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Health

Origins of plague could have emerged centuries before outbreaks, study suggests

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CNN
 — 

In the largest DNA analysis of its kind, scientists have found evidence to suggest that historic plague pandemics, such as the Black Death, were not caused by newly evolved strains of bacteria but ones that could have emerged up to centuries before their outbreaks.

The plague-causing bacterium Yersinia pestis is dated to have first emerged in humans about 5,000 years ago. Through animals and trade routes, Y. pestis spread globally over time on multiple occasions, according to a study published Thursday in the journal Communications Biology.

It caused the first plague pandemic in the sixth to eighth centuries and the second one in the 14th to 19th centuries. The latter pandemic is thought to have started with the medieval Black Death outbreak, which is estimated to have killed more than half of Europe’s population. The bacterium also caused the third plague pandemic between the 19th and 20th centuries.

By amassing 601 Y. pestis genome sequences, including modern and ancient strains, researchers from Canada and Australia were able to calculate the time when the bacterial strains likely emerged as a threat. They divided the different strains of the plague bacterium and analyzed each strain population individually.

The strain responsible for the Black Death, which the study says is thought to have begun in 1346, was newly estimated to have diverged from an ancestral strain between 1214 and 1315 — up to 132 years earlier.

The strain of Y. pestis associated with the first plague pandemic was previously recorded as first appearing during the Plague of Justinian, which began in 541. However, the researchers estimated that the strain was already present between 272 and 465 — up to almost 270 years before the outbreak.

“It shows that each major plague pandemic has likely emerged many decades to centuries earlier than what the historical record suggests,” study coauthor and evolutionary geneticist Hendrik Poinar, director of McMaster University’s Ancient DNA Centre in Canada, told CNN via email Thursday.

He added that the bacterium emerged, created small epidemics and then “for reasons we don’t quite understand,” such as famine or war, “it takes off.”

The study authors estimated that individually assessed bacterial strains from the third plague pandemic diverged from an ancestral strain between 1806 and 1901, with highly localized plague cases beginning to appear in southern China between 1772 and 1880 and later diverging into various strains that spread globally out of Hong Kong between 1894 and 1901.

The study also found evidence to support recent academic research suggesting that the third and second plague pandemics were not mutually exclusive events, but that the third was partly the continuation or tail end of the second. Despite the pandemics having their own diverse genetic lineages that evolved differently, the third descended directly from the 14th century strain that caused the second.

Poinar called this finding significant because “it takes into account that most of the history of this bacterium has been a Eurocentric view, so while plague supposedly disappeared from Europe in the 18th (century), it continued to rage in the Ottoman Empire and throughout the Middle East and likely North Africa.”

However, even with so many sequences of the plague bacterium, researchers were not able to determine the path of the global spread of the plague.

A lot of the genetic samples come from Europe. For example, the emergence of the bacterium in Africa has led to 90% of all modern plague cases occurring on the continent, yet there are no ancient sequences from the region, which is represented by just 1.5% of all genome samples — making it difficult to date the appearance of Y. pestis in Africa.

There is also far less surviving historical evidence from the second plague pandemic to help estimate its geographic origins compared with the third, with the earliest textual evidence of the pandemic in Europe coming from the Black Death in 1346, the study authors said. The researchers estimated that the second pandemic originated in Russia.

A study published in the journal Nature in June used DNA analysis to find the plague bacterium in three individuals who are dated to have died in 1338 in what’s now Kyrgyzstan in Central Asia. It provided evidence that the Black Death came from a strain originating in the area near Lake Issyk-Kul in Kyrgyzstan in the early 14th century.

The latest study concluded that more ancient DNA will be needed to refine current estimates on the early events of the second pandemic.

Via email, Poinar described the strain from Kyrgyzstan as “really fascinating” but said that it “still doesn’t sit at the root. So I would guess we’re still looking for something a good 20-50 years earlier.”

He and the other authors noted that the only way to estimate the evolution of the plague bacterium strains precisely “is with well dated sequences, such as those from skeletal remains at Lake Issyk-Kul.”

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Health

Aging can be reversed in mice. Are people next?

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CNN
 — 

In Boston labs, old, blind mice have regained their eyesight, developed smarter, younger brains and built healthier muscle and kidney tissue. On the flip side, young mice have prematurely aged, with devastating results to nearly every tissue in their bodies.

