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‘Type’ Casting: Flagship-Founded Serif Modifying DNA into New Therapy Class

What happens when the scalability and redosability of messenger RNA (mRNA) is combined with the durability and programmability of gene therapy?

According to Serif Biomedicines, a five-year-old startup that emerged from stealth mode this month, the result is “modified DNA,” a new class of therapeutics designed to be programmable, durable, scalable, and redosable—while minimizing the drawbacks of both mRNA and gene therapy.

Modified DNA builds upon generative protein and mRNA platforms created by Flagship Pioneering, the venture capital giant which founded Serif in 2021. On April 21, Flagship formally launched Serif with an initial commitment of $50 million in financing—capital that Serif intends to use toward developing its scalable platform for optimizing and manufacturing Modified DNA treatments, aided by artificial intelligence (AI), and advancing its first drug discovery programs.

“The reason we’re bringing the company out of stealth mode now is we think we have made progress. We’ve made real progress that we’re excited to share with the world, that we’re excited to get feedback from the broader scientific community on, and we want to tell that story more broadly,” Jacob (Jake) Rubens, PhD, Serif’s co-founder and CEO, and an Orig­i­na­tion Part­ner at Flag­ship Pio­neer­ing, told GEN.

“It’s been on our minds for a long time: What might be possible when DNA becomes an engineerable biotechnology for the first time?”

It’s a question pursued by numerous researchers and companies over the years as they sought to capitalize on DNA’s qualities of being a durably expressing molecule capable of coding for any gene, producing proteins or RNAs in a cell-specific way, as well as being scalable to manufacture and capable of re-dosing for patients.

“Those are, I think, the key differentiating attributes of theoretical DNA medicines. So the question for us became not, would this be valuable if we could do it, but why hasn’t anyone done it yet?” Rubens explained. “We’ve known about the centrality of DNA in biology, the central information molecule in DNA. We’ve known this for 75 years since Watson and Crick’s seminal discoveries around how the structure of DNA enabled it to function as an information molecule.”

Two key problems

Jacob (Jake) Rubens, PhD, Serif Biomedicines co-founder and CEO

“And when we looked at this space,” he continued, “we saw that there were two key problems: The first is that DNA is a highly inflammatory molecule. The second is that DNA needs to be delivered not just into a cell, but into the nucleus, the center of the cell.”

To create Mod­i­fied DNA, Serif alters the struc­tur­al and chem­i­cal form of DNA in order to min­i­mize innate immuno­genic­i­ty as lipid nanoparticles drop off the DNA not in the nucleus, but in the cytoplasm of the cell.

Once inside the cell nucleus, Mod­i­fied DNA reverts to unmod­i­fied DNA, enabling tran­scrip­tion into ther­a­peu­tic RNA and proteins. The resulting treatments are designed to last longer, be giv­en more than once, and be pro­grammed for cell-spe­cif­ic expres­sion. To enhance durability, Serif delivers with its Mod­i­fied DNA proteins which help the DNA access the nucleus. The proteins, called mRNA co-fac­tors, are designed to tran­sient­ly express pro­teins that enhance entry into the nucleus and gene expression.

Pending an announcement it expects to make later this year, Serif isn’t revealing specifics of its initial drug discovery programs, except to say that they focus on rare diseases and immune programming.

“This is not meant to be a limited list of where we could go but the areas that we think we’re going to go first, which are likely in addressing protein deficiencies in genetic diseases,” Rubens said.

Modified DNA has shown itself to be disease agnostic, he added, reflecting DNA’s qualities as a general, programmable information molecule: “One of the reasons we’re so excited about, the future of modified DNA as a new biotechnology akin to RNA, akin to protein, is its centrality in biology. It is the fundamental information molecule inside of all of us, inside of every living thing on this planet. So that is really the existence proof that it is generalizable.”

Tolerability and sustained expression

Also later this year, Serif plans to present data at an as-yet-unspecified scientific conference that will show modified DNA’s tolerability in non-human primates, as well as sustained gene expression with therapeutic effects in preclinical models following intravenous (IV) administration.

Serif aims to transform Modified DNA into treatments as effectively and commercially successfully as Amgen, Genentech (now a member of the Roche Group), and later Regeneron did with engineered proteins, as Alnylam Pharmaceuticals did with small interfering RNA (siRNA), and as Moderna more recently accomplished with mRNA—most notably in developing its SpikeVax® COVID-19 vaccine, which the FDA authorized for emergency use in 2020 and fully approved in 2022.

Flagship launched Moderna in 2010; the company went public in 2018 by raising $604 million, the largest-ever U.S. biotech initial public offering (IPO) until Kailera Therapeutics raised $625 million earlier this month.

At Flagship, Rubens is a sci­en­tist entre­pre­neur who leads the firm’s Pio­neer­ing Busi­ness Unit, which establishes and grows com­pa­nies based on new biotechnology. In addition to Serif, Rubens co-founded Quo­tient Ther­a­peu­tics, which develops therapies based on its somatic genomics platform; Tessera Ther­a­peu­tics, which writes therapeutic messages into the genome through a genome engineering approach called GeneWriting™; and Sana Biotech­nol­o­gy, a developer of treatments based on engineered cells. He also launched Kalei­do Bio­sciences, a microbiome therapeutics company that ceased operations in 2022.

Before join­ing Flagship, Jake received his PhD in micro­bi­ol­o­gy from MIT, work­ing with Tim Lu, MD, PhD, a core member of the Synthetic Biology Center, through the sup­port of a Nation­al Sci­ence Foun­da­tion Grad­u­ate Research Fel­low­ship. At MIT, Jake helped enable ​“intel­li­gent” cell therapies by invent­ing gene cir­cuits that allow engi­neered cells to do nov­el ana­log, dig­i­tal, and hybrid com­pu­ta­tions.

Based in Cambridge, MA, Serif employs about 50 people and as of Wednesday was disclosing five open positions on its website in its three areas of focus: Chemistry (associate scientist and senior scientist, both specializing in LNP formulations), Molecular Biology (research associate and senior scientist), and Research/Discovery (scientist specializing in bioanalytical assays).

“I’m not at this point going to provide any guidance on how much more we will or won’t grow,” Rubens said. “We’re quite agile and responsive to the company’s needs.”

The post ‘Type’ Casting: Flagship-Founded Serif Modifying DNA into New Therapy Class appeared first on GEN – Genetic Engineering and Biotechnology News.

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Obesity Leaves Lasting DNA Methylation Memory in Immune Cells

A new study suggests that obesity leaves a durable molecular imprint on the immune system, one that persists long after weight loss and may continue to influence disease risk. Researchers at the University of Birmingham report that key immune cells retain an “epigenetic memory” of obesity, potentially sustaining inflammation and metabolic dysfunction even after patients return to a healthy weight.

The findings, published in EMBO Reports, provide a mechanistic explanation for a long-standing clinical observation: that individuals who lose weight often remain at elevated risk for conditions such as type 2 diabetes, cardiovascular disease, and certain cancers.

Immune cells retain a “memory” of obesity

The study focuses on CD4+ helper T cells, central regulators of immune coordination. By analyzing patient samples across multiple cohorts, including individuals undergoing pharmacological weight loss, rare genetic obesity syndromes, and lifestyle interventions, the researchers identified persistent epigenetic modifications in these cells.

Specifically, obesity was associated with changes in DNA methylation, a process in which chemical tags are added to DNA and alter gene expression without changing the underlying sequence. These modifications effectively encode a molecular memory of prior metabolic state.

As explained by the authors, these epigenetic marks can persist for years after weight loss. “The findings suggest that short-term weight loss may not immediately reduce the risk of some disease conditions associated with obesity,” said Claudio Mauro, PhD, senior author of the study. Instead, the immune system appears to retain a record of past metabolic stress that continues to influence cellular behavior.

Persistence beyond weight loss

The durability of this imprint is striking. The study estimates that obesity-associated DNA methylation patterns in T cells may persist for five to ten years after successful weight reduction. This suggests that immune remodeling lags far behind metabolic normalization.

Supporting this, the team observed similar patterns across diverse experimental systems, including human clinical samples and mouse models of diet-induced obesity. Together, these data point to a conserved biological mechanism rather than a transient or context-specific effect.

