Hilton Pharma (Pvt) Ltd.

On Wednesday, Amazon confirmed that it is shutting down Amazon Care and Care Medical that were at the heart of its employer-sponsored hybrid primary and urgent care business. The business dates back to 2019 when the e-commerce giant decided to begin offering its own employees virtual clinics 24/7. Later, Amazon expanded the in-person and telehealth platform to employers and workers in all 50 states. Ironically enough, Haven also shut down three years after inception. Recall that Haven, a joint venture between Amazon, JPMorgan Chase and Berkshire Hathaway, was supposed to herald a new era in managing runaway employee healthcare costs through tech and innovation. That failure was likely a humbling of sorts for the marquee trio — all the happy talk and promotional news releases aside, who could know that healthcare could be quite so complicated? Channeling a flummoxed Trump here…. For Amazon, the shuttering of its healthcare delivery service represents a second failure. Less than six months ago, the physician leading the Care Medical business was lauding Amazon for being “customer obsessed” and a sanctuary for burned out physicians. Now with the acknowledgment of failure there is a lesson. For all the tech bros out there eager to ram technology down the inefficient, hopelessly-fragmented and in-need-of-rescuing healthcare industry, this should serve as a clear cautionary tale. You cannot shortchange the quality of healthcare delivery as the Washington Post so incisively reported about Amazon Care, to satisfy a corporate mantra of faster, better, cheaper. But is the shuttering of Amazon Care and Care Medical anything besides a second and perhaps greater public humbling after the Haven saga? Does it fundamentally alter the Seattle company’s ambitions in healthcare, its urge to get a piece of the large and lucrative healthcare pie, its ability to usher in change, it’s chance for success? Before we get to that, let’s delve into the details of the news first. The death knell for Amazon Care and Care Medical is coming on December 31, after which the businesses will cease to exist, according to a memo that Neil Lindsay, senior vice president of Amazon Health Services sent to the the company’s health services team. The memo was shared with MedCity News by an Amazon spokeswoman. Essentially, the determination was made that the business had no long term future for Amazon’s employer customers. To calm what was bound to cause consternation within the affected employee base, Lindsay added that many Amazon Care and Care Medical employees will find work within the company’s Health Services business. It isn’t clear how many people work at either Amazon Care or Care Medical though a search of the latter entity on LinkedIn connects to profiles of 94 employees. A spokeswoman who shared Lindsay’s communication with employees did not respond to additional queries about headcount. It’s also not clear how many customers Amazon Care and Care Medical have — beyond what has been publicly reported by MedCity News and others — Whole Foods Market (an Amazon subsidiary), Precor, Silicon Labs, TrueBlue and Hilton. Lindsay’s memo appears to hint at the obvious — Amazon Care never really gained traction and therefore Amazon deemed it dispensable. A healthcare corporate venture capitalist lauded the “rational decision” that Amazon took in deciding to shut down Amazon Care and Care Medical. “I love how Amazon keeps trying to crack the employer health market – first with Haven, then with Care and now with One Medical,” said Michael Yang, managing director of OMERS Ventures, the venture arm of the the pension plan for Ontario’s municipal employees, in an email. The retailer is spending a pretty penny — $3.9 billion — to acquire One Medical though the deal hasn’t closed yet. Yang noted that the San Francisco company has a “far more substantive footprint in the employer market” in comparison with Amazon Care. In other words, the fact that Amazon is acknowledging failure and moving on, is really not a big deal and doesn’t change the company’s growing ambitions in healthcare. So does the failure even matter? “Well, healthcare is hard, so we should expect failures but if anything their ambitions are only getting bigger,” Yang said of Amazon. “Whether they kept Care going or shut it down is immaterial. The big deal is One Medical and whatever else they pursue.” Another healthcare industry player and thought leader agreed. “[Amazon] previously had a skunk works (Amazon Care and Care Medical) and [it] basically acquired a scaled, clinical operation with the right clinical and regulatory controls in place (One Medical),” said Sachin Jain, CEO of SCAN Health Plan, a Medicare Advantage plan. So, this might just be a fancy way of saying that they’re collapsing that Amazon Care into One Medical,” [Note that the One Medical acquisition is not complete yet.] In other words, “they are playing to win and realize that building it organically wasn’t going to cut it,” Yang declared, adding that he won’t bet against Amazon despite this setback. Even after the much-touted Haven floundered, there were similar sentiments: you can’t count Amazon out, you can’t bet against it. But selling healthcare services isn’t like selling books or any other consummable and faster, better, cheaper may not exactly translate to great outcomes. “I’m not close to the Amazon Care story, but there’s a broader trend in our industry that is replacing specialists with generalist doctors, replacing physicians with nurse practitioners, replacing nurse practitioners with RNs, replacing RNs with community health workers,” Jain pointed out. “And unless you’re kind of founded with really strong clinical DNA, lots of organizations are going to make a lot of mistakes and it’s, you know, it’s not, it’s not clear where that DNA was going to come from, you know, within Amazon.” Perhaps this is why Amazon isn’t exactly stopping with the acquisition of One Medical. Reportedly, it is also one of the suitors bidding for Signify Health that is a value-based care company with a market cap of $6.6 billion. Based in Dallas, Signify Health is