Archive for the ‘Uncategorized’ Category

by Morgan McFall-Johnsen

The NASA scientist Jessie Christiansen made a video that traces our solar system’s movement through the Milky Way as dinosaurs emerged, went extinct, and were replaced by mammals on Earth.

Our sun orbits the galaxy’s center, so many dinosaurs roamed the Earth while the planet was on the other side of the Milky Way.

Our solar system’s orbit keeps us just the right distance from the galaxy’s chaotic center for life to exist.

When dinosaurs ruled the Earth, the planet was on a completely different side of the galaxy.

A new animation by the NASA scientist Jessie Christiansen shows just how long the dinosaurs’ reign lasted — and how short the era of humans has been in comparison — by tracing our solar system’s movement through the Milky Way.

Our sun orbits the galaxy’s center, completing its rotation every 250 million years or so. So Christiansen’s animation shows that the last time our solar system was at its current point in the galaxy, the Triassic period was in full swing and dinosaurs were just emerging. Many of the most iconic dinosaurs roamed the Earth when the planet was in a very different part of the Milky Way.

Christiansen got the idea to illustrate this history when she was leading a stargazing party at the California Institute of Technology in Pasadena. Attendees were astonished when she mentioned that our solar system was across the galaxy when dinosaurs roamed.

“That was the first time I realized that those time scales — archaeological, fossil-record time scales and astronomical time scales — actually kind of match along together,” Christiansen told Business Insider. “Then I had this idea that I could map out dinosaur evolution through the galaxy’s rotation.”

Christiansen said it took her about four hours to make the film using timed animations in PowerPoint. She also noted a couple of minor corrections to the text in her video: Plesiosaurs are not dinosaurs, and we complete a galactic orbit every 250 million years, not 200 million years.

‘A spiral through space’

But galactic movement is more complicated than the video shows. The other stars and planetary systems in the galaxy are also moving, at different speeds and in different orbits. The inner portions spin faster than the outer regions.

What’s more, the galaxy itself is moving through space, slowly approaching the nearby Andromeda galaxy.

“The animation kind of makes it seem like we’ve come back to the same spot, but in reality the whole galaxy has moved a very long way,” Christiansen said. “It’s more like we’re doing a spiral through space. As the whole galaxy’s moving and we’re rotating around the center, it kind of creates this spiral.”

So in the solar system’s rotation around the galactic center, we’re not returning to a fixed point. The neighborhood is different from the last time we were here.

Earth, however, is not drastically different; it still supports complex life. That’s partially thanks to the path of our sun’s galactic orbit.

“Our solar system doesn’t travel to the center of the galaxy and then back again,” Christiansen said. “We always stay about this distance away.”

In other words, even as our solar system travels through the Milky Way, it doesn’t approach the inhospitable center, where life probably wouldn’t survive.

“There’s a lot of stars, it’s dynamically unstable, there’s a lot of radiation,” Christiansen said. “Our solar system certainly doesn’t pass through that.”

That’s a huge part of why dinosaurs, mammals, or any other form of life can exist on Earth.

https://www.businessinsider.com/video-nasa-scientist-dinosaurs-milky-way-2019-10

by NICOLETTA LANESE

Kent Kiehl and his research team regularly park their long, white trailer just outside the doors of maximum-security prisons across the US. Inside the vehicle sits the bulky body of a mobile MRI machine. During each visit, people from the prison make their way to and from the vehicle in hourly shifts to have their brains scanned and help to answer an age-old question: What makes a murderer?

“It’s not an uncommon thing for [incarcerated people], while they’re getting a scan, to be like, ‘I’ve always been different. Can you tell me why I’ve always been so different?’” says Kiehl, a neuroscientist at the University of New Mexico and the Albuquerque-based nonprofit Mind Research Network (MRN) who helped design the mobile MRI system back in the early 2000s.


SCAN-MOBILE: Kiehl and his colleagues made more than 75 modifications to a trailer and the MRI system inside to outfit both for the team’s unique research.

The author of The Psychopath Whisperer: The Science of Those Without a Conscience, Kiehl has been fascinated by the criminal mind since he was an undergraduate at the University of California, Davis. Now, as director of mobile imaging at MRN, he oversees efforts to gather brain scans from thousands of people held in US prisons to learn what features, if any, might differ from scans of the general population.

This massive dataset recently allowed Kiehl to examine the brain structures of more than 800 men held in state prisons in New Mexico and Wisconsin in an attempt to distinguish incarcerated people who have committed homicide from those who have committed other crimes.

First, Kiehl and his colleagues laboriously sorted the pool of people who had volunteered for the study into three categories based on their crimes: homicide, violent offenses that were not homicide, or non-violent or minimally violent transgressions. The team relied on official convictions, self-reported homicides, and confidential interviews with participants to determine who attempted or committed murder—both offenses that got a “homicide” label in their dataset.

People charged with felony murder—meaning that they had committed a serious felony that was in some way connected to a person’s death, even though they hadn’t intended to kill the victim—and people whose cases indicated considerable doubt about a judgment of homicide were not counted among murderers. And occasionally, people were moved from another category into the homicide group, Kiehl says. The researchers excluded people with abnormal radiology reports, traumatic brain injury, or diagnosed psychotic disorders from the study.

Controlling for substance use severity, time in prison, age, and IQ, the team analyzed the MRI data to look for differences among the study participants. Compared with the other two groups, the 200 men who had committed homicide showed significantly reduced gray matter in several brain regions that play important roles in behavioral control and social cognition.

“I think that the intriguing thing was, first, that they found a difference,” says Hannes Vogel, a neuropathologist at Stanford University Medical Center who was not involved in the work. “And second of all, that it correlates with some of the brain centers that deal with behavior and social interaction.”

Lora Cope, a neuroscientist who studies substance disorders at the University of Michigan, notes in an email to The Scientist that the team’s mobile MRI system has now been used in correctional facilities all over New Mexico and Wisconsin, and “has really revolutionized this area of research.” Indeed, the MRN has now used the equipment to collect roughly 6,500 scans from more than 3,000 research participants since its first outing in 2007.

Although Cope wasn’t involved in the current project, she worked with Kiehl a few years ago while earning her doctorate at the University of New Mexico. After speaking with members of the Avielle Foundation, named for a six-year-old victim of the 2012 Sandy Hook Elementary School shooting, the two researchers spearheaded a study of more than 150 incarcerated young males, 20 of whom had been convicted of homicide, held at a maximum-security detention facility within the state. “Jeremy, [Avielle’s] father, really wanted to know if there was anything neuroscience could tell us about boys who commit homicide,” says Kiehl.

As in the current study, Cope and Kiehl deployed the mobile scanner to collect MRI scans of the incarcerated teens in New Mexico and discovered differences between those who had committed homicide and their imprisoned peers. The homicide offenders “had significantly less gray matter volume in parts of their temporal lobes,” Cope says. When Kiel compared the data from that study with the results of his latest project, he found a high degree of overlap. “Lo and behold . . . we found and replicated every region that was different in the boys and was different in the adult males, and in the same way,” he says.

