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Looking to space to cure osteoarthritis



knee research image

In 1976, Alan Grodzinsky ’71, ScD ’74, was feeling a little frustrated. 

He had spent two years teaching a basic course on semiconductor physics and circuits in MIT’s Department of Electrical Engineering and Computer Science, learning the material in the fast-moving field as he went along. That didn’t leave him any time for research. Then a golden opportunity arose.

With the help of the late Irving London, founder of the Harvard-MIT Program in Health Sciences and Technology, Grodzinsky won a sabbatical at Boston Children’s Hospital under the mentorship of the late Mel Glimcher, chief of orthopedic surgery and a pioneering researcher on the biology of human bones and collagen.

Glimcher wanted to start a research project on cartilage, the tough matrix of fibers that lines the joints, and on osteoarthritis, the chronic, painful disease that breaks that cartilage down.

It was a perfect fit for the 29-year-old Grodzinsky, who had earned his ScD studying the electrical properties of collagen, one of the constituents of cartilage. By year’s end, he was on the path he has followed ever since: trying to find effective treatments for osteoarthritis, the leading cause of chronic pain and disability around the world. It affects more than 30 million Americans, and hundreds of millions globally.

“It’s a huge financial burden and disability burden. And while it’s not fatal, it certainly contributes to loss of quality of life,” says Joseph Buckwalter, an orthopedic surgeon and osteoarthritis expert based in Iowa, who has known Grodzinsky for decades. “The costs of total joint replacements, mainly knees and hips, is one of our major health expenditures.”

No plan for pain

The US Food and Drug Administration has not approved any disease-modifying medications for osteoarthritis—drugs that treat the underlying condition rather than just the symptoms. The most sufferers can hope for, Grodzinsky says, are pain relievers like Motrin, occasional injections of steroids, and eventually joint replacement surgery. More than a million knee and hip replacements are done in the US each year, and the number is expected to soar as the population ages.

While older people are most susceptible to osteoarthritis, Grodzinsky has focused much of his research on younger people, particularly female athletes, who often develop the condition after knee injuries.

Tens of thousands of young women suffer injuries to the anterior cruciate ligaments of their knees each year. “When I teach my course at MIT related to biomechanics,” Grodzinsky says, “I ask about ACL injuries, and just as many hands go up today as in the past. I taught a Harvard Medical School course recently, and of the 20 students in the class, four women had suffered ACL tears, and one was on her third surgery.”

Doctors can fix these tears, he says, but both men and women who suffer joint injuries are still at high risk of developing osteoarthritis in subsequent years. And while knee replacements can counteract the effects of osteoarthritis, doctors are reluctant to perform such surgery on younger people because it will probably need to be repeated after the first artificial joint wears out.

A knee implant can last years, says Buckwalter, but “I would have nightmares doing it in someone under 40, because the odds are almost overwhelming that they’ll need another one.”

Nanoparticle Rx

Researchers have identified existing drugs that might alleviate the onset of osteoarthritis, but they are hampered by the fact that cartilage does not have a natural blood supply, Grodzinsky says. When doctors inject a steroid in the knee joint to reduce inflammation, the body clears most of the medication before it can get into the cartilage.

To tackle this problem, his lab has pioneered research involving nanoparticles, human cadaver knees, and even missions to the International Space Station.

Six days after an arthritic knee was treated with nanoparticles containing insulin-like growth factor 1 (blue), the particles have penetrated through the cartilage of the knee joint.


Starting with that sabbatical more than four decades ago, Grodzinsky learned a vital fact about cartilage. While the tissue fibers themselves provide some of the support for our joints, much of its strength comes from its electrostatic properties. “It turns out about half the compressive mechanical stiffness of our cartilage is due to electrostatic repulsive interactions between negatively charged sugar chains,” he says.

This negatively charged tissue matrix also offers a way to deliver drugs directly into the tissue: by loading them into positively charged nanoparticles. Grodzinsky’s team has been able to show in human cadaver knee cartilage that such particles can counteract the early inflammation and damage caused by injuries. 

