Illustration by USC Viterbi; Photos by Ryan Fletcher/iStock, Jezperklauzen/iStock, oorka/iStock, HodagMedia/iStock

10 Unsolved Mysteries

From Amelia Earhart to cancer, Trojan engineers share their best insights.

  1. What happened to Amelia Earhart?

    “What we surmised, in the end, was that she likely descended toward Howland Island a little early, probably hoping to be down underneath the clouds for a better look at the island … and avoid overflying it on the descent. Unfortunately, it’s tough to acquire the small island visually at low altitudes. Nearing the end of their fuel supply, not locating Howland Island and being awake nearly 24 hours, they likely inadvertently impacted the water, possibly just 20 nautical miles from their destination. Over water, judging altitude is challenging, and an inadvertent water impact was possible with a very fatigued Amelia intensely focused on searching for the island.”

    Capt. Chris Nutter, an instructor in the USC Aviation Safety and Security Program, was part of the Waitt Institute’s 2009 deep sea search for Earhart’s aircraft in the South Pacific area where the plane is believed to have crashed.


  2. The Voynich Manuscript may be the most mysterious manuscript in the world. What is it, and how would you solve it?

    “An undeciphered artifact is a physical object — a book, tablet or inscription — with mysterious writing that we can no longer read or understand. Some artifacts come from antiquity, while modern examples include the enciphered letters of the notorious Zodiac serial killer. It’s thrilling to solve one of these puzzles.

    “The holy grail of such artifacts is the Voynich Manuscript, a 240-page book handwritten in the 15th century. The illustrations are bizarre enough — grafted plants, cosmological charts, bathing pools of green liquid — but it’s the text that has everyone baffled. The Voynich contains nearly 38,000 words written in an unknown alphabet by several human scribes. Is it an old writing system? An invented language? A cipher? A nonsense hoax? Empirical work turns up intriguing patterns like prefixes, suffixes and the ‘burstiness’ of certain Voynich words, similar to how the word ‘artifact’ appears several times on the page you are reading right now while occurring sparsely, if at all, in the rest of the magazine.

    “How to solve it? We might be inspired by how one of the Zodiac killer’s letters was solved in 2021: human guesswork about how the artifact might have been constructed, plus massive computer power aimed at reversing that construction.”

    — Kevin Knight, former Dean’s Professor of Computer Science at USC Information Sciences Institute from 1993 to 2020.


  3. Does P=NP?

    “The P versus NP question is arguably one of the most profound questions ever posed by humans. It asks: If it is easy to check the solution to a problem, is it also easy to find the solution?

    “The class P, short for polynomial time, consists of all algorithmic problems that can be solved ‘efficiently,’ i.e., in a reasonable time. Problems we can effectively solve at scale, such as multiplying numbers or finding a route between two locations in a network, are in P.

    “The class NP, short for nondeterministic polynomial time, consists of all problems for which a correct or ‘good’ solution, if provided, can be verified efficiently. This is a looser requirement than actually finding the solution efficiently, so every problem in P is also in NP. However, there are many important problems in NP for which no efficient algorithm is yet known, nor has it been ruled out. In other words, we know they are in NP, but we do not know whether they are in P. For example, no efficient algorithm is known for finding a large clique of friends in a social network, but it only takes some simple bookkeeping to verify that a given list of accounts form a large clique. Other examples of NP problems not known to be in P include the famous traveling salesman problem, the problem of packing objects in a knapsack, and finding a short proof to a mathematical statement.

    “A beautiful line of work in theoretical computer science showed that there are some problems in NP which are ‘as hard as NP gets’ in the following sense: If you find an efficient algorithm for one of these problems, then you could mechanically turn it into an efficient algorithm for any other problem in NP, no matter how different. These problems were termed NP-complete. All the problems we mentioned in the previous paragraph happen to be NP-complete, as are most, but not all, practical problems in NP which are not known to be in P.

    “If you show that just one NP-complete problem is in P — say, by coming up with an efficient algorithm for it — it would imply that all NP problems are in P, and therefore P=NP. In ‘Lord of the Rings’ parlance, there is one algorithm that rules them all! Conversely, if you show that just one NP-complete problem is not in P by ruling out an efficient algorithm somehow, then none of the NP-complete problems are in P, and P does not equal NP. This drastic dichotomy is the essence of the P versus NP question: We either live in a world where most computational tasks that so far elude us are in fact efficiently solvable, or we live in a world where almost none of them are. There is no gray area here!