The latest study’s finding that MRI data can distinguish homicide offenders not only from people who committed non-violent crimes, but also from those who performed other violent crimes, is particularly interesting, says Harold Koenigsberg, a psychiatrist at Icahn School of Medicine at Mount Sinai. “I would have thought there would be more of an overlap between [homicide and violent non-homicide offenders],” he says. “I’m surprised that it was so specific to homicide.”


ANATOMY OF A MURDERER: Homicide offenders exhibited reduced gray matter density compared with other violent offenders in the regions of the brain highlighted blue and green above.

Koenigsberg notes that homicidal violence can itself be split into two categories: impulsive and instrumental. Impulsive violence is born of unbridled emotions and overblown reactions, a brand of behavior linked to poor frontal lobe functioning and abnormal serotonin levels. Instrumental violence, on the other hand, is premeditated and is associated with other brain changes, such as reduced amygdala activation during emotion processing. “These two groups, we think that they have different biologies,” says Koenigsberg. Kiehl’s dataset could be enriched by adding measures of neurotransmitter release and electrical activity, along with related behavioral assessments, he suggests, and with both functional and structural data, psychologists might learn more about what gives rise to these distinct behavioral phenotypes.

Koenigsberg, Vogel, and Kiehl all note that the structural data collected in the current study cannot on its own be used to predict who has committed homicide, let alone who might in the future. Nonetheless, the paper may find its way into the courtroom, says Vogel. If lawyers felt so inclined, they could try to “find an expert on one side who will quote this [paper]” in defense of someone who has committed a homicide, by arguing a client’s actions were due to brain abnormalities and thus out of his or her control. Or, a prosecutor could potentially use the paper to argue that MRI findings should be admissible as evidence that a defendant has committed a homicide, says Vogel, who has served as a consultant for court cases in California and Nevada, and helped investigate the brain of the Route 91 Harvest music festival shooter in 2017. “But then you’re [also] going to find an expert that will tear that [testimony] to pieces.”

Kiehl notes that his MRI study could also someday contribute to new evidence-based measures of homicidal risk. These measures could supplement current measures of violent behavior, such as psychological questionnaires, if future studies demonstrated they carried predictive weight, he says. Beyond courts of law, he also suggests that understanding how violent behavior arises could pave the way to better psychological treatment aimed at both rehabilitation and prevention.

https://www.the-scientist.com/notebook/secrets-in-the-brains-of-people-who-have-committed-murder-66589



Researchers found that a black-box algorithm predicted patient death better than humans.

They used ECG results to sort historical patient data into groups based on who would die within a year.

Although the algorithm performed better, scientists don’t understand how or why it did.

Albert Einstein’s famous expression “spooky action at a distance” refers to quantum entanglement, a phenomenon seen on the most micro of scales. But machine learning seems to grow more mysterious and powerful every day, and scientists don’t always understand how it works. The spookiest action yet is a new study of heart patients where a machine-learning algorithm decided who was most likely to die within a year based on echocardiogram (ECG) results, reported by New Scientist.

The algorithm performed better than the traditional measures used by cardiologists. The study was done by researchers in Pennsylvania’s Geisinger regional healthcare group, a low-cost and not-for-profit provider.

Much of machine learning involves feeding complex data into computers that are better able to examine it really closely. To analogize to calculus, if human reasoning is a Riemann sum, machine learning may be the integral that results as the Riemann calculation approaches infinity. Human doctors do the best they can with what they have, but whatever the ECG algorithm is finding in the data, those studying the algorithm can’t reverse engineer what it is.

The most surprising axis may be the number of people cardiologists believed were healthy based on normal ECG results: “The AI accurately predicted risk of death even in people deemed by cardiologists to have a normal ECG,” New Scientist reports.

To imitate the decision-making of individual cardiologists, the Geisinger team made a parallel algorithm out of the factors that cardiologists use to calculate risk in the accepted way. It’s not practical to record the individual impressions of 400,000 real human doctors instead of the results of the algorithm, but that level of granularity could show that cardiologists are more able to predict poor outcomes than the algorithm indicates.

It could also show they perform worse than the algorithm—we just don’t know. Head to head, having a better algorithm could add to doctors’ human skillset and lead to even better outcomes for at-risk patients.

Machine learning experts use a metric called area under the curve (AUC) to measure how well their algorithm can sort people into different groups. In this case, researchers programmed the algorithm to decide which people would survive and which would die within the year, and its success was measured in how many people it placed in the correct groups. This is why future action is so complicated: People can be misplaced in both directions, leading to false positives and false negatives that could impact treatment. The algorithm did show an improvement, scoring 85 percent versus the 65 to 80 percent success rate of the traditional calculus.

As in other studies, one flaw in this research is that the scientists used past data where the one-year window had finished. The data set is closed and scientists can directly compare their results to a certain outcome. There’s a difference—and in medicine it’s an ethical one—between studying closed data and using a mysterious, unstudied mechanism to change how we treat patients today.

Medical research faces the same ethical hurdles across the board. What if intervening based on machine learning changes outcomes and saves lives? Is it ever right to treat one group of patients better than a control group that receives less effective care? These obstacles make a big difference in how future studies will pursue the results of this study. If the phenomenon of better prediction holds up, it may be decades before patients are treated differently.

https://www.popularmechanics.com/science/health/a29762613/ai-predict-death-health/

Biology encodes information in DNA and RNA, which are complex molecules finely tuned to their functions. But are they the only way to store hereditary molecular information? Some scientists believe life as we know it could not have existed before there were nucleic acids, thus understanding how they came to exist on the primitive Earth is a fundamental goal of basic research. The central role of nucleic acids in biological information flow also makes them key targets for pharmaceutical research, and synthetic molecules mimicking nucleic acids form the basis of many treatments for viral diseases, including HIV. Other nucleic acid-like polymers are known, yet much remains unknown regarding possible alternatives for hereditary information storage. Using sophisticated computational methods, scientists from the Earth-Life Science Institute (ELSI) at the Tokyo Institute of Technology, the German Aerospace Center (DLR) and Emory University explored the “chemical neighbourhood” of nucleic acid analogues. Surprisingly, they found well over a million variants, suggesting a vast unexplored universe of chemistry relevant to pharmacology, biochemistry and efforts to understand the origins of life. The molecules revealed by this study could be further modified to gives hundreds of millions of potential pharmaceutical drug leads.

Nucleic acids were first identified in the 19th century, but their composition, biological role and function were not understood by scientists until the 20th century. The discovery of DNA’s double-helical structure by Watson and Crick in 1953 revealed a simple explanation for how biology and evolution function. All living things on Earth store information in DNA, which consists of two polymer strands wrapped around each other like a caduceus, with each strand being the complement of the other. When the strands are pulled apart, copying the complement on either template results in two copies of the original. The DNA polymer itself is composed of a sequence of “letters”, the bases adenine (A), guanine (G), cytosine (C) and thymine (T), and living organisms have evolved ways to make sure during DNA copying that the appropriate sequence of letters is almost always reproduced. The sequence of bases is copied into RNA by proteins, which then is read into a protein sequence. The proteins themselves then enable a wonderland of finely-tuned chemical processes which make life possible.