The experiments show aging is a reversible process, capable of being driven “forwards and backwards at will,” said anti-aging expert David Sinclair, a professor of genetics in the Blavatnik Institute at Harvard Medical School and codirector of the Paul F. Glenn Center for Biology of Aging Research.

Our bodies hold a backup copy of our youth that can be triggered to regenerate, said Sinclair, the senior author of a new paper showcasing the work of his lab and international scientists.

The combined experiments, published for the first time Thursday in the journal Cell, challenge the scientific belief aging is the result of genetic mutations that undermine our DNA, creating a junkyard of damaged cellular tissue that can lead to deterioration, disease and death.

“It’s not junk, it’s not damage that causes us to get old,” said Sinclair, who described the work last year at Life Itself, a health and wellness event presented in partnership with CNN.

“We believe it’s a loss of information — a loss in the cell’s ability to read its original DNA so it forgets how to function — in much the same way an old computer may develop corrupted software. I call it the information theory of aging.”

Jae-Hyun Yang, a genetics research fellow in the Sinclair Lab who coauthored the paper, said he expects the findings “will transform the way we view the process of aging and the way we approach the treatment of diseases associated with aging.”

While DNA can be viewed as the body’s hardware, the epigenome is the software. Epigenes are proteins and chemicals that sit like freckles on each gene, waiting to tell the gene “what to do, where to do it, and when to do it,” according to the National Human Genome Research Institute.

The epigenome literally turns genes on and off. That process can be triggered by pollution, environmental toxins and human behaviors such as smoking, eating an inflammatory diet or suffering a chronic lack of sleep. And just like a computer, the cellular process becomes corrupted as more DNA is broken or damaged, Sinclair said.

“The cell panics, and proteins that normally would control the genes get distracted by having to go and repair the DNA,” he explained. “Then they don’t all find their way back to where they started, so over time it’s like a Ping-Pong match, where the balls end up all over the floor.”

In other words, the cellular pieces lose their way home, much like a person with Alzheimer’s.

“The astonishing finding is that there’s a backup copy of the software in the body that you can reset,” Sinclair said. “We’re showing why that software gets corrupted and how we can reboot the system by tapping into a reset switch that restores the cell’s ability to read the genome correctly again, as if it was young.”

It doesn’t matter if the body is 50 or 75, healthy or wracked with disease, Sinclair said. Once that process has been triggered, “the body will then remember how to regenerate and will be young again, even if you’re already old and have an illness. Now, what that software is, we don’t know yet. At this point, we just know that we can flip the switch.”

The hunt for the switch began when Sinclair was a graduate student, part of a team at the Massachusetts Institute of Technology that discovered the existence of genes to control aging in yeast. That gene exists in all creatures, so there should be a way to do the same in people, he surmised.

To test the theory, he began trying to fast-forward aging in mice without causing mutations or cancer.

“We started making that mouse when I was 39 years old. I’m now 53, and we’ve been studying that mouse ever since,” he said. “If the theory of information aging was wrong, then we would get either a dead mouse, a normal mouse, an aging mouse or a mouse that had cancer. We got aging.”

With the help of other scientists, Sinclair and his Harvard team have been able to age tissues in the brain, eyes, muscle, skin and kidneys of mice.

To do this, Sinclair’s team developed ICE, short for inducible changes to the epigenome. Instead of altering the coding sections of the mice’s DNA that can trigger mutations, ICE alters the way DNA is folded. The temporary, fast-healing cuts made by ICE mimic the daily damage from chemicals, sunlight and the like that contribute to aging.

ICE mice at one year looked and acted twice their age.

Now it was time to reverse the process. Sinclair Lab geneticist Yuancheng Lu created a mixture of three of four “Yamanaka factors,” human adult skin cells that have been reprogrammed to behave like embryonic or pluripotent stem cells, capable of developing into any cell in the body.

The cocktail was injected into damaged retinal ganglion cells at the back of the eyes of blind mice and switched on by feeding mice antibiotics.

“The antibiotic is just a tool. It could be any chemical really, just a way to be sure the three genes are switched on,” Sinclair told CNN previously. “Normally they are only on in very young, developing embryos and then turn off as we age.”

The mice regained most of their eyesight.

Next, the team tackled brain, muscle and kidney cells, and restored those to much younger levels, according to the study.