The initial nanoparticle work was started several years ago by Grodzinsky’s former doctoral student Ambika Bajpayee, MNG ’07, PhD ’15, now a professor at Northeastern University. Bajpayee then collaborated with Paula Hammond, head of MIT’s chemical engineering department, who had pioneered the use of nanoparticles to deliver drugs to cancerous tumors. 

In the Grodzinsky lab, the drug-­containing nanoparticles are injected into animals’ joints, just as they would be in human patients, he says, and “once they’re inside, if they’re used at the right concentration, they can stay inside for many weeks,” nestled in the fibrous matrix. 

The group has concentrated on delivering two medications that are already approved for human use. 

One is the anti-inflammatory dexamethasone, which also has been used successfully to treat breathing problems in some hospitalized covid-19 patients. The other is insulin-like growth factor 1 (IGF-1), a hormone that promotes growth of bone and cartilage tissue and has been used in children born smaller than normal.

The dexamethasone lessens the breakdown of cartilage after an injury, Grodzinsky says, while IGF-1 can promote tissue repair.

Animal studies using IGF-1 have been done in a collaboration with Hammond, and Grodzinsky’s lab has extended this experimental treatment to human tissues as well, relying on samples from dead people. So far, the lab has been able to obtain pieces of knee bone, cartilage, and synovial joint capsule from 45 donors, says Garima Dwivedi, a postdoctoral researcher in the lab. 

Dwivedi and her colleagues put the samples in wells built into plastic plates and keep them metabolically active. Then they apply a mechanical impact that mimics what happens in a knee injury. That releases inflammatory molecules known as cytokines and begins a process similar to what happens in osteoarthritis.

Outer space

In this work, the researchers put the nanoparticles in the culture medium that bathes the tissue samples—a technique they could also use in future experiments on the space station, which has become a magnet for researchers studying diseases of aging.

Scientists have known for years that human tissues age more quickly in low Earth orbit than on Earth, though the reasons are somewhat mysterious. One analysis estimated that astronauts’ muscles and bones atrophy 10 times faster in microgravity. 

Figuring out how to repair joint damage may be crucial for future long- term space missions.

With funding from the NIH and NASA, Grodzinsky’s lab sent samples of knee cartilage-bone plugs and synovium tissues to the ISS in 2019 and 2020. They hoped to determine whether osteoarthritis-like disease could be initiated “in a dish” to simulate what happens in humans after a knee injury—using the microgravity environment to explore and eliminate the mechanical processes at work—and to try treating it with dexamethasone and IGF-1. 

Preliminary results have been encouraging, he says. On the most recent trip to the ISS, the lab found that both drugs reduced damage in the many of the cartilage samples. 

“Since most researchers these days stress that there will not likely be a single magic bullet, we believe the ability to test combinations of drugs in vitro is an important step forward,” Grodzinsky says.

The work in microgravity may also pay dividends for future space missions, Dwivedi says. Astronauts, who exercise intensively in space to counteract the atrophy that muscles and bones tend to suffer in weightless conditions, are three times more likely to get impact injuries than people on Earth, she says, so figuring out how to repair joint damage may be crucial for future long-term space missions.

Compassionate mentorship

Grodzinsky always seemed destined to find a home at MIT.

Growing up on Long Island, where he attended public schools in the booming postwar suburb of East Meadow, he sometimes visited his older brother, Stephen Grodzinsky ’65, SM ’67, at Burton House. He remembers thinking, “This looks great to me.”

He went on to get his ScD under the late James Melcher, director of the school’s Laboratory for Electromagnetic and Electronic Systems. But soon a recession hit, and the only positions he was offered were a postdoc in icy Saskatchewan and an assistant professorship in music and engineering in Brazil. His mentors—including Ioannis Yannas, best known for inventing artificial skin—encouraged him to stick around, offering him a teaching position in electrical engineering. He has been at the Institute ever since.

In 1995, MIT set up the Center for Biomedical Engineering to advance research in what was then a new field. Three years later, Grodzinsky was named to his current post as its director. At that time, his faculty affiliation changed to the newly formed Department of Biological Engineering, with joint appointments in EECS and mechanical engineering.

Grodzinsky believes any research success he has achieved has been the direct result of the “tremendous PhD students and postdocs we were able to get at MIT.” They in turn have prospered under his compassionate mentorship.

