Daily Archives: January 23, 2024

Tumors constantly shed DNA from dying cells, which briefly circulates in the patients bloodstream before it is quickly broken down. Many companies have created blood tests that can pick out this tumor DNA, potentially helping doctors diagnose or monitor cancer or choose a treatment.

The amount of tumor DNA circulating at any given time, however, is extremely small, so it has been challenging to develop tests sensitive enough to pick up that tiny signal. A team of researchers from MIT and the Broad Institute of MIT and Harvard has now come up with a way to significantly boost that signal, by temporarily slowing the clearance of tumor DNA circulating in the bloodstream.

The researchers developed two different types of injectable molecules that they call priming agents, which can transiently interfere with the bodys ability to remove circulating tumor DNA from the bloodstream. In a study of mice, they showed that these agents could boost DNA levels enough that the percentage of detectable early-stage lung metastases leapt from less than 10 percent to above 75 percent.

This approach could enable not only earlier diagnosis of cancer, but also more sensitive detection of tumor mutations that could be used to guide treatment. It could also help improve detection of cancer recurrence.

You can give one of these agents an hour before the blood draw, and it makes things visible that previously wouldnt have been. The implication is that we should be able to give everybody whos doing liquid biopsies, for any purpose, more molecules to work with, says Sangeeta Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and of Electrical Engineering and Computer Science at MIT, and a member of MITs Koch Institute for Integrative Cancer Research and the Institute for Medical Engineering and Science.

Bhatia is one of the senior authors of the new study, along with J. Christopher Love, the Raymond A. and Helen E. St. Laurent Professor of Chemical Engineering at MIT and a member of the Koch Institute and the Ragon Institute of MGH, MIT, and Harvard and Viktor Adalsteinsson, director of the Gerstner Center for Cancer Diagnostics at the Broad Institute.

Carmen Martin-Alonso PhD 23, MIT and Broad Institute postdoc Shervin Tabrizi, and Broad Institute scientist Kan Xiong are the lead authors of the paper, which appears today in Science.

Better biopsies

Liquid biopsies, which enable detection of small quantities of DNA in blood samples, are now used in many cancer patients to identify mutations that could help guide treatment. With greater sensitivity, however, these tests could become useful for far more patients. Most efforts to improve the sensitivity of liquid biopsies have focused on developing new sequencing technologies to use after the blood is drawn.

While brainstorming ways to make liquid biopsies more informative, Bhatia, Love, Adalsteinsson, and their trainees came up with the idea of trying to increase the amount of DNA in a patients bloodstream before the sample is taken.

A tumor is always creating new cell-free DNA, and thats the signal that were attempting to detect in the blood draw. Existing liquid biopsy technologies, however, are limited by the amount of material you collect in the tube of blood, Love says. Where this work intercedes is thinking about how to inject something beforehand that would help boost or enhance the amount of signal that is available to collect in the same small sample.

The body uses two primary strategies to remove circulating DNA from the bloodstream. Enzymes called DNases circulate in the blood and break down DNA that they encounter, while immune cells known as macrophages take up cell-free DNA as blood is filtered through the liver.

The researchers decided to target each of these processes separately. To prevent DNases from breaking down DNA, they designed a monoclonal antibody that binds to circulating DNA and protects it from the enzymes.

Antibodies are well-established biopharmaceutical modalities, and theyre safe in a number of different disease contexts, including cancer and autoimmune treatments, Love says. The idea was, could we use this kind of antibody to help shield the DNA temporarily from degradation by the nucleases that are in circulation? And by doing so, we shift the balance to where the tumor is generating DNA slightly faster than is being degraded, increasing the concentration in a blood draw.

The other priming agent they developed is a nanoparticle designed to block macrophages from taking up cell-free DNA. These cells have a well-known tendency to eat up synthetic nanoparticles.

DNA is a biological nanoparticle, and it made sense that immune cells in the liver were probably taking this up just like they do synthetic nanoparticles. And if that were the case, which it turned out to be, then we could use a safe dummy nanoparticle to distract those immune cells and leave the circulating DNA alone so that it could be at a higher concentration, Bhatia says.

Earlier tumor detection

The researchers tested their priming agents in mice that received transplants of cancer cells that tend to form tumors in the lungs. Two weeks after the cells were transplanted, the researchers showed that these priming agents could boost the amount of circulating tumor DNA recovered in a blood sample by up to 60-fold.

