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Scientists discover molecules that store much of the carbon in space
A team led by researchers at MIT has discovered that a distant interstellar cloud contains an abundance of pyrene, a type of large, carbon-containing molecule known as a polycyclic aromatic hydrocarbon (PAH).
The discovery of pyrene in this far-off cloud, which is similar to the collection of dust and gas that eventually became our own solar system, suggests that pyrene may have been the source of much of the carbon in our solar system. That hypothesis is also supported by a recent finding that samples returned from the near-Earth asteroid Ryugu contain large quantities of pyrene.
“One of the big questions in star and planet formation is: How much of the chemical inventory from that early molecular cloud is inherited and forms the base components of the solar system? What we’re looking at is the start and the end, and they’re showing the same thing. That’s pretty strong evidence that this material from the early molecular cloud finds its way into the ice, dust, and rocky bodies that make up our solar system,” says Brett McGuire, an assistant professor of chemistry at MIT.
Due to its symmetry, pyrene itself is invisible to the radio astronomy techniques that have been used to detect about 95 percent of molecules in space. Instead, the researchers detected an isomer of cyanopyrene, a version of pyrene that has reacted with cyanide to break its symmetry. The molecule was detected in a distant cloud known as TMC-1, using the 100-meter Green Bank Telescope (GBT), a radio telescope at the Green Bank Observatory in West Virginia.
McGuire and Ilsa Cooke, an assistant professor of chemistry at the University of British Colombia, are the senior authors of a paper describing the findings, which appears today in Science. Gabi Wenzel, an MIT postdoc in McGuire’s group, is the lead author of the study.
Carbon in space
PAHs, which contain rings of carbon atoms fused together, are believed to store 10 to 25 percent of the carbon that exists in space. More than 40 years ago, scientists using infrared telescopes began detecting features that are thought to belong to vibrational modes of PAHs in space, but this technique couldn’t reveal exactly which types of PAHs were out there.
“Since the PAH hypothesis was developed in the 1980s, many people have accepted that PAHs are in space, and they have been found in meteorites, comets, and asteroid samples, but we can’t really use infrared spectroscopy to unambiguously identify individual PAHs in space,” Wenzel says.
In 2018, a team led by McGuire reported the discovery of benzonitrile — a six-carbon ring attached to a nitrile (carbon-nitrogen) group — in TMC-1. To make this discovery, they used the GBT, which can detect molecules in space by their rotational spectra — distinctive patterns of light that molecules give off as they tumble through space. In 2021, his team detected the first individual PAHs in space: two isomers of cyanonaphthalene, which consists of two rings fused together, with a nitrile group attached to one ring.
On Earth, PAHs commonly occur as byproducts of burning fossil fuels, and they’re also found in char marks on grilled food. Their discovery in TMC-1, which is only about 10 kelvins, suggested that it may also be possible for them to form at very low temperatures.
The fact that PAHs have also been found in meteorites, asteroids, and comets has led many scientists to hypothesize that PAHs are the source of much of the carbon that formed our own solar system. In 2023, researchers in Japan found large quantities of pyrene in samples returned from the asteroid Ryugu during the Hayabusa2 mission, along with smaller PAHs including naphthalene.
That discovery motivated McGuire and his colleagues to look for pyrene in TMC-1. Pyrene, which contains four rings, is larger than any of the other PAHs that have been detected in space. In fact, it’s the third-largest molecule identified in space, and the largest ever detected using radio astronomy.
Before looking for these molecules in space, the researchers first had to synthesize cyanopyrene in the laboratory. The cyano or nitrile group is necessary for the molecule to emit a signal that a radio telescope can detect. The synthesis was performed by MIT postdoc Shuo Zhang in the group of Alison Wendlandt, an MIT associate professor of chemistry.
Then, the researchers analyzed the signals that the molecules emit in the laboratory, which are exactly the same as the signals that they emit in space.
Using the GBT, the researchers found these signatures throughout TMC-1. They also found that cyanopyrene accounts for about 0.1 percent of all the carbon found in the cloud, which sounds small but is significant when one considers the thousands of different types of carbon-containing molecules that exist in space, McGuire says.
