It’s hard to imagine that even today, there are still places on Earth that largely remain unexplored and uninhabited. These last frontiers of our world are home to a variety of plants and animals that have never been classified, some of the most unique landscapes one could find, and even groups of people that remain isolated or in limited contact with the outside world. 

10. Vale Do Javari, Brazil

The Javari Valley in the Amazon rainforest is home to several isolated indigenous tribes, some of them having lived there for tens of thousands of years. It’s the largest concentration of uncontacted tribes in the world, and many of them have managed to preserve their traditional ways of life and culture even today. Their first recorded contact with the outside world was in the 19th century, when rubber tappers first arrived in the region, followed by foreign missionaries in the 20th century.

The Javari tribes are believed to be some of the last remaining uncontacted tribes in the world, though that’s rapidly changing. While various Brazilian governments in the past have made efforts to protect them – like increasing patrols and enforcing stricter penalties for illegal activity in the valley – their way of life is regularly threatened by poachers, illegal loggers, and cocaine smugglers, as the Javari valley falls on a major smuggling route. 

9. Cape Melville, Australia

The “lost world” of Cape Melville is a unique plateau ecosystem in northern Australia, accidentally discovered by researchers on an expedition in the region back in 2013. It’s an isolated plateau on top of Cape Melville – a remote mountain on the Cape York Peninsula. The plateau is known for a distinctive type of vegetation that is found nowhere else in the world, and is home to many species of flora and fauna that have never been documented.

That includes a type of primitive gecko previously thought to be extinct for millions of years, a gold-colored lizard, a brown spotted frog, and many others. Further expeditions in the years since have revealed other plant and animal species unique to the plateau, though scientific research remains limited due to the remoteness and inaccessibility of the region. 

8. Fiordland National Park, New Zealand

The Fiordland National Park on South Island, New Zealand is one of the largest national parks in the world. At over 1.2 million hectares, it’s home to countless fiords, mountains, streams, forests, lakes, and valleys, making it an ideal place for explorers and adventurers. One can find many endemic species of plants and animals in the many nooks and corners of the park, along with pristine, untouched landscapes unique to the region. 

Fiordland has a long and rich history, with evidence of human occupation dating back to at least the 13th century BC. For most of that time, large parts of the park have remained inaccessible due to the rugged terrain and harsh weather conditions. Even today, Fiordland remains mostly unexplored, with much of the region still waiting to be discovered and studied by professional teams.

7. Mariana Trench, Pacific Ocean

The Mariana trench in the western Pacific Ocean is the deepest part of the Earth’s oceans, reaching a depth of about 36,201 feet, or about seven miles, at its deepest point. As one can expect, much of the underwater region remains unexplored, largely due to its extreme depth, pressure, and cold temperatures that make it almost impossible for scientists to reach it.

Geologically, the Mariana trench is a part of a global network of underwater troughs formed by the collision of two tectonic plates. At its deepest points, the pressure can reach more than eight tons per square inch, which is about thousand times stronger than the pressure on the surface. While the ocean is already largely unexplored, it’s particularly difficult to mount research expeditions to the Mariana trench with traditional methods due to its extreme depth. Till date, only three people have managed to reach it with specialized equipment. 

6. Papua New Guinea

Papua New Guinea is an island country in the southwestern Pacific Ocean. Despite being the third largest island nation in the world, it remains one of the most unexplored and mysterious countries on the planet, largely due to its remote location, uneven terrain, and limited infrastructure. Only a small percentage of Papua New Guinea’s land has been explored by outsiders, leaving out a vast expanse of uncharted territory that are home to many diverse and unique ecosystems.

The country’s dense rainforests, high mountains, and volcanic islands make it a challenging destination for explorers and scientists. The terrain is often steep and difficult to traverse, and many areas are inaccessible by road, requiring air or water transport. In addition, Papua New Guinea is known for its biodiversity and high number of endemic species, even if we’re yet to document and classify all of them. 

5. Patagonia, Chile

Patagonia refers to the southern end of South America, comprising large parts of southern Chile and Argentina. It’s one of the most sparsely-populated and remote regions on Earth, with a population density of about 1.5 people per square kilometer. Patagonia is known for the diversity of its landscapes, as it’s home to everything from glacial fjords, steppes, deserts, and rainforests.  

Due to its remoteness, Patagonia remains mostly uninhabited and unexplored. The area is known for its extreme weather – particularly in the fjord region – with powerful storms and other unpredictable weather conditions making larger scientific expeditions impossible. The infrastructure is another problem, as there’s no way to access many of the region’s remote parts by road. As a result, Patagonia features some of the most pristine landscapes and ecosystems in the world.