Once the blood sample is taken, it can be run through the same kinds of sequencing tests now used on liquid biopsy samples. These tests can pick out tumor DNA, including specific sequences used to determine the type of tumor and potentially what kinds of treatments would work best.

Early detection of cancer is another promising application for these priming agents. The researchers found that when mice were given the nanoparticle priming agent before blood was drawn, it allowed them to detect circulating tumor DNA in blood of 75 percent of the mice with low cancer burden, while none were detectable without this boost.

One of the greatest hurdles for cancer liquid biopsy testing has been the scarcity of circulating tumor DNA in a blood sample, Adalsteinsson says. Its thus been encouraging to see the magnitude of the effect weve been able to achieve so far and to envision what impact this could have for patients.

After either of the priming agents are injected, it takes an hour or two for the DNA levels to increase in the bloodstream, and then they return to normal within about 24 hours.

The ability to get peak activity of these agents within a couple of hours, followed by their rapid clearance, means that someone could go into a doctors office, receive an agent like this, and then give their blood for the test itself, all within one visit, Love says. This feature bodes well for the potential to translate this concept into clinical use.

The researchers have launched a company called Amplifyer Bio that plans to further develop the technology, in hopes of advancing to clinical trials.

A tube of blood is a much more accessible diagnostic than colonoscopy screening or even mammography, Bhatia says. Ultimately, if these tools really are predictive, then we should be able to get many more patients into the system who could benefit from cancer interception or better therapy.

The research was funded by the Koch Institute Support (core) Grant from the National Cancer Institute, the Marble Center for Cancer Nanomedicine, the Gerstner Family Foundation, the Ludwig Center at MIT, the Koch Institute Frontier Research Program via the Casey and Family Foundation, and the Bridge Project, a partnership between the Koch Institute and the Dana-Farber/Harvard Cancer Center.

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Researchers improve blood tests' ability to detect and monitor cancer - MIT News

Over two decades after the Sept. 11 terror attacks, New York City officials have identified the remains of a man who lost his life in the World Trade Center.

John Ballantine Nivenfrom Oyster Bay, New York, is the 1,650th person from the attacks identified using advanced DNA analysis, according to theNew York City medical examiner.

Niven was 44 years old at the time of his death, and he is the first person to be identified sinceSeptember 2023.

While the pain from the enormous losses on September 11th never leaves us, the possibility of new identifications can offer solace to the families of victims, said New York City Mayor Eric Adams in a press release. I'm grateful for the ongoing work from the Office of Chief Medical Examiner that honors the memory of John Ballantine Niven and all those we lost.

Niven's identification was confirmed through ongoing DNA testing of remains recovered in 2001 by using advanced next-generation sequencing technology, which is often used by the U.S. military to identify the remains of missing American service members.

Our solemn promise to find answers for families using the latest advances in science stands as strong today as in the immediate days after the World Trade Center attacks, Chief Medical Examiner Dr. Jason Graham noted. This new identification attests to our agencys unwavering commitment and the determination of our scientists.

However, the process still takes some time, as out of the 2,753 people who lost their lives in the Sept. 11 attacks, approximately 40%, or 1,103 victims, still remain unidentified.

SEE MORE: Five suspected 9/11 terrorists were never tried after the attacks

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1,650th victim of 9/11 identified through advanced DNA testing - FOX 17 West Michigan News

Scientists produced the most complete catalog of marine microbe DNA yet, including data from the deeper zones of the oceans. Rowan Coe via Getty Images

As of Tuesday, scientists around the world have an exciting new tool at their disposal: the largest-ever collection of marine microbe genomes, organized in an online database.

The catalog, described in the journal Frontiers in Science, is an open-source digital library of genetic codes from the oceans organismsand scientists say it may open doors to drug development or innovations in energy and agriculture.

Genes and proteins derived from marine microbes have endless potential applications, study co-author Carlos Duarte, a marine ecologist at the King Abdullah University of Science and Technology (KAUST) in Saudi Arabia, says to Nature News Carissa Wong. We can probe for new antibiotics; we can find new enzymes for food production. If they know what theyre searching for, researchers can use our platform to find the needle in the haystack that can address a specific problem.

To build the database, researchers analyzed thousands of marine samples collected over the last 15 years, from all five oceans and the Mediterranean Sea. The samples were sourced from a variety of past expeditions and studies, such as the global Tara Oceans expedition that ran from 2009 to 2013. The DNA represented bacteria, fungi and viruses from a variety of geographies and oceanic depths.