Small errors occasionally occur during DNA copying, and others are sometimes introduced by environmental mutagens. These small errors are the fodder for natural selection: some of these errors result in sequences which produce fitter organisms, though most have little effect, and many even prove lethal. The ability of new sequences to allow their hosts to better survive is the “ratchet” which allows biology to almost magically adapt to the constantly changing challenges the environment provides. This is the underlying reason for the kaleidoscope of biological forms we see around us, from humble bacteria to tigers, the information stored in nucleic acids allows for “memory” in biology. But are DNA and RNA the only way to store this information? Or are they perhaps just the best way, discovered only after millions of years of evolutionary tinkering?

“There are two kinds of nucleic acids in biology, and maybe 20 or 30 effective nucleic acid-binding nucleic acid analogues. We wanted to know if there is one more to be found or even a million more. The answer is, there seem to be many, many more than was expected,” says professor Jim Cleaves of ELSI.

Though biologists don’t consider them organisms, viruses also use nucleic acids to store their heritable information, though some viruses use a slight variant on DNA, RNA, as their molecular storage system. RNA differs from DNA in the presence of a single atom substitution, but overall RNA plays by very similar molecular rules as DNA. The remarkable thing is, among the incredible variety of organisms on Earth, these two molecules are essentially the only ones biology uses.

Biologists and chemists have long wondered why this should be. Are these the only molecules that could perform this function? If not, are they perhaps the best, that is to say, other molecules could play this role, and perhaps biology tried them out during evolution?

The central importance of nucleic acids in biology has also long made them drug targets for chemists. If a drug can inhibit the ability of an organism or virus to pass its knowledge of how to be infectious on to offspring, it effectively kills the organisms or virus. Mucking up the heredity of an organism or virus is a great way to knock it dead. Fortunately for chemists, and all of us, the cellular machinery which manages nucleic acid copying in each organism is slightly different, and in viruses often very different.

Organisms with large genomes, like humans, need to be very careful about copying their hereditary information and thus are very selective about not using the wrong precursors when copying their nucleic acids. Conversely, viruses, which generally have much smaller genomes, are much more tolerant of using similar, but slightly different molecules to copy themselves. This means chemicals that are similar to the building blocks of nucleic acids, known as nucleotides, can sometimes impair the biochemistry of one organism worse than another. Most of the important anti-viral drugs used today are nucleotide (or nucleoside, which are molecule differing by the removal of a phosphate group) analogues, including those used to treat HIV, herpes and viral hepatitis. Many important cancer drugs are also nucleotide or nucleoside analogues, as cancer cells sometimes have mutations that make them copy nucleic acids in unusual ways.

“Trying to understand the nature of heredity, and how else it might be embodied, is just about the most basic research one can do, but it also has some really important practical applications,” says co-author Chris Butch, formerly of ELSI and now a professor at Nanjing University.

Since most scientists believe the basis of biology is heritable information, without which natural selection would be impossible, evolutionary scientists studying the origins of life have also focused on ways of making DNA or RNA from simple chemicals that might have occurred spontaneously on primitive Earth. Once nucleic acids existed, many problems in the origins of life and early evolution would make sense. Most scientists think RNA evolved before DNA, and for subtle chemical reasons which make DNA much more stable than RNA, DNA became life’s hard disk. However, research in the 1960s soon split the theoretical origins field in two: those who saw RNA as the simple “Occam’s Razor” answer to the origins-of-biology problem and those who saw the many kinks in the armour of RNA’s abiological synthesis. RNA is still a complicated molecule, and it is possible structurally simpler molecules could have served in its place before it arose.

Co-author Dr. Jay Goodwin, a chemist with Emory University says “It is truly exciting to consider the potential for alternate genetic systems, based on these analogous nucleosides – that these might possibly have emerged and evolved in different environments, perhaps even on other planets or moons within our solar system. These alternate genetic systems might expand our conception of biology’s ‘central dogma’ into new evolutionary directions, in response and robust to increasingly challenging environments here on Earth.”

Examining all of these basic questions, which molecule came first, what is unique about RNA and DNA, all at once by physically making molecules in the laboratory, is difficult. On the other hand, computing molecules before making them could potentially save chemists a lot of time. “We were surprised by the outcome of this computation,” says co-author Dr. Markus Meringer, “it would be very difficult to estimate a priori that there are more than a million nucleic-acid like scaffolds. Now we know, and we can start looking into testing some of these in the lab.”

“It is absolutely fascinating to think that by using modern computational techniques we might stumble upon new drugs when searching for alternative molecules to DNA and RNA that can store hereditary information. It is cross-disciplinary studies such as this that make science challenging and fun yet impactful,” says co-author Dr. Pieter Burger, also of Emory University.

###

Reference:

Henderson James Cleaves, II*1,2,3, Christopher Butch1,3,4, Pieter Buys Burger4, Jay Goodwin4, and Markus Meringer5, One Among Millions: The Chemical Space of Nucleic Acid-Like Molecules, Journal of Chemical Information and Modeling, DOI: 10.1021/acs.jcim.9b00632

1. Earth-Life Science Institute, Tokyo Institute of Technology, 2-12-IE-1 Ookayama, Meguro-ku, Tokyo 152-8551, Japan
2. Institute for Advanced Study, Princeton, New Jersey 08540, United States

3. Blue Marble Space Institute for Science, 1515 Gallatin St. NW, Washington, DC 20011, United States

4. Department of Chemistry, Emory University, 1515 Dickey Dr., Atlanta, Georgia 30322, United States

5. German Aerospace Center (DLR), Earth Observation Center (EOC), Münchner Straße 20, 82234 Oberpfaffenhofen-Wessling, Germany

https://www.eurekalert.org/pub_releases/2019-11/tiot-dio103119.php

By SUSANNE RUST

Five thousand miles west of Los Angeles and 500 miles north of the equator, on a far-flung spit of white coral sand in the central Pacific, a massive, aging and weathered concrete dome bobs up and down with the tide.

Here in the Marshall Islands, Runit Dome holds more than 3.1 million cubic feet — or 35 Olympic-sized swimming pools — of U.S.-produced radioactive soil and debris, including lethal amounts of plutonium. Nowhere else has the United States saddled another country with so much of its nuclear waste, a product of its Cold War atomic testing program.

Between 1946 and 1958, the United States detonated 67 nuclear bombs on, in and above the Marshall Islands — vaporizing whole islands, carving craters into its shallow lagoons and exiling hundreds of people from their homes.

U.S. authorities later cleaned up contaminated soil on Enewetak Atoll, where the United States not only detonated the bulk of its weapons tests but, as The Times has learned, also conducted a dozen biological weapons tests and dumped 130 tons of soil from an irradiated Nevada testing site. It then deposited the atoll’s most lethal debris and soil into the dome.

Now the concrete coffin, which locals call “the Tomb,” is at risk of collapsing from rising seas and other effects of climate change. Tides are creeping up its sides, advancing higher every year as distant glaciers melt and ocean waters rise.