This persistent immune memory may help explain why relapse and long-term complications are common in obesity. As noted by Belinda Nedjai, PhD, of Queen Mary University of London, “the immune system retains a molecular record of past metabolic exposures, which may have implications for long-term disease risk and recovery.”

Disruption of cellular housekeeping and aging

At the functional level, the epigenetic changes identified in T cells appear to disrupt two critical biological processes: autophagy and immune senescence.

Autophagy, the process by which cells degrade and recycle damaged components, is essential for maintaining cellular health. The study suggests that obesity-associated DNA methylation impairs this pathway, reducing the cell’s ability to clear waste and maintain homeostasis.

In parallel, the researchers observed effects on immune aging, or senescence. Dysregulated T cells exhibited features of premature aging, potentially contributing to chronic inflammation and reduced immune resilience.

Together, these alterations could create a persistent pro-disease environment, even after weight loss. This reframes obesity not simply as a reversible metabolic state, but as a condition capable of inducing long-term immune reprogramming.

Implications for treatment strategies

The findings have direct implications for how obesity is managed clinically. If immune dysfunction persists for years after weight loss, then short-term interventions may be insufficient to fully restore health.

Instead, sustained weight maintenance—and potentially additional therapies targeting immune reprogramming—may be required. Mauro noted that “ongoing weight management following loss will see the ‘obesity memory’ slowly fade,” though this process may take years.

The study also points to potential therapeutic strategies. Drugs such as SGLT2 inhibitors, already used in diabetes treatment, may help accelerate the reversal of these epigenetic changes by reducing inflammation and promoting clearance of dysfunctional cells.

Rethinking obesity as a chronic immuno-metabolic disease

Beyond its immediate clinical implications, the study contributes to a broader conceptual shift in how obesity is understood. Rather than being defined solely by excess adiposity, obesity emerges as a condition that induces lasting systemic changes, particularly within the immune system.

As Andy Hogan, PhD, of Maynooth University emphasized, “obesity is a chronic progressive and relapsing disease,” and these findings help explain the biological basis of that persistence.

By identifying an epigenetic “memory” within immune cells, the work highlights a previously underappreciated dimension of metabolic disease: its capacity to reprogram immune function over the long term.

Looking ahead

The discovery of obesity-induced immune memory raises new questions about reversibility and intervention. Can these epigenetic marks be actively erased? And if so, how can therapies be designed to accelerate immune recovery?

Future research will likely focus on targeting these pathways directly, with the aim of restoring normal immune function and reducing long-term disease risk.

For now, the findings underscore a key message: losing weight is only part of the story. Fully reversing the biological impact of obesity may require sustained intervention—not just at the metabolic level, but at the level of the immune system itself.

The post Obesity Leaves Lasting DNA Methylation Memory in Immune Cells appeared first on Inside Precision Medicine.

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Anticancer Strategy Targets Defense Mechanism in Senescent Cells

Scientists headed by a team at MRC Laboratory of Medical Sciences (LMS) and Imperial College London have found that a new set of drugs can exploit a recently-revealed weakness in senescent—or ‘zombie-like’—cells, a finding that could lead to new treatments for cancer and age-associated diseases.

Senescent cells walk a tightrope, risking cell death with high levels of iron and other damaging agents, but compensating for this by overproducing a protective protein, GPX4, which staves off death. The team showed that targeting this defense mechanism removes the shield and could be used to treat diseases that are associated with senescence, including cancer. Tests showed that combining anticancer therapies with GPX4 inhibitors eliminated senescent tumor cells in models of melanoma, prostate and ovarian cancer. This approach, they say, could complement existing treatments to bring much-needed improvements for cancer patients.

Mariantonietta D’Ambrosio, PhD, a postdoctoral researcher at the LMS, is first author of the international research team’s published paper in nature cell biology, titled “Electrophilic compound screening identifies GPX4-dependent ferroptosis as a senescence vulnerability.”

Cancers grow as a result of unconstrained cell division. But within most tumors, there is a portion that does not divide at all: senescent cells. Chemotherapy often increases the proportion of senescent cells in a tumor as it aims to stem the rapid proliferation, the team explained. However, while these senescent cells don’t directly increase the size of a tumor, they can wreak havoc in their own way.

Senescent cells, which are also a defining feature of aging conditions such as fibrosis, influence neighboring cells by secreting molecules that increase proliferation, the spread of the cancer, and unwanted immune system activity. “Senescent cells drive aging and age-related pathologies, including cancer,” the team wrote. There is therefore an increasing interest in developing drugs that directly target and kill senescent cells, in cancer and beyond. “Consequently, senolytics, drugs that selectively kill senescent cells, have broad therapeutic appeal,” they continued. “Compounds that selectively kill senescent cells (senolytics) can treat different age-related pathologies.”

The study by D’Ambrosio and colleagues has identified a new approach to killing senescent cells in cancer.  “Senescence was considered for a long time to be positive, because senescent cells don’t proliferate, which is the core feature of cancer,” D’Ambrosio explained. “Normal chemotherapy induces senescence blocking the proliferation of cancer cells, so the tumor doesn’t get bigger. But with time you also see the negative side of the senescent cells, because they secrete a lot of factors that influence neighboring cells and induce even more proliferation, metastasis, and recruitment of bad parts of the immune system that will provoke even more aggressiveness in the tumor.  For this reason, we tried to find some drugs that were able to kill the senescent cells.”

The researchers cast a broad net in their search for new drugs that might kill senescent cells. Together with collaborators at the Department of Medicinal Chemistry at Imperial, they decided to examine covalent compounds, a class of inhibitors that can form a covalent bond with their target, which can result in the inhibition of proteins previously considered undruggable. The investigators introduced 10,000 different covalent compounds to both senescent cells and normal cells, looking for the ones that preferentially killed senescent cells and classing the drug as “senolytic,” or senescent-killing.

They narrowed their results down to just four promising compounds and found that three of them affected a particular protein, GPX4, which has a protective role in cells, helping stave off ferroptosis, a type of cell death associated with high levels of iron and destructive reactive oxygen species. To protect themselves against the high levels of iron and other ferroptosis-causing agents, senescent cells have high levels of GPX4. It is like proactively taking a painkiller so a person can keep running on an ankle. The damage and danger remains, but the immediate risks are bypassed. Removing the painkiller makes the pain unbearable.

“Senescent cells are primed for ferroptosis and upregulate GPX4 as a protective mechanism,” the team noted. Ferroptosis had only recently been revealed as a potential weakness of senescent cells. D’Ambrosio commented, “recent papers have shown this predisposition of senescent cells to ferroptosis, but it’s a new senescence vulnerability. That creates an opportunity for us to exploit. So now there is research to find senolytic drugs to kill cells through ferroptosis.”

The researchers found that blocking the activity of GPX4 removes the shield, making fatal ferroptosis unavoidable. The authors further commented, “We concentrated our studies on four chloroacetamides displaying senolytic activity in different models of senescence … GPX4 was a target of three of the four senolytic chloroacetamides. GPX4 is a glutathione peroxidase that prevents ferroptosis by reducing lipid peroxidation.”

The team tested their drugs with three different mouse models of cancer and saw improved outcomes as a result of senescent cell death in each case. Translating this to patients could be a huge asset to cancer treatments. “In mouse models we saw that these drugs reduced tumor size, and improved survival,” noted professor Jesus Gil, PhD, senior author and head of the senescence group at the LMS. “Now we need to see the effect on the immune system. Is the improvement also awakening the ‘good side’ of the immune system (T cells, natural killer cells) that helps to kill the tumor? … Once we know more, the next step is to understand which cancer cell types or specific patients might better respond to this treatment. For example, if a patient undergoing chemotherapy overexpressed GPX4 then you could use this approach in combination with existing drugs to improve efficacy.”

This approach offers a much-needed new perspective on cancer therapy, pinpointing senescent cells as an underexploited target. D’Ambrosio says it has potential to transform treatment. “Targeting senescence is a huge opportunity for cancer treatments, and ultimately it can play a supporting role in addition to chemotherapy and immunotherapy.”

The post Anticancer Strategy Targets Defense Mechanism in Senescent Cells appeared first on GEN – Genetic Engineering and Biotechnology News.

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The missing step between hype and profit

This story originally appeared in The Algorithm, our weekly newsletter on AI. To get stories like this in your inbox first, sign up here.