In the past, barriers to DNA sequencing presented a major roadblock for scientistseven when the genetic samples were collected and in hand, their efforts could be foiled by cost, time or the condition of the DNA. As of 2022, 303 million unique marine microbial genes had been sequenced.

The teams breakthrough came via sequencing and technological advances. Improvements in the speed and accuracy of supercomputing, as well as developments in artificial intelligence and shotgun DNA sequencing, allowed the team to analyze more than 2,100 metagenomes, or bulk quantities of genetic material. All told, they sequenced approximately 317 million unique groups of microbial genes to create the most complete catalog yet.

In particular, the study took a close look at life accustomed to the extreme conditions of the oceanic twilight zone. Stretching between 650 and 3,300 feet below the surfacejust out of range for sunlightthis region is home to some of Earths most unique creatures, with adaptations driven by such a harsh habitat.

Within the twilight zone, researchers were surprised to discover that more than half of the unique gene clusters found belonged to fungi.

There have been some indications of [fungi abundance at this level] before, so this is another piece of the puzzle, lead author Elisa Laiolo, a marine biologist at KAUST, says to the Guardians Sophie Kevany.

Drugs like penicillin, for example, were developed from fungi. And the ones found in the deep ocean have evolved rare traits that could be useful to scientists developing medicines. That could potentially lead to the discovery of new species with unique biochemical properties, Fabio Favoretto, a marine ecologist at the Scripps Institution of Oceanography who was not involved in the research, tells the Guardian.We might find something like [penicillin] from these ocean fungi.

Examining marine microbes also shed light on viruses role in increasing genetic diversity, which they do by moving genes between organisms.

The study suggests avenues for future researchfor example, the scientists identified a wide gap in knowledge about the deep sea and ocean floor. They also point out that their catalog can serve as a baseline for the diversity of marine microbes, which could allow future researchers to gauge the impact of human activitiessuch as deep-sea mining or burning fossil fuelson these organisms, per Nature News.

For the catalog to truly be effective, the team says, countries and scientists need to prioritize the dissemination of knowledge. The 2023 high seas treaty, which nearly 200 countries signed, maintains that a marine gene is owned by the country that discovers it, though its benefits must be shared. Still, the agreement was unclear on how that would work.

Such uncertainty must be resolved now we have reached the point where genetic and artificial intelligence technologies could unlock unprecedented innovation and progress in blue biotechnology, Duarte says in a statement.

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DNA From the Ocean's 'Twilight Zone' Could Lead to New Lifesaving Drugs, Scientists Say - Smithsonian Magazine

Some 9,700 years ago on an autumn day, a group of people were camping on the west coast of Scandinavia. They were hunter-gatherers that had been fishing, hunting and collecting resources in the area.

Some teenagers, both boys and girls, were chewing resin to produce glue, just after eating trout, deer and hazelnuts. Due to a severe gum infection (periodontitis), one of the teenagers had problems eating the chewy deer-meat, as well as preparing the resin by chewing it.

This snapshot of the Mesolithic period, just before Europeans started farming, comes from analysis of DNA left in the chewed resin that we have conducted, now published in Scientific Reports.

The location is now known as Huseby Klev, situated north of Gothenburg (Gteborg), Sweden. It was excavated by archaeologists in the early 1990s, and yielded some 1,849 flint artefacts and 115 pieces of resin (mastic). The site has been radiocarbon dated to between 10,200 and 9,400 years ago, with one of the pieces of resin dated to 9,700 years ago.

Some of the resin has teeth imprints, indicating that children, actually teenagers, had been chewing them. Masticated lumps, often with imprints of teeth, fingerprints or both, are not uncommon to find in Mesolithic sites.

The pieces of resin we have analysed were made of birch bark pitch, which is known to have been used as an adhesive substance in stone tool technology from the Middle Palaeolithic onward. However, they were also chewed for recreational or medicinal purposes in traditional societies.

A variety of substances with similar properties, such as resins from coniferous trees, natural bitumen, and other plant gums, are known to have been used in analogous ways in many parts of the world.

In some of the resin, half the DNA extracted was of human origin. This is a lot compared to what we often find in ancient bones and teeth.

It represents some of the oldest human genomes from Scandinavia. It has a particular ancestry profile common among Mesolithic hunter gatherers who once lived there.

Some of the resin contains male human DNA while others have female DNA. We think that teenagers of both sexes were preparing glue for use in tool making, such as attaching a stone axe to a wooden handle.