Officials in the Marshall Islands have lobbied the U.S. government for help, but American officials have declined, saying the dome is on Marshallese land and therefore the responsibility of the Marshallese government.

“I’m like, how can it [the dome] be ours?” Hilda Heine, the president of the Republic of the Marshall Islands, said in an interview in her presidential office in September. “We don’t want it. We didn’t build it. The garbage inside is not ours. It’s theirs.”

To many in the Republic of the Marshall Islands, Runit Dome is the most visible manifestation of the United States’ nuclear legacy, a symbol of the sacrifices the Marshallese made for U.S. security, and the broken promises they received in return.

They blame the United States and other industrialized countries for global climate change and sea level rise, which threaten to submerge vast swaths of this island nation’s 29 low-lying atolls.

Over the last 15 months, a reporting team from the Los Angeles Times and Columbia University’s Graduate School of Journalism made five trips to the Marshall Islands, where they documented extensive coral bleaching, fish kills and algae blooms — as well as major disease outbreaks, including the nation’s largest recorded epidemic of dengue fever. They interviewed folk singers who lost their voices to thyroid cancers and spent time in Arkansas, Washington and Oregon, where tens of thousands of Marshallese have migrated to escape poverty and an uncertain future.

Marshallese leaders acknowledge that America doesn’t bear full responsibility for their nation’s distress. But they say the United States has failed to take ownership of the environmental catastrophe it left behind, and they claim U.S. authorities have repeatedly deceived them about the magnitude and extent of that devastation.

A Times review of thousands of documents, and interviews with U.S. and Marshallese officials, found that the American government withheld key pieces of information about the dome’s contents and its weapons testing program before the two countries signed a compact in 1986 releasing the U.S. government from further liability. One example: The United States did not tell the Marshallese that in 1958, it shipped 130 tons of soil from its atomic testing grounds in Nevada to the Marshall Islands.

U.S. authorities also didn’t inform people in Enewetak, where the waste site is located, that they’d conducted a dozen biological weapons tests in the atoll, including experiments with an aerosolized bacteria designed to kill enemy troops.

U.S. Department of Energy experts are encouraging the Marshallese to move back to other parts of Enewetak, where 650 now live, after being relocated during the U.S. nuclear tests during the Cold War. But many Marshallese leaders no longer trust U.S. assurances of safety.

“We didn’t know the Runit Dome waste dump would crack and leak…. We didn’t know about climate change,” said Jack Ading, a Marshallese senator from Enewetak Atoll. “We weren’t nuclear scientists who could independently verify what the U.S. was telling us. We were just island people who desperately wanted to return home.”

Adding to the alarm is a study published this year by a team of Columbia University scientists showing levels of radiation in some spots in Enewetak and other parts of the Marshall Islands that rival those found near Chernobyl and Fukushima.

Such discoveries could give Marshallese leaders fresh ammunition to challenge the 1986 compact, which is up for renegotiation in 2023, and also to press the United States to honor property and health claims ordered by an international tribunal.

The tribunal, established by the two countries in 1988, concluded the United States should pay $2.3 billion in claims, but Congress and U.S courts have refused. Documents show the U.S. paid just $4 million.

The U.S. position is that it has already paid more than $600 million for the resettlement, rehabilitation and radiation-related healthcare costs of communities affected by the nuclear testing, said Karen Stewart, the U.S. ambassador to the Republic of the Marshall Islands. She said inflation brings the number closer to $1 billion.

“The United States recognizes the effects of its testing and has accepted and acted on its responsibility to the people of the Republic of the Marshall Islands,” Stewart said in a statement.

In September, the Marshallese parliament, the Nitijela, approved a national nuclear strategy, which calls for a risk analysis and environmental survey of Runit Dome, an assessment of legal options for its cleanup and a new attempt to secure the $2.3 billion ordered by the tribunal.

Last month, Marshall Islands lawmakers called on the international community to reduce greenhouse gases causing what they declared to be a “national climate crisis.”

China is taking an increasing interest in the Marshall Islands and other Pacific island nations, in part because of their strategic location and Beijing’s interest in reducing U.S. influence in the region. Those inroads by China have alarmed U.S. leaders, forcing them to pay more attention to the grievances of Marshallese leaders such as Heine.

“This heightened interest,” Heine said, “should bode well for us.”

From the U.S. mainland, it takes more than a day to fly to the Marshall Islands, and only one commercial airline makes the trip.

The “Island Hopper,” United Airlines Flight 154, starts at Honolulu, making stops in the Marshall Islands at Majuro and Kwajalein before heading west toward the Micronesian islands of Kosrae, Pohnpei and Chuuk, and finally terminating in Guam.

The next day, it doubles back.

As it approaches Majuro, the blue-scape of the ocean is broken by an oblong necklace of white-coral-beached islands, dotted with coconut, pandanus and breadfruit trees.

The Marshall Islands’ atolls are the remnants of ancient volcanoes that once protruded from these cerulean seas. They were settled 3,000 years ago by the ancestors of present-day Marshallese who crossed the ocean on boats from Asia and Polynesia. For American officials in the mid-1940s, this 750,000-square-mile expanse of ocean, nearly five times larger than the state of California, must have seemed like a near-perfect spot to test their growing atomic arsenal.

“The Marshall Islands were selected as ground zero for nuclear testing precisely because colonial narratives portrayed the islands as small, remote and unimportant,” said Autumn Bordner, a former researcher at Columbia University’s K=1 Project, which has focused on the legacy of nuclear testing in the Marshall Islands, and now a research fellow in ocean law and policy at UC Berkeley’s Center for Law, Energy & the Environment.

Nerje Joseph, 72, was a witness to the largest thermonuclear bomb tested by the United States: the Castle Bravo detonation. She was 7 years old at the time, living with her family in Rongelap Atoll, 100 miles east of Bikini Atoll — a tropical lagoon commandeered for nuclear testing.

On March 1, 1954, Joseph recalls waking up and seeing two suns rising over Rongelap. First there was the usual sun, topping the horizon in the east and bringing light and warmth to the tropical lagoon near her home. Then there was another sun, rising from the western sky. It lighted up the horizon, shining orange at first, then turning pink, then disappearing as if it had never been there at all.

Joseph and the 63 others on Rongelap had no idea what they had just witnessed. Hours later, the fallout from Castle Bravo rained down like snow on their homes, contaminating their skin, water and food.

According to Joseph and government documents, U.S. authorities came to evacuate the Rongelapese two days later. By that time, some islanders were beginning to suffer from acute radiation poisoning — their hair fell out in clumps, their skin was burned, and they were vomiting.


Nerje Joseph, 72, was 7 years old when the United States detonated its largest nuclear bomb. The Castle Bravo test sent a mushroom cloud into the sky and unexpectedly irradiated parts of the northern Marshall Islands that she and her family called home.

“More than any other place, the Marshall Islands is a victim of the two greatest threats facing humanity — nuclear weapons and climate change,” said Michael Gerrard, a legal scholar at Columbia University’s law school. “The United States is entirely responsible for the nuclear testing there, and its emissions have contributed more to climate change than those from any other country.”