    “Let us reflect for a moment on the meaning behind the P versus NP question. Many, if not most, of the tasks humans would like to perform, whether in science, engineering, planning or whatever walk of life, can be posed as a problem in NP: Find me a plan or design or idea that satisfies these easily recognizable criteria, if such a thing exists. Typically, we think of many such tasks as requiring a certain degree of ‘ingenuity’ to successfully complete, even though no ingenuity is required to recognize a successful solution once found. We tend to view ingenuity as an amorphous human trait that cannot be pinned down by some well-described formula or algorithm.

    “The P versus NP question can be viewed as asking whether such ingenuity can be automated. This is quite a profound question about the nature of reality. Most working computer scientists, if pressed to make a guess, would put their money on No, P does not equal NP. More likely, this ‘algorithm that rules them all’ does not exist, though a proof of this might require deep and complicated mathematics yet to be invented. That said, algorithms have historically often surprised us, so one cannot be too sure!”

    — Shaddin Dughmi is USC Viterbi associate professor of computer science.


  4. What do all these UFO videos tell us about the likelihood of aliens?

    “As intriguing as they are, UFO video clips made available to the public reveal very little to confirm or deny aliens or other extraterrestrial agents operating in our domain. But it is important to remember that all nations worry about their common defense and will not reveal, let alone exchange, any credible information regarding strange or unexplainable happenings they see as potential threats to the establishment. Since we are a curious species by nature, we continue to wonder and search for life and fellow beings elsewhere in the cosmos. However, our current technologies and skills are inadequate to fully appreciate or understand the inner workings of life and our own biosphere, let alone others. As we are becoming more aware of the stupendous energetics involved in cosmic phenomena, we are also experiencing the adverse effects of three centuries of human industrial activity on nature. That may offer some clues to the alien mystery, perhaps.

    “I think someday we will meet, greet and conference with aliens when our sciences and technologies are evolved enough to interact with the much older civilizations in our galactic neighborhood and beyond that have thoroughly mastered the art and science of living in harmony with nature.”

    Madhu Thangavelu, a USC Viterbi lecturer in astronautical engineering, is an expert in the design of complex space projects, including space stations and exploratory missions.


  5. What is our best hope to cure cancer?

    “Traditionally, surgery, chemotherapy and radiation therapy are the main methods to treat cancer. Small molecule compounds targeting specific molecular events have also become prevalent for cancer therapies. However, these treatments typically lack a high precision and can cause severe side effects.

    “In the past decades, large biological molecules such as antibodies have become promising as effective therapeutics for various diseases, including cancer. In particular, antibodies triggering the patient’s immune system to attack tumors have demonstrated their power in shrinking and even eradicating tumors in a small percentage of patients. With the new ‘living drug’ approach, chimeric antigen receptor (CAR) T immune cells show potential as paradigm-shifting therapeutic agents for cancer treatment by generating memory T-cells that can last for years, suppressing cancer relapse.

    “CAR T has had remarkable success in treating blood cancers. However, life-threatening activities against normal, nonmalignant cells and tissues are major problems that must be overcome to improve the cell-based immunotherapy for broad applications toward solid tumors. It is expected that engineering approaches to develop genetically engineered immune cells, precisely controllable in space and time, will open new opportunities to bring about successful treatment for a broad range of cancers, including solid tumors.”

    — Peter Yingxiao Wang, chair of the Alfred E. Mann Department of Biomedical Engineering, is an expert in precision medicine, including controllable engineered cells that can directly target tumors.


  6. What happened to Malaysian Airlines Flight 370 (MH370), which vanished in 2014 with 239 passengers aboard?

    “I have two competing hypotheses based on my experience teaching Human Factors in Aviation Safety for many years at the 70-year-old, world-renowned USC Aviation Safety and Security Program.