But what of the other half of the DNA that was of non-human origin? Most of this DNA is from organisms such as bacteria and fungi that have lived in the mastic since it was discarded 9,700 years ago. But some of it was from bacteria living in the human that chewed it, along with material the human had been chewing on before they put the birch bark pitch in their mouths.

Analysing all this DNA is a demanding task and treads new ground. We had to both adapt existing computing tools and also develop some new analytical strategies. As such, this work has become the starting point for developing a new workflow for this kind of analysis.

This includes mining the DNA using different strategies to characterise it, trying to piece together short DNA fragments into longer ones and using machine learning techniques to work out which DNA fragments belong to pathogens (harmful microorganisms). It also involves comparing the data to what we see in the mouths of modern people with tooth decay (caries) and periodontitis.

Naturally, we found the kind of bacteria that would be expected in an oral microbiome, the range of naturally occurring microorganisms found in the mouth. We also found traces of bacteria implicated in conditions such as tooth decay or caries (Streptococcus mutans), and systemic diseases such as Hib disease and endocarditis. There were also bacteria that can cause abscesses.

Although these pathogenic microorganisms were present at an elevated frequency, they were not clearly above the level expected for a healthy oral microbiome. There is thus no conclusive evidence that members of the group suffered from diseases these microorganisms are associated with.

What we did find, however, was an abundance of bacteria associated with serious gum disease periodontitis. When we applied a machine learning strategy (in this case, a technique called Random Forest modelling) we reached the conclusion that the girl who chewed one of the pieces of resin had probably suffered from periodontitis with more than a 75% probability.

We also found DNA from larger organisms than just bacteria. We found DNA for red deer, brown trout and hazelnuts. This DNA probably came from material the teenagers had been chewing before they put the birch pitch in their mouths.

However, we need to be a little bit cautious because exactly what we find is also dependent on the comparison data that we have. As genomes from eukaryotic organisms the group that includes plants and animals are larger and more complex than those from microorganisms, it is more complicated to assemble a eukaryotic genome of high quality.

There are fewer eukaryotic genomes in the samples of resin, and they are of lower quality. This means that our brown trout, for example, may not actually be a brown trout, but we at least feel certain it is from the salmon family.

We also found a lot of fox DNA, but this is harder to interpret. Fox meat may have been a part of the diet, but these teenagers could also have chewed on tendons and fur from foxes for use in textiles. Alternatively, the fox DNA could even be from territorial marking and got into the resin after it was spat out.

However, what we have learned for sure represents a big step in understanding these fascinating records of human culture from the Stone Age. As we analyse more of these, even more surprises could emerge.

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DNA from stone age chewing gum sheds light on diet and disease in Scandinavia's ancient hunter-gatherers - The Conversation

An expert has said the identity of DB Cooper could be revealed for the first time thanks to a DNA breakthrough.

On 24 November 1971, Northwest Airlines Flight 305 was hijacked by a mystery man who claimed to be carrying a bomb - he demanded $200,000 in ransom before donning a parachute and jumping from the plane.

The only clue he left behind was a clip-on tie from the US retail chain JCPenney.

Speaking to the Sun, he said that he had recently met with scientist Tom Kaye who has tested the tie twice using a special device that is able to collect the smallest particles.

Kaye was initially hoping to analyse the tie for traces of certain chemicals or metals which could help shed some light on its owner - but the duo claim the device is also able to collect DNA.

The pair now plan on sharing the DNA they captured with a lab that specialises in metagenomic DNA analysis - an incredibly advanced type of DNA analysis that enables scientists to separate individual strands of DNA.

He told the publication: "Metagenomic DNA is the holy grail where this is concerned because it can separate individually all of the DNA profiles on the tie, even for something like a dog.

"So if DB Cooper had a dog, we'd be able to find that on there.

"It's critically important because [...] let's say you have a dozen different DNA profiles on that tie from everyone who has come into contact with it over the years, including various FBI agents and Cooper himself.

"We will be able to separate all of those strands individually, and - while we won't know which one is Cooper's - we will be able to gradually narrow them down."

If all goes well, Ulis is hopeful that this case could be closed by the end of the year.

"By December 31, 2024, this is going to be a new world as far as this case is concerned," he said.

"We're either going to have figured out who this guy is, or we're gonna have a solid DNA profile to work with that's going to be pointing us in the right direction."

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DB Cooper 'will finally be identified' after 53 years due to huge DNA breakthrough - LADbible