“One of our breakthroughs was to realize that if you use this particular set of three pluripotent stem cells, the mice don’t go back to age zero, which would cause cancer or worse,” Sinclair said. “Instead, the cells go back to between 50% and 75% of the original age, and they stop and don’t get any younger, which is lucky. How the cells know to do that, we don’t yet understand.”

Today, Sinclair’s team is trying to find a way to deliver the genetic switch evenly to each cell, thus rejuvenating the entire mouse at once.

“Delivery is a technical hurdle, but other groups seem to have done well,” Sinclair said, pointing to two unpublished studies that appear to have overcome the problem.

“One uses the same system we developed to treat very old mice, the equivalent of an 80-year-old human. And they still got the mice to live longer, which is remarkable. So they’ve kind of beaten us to the punch in that experiment,” he said.

“But that says to me the rejuvenation is not just affecting a few organs, it’s able to rejuvenate the whole mouse because they’re living longer,” he added. “The results are a gift and confirmation of what our paper is saying.”

What’s next? Billions of dollars are being poured into anti-aging, funding all sorts of methods to turn back the clock.

In his lab, Sinclair said his team has reset the cells in mice multiple times, showing that aging can be reversed more than once, and he is currently testing the genetic reset in primates. But decades could pass before any anti-aging clinical trials in humans begin, get analyzed and, if safe and successful, scaled to the mass needed for federal approval.

But just as damaging factors can disrupt the epigenome, healthy behaviors can repair it, Sinclair said.

“We know this is probably true because people who have lived a healthy lifestyle have less biological age than those who have done the opposite,” he said.

His top tips? Focus on plants for food, eat less often, get sufficient sleep, lose your breath for 10 minutes three times a week by exercising to maintain your muscle mass, don’t sweat the small stuff and have a good social group.

“The message is every day counts,” Sinclair said. “How you live your life even when you’re in your teens and 20s really matters, even decades later, because every day your clock is ticking.”

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Idaho murders: Suspect in student killings was seen multiple times wearing gloves, also placing garbage bags outside Pennsylvania home, source says

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CNN
 — 

The man accused of murdering four University of Idaho students in November had thoroughly cleaned the interior and exterior of his car and was also seen wearing surgical gloves multiple times before being apprehended, a law enforcement source tells CNN.

Bryan Kohberger, 28, is currently the sole suspect in the gruesome stabbings of students Kaylee Goncalves, 21; Madison Mogen, 21; Xana Kernodle, 20; and Ethan Chapin, 20, who were found dead inside their off-campus house in Moscow, Idaho, on November 13.

Kohberger, who was pursuing a PhD in criminal justice at Washington State University at the time of the killings, “cleaned his car, inside and outside, not missing an inch,” according to the law enforcement source.

The source, who spoke on the condition of anonymity, was briefed on observations made by investigators during four days of surveillance leading up to Kohberger’s arrest at his family’s Pennsylvania home on December 30.

As Kohberger now remains behind bars in Idaho awaiting his January 12 status hearing, new details have emerged elucidating some of the suspect’s movements in the days leading up to his arrest.

A surveillance team assigned to Kohberger was tasked with two missions, according to multiple law enforcement sources: keep eyes on Kohberger so they could arrest him as soon as a warrant was issued, and try to obtain an object that would yield a DNA sample from Kohberger, which could then be compared to DNA evidence found at the crime scene.

Kohberger was seen multiple times outside the Pennsylvania home wearing surgical gloves, according to the law enforcement source.

In one instance prior to Kohberger’s arrest, authorities observed him leaving his family home around 4 a.m. and putting trash bags in the neighbors’ garbage bins, according to the source. At that point, agents recovered garbage from the Kohberger family’s trash bins and what was observed being placed into the neighbors’ bins, the source said.

The recovered items were sent to the Idaho State Lab, per the source.

Last Friday, a Pennsylvania State Police SWAT team then moved in on the Kohberger family home, breaking down the door and windows in what is known as a “dynamic entry” – a tactic used in rare cases to arrest “high risk” suspects, the source added.

On Thursday, Kohberger had his initial court appearance in Idaho after he was booked into the Latah County jail Wednesday night following his extradition from Pennsylvania.

Kohberger is charged with four counts of first-degree murder and one count of burglary. He did not enter a plea at the hearing.

Authorities spent nearly two months investigating before they were able to name publicly a suspect, a task that grabbed national attention and rattled the victims’ loved ones as well as the community – which had not recorded a murder in years.