“It has been a pleasure to work with him, primarily because he gives you a lot of independence for your own ideas to develop,” says postdoc Dwivedi. “And no matter who you are and what stage of career you’re in, he listens to you with utmost attention and respect.”

Professor Gropdzinsky and wife Gail
Grodzinsky and his wife, Gail, now a pediatric neuropsychologist at Boston Children’s Hospital, met playing chamber music.


She also appreciates his personal support. When her parents in India contracted covid in April, he “gave me completely free time to help take care of them,” she says. 

Grodzinsky himself has managed to avoid osteoarthritis, even though, at age 74, he is in a prime risk category for the disease. 

Maybe, he muses, it’s because his avocation as a musician has kept him limber. After years of piano lessons at the Third Street Music School Settlement in New York, he became the principal violist of the MIT Symphony Orchestra as an undergraduate. He also played in freelance string quartets after finishing his ScD and met his wife, Gail, playing chamber music.

After officially setting foot on campus as a student at age 18, he says with a smile, “somehow, I’ve never been able to find a way to leave.”


The hunter-gatherer groups at the heart of a microbiome gold rush



The hunter-gatherer groups at the heart of a microbiome gold rush

The first step to finding out is to catalogue what microbes we might have lost. To get as close to ancient microbiomes as possible, microbiologists have begun studying multiple Indigenous groups. Two have received the most attention: the Yanomami of the Amazon rainforest and the Hadza, in northern Tanzania. 

Researchers have made some startling discoveries already. A study by Sonnenburg and his colleagues, published in July, found that the gut microbiomes of the Hadza appear to include bugs that aren’t seen elsewhere—around 20% of the microbe genomes identified had not been recorded in a global catalogue of over 200,000 such genomes. The researchers found 8.4 million protein families in the guts of the 167 Hadza people they studied. Over half of them had not previously been identified in the human gut.

Plenty of other studies published in the last decade or so have helped build a picture of how the diets and lifestyles of hunter-gatherer societies influence the microbiome, and scientists have speculated on what this means for those living in more industrialized societies. But these revelations have come at a price.

A changing way of life

The Hadza people hunt wild animals and forage for fruit and honey. “We still live the ancient way of life, with arrows and old knives,” says Mangola, who works with the Olanakwe Community Fund to support education and economic projects for the Hadza. Hunters seek out food in the bush, which might include baboons, vervet monkeys, guinea fowl, kudu, porcupines, or dik-dik. Gatherers collect fruits, vegetables, and honey.

Mangola, who has met with multiple scientists over the years and participated in many research projects, has witnessed firsthand the impact of such research on his community. Much of it has been positive. But not all researchers act thoughtfully and ethically, he says, and some have exploited or harmed the community.

One enduring problem, says Mangola, is that scientists have tended to come and study the Hadza without properly explaining their research or their results. They arrive from Europe or the US, accompanied by guides, and collect feces, blood, hair, and other biological samples. Often, the people giving up these samples don’t know what they will be used for, says Mangola. Scientists get their results and publish them without returning to share them. “You tell the world [what you’ve discovered]—why can’t you come back to Tanzania to tell the Hadza?” asks Mangola. “It would bring meaning and excitement to the community,” he says.

Some scientists have talked about the Hadza as if they were living fossils, says Alyssa Crittenden, a nutritional anthropologist and biologist at the University of Nevada in Las Vegas, who has been studying and working with the Hadza for the last two decades.

The Hadza have been described as being “locked in time,” she adds, but characterizations like that don’t reflect reality. She has made many trips to Tanzania and seen for herself how life has changed. Tourists flock to the region. Roads have been built. Charities have helped the Hadza secure land rights. Mangola went abroad for his education: he has a law degree and a master’s from the Indigenous Peoples Law and Policy program at the University of Arizona.

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The Download: a microbiome gold rush, and Eric Schmidt’s election misinformation plan



The Download: a microbiome gold rush, and Eric Schmidt’s election misinformation plan

Over the last couple of decades, scientists have come to realize just how important the microbes that crawl all over us are to our health. But some believe our microbiomes are in crisis—casualties of an increasingly sanitized way of life. Disturbances in the collections of microbes we host have been associated with a whole host of diseases, ranging from arthritis to Alzheimer’s.