“While 0.1 percent doesn’t sound like a large number, most carbon is trapped in carbon monoxide (CO), the second-most abundant molecule in the universe besides molecular hydrogen. If we set CO aside, one in every few hundred or so remaining carbon atoms is in pyrene. Imagine the thousands of different molecules that are out there, nearly all of them with many different carbon atoms in them, and one in a few hundred is in pyrene,” he says. “That is an absolutely massive abundance. An almost unbelievable sink of carbon. It’s an interstellar island of stability.”
Ewine van Dishoeck, a professor of molecular astrophysics at Leiden Observatory in the Netherlands, called the discovery “unexpected and exciting.”
“It builds on their earlier discoveries of smaller aromatic molecules, but to make the jump now to the pyrene family is huge. Not only does it demonstrate that a significant fraction of carbon is locked up in these molecules, but it also points to different formation routes of aromatics than have been considered so far,” says van Dishoeck, who was not involved in the research.
An abundance of pyrene
Interstellar clouds like TMC-1 may eventually give rise to stars, as clumps of dust and gas coalesce into larger bodies and begin to heat up. Planets, asteroids, and comets arise from some of the gas and dust that surround young stars. Scientists can’t look back in time at the interstellar cloud that gave rise to our own solar system, but the discovery of pyrene in TMC-1, along with the presence of large amounts of pyrene in the asteroid Ryugu, suggests that pyrene may have been the source of much of the carbon in our own solar system.
“We now have, I would venture to say, the strongest evidence ever of this direct molecular inheritance from the cold cloud all the way through to the actual rocks in the solar system,” McGuire says.
The researchers now plan to look for even larger PAH molecules in TMC-1. They also hope to investigate the question of whether the pyrene found in TMC-1 was formed within the cold cloud or whether it arrived from elsewhere in the universe, possibly from the high-energy combustion processes that surround dying stars.
The research was funded in part by a Beckman Foundation Young Investigator Award, the Schmidt Family Futures Foundation, the U.S. National Science Foundation, the Natural Sciences and Engineering Research Council of Canada, the Goddard Center for Astrobiology, and the NASA Planetary Science Division Internal Scientist Funding Program.
SMART researchers develop a method to enhance effectiveness of cartilage repair therapy
Researchers from the Critical Analytics for Manufacturing Personalized-Medicine (CAMP) interdisciplinary research group at the Singapore-MIT Alliance for Research and Technology (SMART), MIT’s research enterprise in Singapore, alongside collaborators from the National University of Singapore Tissue Engineering Programme, have developed a novel method to enhance the ability of mesenchymal stromal cells (MSCs) to generate cartilage tissue by adding ascorbic acid during MSC expansion. The research also discovered that micro-magnetic resonance relaxometry (µMRR), a novel process analytical tool developed by SMART CAMP, can be used as a rapid, label-free process-monitoring tool for the quality expansion of MSCs.
Articular cartilage, a connective tissue that protects the bone ends in joints, can degenerate due to injury, age, or arthritis, leading to significant joint pain and disability. Especially in countries — such as Singapore — that have an active, aging population, articular cartilage degeneration is a growing ailment that affects an increasing number of people. Autologous chondrocyte implantation is currently the only Food and Drug Administration-approved cell-based therapy for articular cartilage injuries, but it is costly, time-intensive, and requires multiple treatments. MSCs are an attractive and promising alternative as they have shown good safety profiles for transplantation. However, clinical use of MSCs is limited due to inconsistent treatment outcomes arising from factors such as donor-to-donor variability, variation among cells during cell expansion, and non-standardized MSC manufacturing protocols.
The heterogeneity of MSCs can lead to variations in their biological behavior and treatment outcomes. While large-scale MSC expansions are required to obtain a therapeutically relevant number of cells for implantation, this process can introduce cell heterogeneity. Therefore, improved processes are essential to reduce cell heterogeneity while increasing donor cell numbers with improved chondrogenic potential — the ability of MSCs to differentiate into cartilage cells to repair cartilage tissue — to pave the way for more effective and consistent MSC-based therapies.
In a paper titled “Metabolic modulation to improve MSC expansion and therapeutic potential for articular cartilage repair,” published in the scientific journal Stem Cell Research and Therapy, CAMP researchers detailed their development of a priming strategy to enhance the expansion of quality MSCs by modifying the way cells utilize energy. The research findings have shown a positive correlation between chondrogenic potential and oxidative phosphorylation (OXPHOS), a process that harnesses the reduction of oxygen to create adenosine triphosphate — a source of energy that drives and supports many processes in living cells. This suggests that manipulating MSC metabolism is a promising strategy for enhancing chondrogenic potential.