Still, the public’s view of the case remains mired with questions. As of late Thursday, it remains unclear what motivated the killings. It’s also unclear how the suspect entered the house after authorities said there was no sign of forced entry or why two roommates who were inside the residence at the time of the killings survived the attacks.

Here’s how investigators narrowed the search to Kohberger:

  • DNA: Trash recovered from Kohberger’s family home revealed that the “DNA profile obtained from the trash” matched a tan leather knife sheath found “laying on the bed” of one of the victims, according to a probable cause affidavit released Thursday. The DNA recovered from the trash “identified a male as not being excluded as the biological father” of the suspect whose DNA was found on the sheath. “At least 99.9998% of the male population would be expected to be excluded from the possibility of being the suspect’s biological father,” the affidavit said.
  • Phone records: Authorities found the suspect’s phone was near the victims’ Moscow, Idaho, home at least a dozen times between June 2022 to the present day, according to the affidavit. The records also reveal Kohberger’s phone was near the crime scene hours after the murders that morning between 9:12 a.m. and 9:21 a.m, the document says. The killings were not reported to authorities until just before noon.
  • A white sedan: A Hyundai Elantra was seen near the victims’ home around the time of their killings. Officers at Washington State University identified a white Elantra and later learned it was registered to Kohberger. The same car was also found at the suspect’s Pennsylvania family home when he was arrested last Friday. The suspect’s university is about a 10-minute drive from the Idaho crime scene.

One of two roommates who were not harmed in the attacks said she saw a masked man dressed in black inside the house on the morning of the killings, according to the probable cause affidavit.

Identified as D.M. in the court document, the roommate said she “heard crying” in the house that morning and also heard a man’s voice say, ‘It’s OK, I’m going to help you.’” D.M. said she then saw a “figure clad in black clothing and a mask that covered the person’s mouth and nose walking towards her,” the affidavit continued.

“D.M. described the figure as 5’ 10” or taller, male, not very muscular, but athletically built with bushy eyebrows,” the affidavit says. “The male walked past D.M. as she stood in a ‘frozen shock phase.’

“The male walked towards the back sliding glass door. D.M. locked herself in her room after seeing the male,” the document says, adding the roommate did not recognize the male.

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Health

Dr. Sanjay Gupta: 6 keys to keeping sharp in 2023

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Editor’s Note: CNN Chief Medical Correspondent Dr. Sanjay Gupta is a practicing neurosurgeon and the author of the new book, “12 Weeks to a Sharper You: A Guided Program.”



CNN
 — 

At least once a year, we read a sparkling headline about some promising new drug that might help patients with Alzheimer’s disease. And at least once a year, we also hear about failed drug trials and reversals of promises that a cure-all is in sight. I wrote a book about how to keep your brain sharp that came out two years ago. Since then, not much has changed in our understanding of how we can preserve our memories, and the lessons remain as relevant as ever. But one thing has become abundantly clearer: Preventing and even treating forms of dementia are largely driven by lifestyle and the choices we make daily. You are not necessarily doomed to whatever fate you think sits stuck in your genes. If there’s one fact that’s increasingly apparent in scientific circles, it’s that our lifestyle choices contribute mightily to our aging process and risk for disease, likely as much – or perhaps even more – than our genetics.

Indeed, your everyday experiences – including what you eat, how much you move, with whom you socialize, what challenges you face, what gives you a sense of purpose, how well you sleep, and what you do to reduce stress – factor much more into your brain health and overall wellness than you might imagine. We may never have a drug that everyone can take to avoid, let alone cure, dementia and other neurodegenerative diseases. But we all can access the same toolkit proven to help stack the deck in our favor for a sharp brain for life. The program I outline in my book, and which informed the interactive workbook I have coming out this week – “12 Weeks to a Sharper You: A Guided Program” – features all the practical tools you need to implement in your life today. They can help stave off brain decline, and also help you feel less anxious, sleep better, improve energy, think more clearly, make better decisions, become more resilient to daily stress, and even lose weight and boost immunity – all resolutions most of us aim to make at the transition to a new year filled with hope and high expectations. We all know that change is a challenge, and changing long-established habits takes effort. But it doesn’t have to be tortuous, and it is really not that hard to do. Let me give you six things that will help you in 2023 – your keys to the kingdom of mental sharpness.