In February, I picked up a flyer at an anti-AI march in London. I can’t say for sure whether or not its writers meant to riff on South Park’s underpants gnomes. But if they did, they nailed it: “Step 1: Grow a digital super mind,” it read. “Step 2: ? Step 3: ?”

Produced by Pause AI, an international activist group that co-organized the protest, it ended with this plea to the reader: “Pause AI until we know what the hell Step 2 is.” 

In the South Park episode “Gnomes,” which first aired in 1998, Kenny, Kyle, Cartman, and Stan discover a community of gnomes that sneak out at night to steal underpants from dressers. Why? The gnomes present their pitch deck. “Phase 1: Collect underpants. Phase 2: ? Phase 3: Profit.”

The gnomes’ business plan has since become one of the greats among internet memes, used to satirize everything from startup strategies to policy proposals. Memelord in chief Elon Musk once invoked it in a talk about how he planned to fund a mission to Mars. Right now, it captures the state of AI. Companies have built the tech (Step 1) and promised transformation (Step 3). How they get there is still a big question mark.

As far as Pause AI is concerned, Step 2 must involve some kind of regulation. But exactly what it will call for and who will enforce it are up for debate.

AI boosters, on the other hand, are convinced that Step 3 is salvation and tend to glaze over the middle bit. They see us racing toward sunny uplands on the back of an “economically transformative technology,” as OpenAI’s chief scientist, Jakub Pachocki, put it to me a few weeks ago. They know where they want to go—more or less: It’s hazy up there and still some way off. But everyone’s taking a different route. Will they all make it? Will anyone?

For every big claim about the future, there is a more sober assessment of how the rubber meets the road—one that quells the hype. Consider two recent studies. One, from Anthropic, predicted what types of jobs are going to be most affected by LLMs. (A takeaway: Managers, architects, and people in the media should prepare for change; groundskeepers, construction workers, and those in hospitality, not so much.) But their predictions are really just guesses, based on what kinds of tasks LLMs seem to be good at rather than how they really perform in the workplace.   

Another study, put out in February by researchers at Mercor, an AI hiring startup, tested several AI agents powered by top-tier models from OpenAI, Anthropic, and Google DeepMind on 480 workplace tasks frequently carried out by human bankers, consultants, and lawyers. Every agent they tested failed to complete most of its duties.   

Why is there such wide disagreement? There are a number of factors. For a start, it’s crucial to consider who is making the claims (and why). Anthropic has skin in the game. What’s more, most of the people telling us that something big is about to happen have reached that conclusion largely on the basis of how fast AI coding tools are getting. But not all tasks can be hacked with coding. Other studies have found that LLMs are bad at making strategic judgment calls, for example.

What’s more, when they’re deployed, the tools aren’t just dropped into a cleanroom. They need to work in places contaminated with people and existing workflows. And sometimes adding AI will make things worse. Sure, maybe those workflows need to be torn up and refashioned around the new technology for it to achieve transformative status, but that will take time (and guts).  

That big hole? It’s right where Step 2 should be. The lack of agreement on exactly what’s about to happen—and how—creates an information vacuum that gets filled by the latest wild claim of the week, evidence be damned. We’re so unmoored from any real understanding of what’s coming and how it will be deployed that a single social media post can (and does) shake markets.

We need fewer guesses and more evidence. But that’s going to require transparency from the model makers, coordination between researchers and businesses, and new ways to evaluate this technology that tell us what really happens when it’s rolled out in the real world.

The tech industry (and with it the world’s economy) rests on the held-out promise that AI really will be transformative. But that is not yet a sure bet. Next time you hear bold claims about the future, remember that most businesses are still figuring out what to do with their underpants.

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Rebuilding the data stack for AI

Artificial intelligence may be dominating boardroom agendas, but many enterprises are discovering that the biggest obstacle to meaningful adoption is the state of their data. While consumer-facing AI tools have dazzled users with speed and ease, enterprise leaders are discovering that deploying AI at scale requires something far less glamorous but far more consequential: data infrastructure that is unified, governed, and fit for purpose.

That gap between AI ambition and enterprise readiness is becoming one of the defining challenges of this next phase of digital transformation. As Bavesh Patel, senior vice president of Databricks, puts it, “the quality of that AI and how effective that AI is, is really dependent on information in your organization.” Yet in many companies, that information remains fragmented across legacy systems, siloed applications, and disconnected formats, making it nearly impossible for AI systems to generate trustworthy, context-rich outputs.

“Really, the big competitive differentiator for most organizations is their own data and then their third-party data that they can add to it,” says Patel.

For enterprise AI to deliver value, data must be consolidated into open formats, governed with precision, and made accessible across functions. Without that foundation, businesses risk “terrible AI,” as Patel bluntly describes it. That means moving beyond siloed SaaS platforms and disconnected dashboards toward a unified, open data architecture capable of combining structured and unstructured data, preserving real-time context, and enforcing rigorous access controls. When the groundwork is laid correctly, organizations can move toward measurable outcomes, unlocking efficiencies, automating complex workflows, and even launching entirely new lines of business.

That value focus is critical, says Rajan Padmanabhan, unit technology officer at Infosys, especially as enterprises seek precision in the outputs driving business decisions. Rather than treating AI initiatives as isolated innovation projects, leading companies are tying AI deployment directly to business metrics, using governance frameworks to determine what delivers results and what should be abandoned quickly.

“We see this big opportunity just with AI literacy with business users, where they’re very eager to understand how they should be thinking about AI,” adds Patel. “What does AI mean when you peel the covers? What are the pieces and the building blocks that you need to put in place, both from a technology and a training and an enablement standpoint?”

The possibilities ahead are substantial. As AI agents evolve from copilots into autonomous operators capable of managing workflows and transactions, the organizations that win will be those that build the right foundation now.

“What we are seeing as a new way of thinking is moving from a system of execution or a system of engagement to a system of action,” notes  Padmanabhan. “That is the new way we see the road ahead.”

The future of AI in the enterprise will be determined by whether businesses can turn fragmented information into a strategic asset capable of powering both smarter decisions and entirely new ways of operating.

This episode of Business Lab is produced in partnership with Infosys Topaz.

Full Transcript:

Megan Tatum: From MIT Technology Review, I’m Megan Tatum, and this is Business Lab, the show that helps business leaders make sense of new technologies coming out of the lab and into the marketplace.

This episode is produced in partnership with Infosys Topaz.

Now, recent advancements in AI may have unlocked some compelling new industrial applications, but a reliance on inadequate data models means that many enterprises are hitting a brick wall. AI and agentic AI in particular place a whole new set of demands on data. The technology requires greater access, context, and guardrails to operate effectively. Existing data models often fall short. They’re too fragmented or siloed. Data itself often lacks quality. To bridge the gap, they require an AI-ready upgrade.

Two words for you: data reconfigured.

My guest today, are Bavesh Patel, senior vice president for Go-to-Market at Databricks, and Rajan Padmanabhan, unit technology officer for data analytics and AI at Infosys.

Welcome, Bavesh and Rajan.

Rajan Padmanabhan: Thank you. Thanks for having us.

Bavesh Patel: Thanks for having us.

Megan: Fantastic. Thank you both so much for joining us today. Bavesh, if I could come to you first, when we talk about AI-ready data, what exactly do we mean? What new demands does AI place on data, and how does this impact the way it needs to be structured and used?

Bavesh: Yeah. Great question. Appreciate you hosting us today. I think that obviously the whole world is enamored with AI because of all of the power that we can all see as users. AI is now democratized across hundreds of millions of users. And when we think about enterprises and businesses using AI, the quality of that AI and how effective that AI is really dependent on information in your organization, and that’s data. And what we found is that most enterprises, their data is kind of locked away in these different applications and different systems. And it’s very difficult to get a good view of, what is all my data? How trustworthy is it? How recent and fresh is it? And all of that is being injected into the AI. Unless you have a proper understanding of your data, the ability to ensure that it’s data that’s accurate and that can be used so that the AI can take advantage of it, you’re actually going to end up having terrible AI.

We see a lot of customers spend time on cleansing their data, organizing their data, making sure it’s access controlled correctly, and that tends to be the fuel of good AI.

Megan: Yeah. It’s such a foundational thing, isn’t it? But it can be missed, I think, quite easily. Rajan, what difference can having AI-ready data really make for enterprises as they unlock that full potential of AI and its applications?