4. Yucatán Peninsula, Mexico

Yucatán is a peninsula in south-east Mexico, bordered by the Gulf of Mexico to the west and the Caribbean Sea to the east. It’s home to one of the largest underwater cave systems in the world, and the vast majority of these caves are yet to be fully explored. They’re only accessible through natural sinkholes that lead down to the underground network of rivers and lakes, also known as cenotes.

Despite the ever-growing interest in cave diving and exploration, there are still thousands of unexplored caves and cenotes in the Yucatán Peninsula, as many of them are inaccessible and incredibly dangerous to traverse. In addition to the cenotes, there are also many flooded underwater cave systems that might take hundreds of years to discover, let alone fully map out. The Sistema Sac Actun, for example, is the largest underwater cave system in the world, extending over a total length of over 347 kilometers. 

3. Tepui Mountains, South America

Tepuis are table-top mountains reaching heights of over 10,000 feet, making them prime areas for scientific exploration due to their isolated and untouched ecosystems. They’re found in the Guiana Shield – a South-American region that covers parts of Venezuela, Brazil, and Guyana. These mountains are characterized by their steep cliffs, unique flora and fauna, and extreme isolation of ecosystems, which has resulted in the evolution of numerous endemic species. 

Due to their remote nature, the tepui territory remains unexplored. Many of these mountains with steep cliffs are located in remote areas that are difficult to access, and the terrain makes professional exploration dangerous and costly. Additionally, limited funding and resources available for scientific expeditions means that only a handful of researchers have been able to study this ecosystem.

2. Son Doong Cave, Vietnam

The Son Doong cave in the Quang Binh province of central Vietnam is easily the largest known cave in the world. First discovered in 1990 by a local named Ho Khanh, it was only fully explored by the British Vietnam Caving Expedition team in 2009. Son Doong Cave is part of a larger, unmapped cave network in the area, and many believe that it’s only one part of much larger cave systems that are yet to be discovered. According to one estimate, about 70% of the region’s caves remain unexplored due to inaccessibility. 

The Son Doong is approximately 5.5 miles long, with a height of over 650 feet and width of about 500 feet in some places. It was formed over millions of years by the erosion of limestone, giving way to numerous caverns and underwater systems no one has ever seen. It also contains its own unique ecosystem, with underground rivers, waterfalls, and even a jungle inside the cave network.  While it’s a popular destination for adventurous tourists and explorers, access to Son Doong is tightly controlled due to safety concerns, with only a limited number of permits issued each year.

1. 40% Of Australia

Australia is easily one of the least inhabited countries in the world, mostly because a large part of it is an inhospitable, barren wasteland. It’s also perhaps one of the last unexplored regions on Earth, as exploration and habitation in the Australian outback – an umbrella term for the desert regions in the country’s interior – is still extremely difficult. 

According to a 2008 report by two conservation agencies – the Pew Environment Group and Nature Conservancy – more than 40% of Australia is still untouched by outside contact. They classified it alongside Antarctica, the Amazon, the Sahara Desert, and Canada’s northern Boreal region as one of the last remaining wilderness zones, which is saying something in a country that already adds about 1,000 new species to the tree of life every year. According to another, more recent study, about 500,000 Australian species are still undocumented, and it would take at least 400 years to complete even a basic sweep of all of its diverse flora and fauna.

Modern medicine has advanced so dramatically in the last century that it’s hard to believe that so much is still unexplained. But doctors are often faced with medical mysteries, those phenomena that currently lack a confirmed cause or full explanation.

Although we can’t list every medical mystery here, these 10 examples are a great way to illustrate how medicine continues to grow and transform over time. They also show how much new research is always needed.

10 Medical Student Syndrome

Nearly everyone has had those fleeting thoughts that they’re experiencing a symptom from a severe, undiagnosed disease. Throughout medical school, future doctors learn about thousands of diseases with various signs and symptoms that they are expected to recognize in their own patients one day. An interesting phenomenon that seems to occur in some of these people is known as “medical student syndrome.”

This occurs when medical students believe they are experiencing the symptoms of a disease that they are studying. As opposed to illness anxiety disorder, these delusions are transient.^[1]

It is unknown exactly why this occurs. But researchers believe that medical students create a mental schema as they learn about a disease and some students begin to recognize normal bodily sensations as part of this disease schema.

One study found that up to 78.8 percent of randomly sampled medical students suffer from a form of medical student syndrome. For some, this illness anxiety can be debilitating and lead to unnecessary medical bills. Despite widespread knowledge of this syndrome, it continues to propagate and affect hundreds of students each year.