The Castle Bravo test and others in the Marshall Islands helped the U.S. establish the credibility of its nuclear arsenal as it raced against its Cold War adversary, the Soviet Union, to develop new atomic weapons. But the testing came at a horrible price; Joseph and other Marshallese ended up becoming human guinea pigs for U.S. radiation research.

Three years after Castle Bravo, U.S. authorities encouraged Joseph, her family and her neighbors to return to Rongelap.

U.S. government documents from the time show that officials weighed the potential hazards of radiation exposure against “the current low morale of the natives” and a “risk of an onset of indolence.” Ultimately they decided to go forward with the resettlement so researchers could study the effects of lingering radiation on human beings.

“Data of this type has never been available,” Merrill Eisenbud, a U.S official with the Atomic Energy Commission, said at a January 1956 meeting of the agency’s Biology and Medicine Committee. “While it is true that these people do not live the way that Westerners do, civilized people, it is nonetheless also true that they are more like us than the mice.”

The resettlement proved catastrophic for the people of Rongelap. Cancer cases, miscarriages and deformities multiplied. Ten years later, in 1967, 17 of the 19 children who were younger than 10 and on the island the day Bravo exploded had developed thyroid disorders and growths. One child died of leukemia.

In 1985, the people of Rongelap asked Greenpeace to evacuate them again after the United States refused to relocate them or to acknowledge their exposure, according to government documents and news reports from the time.

Joseph, who had her thyroid removed because of her radiation exposure, has spent nearly seven decades taking daily thyroid medication, enabling her body to produce hormones it otherwise would not generate.

A quiet, dignified woman with thick, wavy gray hair, Joseph lives in a cinder-block home in Majuro, the capital, a setting far different from the pristine atoll where she grew up.

Composed of three low-lying islands connected by one flood-prone road, Majuro is long and narrow and home to roughly half the population of the Marshall Islands, about 28,000 people. Taxis crawl the length of this lone road, fitting as many riders into their vehicles as they can accommodate. Visitors opting to walk are encouraged to carry long sticks to beat away packs of feral dogs that roam the streets.

Joseph says she misses her home, but she knows she may never go back.

“We had a oneness when we lived on Rongelap,” she said of her childhood. “We worked together, we ate together, we played together. That has been lost.”

The legacy of the testing program is most evident at Enewetak, an atoll that took the brunt of the United States’ late-stage nuclear detonations before an international ban on atmospheric testing in 1963.

A string of 40 islands to the west of Bikini, Enewetak was once a postcard-perfect ring of coral reefs, white-sand beaches and coconut trees, where roughly 450 dri-Enewetak and dri-Enjebi — the two clans that lived in the atoll — gathered breadfruit and pandanus, and harvested fish and clams from the lagoon.

Between 1948 and 1958, the U.S. military detonated 43 atomic bombs here. After agreeing to a 1958 temporary moratorium on nuclear testing with the United Kingdom and the Soviet Union, the U.S. began using the atoll as a conventional and bioweapons testing ground. For the next 18 years, the U.S. shot ballistic missiles at it from California, tested virulent forms of bacteria on its islands and detonated a series of other large, conventional bombs in the lagoon.

In 1972, after the U.S had nearly exhausted its military interest in the region, it invited the leaders of Enewetak back to see the atoll for the first time since 1946.

According to a Department of Energy report of the event, the Enewetak leaders “were deeply gratified to be able to visit their ancestral homeland, but they were mortified by what they saw.”

The islands were completely denuded. Photos show an apocalyptic scene of windswept, deforested islands, with only the occasional coconut tree jutting up from the ground. Elsewhere, crumbling concrete structures, warped tarmac roads and abandoned construction and military equipment dotted the barren landscape.

The damage they saw on that visit was the result of nearly three decades of U.S. military testing.

The United States had detonated 35 bombs in the Marshall Islands in 112 days in 1958. Nine of these were on Enewetak’s Runit Island. With names such as Butternut, Holly and Magnolia, the bombs were detonated in the sky, underwater and on top of islands.

One test shot, Quince, misfired Aug. 6, 1958, and sprayed plutonium fuel across Runit Island. The Department of Defense and the Lawrence Livermore National Laboratory, which was sponsoring the test, ordered soldiers into the contaminated ground zero to prepare the site for the next bomb, 12 days later.

Soldiers swarmed in with bulldozers and earthmoving equipment, pushing the radioactive soil into big debris piles that they shoved into the lagoon, the ocean or possibly left alone; government reports differ on these details.

What is clear, and which has never been reported before, is that 130 tons of soil transported 5,300 miles from an atomic test site in Nevada was dumped into a 30-foot-wide, 8-foot-deep “conical plug” where the next bomb, Fig, was detonated.

Archived documents suggest the soil was used as part of an experiment, to help scientists understand how soil types contribute to different blast impacts and crater sizes.

Terry Hamilton, a researcher at the Lawrence Livermore National Laboratory and today the Department of Energy’s point person on the Marshall Islands’ nuclear issues, said the soil was clean and taken from Area 10 at the Nevada Test Site. That area of the Nevada site had been the site of two nuclear blasts in 1951 and 1955, according to government records.

“It is appalling that the Marshallese people, and in particular the people of Enewetak, are just learning about this for the first time,” said Sen. Ading, the Marshallese minister of justice, immigration and labor.

A decade later, in 1968, teams from the Department of Defense set up a new experiment. This time, they were testing biological weapons — bombs and missiles filled with bacteria designed to fell enemy troops.

According to a 2002 military fact sheet and Ed Regis, the author of “The Biology of Doom,” U.S. government scientists came to Enewetak with “their boats and monkeys, space suits and jet fighter planes” and then sprayed clouds of biologically enhanced staphylococcal enterotoxin B, an incapacitating biological agent known to cause toxic shock and food poisoning and considered “one of the most potent bacterial superantigens.”

The bacteria were sprayed over much of the atoll — with ground zero at Lojwa Island, where U.S. troops were stationed 10 years later for the cleanup of the atoll.

According to military documents, the weapons testers concluded a single weapon could cover 926.5 square miles — roughly twice the size of modern-day Los Angeles — and produce a 30% casualty rate.

Records of the test, including a two-volume, 244-page account of operation “Speckled Start,” as it was called, are still classified, according to the Defense Technical Information Center, a branch of the Department of Defense.

Today, 40 years after it was constructed, the Tomb resembles an aged, neglected and slightly diminutive cousin of the Houston Astrodome.

Spiderweb cracks whipsaw across its cap and chunks of missing concrete pock its facade. Pools of brown, brackish water surround its base, and vines and foliage snake up its sides.

The Tomb, which was built atop an unlined crater created by a U.S. nuclear bomb, was designed to encapsulate the most radioactive and toxic land-based waste of the U.S. testing programs in Enewetak Atoll. This included irradiated military and construction equipment, contaminated soil and plutonium-laced chunks of metal pulverized by the 43 bombs detonated in this 2.26-square-mile lagoon, according to U.S. government documents.