Skip the crash diet and simply work on following the S.H.A.R.P. protocol: Slash the sugar and salt; Hydrate smartly; Add more omega-3 fatty acids from dietary sources; Reduce portions; and Plan ahead. The S.H.A.R.P. protocol is the easiest way to gravitate toward healthier foods in general and minimize the amount of processed, brain-busting junk. And if you need just one single thing to focus on here, start with the sugar. The average American consumes nearly 20 teaspoons of added sugar daily, most of that in the highly processed form of fructose, derived from high-fructose corn syrup. My guess is that a lot of this sugar intake comes in the form of a liquid – soda, energy drinks, juices and flavored teas. Swap sugar-laden drinks with water and you’ll take on two steps. That’s how to hydrate smartly.

Physical exertion is the only thing we’ve scientifically documented to improve brain health and function, and it may even slow memory loss. It’s the brain’s only superfood. And it needn’t be formal or require equipment. Walk more, take the stairs, and get up for light activity for two minutes every hour. According to the US Centers for Disease Control and Prevention, cognitive decline is almost twice as common among adults who are inactive compared to those are active. In 2022, a large international study that tracked the health of more than half a million people showed that the simple act of performing household chores like cooking, cleaning and washing the dishes can cut the risk of dementia by a stunning 21%. That put chores as the second biggest protective activity behind more obvious things such as riding a bike. In this same study, regular movement was shown to reduce risk of dementia by 35%, followed by meeting up with friends and family (a 15% lower risk). Again, simple things with huge payoffs.

On a scale of 1 to 10, with 10 being the most extreme, how would you rate your stress level? What if I told you that stress is now considered a trigger for silent neurodegeneration, which occurs years before symptoms develop? Scores of well-designed studies routinely show that chronic stress can impair your ability to learn and adapt to new situations, and subtly erode your cognition. More specifically, stress destroys cells in the hippocampus, the brain site responsible for memory storage and retrieval. So, by reducing stress, you not only help preserve cells vital to memory but you also improve focus, concentration and productivity. Don’t let toxic stress get in the way of keeping sharp. Take breaks during the day to engage in an activity that’s peaceful, meditative and stress-reducing. It can be as easy as walking in nature, journal writing, spending time with a pet, or even daydreaming. Download an app today that will give you a guided tour through a deep breathing exercise you can practice daily. I have a trusty meditative routine that calms me down in 90 seconds or less. I simply close my eyes, pay close attention to my breath, and picture my worries in clear bubbles directly in front of me that float weightlessly up and away.

Find what works for you and make it a part of your day – every day.

Are you getting restorative sleep? Contrary to popular belief, sleep is not a state of neural idleness. It is a critical phase during which the body replenishes itself in a variety of ways that ultimately affect every system, from the brain to the heart, the immune system, and all the inner workings of our metabolism. You can think of sleep as your brain’s rinse cycle for clearing out junk that could contribute to decline and disease. Prioritize sleep as you would anything else important. And start with your bedtime routine. Stop looking at screens a full hour before bed – your smartphone included – and prepare for a good night’s sleep. I bumped my pre-sleep prep time from 30 minutes to an hour and it has made all the difference in my energy and productivity the next day.

Are you learning something new every day that’s cognitively stimulating? Staying mentally challenged is vital, so much so that studies show that someone who retires at age 65 has about a 15% lower risk of developing dementia compared with someone retiring at 60, even after other factors are taken into account. Retire late, or never at all. Choose different routes to familiar destinations. Brush your teeth with the non-dominant hand. Skip the solitary games and crossword puzzles and pick up a new hobby that involves other people. Which brings me to the final key …

We are social creatures who need social connection to thrive, especially when it comes to brain health. Call a friend today. Invite a neighbor over for dinner. Go for a walk with a buddy and talk about your problems. Cherish those relationships. The strength of our connections with others can predict the health of both our bodies and our brains as we go through life. Good relationships protect us. They are a secret sauce to a long, sharp life.

As of 2022, scientists have documented a total of about 75 genes connected to the development of Alzheimer’s disease, but carrying these genes is not a one-way ticket to decline. How those genes express themselves and behave may depend largely on your daily habits. Remember that a disease like Alzheimer’s is multifactorial, made up of different pathological features. Which is why prevention and treatments are increasingly becoming personalized – individualized to a person’s biochemistry, from basic parameters like cholesterol levels, blood pressure and blood sugar balance, to the state of one’s oral health and gut microbiome, relics of past infections, and even how well you can see and hear. To that end, it helps to keep your numbers in check. Fon’t let your cholesterol or blood pressure, for instance, run amok. Same goes for your vision and hearing. In recent years, hearing and vision impairment have been added to the list of modifiable risk factors for cognitive decline.