9 Chemo Brain

Many cancer survivors use the term “chemo brain” to describe the thinking and memory problems that occur after chemotherapy treatment. Symptoms can vary from person to person—from difficulty concentrating to memory problems or difficulty multitasking. This is an extremely frustrating phenomenon for those who are undergoing chemotherapy.

For years, many doctors did not believe in this phenomenon. As it became more common, however, physicians began to recognize that this was a real and debilitating experience. Currently, there is no consensus on what is causing chemo brain, but it is believed to be due to more than just chemotherapy treatment. Researchers are trying to find the source of the cognitive difficulties but have been unsuccessful so far.^[2]

8 Klippel-Trenaunay Syndrome

First described in 1900, Klippel-Trenaunay syndrome (KTS) is an extremely rare disease. Affecting blood vessels, bones, and soft tissues, this condition results in three characteristic features: a red birthmark known as a port-wine stain, abnormal bone and soft tissue overgrowth, and venous malformations. The increased size of bone and soft tissue can result in oversized limbs, usually in the lower body and legs. The venous malformations can result in large blood clots.

Famous cases of KTS include Billy Corgan, the lead singer for The Smashing Pumpkins, and Matthias Schlitte, a professional arm wrestler. Notably, Matthias is known for his Popeye-like right forearm that allows him to be an extremely successful arm wrestler. His condition causes the bone in his right forearm to be 33 percent larger than the one in his other forearm. Currently, there is no cure for the condition and physicians have little explanation as to the cause of the disease.^[3]

7 Rip Van Winkle Syndrome

The disease sounds like the work of a fairy tale, but Rip Van Winkle syndrome is far from fantasy. Also known as Kleine-Levin syndrome (KLS), this disease has only a few reported cases and its physiological cause has not been confirmed.

At age 13, Stephen Maier became a victim of KLS following an upper respiratory infection. Out of nowhere, his parents were unable to wake him up. When they finally did, he was completely incoherent.

After many tests, all of which were negative, Stephen was left with no answers. Even tests on brain activity showed no abnormalities. Maier would go through sleeping spells of up to 22 hours a day for 10 to 20 consecutive days. As mysteriously as the disease appeared, it gradually faded away in his twenties.^[4]

In another case of KLS, a 17-year-old female from Pennsylvania experienced a sleeping episode that lasted 64 days—from Thanksgiving to January. She was reported to have slept 22–24 hours a day. When she did awaken to eat and use the bathroom, she was in a sleepwalking state.

In addition to this sleepiness, sufferers can experience increased appetite, hallucinations, anhedonia, childlike behavior, and hypersexuality. Between these episodes, however, the patients are completely asymptomatic.

Although it may seem appealing to some to get so much sleep, patients end up missing out on large parts of their lives. A few theories about the origin of this disease range from a virus to autoimmunity, but its cause is still largely unknown.

6 Cannabinoid Hyperemesis Syndrome

First described in 2004 by J.H. Allen and colleagues, this odd disorder presents with intractable nausea, vomiting, and GI distress. With further study, the researchers found that all these patients shared a common background of long-term cannabis use.

Although little is known about the cause of this phenomenon, two theories have been put forth. The first holds that the toxic buildup of cannabinoids may be the cause. The second has to do with the functionality of cannabinoid receptors in the brain. During these episodes, some patients have reported temporary symptom relief from a hot shower or bath or psychiatric medications. The only known cure is stopping the use of cannabis. Improvement can be seen within one to three months.

These vomiting episodes tend to last for one to two days. What is extremely odd about this disorder is that marijuana is known for its anti-vomiting effect. This paradox is especially problematic for people who use marijuana to treat nausea and vomiting and then end up feeling more nauseated. It is unclear as to why some chronic users develop this disorder while others do not.^[5]

Cannabinoid hyperemesis syndrome is extremely complex, and researchers are still searching for explanations. As the use of marijuana increases, it is an area that will require much more research.

5 Abscopal Effect

Michael Postow and his colleagues put forth a paper describing a patient whose metastatic melanoma tumors began shrinking after the person received the drug ipilimumab and radiotherapy. Published in the New England Journal of Medicine, this report got a lot of attention in the medical community.

The abscopal effect refers to the bizarre phenomenon where metastatic tumors throughout the body shrink in response to localized treatment of a tumor. For many years, there was no explanation for this interesting reaction. In 2004, it was first hypothesized that the immune system may play a role in this systemic shrinking. While researchers are continuing to investigate the cause of what is happening, a firm explanation has yet to be established.^[6]

4 The Lazarus Phenomenon

An 11-month-old girl in the intensive care unit at the University of Rochester Medical Center had been pronounced dead after aggressive cardiopulmonary resuscitation (CPR), seven doses of epinephrine, two bags of fluid, and four shocks to her chest. After two minutes of asystole, the official time of death was called out at 1:58 PM.