It took 4,000 U.S. servicemen three years to scoop up 33 Olympic-sized swimming pools’ worth of irradiated soil and two Olympic swimming pools’ worth of contaminated debris from islands across the atoll and dump it into the crater on Runit Island.

Much of it was mixed in a slurry of concrete and poured into the pit, which was eventually capped with a concrete dome. Six men died during the cleanup; hundreds of others developed radiation-induced cancers and maladies that the U.S. government has refused to acknowledge, according to news reports.

Rising seas could unseal a toxic tomb

More than 3.1 million cubic feet of radioactive material lie within a bomb crater that was capped with an 18-inch-thick cover on Runit Island.

What is underneath the dome

Contaminated debris and soil left behind by 43 nuclear bombs detonated in Enewetak Atoll were cemented and enclosed in a crater from one of the nuclear tests. The dome, constructed in the late ’70s, is showing signs of decay. If it crumbles, its radioactive contents will be released into the lagoon and ocean.

“It’s like they say in the Army,” said Bob Retmier, a retired Huntington Beach-based electrician who did two six-month tours of duty at the dome in 1977 and 1978. “They treat us like mushrooms: They feed us crap and keep us in the dark.”

Retmier, who was in Enewetak with Company C, 84th Engineer Battalion out of Schofield Barracks, Hawaii, said he didn’t know he had been working in a radioactive landscape until he read about the dome in The Times this year.

“They had us mixing that soil into cement,” he said. “There were no masks, or respirators, or bug suits, for that matter. My uniform was a pair of combat boots, shorts and a hat. That was it. No shirt. No glasses. It was too hot and humid to wear anything else.”

According to unclassified military documents, the completion of the dome fulfilled “a moral obligation incurred by the United States.”

Marshallese officials say they were never told that U.S. authorities had doubts about the long-term integrity of the dome to safely store waste.

According to a 1981 military document chronicling the construction of the dome, U.S. government officials met Feb. 25, 1975, to discuss various cleanup options — including ocean dumping and transporting the waste back to the U.S. mainland. Many “of those present seemed to realize that radioactive material was leaking out of the crater even then and would continue to do so,” the document reported.

But because the other options were so expensive, they settled on the dome and relied on military personnel to do the cleaning instead of contractors.

At that meeting, a top Pentagon official was asked what would happen if the dome failed and who would be responsible.

“It would be the responsibility of the United States,” said Lt. Gen. Warren D. Johnson of the U.S. Air Force, who was directing the cleanup process through the Defense Nuclear Agency.

Documents show that as construction teams were finishing the dome by capping it with an 18-inch concrete cover, new, highly contaminated debris was discovered.

In the process of adding that material to the waste site, parts of the concrete top were embedded with contaminated metallic debris.

“It was sloppy,” said Paul Griego, who worked as a contract radiochemist for Eberline Instruments in Enewetak while the military built the dome.

The authors of the report noted that because the dome was “designed to contain material and prevent erosion rather than act as a radiation shield,” the radioactive material in the dome cover was no cause for concern.

Today, U.S. officials maintain that the dome has served its “intended purpose” — to hold garbage, not necessarily to be a radiation shield.

That distinction, though, is not well understood in the Marshall Islands, where many assumed the United States built the dome to protect them.

“My understanding from day one is that the dome was to shield the radiation from leaking out,” Ading said.

Soon after the dome was completed, the winter tides washed more than 120 cubic yards of radioactive debris onto Runit’s shores, prompting U.S. authorities to build a small antechamber adjacent to the dome to hold the new “red-level” debris.

When more debris washed up, they built a second, smaller antechamber.

Then they left.

The U.S. scientific expert on Runit Dome is Hamilton, the Energy Department contractor. He began working on radiation issues nearly three decades ago and is widely respected among nuclear scientists and physicists.

In 2012, Hamilton called the waste site a highly radioactive “point source” whose construction was “not consistent” with U.S. Nuclear Regulatory Commission regulations. He also suggested it could possibly release more plutonium into the surrounding environment.

“Any increases in availability of plutonium will have an impact on food security reserves for the local population,” he wrote with two Lawrence Livermore National Laboratory coauthors, noting a “growing commercial export market” for sea cucumbers in the lagoon.

In more recent years, Hamilton’s message has changed: The islands are safe, U.S. researchers are monitoring the situation, and no one should be concerned.

At a May meeting in Majuro, he told an audience of Marshallese dignitaries, politicians and U.S. officials that the Tomb was bobbing with the tides, sucking in and flushing out radioactive water into the lagoon. Moreover, he said, its physical integrity is “vulnerable to leakage and the sustained impacts of storm surge and sea level rise.”

But Hamilton went on to assure them such a scenario was not cause for alarm. Enewetak lagoon is already so contaminated, he said, that any added radiation introduced by a dome failure would be virtually undetectable — in the lagoon, or in the wider ocean waters.

Hamilton has said that his assessment is based on a sampling of U.S. documents from the 1970s and 1980s suggesting that there is far more contamination in Enewetak lagoon than remains inside the dome. He contends the land is safe for habitation and will remain so, even if the dome crumbles and releases its contents into the contaminated lagoon.

Plutonium is a risk to human health only when it is airborne or introduced via a cut in the skin, Hamilton said. The plutonium in the lagoon, he claims, is not a concern.

“Under existing living conditions, there is no radiological basis why I or anyone else should be concerned about living on Enewetak,” Hamilton said in an email, reflecting a position that other experts find perplexing.

“That’s crazy,” said Holly Barker, a University of Washington anthropologist who serves on the Marshall Islands nuclear commission. The whole point of building the Tomb, she said, was to clean up contamination left behind by the U.S. testing programs.

“Does that mean they didn’t clean it up?” she asked.

Asked about his contradictory messages, Hamilton wrote in an email that his earlier assessment was “put forward to help provide a scientific justification” for securing funding and time for a more thorough analysis of the dome.

“People living on Enewetak do not show elevated levels of plutonium in their bodies,” he said, discounting concerns. “This is the ultimate test.”

To many, Hamilton’s most recent position is just another case of the United States moving the goal posts in the Marshall Islands: It promised a thorough cleanup, only to backtrack in the face of new revelations or costs.

Griego, the radiochemist and the New Mexico state commander of the National Assn. of Atomic Veterans, notes that when Hamilton wrote a report for the Department of Energy in 2013 stating that catastrophic failure of the dome would be inconsequential, the report included a mission statement that cast doubt on its scientific integrity.

According to the document, the report’s purpose was to “address the concerns of the Enewetak community” and “help build public confidence in the maintenance of a safe and sustainable resettlement program on Enewetak Atoll.”

Griego worked as a contractor in Enewetak in 1978.

“I saw the water rising and falling as we filled that dome. I know that limestone is porous. And I know how sick people got,” Griego said. “That dome is dangerous. And if it fails, it’s a problem.”

Climate scientists have been nearly unanimous about one thing: The waters around the Marshall Islands are rising — and growing warmer.

On an August day a year ago, tens of thousands of dead fish washed up on the ocean side of Bikini Atoll.

Dick Dieke Jr., one of seven temporary caretakers working for a Department of Energy contractor there, recalls the water being uncomfortable.