Your DNA provides your body’s core language, but how that DNA behaves tells the story. In the future, interventional therapies that include a combination of lifestyle habits and drugs may help those stories end well. You’ll also track your risk for cognitive decline over time in the future using a simple app on your smartphone that can help you evaluate your physiology (and your memory) in real time and make suggestions tailored for you. Until we all have that technology at our fingertips, the six keys above afford you a great start and will give you a strong foundation.

The ultimate goal is to build what’s called cognitive reserve, which is what scientists call “brain resiliency.” With more cognitive reserve, you support cognitive function and can lower your risk of neurodegenerative issues. It’s like having a backup set of networks in your brain when one fails or, worse, dies and is no longer functional. In many aspects of life, the more backup plans we have, the more chances for success, right? Well, the same is true for our brain’s hard- and soft-wiring. And perhaps the most important key to establishing that reserve is to do so over time – years or even decades – before your risk for decline increases with advanced age.

Always remember this: Cognitive decline is not necessarily inevitable. Research suggests healthy habits you can incorporate into your daily life can help protect your brain health for the long term. Think of health as a “top-down” project. Focus on your brain and everything else will follow. Happy New Year!

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University of Idaho investigation: Police must protect information ‘at all costs,’ experts say

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CNN
 — 

The investigation into the murders of four University of Idaho students is entering a critical stage in its third week, as police are starting to receive forensic testing results from the crime scene, law enforcement experts tell CNN.

Dozens of local, state and federal investigators have yet to identify a suspect or find the murder weapon used in the attack last month in Moscow.

The public, as well as the victims’ family members, have criticized police for releasing little information, in what at times has been a confusing narrative.

But the complex nature of a high-level homicide investigation involves utmost discretion from police, experts say, because any premature hint to the public about a suspect or the various leads police are following can cause it to fall apart.

“What police have been reluctant to do in this case is to say they have a suspect, even though they have had suspects who have risen and fallen in various levels of importance, because that’s the nature of the beast,” said John Miller, CNN chief law enforcement analyst and former deputy commissioner of intelligence and counterterrorism for the New York Police Department.

“Police having no suspects is factually incorrect,” Miller said. “Police have had a number of suspects they’ve looked at, but they have no suspect they’re willing to name. You don’t name them unless you have a purpose for that. That’s not unusual.”

The victims – Ethan Chapin, 20; Kaylee Goncalves, 21; Xana Kernodle, 20; and Madison Mogen, 21 – were found stabbed on the second and third floors of their shared off-campus home on November 13, according to authorities.

The quadruple murder has upended the town of 26,000 residents, which had not recorded a single murder since 2015, and challenged a police department which has not benefited from the experience of investigating many homicides, let alone under the pressure of a national audience, Miller says.

The Moscow Police Department is leading the investigation with assistance from the Idaho State Police, the Latah County Sheriff’s Office and the FBI, which has assigned more than 40 agents to the case across the United States.

“They have really coordinated this into over 100 people that are operating as one team,” Miller said of the homicide investigation.

The FBI plays three important roles in the Idaho investigation, according to Miller.

The first involves its behavioral science unit, which is highly valuable for cases with an unknown offender because it narrows the scope of offender characteristics.

The second is its advanced technology, such as its Combined DNA Indexing System, which allows law enforcement officials and crime labs to share and search through thousands of DNA profiles.

Lastly, the FBI has 56 field offices in major cities throughout the country, which can expand the reach and capability of the investigation.

“The FBI brings a lot to this, as well as experience in a range of cases that would be beyond what a small town typically would have,” Miller said.

Every homicide investigation begins with the scene of the crime, which allows investigators only one chance to record and collect forensic evidence for processing, which includes toxicology reports on the victims, hair, fibers, blood and DNA, law enforcement experts say.

“That one chance with the crime scene is where a lot of opportunities can be made or lost,” Miller said.

Extensive evidence has been collected over the course of the investigation, including 113 pieces of physical evidence, about 4,000 photos of the crime scene and several 3D scans of the home, Moscow police said Thursday.

“To protect the investigation’s integrity, specific results will not be released,” police said.