Rajan: First and foremost, thanks for having us. It’s a pleasure. I think in continuation of what Bavesh talked about, see, data and AI is pretty synonymous. And similarly, the consumer AI and enterprise AI and enterprise agentic AI are different because first and foremost, the business needs to have the context. That context from your enterprise information, which is not only structured, both structured and unstructured and user-generated contents and all forms of data is going to be very, very critical to really get the context right, and really get any model that you pick. That’s where the platforms like Databricks really help with the plethora of models or whether you want to build your own models or whether you want to ground the model based on your data. That is going to be very, very critical. That is where getting the data for AI is going to be very, very critical.

The third critical part, and this actually will be one of the roadblocks for adoption of AI. That’s why if you see the AI adoption on the consumer side is skyrocketing, but on the enterprise side, the enterprises are struggling is primarily around the precision of their output, because you are taking a business decisions where you are taking a buy decision, you are taking a sell decision, or you are trying to recommend something, recommend the content. It could be 20 different use cases. For that, the precision is going to be very critical. We are seeing our customers, the successful customers, definitely for the precision to be more than 92% is not aspiration, that is a must-have. If you have that, definitely being that AI data is going to be the entrepreneur right now for that.

Megan: And I suppose if we’ve outlined there how critical this is, where should enterprises start then, professional perhaps, the level, what are the foundations when it comes to building an AI-ready data model?

Bavesh: Yeah. And I think Rajan hit the nail on the head. I mean, enterprises are grappling with a different set of problems than consumer AI. The first thing is that you’ve got to get a handle on your data. As I mentioned, a lot of the data is locked in. Ensuring that you have ability to put your data in a place where you can understand the holistic view of as much of your data as possible. That kind of starts with putting your data in open formats. A lot of the valuable data today in an organization is locked away in some proprietary SaaS app or some system, and all the datasets aren’t connected together to form that context. The first step is to really do an analysis of what is your data estate? What are the critical pieces of data that need to be put into a place where you can start to understand them and how they’re connected to one another?

Thinking about how do you set up your data catalog, thinking about how do the relationships between the data assets work, putting data governance around it, that seems to be the first step. And if you think about how ChatGPT was built, it took all the data on the internet and then aggregated it, synthesized it, and then built these transformer models, while enterprises, they don’t really have a handle of all their data within the organization. That’s the first foundation that you really want to think about. The second thing is that you don’t want to just go ad hoc, go and do random AI projects. You really need to be thinking about business value. A lot of our customers are looking at AI much more strategically in that they want to be able to get projects on the board with wins and then generate business value.

Building an AI value roadmap, which is connected to how well your data is organized, those two things seem to be foundational to how do you launch AI successfully in your organization.

Megan: That value piece is so important, isn’t it? And as I understand it, Infosys and Databricks have worked closely together to guide organizations through this transformation. I wondered, can you share some examples of the impact you’ve seen enterprises you’ve worked with, Rajan, what difference has it made to the ways in which they can integrate more sophisticated AI and agentic AI applications?

Rajan: Well, that’s a very, very good question. What both Databricks and Infosys has done is we have come up with, a kind of a framework first. First and foremost, it all needs to start with the value. One of the largest food products company where we collaborated together, what we have done is we have applied this framework. The framework consists of six different things. First and foremost, very critical is the value management, which Bavesh touched upon. We have worked together to come up with a 3M measurement framework, what we call adaptability, business value, and then responsible. You can’t just go and do a garage project. It has to be measurable. It should be responsible, follow all those things. That is going to be very critical. And we helped this client to prioritize, which will give them the most value for money, the investments that they are making.

The second critical part here is it is not like most of the enterprises today are not everybody’s AI-born companies. Most of them were born during analog days; most of them were born in digital days. There are companies which are applying AI for modernization, because a lot of your historical information, which is actually helping you to build that long-term context. And that is where we have worked closely with some of the native tools of Databricks, like Lakebridge or the AI assistants that are there, and then create composable services on top of it to help the clients unlock the value bringing into Databricks. And then the second part where we help the client is exactly to the point, the readying of data. Now you brought in the data, now you have to bring both the structured, unstructured, analytical and all these aspects.

And that is where the third layer, we closely work with the Databricks, which is part of leveraging all the great capabilities within the Databricks, be it Unity Catalog, be it the open formats, or be it the gateways and other aspects. We were able to make the data available for this client. What has really helped our client, the third part, is Agent Bricks, which is one of the differentiatiors. It gives you the flavor for the enterprise. That is where we have closely worked, and we built some of our industry-specific agents, be it CPG, be it energy, be it FS. And for this client, what we have done is we have taken some of those CPG-specific use cases. Either it could be on the HR space or the procurement space or on the marketing space. And this has really helped our client be able to build a business capability surrounding this and unlock eight to nine use cases, we call it as a products, agentic AI products, which can really drive more value for them, solving the real business problems.

And this kind of a comprehensive set of frameworks plus set of suites of services, plus our solution assets, Infosys solution assets, as well asunlocking the value from Databricks has really helped these clients. And we see similar patents for a lot of these successful engagements where we were able to continuously drive the value by applying this framework actually.

Megan: Right. Sounds like it made a real material difference. Rajan mentioned a few of the tools in Databricks catalog there, Bavesh. I know you’ve recently worked to launch an operational database for AI agents and apps. I wonder how does a platform like that help organizations in this journey? What makes it different from some of the other platforms out there right now?

Bavesh: Databricks has come to market with a new offering called Lakebase, which is really an OLTP database where you can build your AI apps. And if you think about it, there’s really two main types of data in an enterprise. There’s all the historical data, which is all the things that have happened, and that’s really what your analytics is based on. You have an old app system where you have put all your historical data and Databricks has come to market with what we call the Lakehouse, which is essentially a data warehouse with all of your data that is not operational in nature. It’s historical data. And I think that Lakehouse concept is really pushing forward with AI because a lot of our customers have thousands of users within their business and they need to get data. And what they’ve done is they’ve actually gone down the BI route, which is really building a dashboard or a report.

Most organizations have had thousands of these dashboards and reports proliferate across the organization and then they need to be customized. It just takes a long time for users inside of the business to actually get access to the data. AI now is really making that a lot easier from just the analytics perspective where we can now democratize access to the data, which has really been the holy grail for most data teams. They really want to get out of the way and just give the right data to the right people inside of the business with the right access.

With a product like Genie at Databricks, you can just use English language or whatever your language is to ask questions of the data. And it’ll give you back data that answers your questions in context. It’ll give you not just what ChatGPT will give you, which is information about a topic that’s on the internet, but it will actually tell you, “Well, why did my sales numbers not reflect what I expected in the month of April?”

It’ll give you some root cause analysis based on your enterprise data. Genie is going to be one of these things that’s really important where it’s going to truly kind of democratize data inside of the business. That’s kind of this OLAP world, which is what the Lakehouse is. More recently, we’ve come to market with what we call the Lakebase, which is the OLTP world. What we’re finding is that agents are now being deployed in these organizations, and those agents need a place to keep all of their orchestration, all of the context of what’s happening in that particular workflow. On the one hand, you’ve got users just asking questions. On the other hand, the next chapter is going to be around automating an entire business process. If you’re taking a function like generating a campaign in marketing, right? There are a lot of tools you use and a lot of steps you use.

An agent can come in and really automate a lot of that. But on the back end of that agent, you’re going to need to stand up a real-time database to keep track of all the things that the agent is doing. That’s what Databricks has brought to market, which is this OLTP Lakebase solution. The innovation that we have brought to market is that it’s a modern kind of Postgres database where we have separated the compute and storage, very much like what we did with the data Lakehouse with the data warehouse. But on the Lakebase, the data is on one copy inside of your cloud storage, and then the compute is separated and it’s serverless. You can do things like branching and you can start up the OLTP database really quickly. What we found is that agents are actually starting these Lakebases because they can very quickly go start one up, keep it running, put it down when it needs to, make a copy of it.