  • MH370 suffered from a consequential ‘common mode failure,’ possibly caused by an in-flight power outage. That could have led to a malfunction of some of the aircraft’s critical systems, such as the flight management system, one of which resulted in a similar phenomenon to Helios Airways Flight 522 on August 14, 2005, with uncontrolled decompression leading to hypoxia of crew and passengers — lack of consciousness, no communication, no human in control of flight and crash.
  • Malaysia issued a major Safety Investigation Report on the disappearance of MH370 on July 2, 2018, that confirmed that the aircraft was flown manually as it performed a series of turns across the Malaysian Peninsula. However, the mental state of the crew is one of the human factors involved in that accident that was left out of this report. There is a hypothesis that MH370 Captain Zaharie Ahmad Shah, just like Germanwings Flight 9525 co-pilot Andreas Lubitz in 2015, deliberately caused the crash in a suicidal act. This idea is based on the confluence of facts and frequent updates posted on the reliable website Airlines Ratings by my old friend and prominent Australian aviation analyst and writer Geoffrey Thomas, who is a treasure trove of civil aviation-related information and has been following the MH370 from the very day it was lost on March 8, 2014.

“It is expected that a new undersea search will get underway in 2023 in a new location just outside the area that has already been searched. I hope that with the discovery of the cockpit voice recorder and flight data recorder, the mystery of MH370 will be resolved.”

— Najmedin Meshkati is a professor of civil and environmental engineering, industrial systems engineering, and international relations.


  1. Will people ever travel to other stars?

    “The biggest unsolved mystery in astronautics is reaching exceptionally high speeds of space vehicles, constituting a significant fraction of the speed of light. Such capabilities are crucial for travel to other stars and for settling in attractive places in our galaxy.

    “Learning from unidentified flying objects does not help. Perhaps to the dismay of many, more than one-half of ‘sightings’ of UFOs in the late 1950s and most of the similar events in the 1960s could be attributed to flights of the U-2 and A-12 (SR-71) aircraft. There is no reason to think that much of the excitement in the later years was fundamentally different from the earlier events. My dream of being kidnapped by aliens for in-person learning from them has not materialized.

    “How will we make interstellar flight possible? Nobody knows today. What we do know, however, is that the required breakthrough in physics could only be achieved by promoting excellence in a merit-based environment. It is engineering that will bring us to a flight deck of a starship, not a social engineering that, as history teaches us, is a sure road to mediocrity.”

    — Mike Gruntman, a professor of astronautics and aerospace and mechanical engineering, researches spacecraft and space mission design.


  2. Who is the mysterious founder of bitcoin?

    “It was Halloween, Friday, October 31, just a month after the start of the financial crisis of 2008. A post was made on a cryptography mailing list of several hundred users interested in cryptographic technology and its political impact. The post linked a white paper titled Bitcoin: A Peer-to-peer Electronic Cash System, authored by someone named Satoshi Nakamoto, which later turned out to be a pseudonym. What it described was a protocol with a native token called bitcoin that could be used to transact peer to peer.

    “What Nakamoto invented is nothing short of an engineering marvel. He, she or they succeeded where decades of efforts to invent digital cash had failed.

    “Who is Satoshi Nakamoto? Nakamoto never publicly revealed their identity. We assume that Satoshi Nakamoto is a pseudonym. Since Satoshi is a masculine name in Japanese, this article uses the male pronoun. However, Nakamoto could be a person of any gender or even a group of authors. Several prominent cryptographers, engineers and public figures have been rumored to be Nakamoto: Nick Szabo, a computer scientist and inventor of Bit Gold; Hal Finney, a computer scientist; Wei Dai, inventor of B-money; Dorain Satoshi Nakamoto, an engineer; Len Sassman, a ‘cypherpunk’; and Adam Back, a cryptographer. And there are many others. Was any one of these Satoshi Nakamoto? Or a group of people? How can we unearth their true identity?

    “The bitcoin protocol itself must be anonymous or pseudonymous because its ledger, the blockchain, is public. Such a ledger must not reveal the true identity of owners of bitcoin and thereby the owners’ wealth. Therefore, owners are identified by cryptographic addresses, which is their pseudonym on the blockchain. Similarly, Nakamoto took clever steps to hide their identity, in line with the pseudonymous nature of bitcoin. He, she or they were active in the burgeoning bitcoin community for some time, then disappeared after posting a public message in late 2010. Satoshi Nakamoto has not been heard from since.

    “To try to unravel the mystery of Nakamoto’s identity, one can compare the workings of bitcoin to those of previous works by known cryptographers and computer scientists. Wei Dai and Nick Szabo’s proposals for B-money and Bit Gold come pretty close to bitcoin. But their proposals were never implemented in code.