Latah County Coroner Cathy Mabbutt told CNN she saw “lots of blood on the wall” when she arrived at the scene and police said “some” of the victims had defensive wounds.

Chances are “pretty high” a suspect could have cut themselves during the attack, so police are looking carefully at blood evidence, says Joe Giacalone, adjunct professor at John Jay College of Criminal Justice and retired NYPD sergeant who directed the agency’s Homicide School and Cold Case Squad.

Lab results from the scene can be returned to investigators fairly quickly, but in this case investigators are dealing with mixtures of DNA, which can take longer, he says.

“When you have several donors with the DNA, then it becomes a problem trying to separate those two or three or four. That could be part of the issue … toxicology reports can sometimes take a couple of weeks to come back,” Giacalone added.

The next stage in a homicide investigation is looking at the behavioral aspects of the crime. Two agents with the FBI’s Behavior Analysis Unit were assigned to the case to assess the scene and go over evidence to learn about the suspect or suspects’ behavior, based on the way they carried out the crime, Miller says.

“Understanding the victimology in a mystery can be very important, because it can lead you to motivation, it can lead you to enemies and it can lead you to friends,” he said.

Investigators will learn every detail about the four victims, their relationships with each other and the various people in their lives, Miller says. This includes cell phone records and internet records, he says, as well as video surveillance from every camera surrounding the crime scene.

“When you do an extensive video canvass, you may get a picture of a person, a shadowy figure, and then if you have a sense of direction, you can string your way down all the other cameras in that direction to see if that image reappears,” Miller said.

At this stage, investigators rely on the FBI’s Violent Criminal Apprehension Program, which collects and analyzes information about violent crimes in the United States.

The program can match a suspect’s DNA found at the scene with that of a person who is already in the system. It also scans all crimes across the country to determine if the way the attack was carried out mirrors a previous one, pointing to the same perpetrator, Miller says.

“You always start with people who are close to the victims, whether it’s love, money or drugs,” Giacalone told CNN. “That’s generally the first step that you take because most of us are victimized by someone we know. We have to ask things like, who would benefit from having this person or in this case, a group, killed?”

In an effort to locate the weapon – believed to be a fixed-blade knife – detectives contacted local businesses to see if a similar knife had been purchased recently.

“It’s highly unlikely, although not impossible, that a first-time offender is going to come prepared with a tactical knife and murder multiple people, even in the face of resistance, and that this is going to be their first encounter with violent crime or the use of a knife,” Miller said.

One aspect of a homicide investigation is to “keep the media happy,” according to Giacalone.

“Today in the social media, true crime, community-driven world in these cases, the demand for information is so great that sometimes police departments kind of fill in that blank air and say something just for the sake of saying something, and then realizing that it’s either not 100% true, or it’s misleading,” he said.

It’s critical for police to protect their information at “all costs” and they always know more than what they release to the public. Otherwise, it could cause the suspect to go on the run, he says.

Miller said it’s “not fair” to investigators for the public or media to criticize them for not releasing enough information about the case.

But, ultimately, the department has a moral obligation to share some information with families who are suffering in uncertainty, Miller says, but they must be judicious about what they share.

“If you tell them we have a suspect and we’re close to an arrest but that doesn’t come together, then everybody is disappointed or thinks you messed it up or worse, goes out and figures out who the suspect is and tries to take action on their own,” he said.

Investigators rely on the trove of physical and scientific evidence, information from the public and national data on violent crimes to cultivate possible leads, Miller says.

Public tips, photos and videos of the night the students died, including more than 260 digital media submissions people have submitted through an FBI form, are being analyzed, police say. Authorities have processed more than 1,000 tips and conducted at least 150 interviews to advance the case.

“Any one of those tips can be the missing link,” Miller said. “It can either be the connective tissue to a lead you already had but were missing a piece, or it can become the brand new lead that solves the case.”

Every tip must be recorded in a searchable database so investigators can go back to them as they learn new details over the course of the investigation, Miller says. While 95% to 99% of public tips may provide no value, one or several might crack the entire case, he adds.

“Police in this case could be nowhere tonight, having washed out another suspect, and tomorrow morning they could be making an arrest,” Miller said of the Idaho investigation. “Or, for the suspect they’re working on today, it might take them another month from now to put together enough evidence to have probable cause. That’s just something they won’t be able to reveal until it happens.”

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