Agents are doing this, then they need the velocity, they need a cost-effective solution. And the beauty of all this is when you take the OLTP, which is all around the Lakebase and the real time, and you take the OLAP, you now have one system for all your data. You don’t have to copy the data around, you don’t have to manage all the permissions, you can set the context against it. We see these AI apps being really the future of how businesses run, where they’re going to take away all of the bottlenecks that humans are having to do repetitive work and automate these using LLMs and all these new technologies. We want to be the default for powering all that because we believe that our Lakebase technology is going to be faster, cheaper, and more secure for an AI database.

Megan: Sounds like a real game changer. And we’ve touched on this a couple of times already, I mean, this idea of value. We know that engaging the commercial value of investments into AI is really high on the priorities right now for senior leaders. How important is this value measure piece when it comes to creating AI-ready data systems, Rajan? How can organizations ensure they’re monitoring what is delivering and what isn’t?

Rajan: This is the paramount importance and most of the successful AI implementations or agentic AI implementations really required this value measurement. I’ll just extend the client example that I talked about, the large food products company, the global products company, to explain this question. I just want to create a metaphor. When the initial digital world came, we have a lot of these analytics primarily around defining those performance management KPIs, fact-based decisioning and other things were evolving over a period of time. Typically, a lot of these metrics are going to be very critical for them to measure how a function, how a business is doing. On a similar line for the value measurement, if I take the same example of the client, what is very critical for an organization is actually to map your outcome that you are expecting.

Iin this case, how do I optimize my spend on direct and indirect purchases? So by applying AI, I would like to identify the areas where I can optimize the spend. That means one of the critical measures that you have is, what is your indirect expense classification and what spends you have been classified and how much you are able to reduce by bringing in this. Establishing these measures and the metrics is going to be very, very critical. And once you establish these base metrics and the measurement, and the beauty of it is some of these metrics, to just extend what Bavesh was talking about, the capabilities that Databricks gives you, like metrics view, features, tools, and other things would actually help you to translate those AI telemetries, business telemetries that is coming from your applications into a measurable metrics in terms of an outcome, which you can actually measure using the Genie room for value management measurement.

Then what happens is two things that you can take, the use case, the products that as I said for this client, the products that we build either on the procurement side or on the marketing research side, if you find there is a value either because of VAC, they identify that they’re able to optimize or it is able to reachability, what is the reach, you can either accelerate that use case and further fine tune that product to expand it. Or there are, if you find it is not really driving the value or I’m not able to see the value that it is going to deliver, you can very well do a fast failure method rather than trying to make it work, you can understand and then you can take a call to pivot it to something else different.

There are three aspects here. What we see from our experience, not only with this client across some of our other clients from industrial manufacturing or FS or in the energy, is by setting up this metrics-driven valuation method upfront and then leveraging the capabilities to establish, transform these telemetries, signals into a measurement, what we call an AI compass room so that you really measure the business stakeholders, whether it is coming from a marketing office or whether it is coming from supply chain office or whether it is coming from a CFO office where they can say, “Hey, this is what it is intended to do, this is what the current measurement, and this is where it’s failing that can help them to pivot.” And this will actually drive and democratize AI, all the agent decay across the enterprise, and that really drives the value.

This is going to be one of the critical part that enterprise needs to do it. And that is where the six part framework that I talked about, applying that framework like value office, applying the ready for AI, applying the transformation fabric. Then the third part is the governance, which is going to be the entrepreneur of this. Then running your operations, not based on SLA, based on the experience level agreements and business metrics for you to continually measure, bringing all these six layers is going to be very critical. That’s when we see the organizations are very successful, and some of our proven examples exactly do the same that this is going to be very critical for organizations from a measurement standpoint.

Megan: Lots of tangible ways there that you can actually gauge value here. And you touched on governance and the impact of AI on governance is another huge talking point among senior leaders and interactions with data are a core part of that. To what extent is having the right governance and security protocols an integral part of having AI-ready data? To Bavesh, what scenarios do these systems need to handle? What does that mean for data models?

Bavesh: This is becoming kind of the prerequisite to deploying a successful AI project. I think MIT produced a report that said 95% of these new AI projects fail to actually generate business value. A big reason for that is you can go and prototype and stand up and vibe code a pilot, but when you’re actually moving a workload into production, you realize that governance becomes so critical.

So what do we really mean by governance? I think the first thing is getting your data in order, like I said, in open formats. Most companies realize now that the way they engage with their customers, the way they develop a drug, the way they approve a person for a credit limit increase, all of that enterprise information is actually their competitive advantage. Because you can go and use a frontier model like ChatGPT or Claude that everybody has access to.

Really the big competitive differentiator for most organizations is their own data and then their third-party data that they can add to it. Getting your data into an open format so you can understand your data and understanding your data is where governance comes in. Because when you think about governance, you really want to be able to find the data.

If I’m an end user or if I’m building an AI product, I want to know what data’s available to me. Can I trust the data? How fresh is the data? Is it coming from my analytics world or do I need a real-time system like a OLTP system? I need to find the data. I also need to make sure that access is controlled in a way that doesn’t cause any huge headaches from my organization. This becomes critical. If I have a whole bunch of PDFs that have purchase orders in them, who actually has access to all that data?

In a clinical trial, for example, in healthcare, you really want to ensure that people across trials don’t have visibility to patient data. Maybe the model that was used to build that was running across trial. Who has access to all the data? Who has access to only parts of the data? You really have to think about this. We also look at semantics of the data. Rajan brought this up right at the beginning of this, which is what is the context? How do we think about the metrics and all the things that the business users know in their head? We need to start codifying that somewhere. We have a product at Databricks called Unity Catalog where you can do the discovery, the access and the business semantics. You also want to share the data.

And in the world of agents, what we see is something called agent sprawl. In a very short order, just like how SaaS applications became very prevalent within any organization where they really solved a business problem. You go to a line of business and you say, “I need to be able to do credit underwriting” or “I am doing a prior authorization use case or pick thousands of use cases.” There’s a SaaS app for that. Much like that, there’s going to be this world in which agents are going to come into play, and most organizations are going to have lots of agents running all the time, but the reality of it is that how did that agent perform? What was the feedback loop from the user? What was the cost of running that workload and is it going up dramatically? And if you don’t have a way to monitor, to understand, and trace all the questions and answers and responses at scale, you’re going to find yourself in a big pickle. This actually could hurt your organization because users will be very confused about what to do.

When you look at governance, most organizations are recognizing that they have to start to understand what is it that they have put in place from a systems, from a process, from a tooling standpoint, focus on one use case, build out the governance for that, but build it in a way that’s going to allow you to become repeatable. AI is not going to be about one use case or two use cases. It’s whoever builds the flywheel of building many use cases in a safe, secure way, in a cost-effective way that’s driving a business outcome. If you don’t apply governance, it’s going to be very hard.

At Databricks, we made a big bet on governance four or five years ago. This is one of the main reasons our company’s growing right now because we can ensure that there’s quality data that’s going into all of your AI. You can use things like Genie and you can use things like Agent Bricks and you can build apps using Lakebase. None of that really works without governance. It’s really what we call the brain inside of Databricks.

Most of our customers spend a lot of time inside of Unity Catalog. And the great news is that AI is helping governance get set up much more quickly. We have a customer that three years ago, they were trying to get all of the data assets across all their domains from the customer, from the loyalty app, from the e-commerce engine. They had to go and map out all this data assets. AI is now doing a lot of their work for them. The human in the loop is just checking things.

We’ve made this much easier with AI. We always think about AI as a business use case and an outcome, which I think is going to be where the biggest value is. But at Databricks, we’re using AI inside of our platform to make it much easier to operate and to make it much easier to provide all the right things for your business. This is a super critical part of how we plan to innovate as AI takes fruition in the market.

Megan: And Rajan, Bavesh touched on this a little bit there, but does the integration of Agentic AI add another layer of complexity here too? What new consideration around governance does that raise?

Rajan: That’s a very, very valid question. I would like to take a metaphor to really explain. We are getting into the world of self-driving cars, robotaxis, and other things. While that takes us to the autonomous world, but still there are rules that you need to adhere to when you are driving on a road. The reason I’m bringing this metaphor is because what is actually required is actually adhering to the rules and different topographies, different things, depends upon where you are driving is going to be very, very critical. The complexity that agents are going to add is basically how you operate with those constraints.

For example, as a UTO, I can do 10 things, but say if I cannot approve a discount for more than 70% or I cannot give something as a bonus for someone because that is a part of the CFO, which an agent should be aware of.