The girl’s family was devastated and asked for her breathing tube to be removed so that they could have some time with their daughter. Fifteen minutes after she was pronounced dead, the tube was removed. Suddenly, the girl began to breathe spontaneously. Her heart began beating again, her color came back, and her gag reflex reappeared. The physicians had never seen anything like this.^[7]

The Lazarus phenomenon is a rare occurrence in which patients experience a delayed return of spontaneous circulation after CPR has been stopped. This bizarre syndrome was initially described in 1982. It was named “Lazarus” after the man who was resurrected by Christ four days after his death.

The explanation for this miraculous ability to come back to life has continued to evade physicians and researchers alike. Some believe that there may be more than one mechanism at work, such as the delayed action of drugs or high potassium.

3 Smoking Aversion From Hepatitis

Thousands of people try various methods to quit smoking every year. While many researchers are learning more about the causes behind nicotine addiction, much less is known about the roots of smoking aversion. However, one interesting trigger has been discovered for immediate smoking aversion—the development of hepatitis A.^[8]

There are various presentations when a person is infected with hepatitis A, depending upon its stage. The first phase (aka the viral replication phase) is largely asymptomatic in most patients. Moving into the prodromal or second phase, patients can experience anorexia, nausea, vomiting, muscle aches, fatigue, itching, and an aversion to smoking. The disease then begins to affect the liver and GI system before resolving.

Although aversion to smoking is a documented effect of acute hepatitis A, little is known about its cause. More research is definitely warranted in this area as the discovery of the cause of the aversion may be extremely helpful to millions of smokers throughout the world.

2 Meat Allergy From Ticks

Last year, the researchers at the National Institute of Allergy and Infectious Diseases were stumped by the increasing number of US cases of anaphylaxis to a molecule found in red meat. Alpha gal is a sugar molecule that is naturally found in beef, pork, lamb, and other red meats.

As researchers delved deeper into the histories of patients with this allergy, they found that most were located in the Southeast and certain parts of New York, New Jersey, and New England. Even more interestingly, all the patients had a history of bites from the lone star tick.

This allergy was particularly hard to diagnose because it presented 3–6 hours after ingestion, unlike common anaphylaxis that presents within 5–30 minutes. The symptoms of this odd anaphylaxis ranged from hives to GI distress to itching and swelling. However, there was no throat swelling. Common allergy tests do not routinely scan for antibodies against alpha gal, so these patients are commonly misdiagnosed.

Dr. Thomas Platts-Mills initially discovered the alpha gal connection.^[9] Some of his patients with a history of lone star tick bites experienced anaphylaxis from the cancer drug cetuximab, which contains alpha gal. Although the source of the allergy has been discovered, the reason that lone star tick bites are associated with alpha-gal allergies remains a mystery.

1 Cellular Memory

Cellular memory is a controversial hypothesis that the body itself is capable of storing memories rather than only the brain. As there is mostly anecdotal evidence to support this theory, many consider it to be pseudoscientific.

Many have linked phantom pain to cellular memory for past trauma to a joint or limb. Cellular memory has also come into play in certain stories of organ transplant patients who develop the traits of their donors.

Researchers at the University of Hawaii evaluated whether organ transplant recipients experienced personality changes following their transplants and if any of these changes paralleled the history of their donors. In a study of 10 patients, each one showed 2–5 changes after the completion of a heart transplant that paralleled his or her donor’s history. These changes in preference occurred in areas such as food, art, recreation, career, and even sex.^[10]

One case involved Claire Sylvia, who received a heart from an 18-year-old male who died in a motorcycle crash. When she awoke from the surgery, she had a strong craving for beer and chicken nuggets, which was out of the ordinary for her. Additionally, she continued to have recurring dreams about someone named Tim L. After searching obituaries, she found that her heart had come from a man named Tim and later discovered that he loved all the foods that she had begun craving.

In a study done by Tufts University, researchers trained a worm and then removed its head and brain, which shrank it to 1/279th of its original size. The worm was then regrown in the lab and still showed signs of its previous training.

The research on cellular memory has a long way to go before this phenomenon is proven to be real. Nevertheless, we still don’t have any explanations for these odd parallels in numerous transplant stories.

Shelby Hoebee is a third-year medical student. While she doesn’t have much free time anymore, she still enjoys writing top 10 lists when inspiration strikes.