indigenous Toba/Qom communities in Argentina and undergraduate students from the University of Washington. Each participant slept with a wristwatch that tracked their movement and sleep. This data was combined with NASA's sun and moon data for each location.

The researchers found that the time the participants went to sleep and how long they slept oscillated during the course of the lunar cycle. On nights leading up to a full moon, when the moon was brighter, people went to sleep later and slept for a shorter time. 

The researchers concluded that moonlight stimulates nocturnal activity, especially for those in rural communities where light pollution is sparse. People in cities, with greater light pollution, went to sleep later and slept for less time in general, but still followed similar patterns to people living with little or no access to artificial light. The researchers state that the artificial light present in cities mimics the effect that moonlight has on sleep for rural communities. 

So next time you are having trouble falling asleep, you may want to look to the moon for an explanation.

Scientists do not completely understand why such an extended course is needed to treat tuberculosis. They do know, however, that antibiotics must enter all of the bacterially-infected cells in order to be effective. Therefore, if scientists could develop antibiotics that enter the host cells as efficiently as the bacteria does, this could shorten the course of treatment required - reducing the risk of antibiotic resistance developing.

Researchers at the Francis Crick Institute in the UK and the University of Western Australia tackled this problem by developing an imaging technique to see which infected lung cells the antibiotics could enter. The team infected mice with Mycobacterium tuberculosis and treated them with the antibiotic bedaquiline. They used a new microscopy method, called CLEIMiT (correlative light, electron, and ion microscopy in tissue), to identify the specific cells that the antibiotic was taken up by.

They found that bedaquiline was unable to enter all of the infected lung cells, meaning while some bacteria were being killed, others managed to evade the treatment. This could explain why such a long treatment regime for tuberculosis is required. CLEIMiT offers the possibility of characterizing current antibiotics that we use to assess their cell-specific uptake, as well as aiding the development of more efficient antibiotics. This will ultimately reduce the risk of the development of antibiotic resistance.

Scientists have been investigating this in the hope of identifying an effective way to treat severe COVID-19. Using different methods of investigation, two pre-prints have reported that a protein called OAS1 influences COVID-19 outcomes. The studies, which have not yet undergone peer review, describe a protective variant in OAS1 that is inherited from Neanderthals.

OAS1 activates enzymes in our cells that are responsible for RNA degradation. SARS-CoV-2, the virus responsible for COVID-19, is an RNA virus, and therefore this protein could potentially serve as part of the immune response against it. The same variant was found to be protective against SARS-CoV, the virus responsible for the 2002-2004 SARS outbreak.

Different people have different forms of proteins due to genetic variation. The Neanderthal variant of OAS1 has greater anti-viral activity than other isoforms. The variant was introduced into the European population via gene flow between Neanderthals and the ancestors of present-day humans. Neanderthal ancestry makes up 1.5-2.1% DNA in people outside of Africa, and many of these genes have been selected for over time.

This is not the first instance of Neanderthal variants influencing COVID-19 outcomes. A study published in Nature in September 2020 detailed a stretch of DNA on chromosome 3, identical to the Neanderthal genome, that tripled the risk of developing severe COVID-19. 

Animals hibernate to survive cold weather and reduced food access by decreasing their metabolic rate and body temperature for months at a time. Accustomed to our modern-day central heating and abundance of supermarkets, the prospect of human hibernation seems like science fiction. However, 430,000 years ago, Earth experienced a period of extreme glaciation — otherwise known as the Ice Age. New research from scientists in Spain suggests evidence that these brutally cold times may have led to hibernation.

Animal hibernation causes high levels of the hormone parathyroid in the blood. This chemical damages bones, leaving long-lasting tell-tale signs. In this study, paleontologists examined human specimens for hyperparathyroidism from the Sima de los Huesos cave — Spanish for "pit of bones." The burial site is home to over 7,500 human fossils, from 29 individuals, between 300,000 and 600,000 years old — making it the largest and oldest collection of human remains to date.

The team studied the bones using a combination of microscopy and CT scans — the same as those used in hospitals. They discovered a plethora of lesions and bone damage indicative of disorders such as rickets, Chronic Kidney Disease — Mineral and Bone Disorder (CKD-MBD) and hyperparathyroidism. The authors propose that these diseases were caused by poor toleration to hibernation.

They argue that these ancestors may have hibernated for up to four months at a time. This strategy was imperative for survival during frigid and food-scarce periods, such as the extreme glaciation 430,000 years ago where these individuals lived.

While this discovery is certainly exciting, it is not entirely conclusive. Fossil experts will likely continue gathering more research to determine whether early humans really did hibernate, or not.

DFTD tumors develop around the head and face and are mostly fatal within a year. As the tumor grows, the solitary animal has difficulty catching prey and feeding. How DFTD affects devil social interactions over the course of the disease, however, has never been studied before. A research team has now tracked affected individuals over time to learn more about the social aspects of DFTD.

Over a six-month period, including the mating and non-mating season, the team monitored the social interactions of 22 Tasmanian devils and their disease progression. The group fitted 12 female and 10 male devils with tracking collars, which emitted different signals when in close proximity to other collared devils. The animals were recaptured each month to monitor their disease status and identify any newly infected individuals.

At the beginning of the study, three devils presented with DFTD tumors, and over the course of the six months, seven more developed symptoms. The researchers discovered that Tasmanian devils afflicted with the transmissible cancer were less likely to interact with others, particularly during the mating season. As their tumor sizes and infection loads increased, their probability of interaction dramatically declined.

This antisocial behavior may be a mechanism adopted by diseased devils to promote the survival of their species — an act of altruism that could prevent their extinction.