That is one aspect, applying the constraints around it and making sure that the agents are adhering to the constraints. The second set of complexity that it builds is the tools to access. As a business, in today’s world, when you define a process, certain processes need a certain set of tools to really actionize it. There are certain entitlements, only people entitled to do certain things based on their identity, based on the need or the situation need, you need to govern. The third is information sharing. While MCP and other aspects are great, UCP and other aspects are great, but one critical thing is what you need to share, what you don’t need to share. And those are the critical considerations.

The last part is learning and relearning. Sometimes when you learn good things, you should keep something. Sometimes it is better for you to completely remove it and reevaluate in a newer way, relearn it in a newer way. These are all the critical things that are required. On the similar line for agents, it is going to be paramount, because when you are operating agents for an enterprise, you need to know, learn, and adhere to certain compliance related rules, business related constraints, and then the entitlement identity, and then sharing whatever that apply to a physical human will also start applying to an agent. That is where this is going to be very critical. This requires a new set of operating systems. That doesn’t really mean now get out of a new thing. That is where I’m just interpreting how Bavesh touched upon the Unity Catalog.

The best part that which we see and some of our clients that which are implementing is extending the Unity Catalog and the capabilities like now you can catalog the tools, catalog the MCP as well as catalog these agents, and then govern those agents based on the constraints, ground them based on the constraints.

It’s going to be very, very critical. Doing it not later, but starting that as part of your strategy and enforcing this as one of the critical dimensions of when you measure the value is also going to be very critical for an organization. It is like making sure that not only building the autonomous car, but as well as making sure that the car drives as per the rules of the road, not going rogue.

Megan: Lots to think about there. Fascinating stuff. Thank you. Just to close, with a quick look ahead, we all know the pace of development in AI and Agentic AI is so rapid. For those organizations that can prioritize AI-ready data now, what are the most compelling use cases for the technology that you can see coming to the fore in the next few years, Bavesh?

Bavesh: I think the excitement level is at its peak. We’ve seen so much investment in AI. I think the reason why there’s a lot of excitement is because you can look at the early adopters and you can see massive amounts of gains that these organizations are seeing. The one thing I will tell you is that the companies that there’s really three categories and the companies that I think are doing well, a lot of them started out with just copilots and things that are just giving people quick answers. Think about it as making an individual productive. That is the first phase. And the ROI on that has been somewhat questionable. With something like Genie, it makes it a lot more effective because it’s actually on your data and your data is contextualized in your organization. I think that’s one level of area that we’re going to see a lot of innovation. We’ll see most organizations just start to get the right information to the right person at the right time. And that has been a dream for a lot of organizations.

The second one is around automating entire business processes. We see functions within marketing, like I described earlier, or whether you’re going through a process of rebates for a company. There’s a whole bunch of steps involved where you have to go into three different apps and export data from Excel and put it over here. There’s thousands of people doing very laborious, monotonous, repeatable work. These agents are really going to help get an immense amount of not only productivity for the business process, but it’s just going to make things faster. Processes that took weeks are now going to take days. Processes that took days are going to take hours and minutes now.

One trend we’ve seen is that the AI world is so dynamic. In a world where you got lots of different players, you want to think about first principles, what are the foundations? You want to think about owning your data, making sure you have a handle on your structured and unstructured data. You want to put governance on that. But the other thing that you want to make sure that you don’t do is lock yourself in.

Today, if you think about it, Gemini is really good with multimodal. Anytime you have pictures or videos or things like that, Gemini just is super good. Whereas if you’re writing code, Claude is really good. If you’re just doing certain types of questions around introspection, ChatGPT is really good. What you really want is an open data platform where you can build your open AI on multiple clouds, which is what we built at Databricks.

I think that’ll help with the second piece, which is you can pick and choose because when you build these agents, you don’t have to be locked into just one. You should be picking the best quality and the best security and the best ROI and cost for a particular workload. One workload may use multiple of these models, and they might be even specific industry models. You need a system and a platform that can really handle this complexity.

I think the third category is business reimagination. A lot of people talk about this where, yes, you’re going to go and take the data and make it available and give everybody access to the data. You’re going to make existing processes much more efficient. But the third thing is there’s going to be brand new things that come out of it.

We have a very large customer who’s a bank and they have built a product that they didn’t have a year ago. Essentially, it’s machine learning and LLMs helping treasury departments forecast what their balances are going to be because they have more data at their fingertips. Historically, it took a long time for the data to get to the bankers. They were not able to really predict what a balance would be for a treasury department. Think about this for a big enterprise company, they have now built a brand new data AI solution that they’re monetizing and it’s generated hundreds of millions of dollars in the first six months. We’re seeing brand new lines of business open up and that is going to be really exciting because that’s where a lot of the transformation is going to happen. There’s going to be productivity. There’s going to be kind of automation at the business process level. Then there’s going to be these big new things that we didn’t even imagine that people are going to come up with.

We are actually seeing the early signals of this in every industry. We see retailers getting data at the hourly and the minute level so that they can integrate much more closely with their supply chains. We’re seeing much more targeted customer 360-degree use cases where as retailers or as consumers, we get annoyed by ads, but now it’s so contextualized and you have so much information about what really matters to your target customer, you’re giving them value added kind of information and that’s engaging them more. There’s a whole bunch of innovation happening with agentic commerce and things like concierge and virtualized shopping.

You look at any industry, there’s definitely new ways of doing things. This is what’s really exciting about AI, but you really have to not get too far ahead without thinking about what are the foundational things. You mentioned this earlier, which is open data platform, making sure you have governance correctly, making sure you think about your historical analytical data and your application data that’s going to be real time, having a good foundation to build on, that’s going to allow you to scale and move more quickly and compete in this new world.

We’re very excited about what we’re seeing with our customers and what they’re building. And honestly, that’s the best part about being in my role at Databricks, which is our teams really go to customers and say, “What are the outcomes you’re driving?” The early signals have been super positive. We’re seeing companies that get serious about all the foundational elements and really are methodical about building really outcome-based AI solutions, that 5% of projects that are being successful, those are wildly successful. That’s why we’re growing as a company because once you get a good project under your belt, that gets visibility within executives.

The last thing is that historically, a lot of tech has been in the IT department. You get the business designing how they want to go to market and how they’re going to compete and what products and services they want to offer. IT was the enabler and in many cases became the cost center and was relegated to rationalizing the portfolio of spend and tools.

But now we’re seeing the business kind of take the lead with AI where they want to understand, they want to know, “Hey, what can I be doing now that was not possible before?” We see this big opportunity just with AI literacy with business users where they’re very eager to understand how they should be thinking about AI. What does AI mean when you peel the covers? What are the pieces and the building blocks that you need to put in place, both from a technology and a training and an enablement standpoint? We’re spending a lot of time with executives helping them along this journey. We definitely see a lot of amazing opportunities ahead.

Megan: Yeah. So much innovation going on. And finally, how about yourself, Rajan? What on the horizon is exciting you the most?

Rajan: I think Bavesh covered quite a bit, but I think the way I’m seeing is today predominantly we are talking about labor shift. That means unlocking the potential of human or shifting the current way of working to the new way of working with the more efficiency game. It’s predominantly more of an efficiency game. I think that is what we are seeing now and the majority of the successful use cases around the labor shift. But what is pretty promising is the two kinds of shift, the business shifts.

What we are seeing as a new way of thinking or the new thing that is coming up is moving from system of execution or a system of engagement to system of action. That is the new way we see the road ahead. That is where some of the points that I touched upon. The business wants to have access to it, but how does it really make the real difference for it?

One classical example that I could clearly see which we have implemented for one of our customers primarily in the manufacturing space, is around the lifecycle of creation of a product and then publishing the content around the product in line with their different B2B marketplaces. Some of those, you are not just talking about recommending, creating, but actually you are able to reimagine this process, which used to involve five different departments, now can be done much faster, but at the same time gives you that veracity in terms of the decisioning that you are able to do and as far as how you’re able to actionize. That is the second thing which we are seeing.

The third part I think is also going to be is the way how the commerce has evolved. There is also not beyond that agentic commerce, but I think what we are seeing is that agent to agent commerce, agent to human commerce and agent to agent payments, agent to human payments, and then the content monetization.