“It didn’t feel good to put my feet in it,” he said. “It was too hot.”

Earlier that day, the typically crystalline and azure waters of the Bikini lagoon, near Nam Island, were cloudy and brown. Sea turtles, reef fish and rays swam slowly through the murk, appearing suddenly out of the cloudy bloom only to disappear just as quickly.

Dive computers showed 92-degree temperatures 30 feet below the surface in the lagoon, an area usually no warmer than 86 degrees in August.

It is impossible to say exactly what caused that day’s massive algae bloom and fish kill, but scientists say such marine incidents will occur more frequently as oceans warm from climate change.

“I’ve never seen or heard of a fish kill in Bikini,” Jack Niedenthal, the Marshall Islands’ secretary of health and human services, said in an interview last summer, just a week after the event. “That’s surprising and deeply upsetting.”

Just a few years ago, the northern Marshall Islands were known for their pristine coral reefs, little disturbed by human contact, in part because many of these isles were radiation no-go zones. But during a visit last year, The Times saw vast expanses of bleached and dead coral around Bikini Atoll, a finding that surprised some familiar with the region.

Elora López, a Stanford University doctoral student, accompanied a PBS documentary film team in 2016 to Bikini Atoll to collect coral samples. The reefs — hundreds of miles from the nearest tourist — were healthy.

But when she returned in 2018, using GPS coordinates to find the same location, all of the corals were dead.

Since 1993, sea levels have risen about 0.3 inches a year in the Marshall Islands, far higher than the global average of 0.11 to 0.14 inches. Studies show sea levels are rising twice as fast in the western Pacific than elsewhere.

Based on forecasts by the Intergovernmental Panel on Climate Change, sea levels could rise 4 to 5 feet by the end of the century, submerging most of the Marshall Islands.

Even if seas rose just half that, said Curt Storlazzi, a geoengineer at the United States Geological Survey, the islands would be in trouble — damaging infrastructure and contaminating most groundwater reserves.

“We have a lot of difficult choices to make,” James Matayoshi, the mayor of Rongelap Atoll, said in a September interview. “If the seas don’t stop rising, we’re going to lose some places. Assuming we can save some, we’ll have to decide which islands, which places, for which people. But who gets to do that?”

The thought of abandoning their homeland is unthinkable for many Marshallese, the nation’s president said.

“Many of our people … want to stay here,” Heine said. “For us, for these people, land is a critical part of our existence. Our culture is based on our land. It is part of us. We cannot think about abandoning the land.”

Outbreaks of certain diseases in the Pacific also have been linked to climate change. The Republic of the Marshall Islands is fighting the largest outbreak of dengue fever in its recorded history — more than 1,000 people have been infected, with the outer atolls quarantined to prevent the spread of disease among people with no access to hospital care.

“Most people talk about rising sea levels when it comes to climate change,” said Niedenthal, the health secretary. “Even more immediate and devastating is what has been happening with disease outbreaks. This is the worst outbreak in Pacific history.”

For many Americans, the Marshall Islands are best known for a movie monster and a cartoon icon. Godzilla, the Japanese-inspired monster of the Pacific, was awakened and mutated by the atomic bombs in Bikini Atoll. SpongeBob SquarePants, the Nickelodeon cartoon character, lives with his friends in Bikini Bottom.

A recent review of California-approved high school history textbooks and curricula showed no mention of the Marshall Islands or the U.S. nuclear testing program and human experimentation program there.

Even less widely known are the Marshallese attempts, for the last three decades, to seek compensation from the U.S. for the health and environmental effects of nuclear testing. They’ve been denied standing to sue in U.S. courts, and Congress has declined their requests.

The Nuclear Claims Tribunal — an independent arbiter established by the U.S.-Marshall Islands compact to process and rule on claims — has ruled in their favor, awarding them more than $2 billion in damages. But the U.S. has paid out only $4 million, according to congressional testimony, and no enforcement mechanism exists.

In the last few years, though, the island nation’s claims have begun to get more visibility.

President Heine has achieved near-celebrity status at international events. The Marshall Islands recently secured a seat on the United Nations Human Rights Council, giving the nation another forum in which to raise its concerns.

A geopolitical shift also has given the islands new leverage. China has increased its reach into the central Pacific, providing aid and loans to dozens of nations, surpassing the United States as the region’s largest trade partner.

“China is trying to erode U.S. influence in the region to weaken the U.S. military presence and create an opening for Chinese military access,” according to a 2018 report from the U.S.-China Economic and Security Review Commission, a congressional committee.

In September, two of the United States’ staunchest allies in the Pacific — Kiribati and the Solomon Islands — severed diplomatic ties with Taiwan, embracing China instead.

Washington has greeted those developments with concern.

In August, Secretary of State Michael R. Pompeo flew to Micronesia to meet with the leaders of several Pacific island nations, including the Marshall Islands.

He announced the United States’ intention to extend the compact with the Marshall Islands — providing aid in exchange for a secure military presence, and working rights for Marshallese in the United States.

The announcement came as a surprise to the Marshallese, who were anticipating the expiration in 2023 of their compact, which includes annual grants from the U.S. that total about $30 million a year.

Marshallese officials read that as a sign that the islands have new negotiating power.

“These are matters of life and death for us,” said Ading, the Enewetak senator. “We can’t afford to rely exclusively on reassurances from one source. We need neutral experts from the international community to weigh in, to confirm or challenge” previous U.S. findings.

Many Marshallese say they don’t want U.S. money or apologies, but just a home in the Marshall Islands that is safe and secure.

Nerje Joseph holds out hope for a day when her children, grandchildren and great-grandchildren can return to her ancestral home in Rongelap and she can be buried in the sands of her youth, alongside her ancestors, under the coconut trees she remembers so well.

“In Los Angeles, you make movies about the Titanic. About people who lost everything,” she said.

“Why don’t you make movies about us?”

https://www.latimes.com/projects/marshall-islands-nuclear-testing-sea-level-rise/?utm_source=Nature+Briefing&utm_campaign=afb6bb4ab4-briefing-dy-20191111&utm_medium=email&utm_term=0_c9dfd39373-afb6bb4ab4-44039353

By Nicoletta Lanese

Smooth balls of ice rolled ashore on a beach in Finland and piled up like a gigantic clutch of turtles’ eggs.

But where did these “ice eggs” come from? Turns out, the frigid orbs were sculpted by a peculiar combination of weather and waves, according to news reports.

Amateur photographer Risto Mattila stumbled upon the strange sight while walking with his wife on Hailuoto Island, a land mass between Finland and Sweden, according to BBC News. The temperature hovered around 32 degrees Fahrenheit (minus 1 degree Celsius) that day, he said, and the wind whipped across the beach. “There, we found this amazing phenomenon. There was snow and ice eggs along the beach near the water line,” he told the BBC.

The “ice eggs” littered an area the length of about one-quarter of a football field and ranged in size from that of an average chicken egg to that of a hefty soccer ball, Mattila said. He snapped a photo, noting that he had “never seen anything like this during 25 years living in the vicinity.”