Using novel PATs developed by CAMP, the researchers explored the potential of metabolic modulation in both short- and long-term harvesting and reseeding of cells. To enhance their chondrogenic potential, they varied the nutrient composition, including glucose, pyruvate, glutamine, and ascorbic acid (AA). As AA is reported to support OXPHOS and its positive impact on chondrogenic potential during differentiation — a process in which immature cells become mature cells with specific functions — the researchers further investigated its effects during MSC expansion.
The addition of AA to cell cultures for one passage during MSC expansion and prior to initiation of differentiation was found to improve chondrogenic differentiation, which is a critical quality attribute (CQA) for better articular cartilage repair. Longer-term AA treatment led to a more than 300-fold increase in the yield of MSCs with enhanced chondrogenic potential, and reduced cell heterogeneity and cell senescence — a process by which a cell ages and permanently stops dividing but does not die — when compared to untreated cells. AA-treated MSCs with improved chondrogenic potential showed a robust shift in metabolic profile to OXPHOS. This metabolic change correlated with μMRR measurements, which helps identify novel CQAs that could be implemented in MSC manufacturing for articular cartilage repair.
The research also demonstrates the potential of the process analytical tool developed by CAMP, micromagnetic resonance relaxometry (μMRR) — a miniature benchtop device that employs magnetic resonance imaging (MRI) imaging on a microscopic scale — as a process-monitoring tool for the expansion of MSCs with AA supplementation. Originally used as a label-free malaria diagnosis method due to the presence of paramagnetic hemozoin particles, μMRR was used in the research to detect senescence in MSCs. This rapid, label-free method requires only a small number of cells for evaluation, which allows for MSC therapy manufacturing in closed systems — a system for protecting pharmaceutical products by reducing contamination risks from the external environment — while enabling intermittent monitoring of a limited lot size per production.
“Donor-to-donor variation, intrapopulation heterogeneity, and cellular senescence have impeded the success of MSCs as a standard of care therapy for articular cartilage repair. Our research showed that AA supplementation during MSC expansion can overcome these bottlenecks and enhance MSC chondrogenic potential,” says Ching Ann Tee, senior postdoc at SMART CAMP and first author of the paper. “By controlling metabolic conditions such as AA supplementation, coupled with CAMP’s process analytical tools such as µMRR, the yield and quality of cell therapy products could be significantly increased. This breakthrough could help make MSC therapy a more effective and viable treatment option and provide standards for improving the manufacturing pipeline.”
“This approach of utilizing metabolic modulation to improve MSC chondrogenic potential could be adapted into similar concepts for other therapeutic indications, such as osteogenic potential for bone repair or other types of stem cells. Implementing our findings in MSC manufacturing settings could be a significant step forward for patients with osteoarthritis and other joint diseases, as we can efficiently produce large quantities of high-quality MSCs with consistent functionality and enable the treatment of more patients,” adds Professor Laurie A. Boyer, principal investigator at SMART CAMP, professor of biology and biological engineering at MIT, and corresponding author of the paper.
The research is conducted by SMART and supported by the National Research Foundation Singapore under its Campus for Research Excellence and Technological Enterprise program.
Study: Hospice care provides major Medicare savings
Hospice care aims to provide a health care alternative for people nearing the end of life by sparing them unwanted medical procedures and focusing on the patient’s comfort. A new study co-authored by MIT scholars shows hospice also has a clear fiscal benefit: It generates substantial savings for the U.S. Medicare system.
The study examines the growth of for-profit hospice providers, who receive reimbursements from Medicare, and evaluates the cost of caring for patients with Alzheimer’s disease and related dementias (ADRD). The research finds that for patients using for-profit hospice providers, there is about a $29,000 savings to Medicare over the first five years after someone is diagnosed with ADRD.
“Hospice is saving Medicare a lot of money,” says Jonathan Gruber, an MIT health care economist and co-author of a paper detailing the study’s findings. “Those are big numbers.”