These are the new set of business opportunities like building new business agentic products. It could be for family techs, it could be for on the consumer side, or it could be on the industrial technology side. These are going to be what I’m calling the economy shift, labor shift, business shift, because that is going to bring a new set of system of actions, moving them from the system of executions or the typical SaaS application with the bolt-on agentic, the so called agentic application. That is going to be a major transformation, and we are underway. But on the technology side, what is very critical for entrepreneuring is in today’s world you have data, analytical data, operational data, and then there is intelligence, there are different facets of it.

I think both this analytical core and operational core is going to really come into one. That’s why we are so gung-ho about the releases of Lakebase and other things because that is the way the future is going to drive. When they are really thinking about being ready for AI technology use cases, they should really think, how do you really create this unified core for the newer world?

The second part is people have to reimagine today, if I take SAP as an example, you do hundreds of edge applications, business applications needed to integrate another thing. Typically, we create sprawl of these integrations. One technology use case, people can say, “Hey, how do I really create a domain-based service mesh on top of this unified core and how do I make it more agentic integration ready?” That is one of the technology use cases that we are advising to the client.

I think now with a lot of the new areas that are coming around SAP, BDC with the Databricks, and this zero-based integration, that makes them rethink the way they need to integrate, the way they need to do things.

The third part, I think from a technology investment and technology, the use cases that most come for the technology that I would talk about is don’t just talk about now. This is the time that you have to, the way you own the people, the FTEs for your organizations. Agents are going to be your new FTEs.

That means that some of the new technology paradigm is going to be you will end up creating these co-intellects within your organization. That means you need to invest on what we call this agentic grid, where it becomes like a unified agentic fabric where every other agents can really collaborate and integrate and building on top of the same, the unified operational analytical core, the unified agentic integration on top of it, which is going to create a new set of experiences, agentic experiences rather than the traditional experiences or conversational experiences.

Then the new collaboration methods are going to be some of the critical aspects from a technology side that people have to really think from a technology standpoint. To start with, I would say you start looking at it from a data standpoint, building that unified core, building that unified integration and building that collaboration layer for both sharing and collaborating with intelligence as well as the agentic collaboration all governed under single umbrella. That is going to be the one critical use case which no one will feel bad about, and they are going to get really a 100X of their investments out of it.

Megan: Certainly no shortage of exciting developments on the horizon. Thank you both so much for that conversation. That was Bavesh Patel, senior vice president for Go-to-Market at Databricks and Rajan Padmanabhan, unit technology officer for data analytics and AI at Infosys, whom I spoke with from Brighton, England.

That’s it for this episode of Business Lab. I’m your host, Megan Tatum. I’m a contributing editor and host for Insights, the custom publishing division of MIT Technology Review. We were founded in 1899 at the Massachusetts Institute of Technology, and you can find us in print, on the web and at events each year around the world. For more information about us and the show, please check out our website at technologyreview.com.

This show is available wherever you get your podcasts, and if you enjoyed this episode, we hope you’ll take a moment to rate and review us. Business Lab is a production of MIT Technology Review, and this episode was produced by Giro Studios. Thanks for listening.

This content was produced by Insights, the custom content arm of MIT Technology Review. It was not written by MIT Technology Review’s editorial staff. It was researched, designed, and written by human writers, editors, analysts, and illustrators. This includes the writing of surveys and collection of data for surveys. AI tools that may have been used were limited to secondary production processes that passed thorough human review.

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How adolescent cannabis use reshapes the developing brain — a systematic review

Background and hypothesisCannabis use initiation during adolescence has increased globally, raising concerns about neurodevelopmental consequences during this critical period when the brain undergoes extensive remodeling in cannabinoid receptor-rich regions.Study designThis systematic review examines neurodevelopmental consequences of adolescent cannabis use, focusing on structural brain changes, cognitive impacts, addiction vulnerability, and long-term outcomes. We searched PubMed, EMBASE, PsycINFO, and Web of Science (2000-2025) for studies examining cannabis effects in adolescent populations. Following PRISMA guidelines, two reviewers screened 3,421 records and assessed 156 full-text articles, including studies with neuroimaging, cognitive assessments, or longitudinal follow-up.Study resultsThirty-six studies involving 8,432 participants met criteria: 23 longitudinal cohorts (62.2%), 8 cross-sectional (22.2%), 4 RCTs (11.1%), and 1 case-control study (2.8%). Neuroimaging revealed dose-dependent alterations including reduced prefrontal cortical and hippocampal/amygdala volumes, accelerated cortical thinning in longitudinal studies, and impaired white matter connectivity correlating with initiation age. Cognitive findings were mixed — some showed persistent deficits after prolonged abstinence in adolescent-onset users, others found no effects after controlling for confounders. Epidemiological studies consistently showed elevated addiction risk (ORs 3.9–7.2) in adolescents versus adults. Long-term associations included educational difficulties, mental health problems, and functional impairment, though causal relationships remained unclear.ConclusionsAdolescent cannabis use associates with structural brain changes, elevated addiction risk, and variable cognitive effects, suggesting greater vulnerability versus adult-onset use. However, methodological limitations including confounders, heterogeneous definitions, and observational designs limit causal inference. Findings support age-specific prevention and specialized interventions while highlighting needs for rigorous longitudinal research establishing causality.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifierCRD420251165329.
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New Markers of Diabetes and Heart Disease Revealed via Genetic Study in Indians

A study in 3,000 Punjabi Sikhs has identified previously unreported molecular pathways that contribute to cardiometabolic disease. Published today in PLOS Medicine, these findings highlight the benefits of including diverse participants in these types of studies, which have historically centered on individuals of European ancestry. 

“Genetic mechanisms that predispose people to type 2 diabetes and cardiovascular disease remain poorly understood, partly because of a lack of sufficient data on non-European ethnic groups,” write the authors of the study, who were led by Dharambir K. Sanghera, PhD, director of the Genetic Epidemiology Laboratory at the University of Oklahoma Health Sciences Center. “Extending these evaluations to diverse cohorts is essential for gaining insights into the molecular pathways involved in disease.”

Sanghera and colleagues conducted a metabolite genome-wide association study to look for links between the human lipidome and cardiometabolic disorders in a Punjabi population originating from Northern India. Epidemiological studies have repeatedly shown that South Asians living abroad experience a higher incidence of type 2 diabetes and are more susceptible to cardiovascular disease compared to other ethnic groups. However, the exact mechanism responsible for this increased risk remains unknown and lipidomic and genome-wide data is lacking for Indian populations. 

“Genome-wide studies have shown that genes influencing blood lipid metabolites are often linked to different diseases,” write the study authors. “However, most of this research has been done on people of European ancestry. Studying more diverse populations is important to better understand how these genetic pathways contribute to disease in different ethnic groups.”

The study looked at genetic influences on 516 lipids in 3,000 Punjabi Sikh individuals and then validated the results in larger cohorts, with both European and non-European ancestry, using data from UK Biobank, GeneRISK, DIAMANT, PROMIS, and other studies. After multiple rounds of testing and correction, results showed strong associations in 36 pairs of lipid metabolites and single nucleotide polymorphisms (SNPs). Among them, 33 had not been reported before, and three were confirmed to be ancestry-specific. 

Further investigation identified a causal association between type 2 diabetes and the metabolite LPC O-16:0, which was paired with a genetic variant in the gene encoding for CD45, a key regulator of immune signaling. Another possible causal relationship was found with PC 38:4, a metabolite shown to protect against coronary artery disease in Indian populations that was paired with a genetic variant in an untranslated region of the FADS1/2 genes. 

“Our study has discovered new metabolite markers and genes that intersect with pathways of inflammation and immuno-vascular diseases, which have not been reported in previous European studies, specifically emphasizing how immune system signaling affects metabolic health,” state the authors. “By identifying unique genetic signatures in Asian Indians, the research advocates for ancestry-specific medical approaches to address chronic immuno-vascular conditions in cardiometabolic disease. These advances could be beneficial in clinical practice, enabling effective personalized therapies and preventive strategies.”

 

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Vitamin D Linked to Lower Diabetes Risk in People with VDR Gene Variant

A genetic analysis of a large U.S. clinical trial suggests that vitamin D supplementation may reduce the risk of progression from prediabetes to type 2 diabetes, but only for those people who harbor specific variants of the vitamin D receptor gene. The study, led by researchers at Tufts University and published in JAMA Network Open, found that daily high-dose vitamin D lowered diabetes risk by 19% in participants with certain genotypes, opening the possibility of using vitamin D as a diabetes prevention strategy.