    “Nakamoto never posted any photos or speech samples. Also, no geolocation information is available. There are time stamps of their postings that could lead to time zones or even possible countries of origin. Nakamoto’s email address on the white paper is listed as GMX is a free German encrypted email provider with a focus on privacy and security.

    “Nakamoto wrote the course code for bitcoin in C++, and transactions are in a language called Script, which is like Forth. Forth is a stack-based language from the 1970s, leading us to believe that Nakamoto might be over 40 or 50 years old. Another clue is that the white paper has words that use American spellings (e.g., characterized instead of characterised ) and others that use British spellings (e.g., flavour instead of flavor). Did he do this on purpose to throw curious people off his trail? Or was the white paper written by several authors?

    “People have done linguistic analysis of his writings and compared them to those of potential candidates for the identity of Nakamoto. Some papers conclude that the most likely candidate is Nick Szabo, which he has denied publicly.

    “So, we are back to square — or should I say, block — one. Anyone who is identified as Nakamoto will most likely deny it. Anyone claiming to be him or her would need to produce proof of their identity by signing a message with a Nakamoto key, or at the very least that they had access to a Nakamoto key. That would be a good start to put a face to the famous pseudonym.

    “Until then, we are mired in this crypto mystery. Where is Sherlock Holmes when you need him?”

    — Nitin Kalé is a USC Viterbi professor of information technology practice and industrial and systems engineering practice.


  3. How do we prevent a cyber Pearl Harbor?

    “The analogy to a Pearl Harbor attack has been used in a variety of discussions around national-level cybersecurity vulnerabilities. The term has been around for decades and was popularized in 2012 by U.S. Defense Secretary Leon E. Panetta. The term is used to describe the potential for a cyber-based attack of the magnitude and with the surprise factor as was seen in the 1941 Japanese naval attack on Pearl Harbor.

    “Conceptually, a devastating national-level cyberattack would likely involve multiple digital-driven critical infrastructures. These may span commercial, energy, transportation, water and power and the Department of Defense. Such an attack spanning multiple sectors is hypothesized to render large portions of society inoperative, as disruptions occur through a cascading series of attacks.

    “So how do we prevent a cyber Pearl Harbor? There is good news and bad news. While any given set of critical infrastructure likely contains some vulnerabilities, achieving a Pearl Harbor effect depends on coordination, timing and triggering of cascading effects, which require careful planning and deployment of insiders. This means that we can and do see isolated attacks but are unlikely to see a Pearl Harbor that is primarily cyber-based. Kinetic attacks require far less effort. Ongoing research, development and commercial products, along with policies and practices, are raising the bar. In reality, the cost of the work effort outweighs the expected results. This does not mean that we are safe, but rather that we need to continue work on all fronts to invest in prevention, detection and response across collections of vulnerable resources critical to our nation to prevent the attacks that impact our economy and productivity. Furthermore, this work requires more than technical cybersecurity; it must include social, human behavior and coordinated physical protections.

    “Finally, framing national-level cyber threats as a potential Pearl Harbor may be a disservice to the community. This analogy creates fear, uncertainty and doubt, may place too much emphasis on the DoD’s role, and removes focus from cyber social misinformation and cyber manipulations such as the role of Russia in the 2016 elections.

    “Preventing cyber Pearl Harbor just might not be the right question.”

    — Terry Benzel is associate director, USC Information Sciences Institute (ISI), and director, Networking and Cybersecurity Division.


  4. Can human explorers survive the radiation of other planets?

    “My particular discipline is human spaceflight, and as we gear up to travel beyond Earth orbit again, the biggest unsolved mystery is what effect the radiation environment outside the Earth’s magnetic field will have long term on the human body. We know exactly what type of radiation is out there, but we do not know exactly what that radiation does to human tissue. Figuring that out will be key to human exploration missions in deep space.

    “How to resolve this? We need to go there and see what happens! The safe way to do this is to do it incrementally, with longer and longer missions to the lunar surface. But it will take a long time to get the long-term data we need on human health. The other option is to just take larger risks and jump right to multiple-year missions to Mars.”

    — Garrett Reisman, a former NASA astronaut, is a USC Viterbi professor of astronautics practice.