Others came upon the ice eggs, too. “This was [an] amazing phenomenon, [I’ve] never seen before. The whole beach was full of these ice balls,” Tarja Terentjeff, who lives in the nearby town of Oulu, told CNN. Another local, Sirpa Tero, told CNN she’d seen icy orbs line the shoreline before, “but not over such a large area.”

Although fairly rare, these ice eggs form similarly to sea glass or rounded stones that wash up on the beach, said BBC Weather expert George Goodfellow. Chunks of ice break off from larger ice sheets in the sea and either taxi to shore on the incoming tide or get pushed in by gusts of wind at the water’s surface, he explained. Waves buffet the ice chunks as they travel, slowly eroding their jagged edges into smooth curves. Seawater sticks and freezes to the forming eggs, causing them to grow like snowballs do as they roll across the ground.

Once the ice chunks reach shore, pounding waves tend to buff out any lingering kinks on their surfaces, leaving behind nothing but sleek and shiny “eggs” for curious tourists to happen upon.

https://www.livescience.com/ice-eggs-in-finland-beach.html?utm_source=Selligent&utm_medium=email&utm_campaign=9881&utm_content=20191108_LS_Essentials_Newsletter+-+adhoc+&utm_term=3675605&m_i=KLvdVq2D1jG_1ZlsN2BtGnhxz5lDWnoT1z5TH7nDwaq0voJwXv3R_F4qtiVoYAKPhitMFL_skBWImJ%2By0oVarC4t%2Bc9VnaCZKB


Francisco Lopera, a neurologist at the University of Antioquia in Medellin, Colombia, has been painstakingly collecting brains, birth and death records from one sprawling Colombian family to study Alzheimer’s.Credit…Federico Rios Escobar for The New York Times


A woman with lots of beta-amyloid buildup (red) in her brain remained cognitively healthy for decades.

by Kelly Servick

In 2016, a 73-year-old woman from Medellín, Colombia, flew to Boston so researchers could scan her brain, analyze her blood, and pore over her genome. She carried a genetic mutation that had caused many in her family to develop dementia in middle age. But for decades, she had avoided the disease. The researchers now report that another rare mutation—this one in the well-known Alzheimer’s disease risk gene APOE—may have protected her. They can’t prove this mutation alone staved off disease. But the study draws new attention to the possibility of preventing or treating Alzheimer’s by targeting APOE—an idea some researchers say has spent too long on the sidelines.

“This case is very special,” says Yadong Huang, a neuroscientist at the Gladstone Institutes in San Francisco, California, who was not involved with the research. “This may open up a very promising new avenue in both research and therapy.”

APOE, the strongest genetic risk factor for Alzheimer’s, has three common forms. A variant called APOE2 lowers risk of the disease. The most common variant, APOE3, doesn’t influence risk. APOE4 raises risk; roughly half of the people with the disease have at least one copy of this variant.

Researchers have long contemplated targeting APOE with therapies. A team at Cornell University will soon start a clinical trial that infuses the protective APOE2 gene into the cerebrospinal fluid of people with two copies of APOE4.

But mysteries about APOE have kept it from becoming a front-runner among drug targets. “It does so many things that it’s confusing,” says Eric Reiman, a neuroscientist at the Banner Alzheimer’s Institute in Phoenix and a co-author on the new paper. The APOE protein binds and transports fats and is abundant in the brain. And the APOE4 variant seems to encourage the formation of sticky plaques of the protein beta-amyloid, which clog the brain in Alzheimer’s. But powerful amyloid-busting drugs have repeatedly failed to benefit patients in clinical trials. Some researchers saw no reason to try an APOE-targeting therapy that seemed to be “just a poor man’s antiamyloid treatment,” Reiman says.

The Colombian woman’s case suggests other ways APOE could affect Alzheimer’s risk. The woman participated in a study led by researchers at the University of Antioquia in Medellín that has tracked roughly 6000 members of her extended family. About one-fifth of them carried an Alzheimer’s-causing mutation in a gene called presenilin 1; these carriers generally developed dementia in their late 40s. Yet the woman didn’t show the first signs of the disease until her 70s, even though she, too, carried the mutation. “She’s definitely an outlier,” says cell biologist Joseph Arboleda-Velasquez of Harvard Medical school in Boston. (The research team is keeping the woman’s name confidential to protect her privacy.)

In Boston, a positron emission tomography scan of the woman’s brain revealed more amyloid buildup than in any other family member who has been scanned. “It was very striking,” says Yakeel Quiroz, a clinical neuropsychologist at Massachusetts General Hospital and Harvard Medical School. But the team found no signs of major damage to neurons, and minimal buildup of another Alzheimer’s hallmark: the misfolded protein tau. Whatever protection this woman had didn’t depend on keeping the brain amyloid-free. Instead, her case supports the idea that tau has a “critical role … in the clinical manifestations of Alzheimer’s disease,” says Jennifer Yokoyama, a neurogeneticist at the University of California, San Francisco.

Genome sequencing revealed two copies of a rare mutation in the APOE gene, the researchers report this week in Nature Medicine. First discovered in 1987, the mutation, known as Christchurch, occurs in a region separate from those that determine a person’s APOE2, 3, or 4 status. (The woman has the neutral APOE3 variant.) Previous research found that the Christchurch mutation—like the more common protective APOE2 mutation—impairs APOE’s ability to bind to and clear away fats and sometimes leads to cardiovascular disease.

The researchers also found that the mutation prevents APOE from binding strongly to other molecules called heparan sulfate proteoglycans (HSPGs), which coat neurons and other cells “like a carpet,” says Guojun Bu, a neuroscientist at the Mayo Clinic in Jacksonville, Florida, who has studied the interaction between these molecules and APOE.

APOE2 may also impair the protein’s ability to bind HSPGs. But how that could protect against disease isn’t clear. One possible clue: Research by neuroscientist Marc Diamond of the University of Texas Southwestern Medical Center in Dallas and his colleagues suggest the toxic tau protein relies on HSPGs to help it spread between cells. Maybe the less APOE binds to HSPGs, the harder it is for tau to spread.

But, Diamond cautions, “It will require much more study to understand if this relationship exists.” The Christchurch mutation might have protective effects unrelated to HSPGs; it’s also possible that mutations other than Christchurch protected the woman.

If hampering APOE’s normal binding really staved off her Alzheimer’s, future treatments might aim to mimic that effect. An antibody or small molecule could latch onto the APOE protein to interfere with binding, gene editing could change the structure of APOE to imitate the Christchurch variant, or a “gene silencing” approach could reduce production of APOE altogether.

Reiman hopes the new study will rally researchers to pursue treatments related to APOE. He, Quiroz, Arboleda-Velasquez, and other collaborators also posted a preprint on the medRxiv server on 2 November showing that people with two copies of APOE2 have lower Alzheimer’s risk than previously thought—about 99% lower than people with two copies of APOE4. “When it comes to finding a treatment that could have a profound impact on the disease,” Reiman says, “APOE may be among the lowest hanging fruit.”

https://science.sciencemag.org/content/366/6466/674