Some might not be completely gone, though. Scientists believe many might still be hiding inside the intestines of people who don’t live in the polluted, processed environment that most of the rest of us share. They’ve been studying the feces of people like the Yanomami, an Indigenous group in the Amazon, who appear to still have some of the microbes that other people have lost. 

But there is a major catch: we don’t know whether those in hunter-gatherer societies really do have “healthier” microbiomes—and if they do, whether the benefits could be shared with others. At the same time, members of the communities being studied are concerned about the risk of what’s called biopiracy—taking natural resources from poorer countries for the benefit of wealthier ones. Read the full story.

—Jessica Hamzelou

Eric Schmidt has a 6-point plan for fighting election misinformation

—by Eric Schmidt, formerly the CEO of Google, and current cofounder of philanthropic initiative Schmidt Futures

The coming year will be one of seismic political shifts. Over 4 billion people will head to the polls in countries including the United States, Taiwan, India, and Indonesia, making 2024 the biggest election year in history.

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Navigating a shifting customer-engagement landscape with generative AI



Navigating a shifting customer-engagement landscape with generative AI

A strategic imperative

Generative AI’s ability to harness customer data in a highly sophisticated manner means enterprises are accelerating plans to invest in and leverage the technology’s capabilities. In a study titled “The Future of Enterprise Data & AI,” Corinium Intelligence and WNS Triange surveyed 100 global C-suite leaders and decision-makers specializing in AI, analytics, and data. Seventy-six percent of the respondents said that their organizations are already using or planning to use generative AI.

According to McKinsey, while generative AI will affect most business functions, “four of them will likely account for 75% of the total annual value it can deliver.” Among these are marketing and sales and customer operations. Yet, despite the technology’s benefits, many leaders are unsure about the right approach to take and mindful of the risks associated with large investments.

Mapping out a generative AI pathway

One of the first challenges organizations need to overcome is senior leadership alignment. “You need the necessary strategy; you need the ability to have the necessary buy-in of people,” says Ayer. “You need to make sure that you’ve got the right use case and business case for each one of them.” In other words, a clearly defined roadmap and precise business objectives are as crucial as understanding whether a process is amenable to the use of generative AI.

The implementation of a generative AI strategy can take time. According to Ayer, business leaders should maintain a realistic perspective on the duration required for formulating a strategy, conduct necessary training across various teams and functions, and identify the areas of value addition. And for any generative AI deployment to work seamlessly, the right data ecosystems must be in place.

Ayer cites WNS Triange’s collaboration with an insurer to create a claims process by leveraging generative AI. Thanks to the new technology, the insurer can immediately assess the severity of a vehicle’s damage from an accident and make a claims recommendation based on the unstructured data provided by the client. “Because this can be immediately assessed by a surveyor and they can reach a recommendation quickly, this instantly improves the insurer’s ability to satisfy their policyholders and reduce the claims processing time,” Ayer explains.

All that, however, would not be possible without data on past claims history, repair costs, transaction data, and other necessary data sets to extract clear value from generative AI analysis. “Be very clear about data sufficiency. Don’t jump into a program where eventually you realize you don’t have the necessary data,” Ayer says.

The benefits of third-party experience

Enterprises are increasingly aware that they must embrace generative AI, but knowing where to begin is another thing. “You start off wanting to make sure you don’t repeat mistakes other people have made,” says Ayer. An external provider can help organizations avoid those mistakes and leverage best practices and frameworks for testing and defining explainability and benchmarks for return on investment (ROI).

Using pre-built solutions by external partners can expedite time to market and increase a generative AI program’s value. These solutions can harness pre-built industry-specific generative AI platforms to accelerate deployment. “Generative AI programs can be extremely complicated,” Ayer points out. “There are a lot of infrastructure requirements, touch points with customers, and internal regulations. Organizations will also have to consider using pre-built solutions to accelerate speed to value. Third-party service providers bring the expertise of having an integrated approach to all these elements.”

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