In recent decades, hospice care has grown substantially. That growth has been accompanied by concerns that for-profit hospice organizations, in particular, might be overly aggressive in pursuing patients. There have also been instances of fraud by organizations in the field. And yet, the study shows that the overall dynamics of hospice are the intended ones: People are indeed receiving palliative-type care, based around comfort rather than elaborate medical procedures, at less cost.
“What we found is that hospice basically operates as advertised,” adds Gruber, the Ford Professor of Economics at MIT. “It does not extend lives on aggregate, and it does save money.”
The paper, “Dying or Lying? For-Profit Hospices and End of Life Care,” appears in the American Economic Review. The co-authors are Gruber, who is also head of MIT’s Department of Economics; David Howard, a professor at the Rollins School of Public Health at Emory University; Jetson Leder-Luis PhD ’20, an assistant professor at Boston University; and Theodore Caputi, a doctoral student in MIT’s Department of Economics.
Charting what more hospice access means
Hospice care in the U.S. dates to at least the 1970s. Patients opt out of their existing medical network and receive nursing care where they live, either at home or in care facilities. That care is oriented around reducing suffering and pain, rather than attempting to eliminate underlying causes. Generally, hospice patients are expected to have six months or less to live. Most Medicare funding goes to private contractors supplying medical care, and in the 1980s the federal government started using Medicare to reimburse the medical expenses from hospice as well.
While the number of nonprofit hospice providers in the U.S. has remained fairly consistent, the number of for-profit hospice organizations grew fivefold between 2000 and 2019. Medicare payments for hospice care are now about $20 billion annually, up from $2.5 billion in 1999. People diagnosed with ADRD now make up 38 percent of hospice patients.
Still, Gruber considers the topic of hospice care relatively under-covered by analysts. To conduct the study, the team examined over 10 million patients from 1999 through 2019. The researchers used the growth of for-profit hospice providers to compare the effects of being enrolled in non-profit hospice care, for-profit hospice care, or staying in the larger medical system.
That means the scholars were not only evaluating hospice patients; by evaluating the larger population in a given area where and when for-profit hospice firms opened their doors, they could see what difference greater access to hospice care made. For instance, having a new for-profit hospice open locally is associated with a roughly 2 percentage point increase in for-profit hospice admissions in following years.
“We’re able to use this methodology to [analyze] if these patients would otherwise have not gone to hospice or would have gone to a nonprofit hospice,” Gruber says.
The method also allows the scholars to estimate the substantial cost savings. And it shows that enrolling in hospice increased the five-year post-diagnosis mortality rate of ADRD patients by 8.6 percentage points, from a baseline of 66.6 percent. Entering into hospice care — which is a reversible decision — means foregoing life-extending surgeries, for instance, if people believe such procedures are no longer desirable for them.
Rethinking the cap
By providing care without more expensive medical procedures, it is understandable that hospice reduces overall medical costs. Still, given that Medicare reimburses hospice organizations, one ongoing policy concern is that hospice providers might aggressively recruit a larger percentage of patients who end up living longer than six additional months. In this way hospice providers might unduly boost their revenues and put more pressure on the Medicare budget.
To counteract this, Medicare rules include a roughly $29,205 cap on per-patient reimbursements, as of 2019. Most patients die relatively soon after entering hospice care; some will outlive the six-month expectation significantly. But hospice organizations cannot exceed that average.
However, the study also suggests the cap is a suboptimal approach. In 2018, 15.5 percent of hospice patients were being discharged from hospice care while still alive, due to the cap limiting hospice capacity. As the paper notes, “patients in hospices facing cap pressure are more likely to be discharged from hospice alive and experience higher mortality rates.”
As Gruber notes, the spending cap is partly a fraud-fighting tool. And yet the cap clearly has other, unintended consquences on patients and their medical choices, crowding some out of the hospice system.
“The cap may be throwing the baby out with the bathwater.” Gruber says. “The government has more focused tools to fight fraud. Using the cap for that is a blunt instrument.”
As long as people are informed about hospice and the medical trajectory it puts them on, then, hospice care appears to be providing a valued service at less expense than other approaches to end-of-life care.
“The holy grail in health care is things that improve quality and save money,” Gruber says. “And with hospice, there are surveys saying people like it. And it certainly saves money, and there’s no evidence it’s doing harm [to patients]. We talk about how we struggle to deal with health care costs in this country, so this seems like what we want.”
The research was supported in part by the National Institute on Aging of the National Institutes of Health.
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