The new findings build on data from the Vitamin D and Type 2 Diabetes (D2d) clinical trial, a multi-site randomized study that enrolled more than 2,000 U.S. adults with prediabetes. Study participants were assigned to receive either 4,000 IU of vitamin D3 daily or a placebo. The subjects were then followed for a median of 2.5 years to assess progression to diabetes. The original trial did not show a statistically significant reduction in diabetes risk across all participants.

“But the D2d results raised an important question: Could vitamin D still benefit some people?” said lead author Bess Dawson-Hughes, MD, a senior scientist at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University. “Diabetes has so many serious complications that develop slowly over years. If we can delay the time period that an individual will spend living with diabetes, we can stop some of those harmful side effects or lessen their severity.”

In their follow-on research, the Tufts noted that subsequent analysis of the D2d trial data showed that outcomes varied based on achieved blood levels of vitamin D in participants. The new study also found a genetic link to those who had improved outcomes.

To explore the role genetics might play, the investigators conducted a post hoc analysis of 2,098 D2d participants who consented to genetic testing. They focused on three common polymorphisms in the vitamin D receptor (VDR) gene: ApaI, BsmI, and FokI. The researchers first examined how vitamin D levels correlated with diabetes risk across genotypes, then evaluated how genetic variants influenced response to supplementation.

The data showed that the ApaI polymorphism is a key determinant of response. Participants with the AA genotype, which was about 30% of the cohort, did not experience a reduction in diabetes risk with vitamin D supplementation. By comparison, those with the AC or CC genotypes, the remaining 70% of participants, showed a 19% lower risk of developing diabetes when treated with vitamin D compared with placebo.

The biological basis for this effect is linked to the role the VDR gene plays in pancreatic β cells, where it influences insulin secretion and glucose regulation. Variations in the receptor may alter how effectively vitamin D exerts these effects, explaining why some individuals benefit from supplementation while others do not.

Earlier research has suggested there is a connection between vitamin D and diabetes risk. In earlier analyses of the D2d trial, participants who maintained higher blood levels of vitamin D experienced substantial reductions in diabetes incidence. These findings were supported by meta-analyses and observational studies, including research from the UK Biobank, which found that genetic variation in VDR could modify its activity.

“We hypothesized that VDR gene variants modify the association between achieved intratrial 25-hydroxyvitamin D (25(OH)D) level and diabetes risk and may modify the effect of vitamin D3 supplementation on the risk of developing diabetes,” the researchers wrote. 25(OH)D is the main form of vitamin D circulating in the blood.

The current study broadens knowledge on the role vitamin D can play in diabetes prevention by identifying the specific polymorphisms at play. The overlap between ApaI and BsmI variants provides further evidence of the role of VDR genetics, although the researchers noted that ApaI alone may be sufficient to identify likely responders.

“This genetic association analysis of the D2d study suggests that genetic variation in the VDR, specifically the ApaI polymorphism, is associated with diabetes risk at higher intratrial 25(OH)D levels and is associated with response to 4000 IU/d of vitamin D3 supplementation among adults with prediabetes,” the researchers wrote.

The implications for clinical care include the potential use of genetic testing to guide preventive treatment. A single test for the ApaI polymorphism could help identify patients with prediabetes who are most likely to benefit from higher-dose vitamin D supplementation.

While the results have established a link between variations in the VDR gene and diabetes development, the research noted that the study was not designed to assess the mechanisms underlying the genetic effects. Further, its sample size limited subgroup analyses by race and ethnicity.

“Our findings suggest we may eventually be able to identify which patients with prediabetes are most likely to benefit from additional vitamin D supplementation,” Dawson-Hughes said. “In principle, this could involve a single, relatively inexpensive genetic test.”

Next steps in this line of research include replicating the findings in independent cohorts and conducting prospective trials designed to test genotype-guided supplementation strategies.

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Presurgery Pembrolizumab May Be the Future for Some Operable CRCs

Groundbreaking data from the Phase II NEOPRISM-CRC trial show that patients given pembrolizumab prior to surgery for certain types of high-risk, operable colorectal cancer (CRC) remain relapse-free for almost three years.

Furthermore, the response to treatment can be predicted by DNA and T cell biomarkers.

At present, the standard of care for people with high-risk stage II or III CRC with deficient DNA mismatch repair (dMMR) or microsatellite instability (MSI), like those included in the study, is surgery followed by chemotherapy, but relapse rates can range from 15% to 40% at three years.

Pembrolizumab is already given to patients with inoperable stage IV dMMR/MSI CRC to shrink the tumors and prolong life, but it is not yet available for patients with operable tumors.

The NEOPRISM-CRC trial investigated whether pembrolizumab could benefit such patients.

For the study, 32 people with large, high-risk stage II or III dMMR/MSI CRC were given three cycles of intravenous pembrolizumab 200 mg followed by surgery.

The researchers, led by Kai-Keen Shiu, from University College London (UCL) Cancer Institute, have previously reported that that 59% of participants had a pathologic complete response (pCR) to pembrolizumab, indicating that there were no cancer cells in tissue samples removed from these patients during surgery.

The data presented at the American Association for Cancer Research Annual Meeting 2026 by Yanrong Jiang, a PhD student at UCL Cancer Institute, focused on survival outcomes and whether biomarkers could predict which patients respond to pembrolizumab.

She reported that, after a mean of 33 months of follow-up, all patients were alive and relapse-free.

Shiu said: “Seeing that no patients have experienced a cancer recurrence after almost three years of follow-up is extremely encouraging and strengthens our confidence that pembrolizumab is a safe and highly effective treatment to improve outcomes in patients with high-risk bowel cancers.”

Blood samples taken throughout the study were assessed for circulating tumor (ct)DNA using the highly sensitive whole genome tumor-informed Personalis NeXT Personal assay, which can track up to 1800 patient-specific variants.

The team found that all 25 patients with evaluable data had detectable ctDNA at baseline.

Remarkably, after one round of treatment with pembrolizumab, 24% of participants no longer had detectable ctDNA. The proportion increased to 43% and 58% after rounds two and three, respectively. Post-surgery, ctDNA was undetectable in all 25 patients.

When the researchers analyzed the ctDNA clearance profiles, they identified three distinct patterns. They designated the first group “super molecular responders.” All six patients in this group had undetectable ctDNA after one cycle of pembrolizumab.

The “dynamic molecular responder” group included 11 patients who cleared ctDNA at different rates—four after cycle two of pembrolizumab, five after cycle three, and the remainder post-surgery, even though the level was decreasing rapidly during immunotherapy.

The final group, termed “poor molecular responders,” included eight patients who showed stable, high levels of ctDNA throughout immunotherapy, with levels only becoming undetectable post-surgery.

Interestingly, the pCR rate varied across the three groups: It was 100% among the super molecular responders and 82% among the dynamic molecular responders, but 0% among the poor molecular responders.

Shiu told Inside Precision Medicine that measuring ctDNA using the Next Personal assay could “potentially trump all standard tests when it comes to informing decision making.”

He suggested that the super molecular responders could potentially consider forgoing surgery altogether, while the poor molecular responders could be considered for treatment intensification, such as the addition of a second immunotherapy agent.

Although ctDNA gives information on how the tumor is responding to treatment, it doesn’t explain why some patients respond and others don’t.

The researchers, therefore, also carried out T cell receptor (TCR) sequencing, which provides a readout of the immune environment within the tumor, specifically whether there are expanded T cell populations that may recognize cancer, explained Marnix Jansen, MD, a clinician scientist and consultant histopathologist who led the translational research on the trial from UCL Cancer Institute.

“We found that patients who achieved a complete response had a higher proportion of expanded T cell clones in their tumors, suggesting a more focused and effective anti-tumor immune response at baseline,” he said.

When the team combined the ctDNA results with the TCR sequencing data, they improved the ability to predict outcomes compared with using either biomarker alone.

“The key implication is that integrating immune and tumor biomarkers in a dynamic model may allow early, data-driven treatment decisions, such as identifying patients who are highly likely to benefit or, conversely, those who may need a change in therapy,” Jansen told Inside Precision Medicine.

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