powering in-home health services, the next place rife with opportunity in healthcare. Sitting within Signify Health is also another company it bought called Caravan, which supports accountable care organizations. In fact, Caravan has within its client base more than 200 health systems and 100 Federally Qualified Health Centers with more than 10,000 primary care providers that collectively manage over 500,000 patients, according to a February MedCity News article. If Amazon is successful in buying Signify Health, it gets another piece of the complex healthcare puzzle, along with primary care and a pharmacy business. But acquiring a novel business doesn’t guarantee success. Amazon Pharmacy, created after the acquisition of PillPack reportedly seems to have much less traction in fundamentally overhauling the prescription drug market. Still, Amazon is trying to build a continuum of care with the customer smack dab in the middle. Only time will tell if its efforts in healthcare can add to its top line while also improving patient outcomes and lowering healthcare costs. “Building a continuum is way easier to put in a press release than it is to do in real life,” Jain declared. “I think the question is going to be like, how do you really make one plus one equal three? Touting corporate efforts through breathless news releases is in the DNA of all corporations, and Amazon is no exception. But given two large failures, perhaps Amazon’s marketing folks should rethink its messaging. The soon-to-be defunct Amazon Care’s LinkedIn page unabashedly declares that the business is “Making healthcare easy for all.” There is no easy button in healthcare. Period. [Editor’s Note: Author owns stock in Amazon]

Bioengineers used deactivated Cas9 fusion proteins to synthetically control gene expression and reveal new details about natural processes in human cells. Rice University researchers have demonstrated that CRISPR-Cas9, increasingly famous as a gene-editing tool, can be employed in powerful additional ways in human cells. A team led by Rice bioengineer Isaac Hilton and graduate student Kaiyuan Wang used deactivated Cas9 (dCas9) proteins to target key segments of the human genome and synthetically trigger the transcription of human genes. By using dCas9 to recruit proteins that can naturally turn genes on, the Rice team was able to reveal important details about human promoters and enhancers -- the pieces of our DNA that coordinate when, and to what extent, our genes are turned on -- which in turn controls the behaviors of our cells. "We're using these synthetic biology tools to improve the ability to engineer gene expression and program human cells, and consequently to better understand how our genes work naturally," Hilton said. "These types of studies are important because in the long run this knowledge and these technical capabilities can enable better gene and cell therapies and biotechnologies." Hilton said the study in Nucleic Acids Research highlights the growing potential of CRISPR-Cas9-based tools for synthetic gene control and cellular engineering. The team's strategy also demonstrates the power of dCas9 to influence and understand the epigenetic factors that animate the human genome. "Only around 2% of our genome contains protein-coding genes, and the remaining 98% is so-called noncoding DNA," Hilton said. "Enhancers and promoters are key parts of our noncoding genomes and, although the vast majority of these elements do not make conventional genes, there is fascinating genetic variation in noncoding DNA. This variation gives us the magnificent diversity that enables our species to be both amazing and adaptable. "However, genetic variation in noncoding DNA is also strongly correlated with many diseases, and even subtle differences in these regions can be linked to pathologies," he said. "A pressing challenge is that it is often very difficult to pinpoint how these differences influence disease onset and treatments. "Our goal and our hope is that technologies and approaches like ours can help researchers get closer to making those important connections, and to ultimately predict and thoughtfully intervene in disease," Hilton said. By synthetically activating noncoding DNA, the researchers demonstrated how promoters -- short DNA sequences that mark the start sites of genes -- and enhancers can communicate. Remarkably, enhancers can be thousands of base pairs away from their promoters but can stimulate gene transcription by recruiting activator proteins and by forming direct physical contacts with associated promoters. "Enhancers can also sometimes make mysterious transcripts called enhancer RNAs (eRNAs)," Hilton said. "Kai showed that CRISPR technologies can be used to turn on these eRNAs, and that in some cases, this fosters a type of genomic tracking, wherein an enhancer can be dragged along DNA to engage with downstream promoters. "It also appears that along the way, vital transcriptional and epigenetic information can be deposited," he said. "It is exciting to speculate that this information could serve as sort of gene expression bookmarking that reinforces subsequent rounds of transcription in a type of positive epigenetic feedback." Their strategy revealed that enhancers and promoters can have "intrinsic reciprocity." While they knew that signals can be transmitted from an enhancer to a promoter, they learned that this transmission can go the other way as well. "We see regulation taking place from a promoter to an upstream enhancer," Wang said. "Mechanistically, that's considered noncanonical and thus rather surprising." They also found that CRISPR activators can increase the frequency of physical contacts between enhancers and promoters, but only when targeted to an enhancer, suggesting a sort of one-way street for increasing physical contacts. "We now know that these pieces of DNA can send messages in both directions, but that there appears to be an significant aspect of directionality for physical contact," Hilton said. "There is certainly reciprocity, but it seems that the predominant regulatory mode here is one in which an enhancer tracks toward a corresponding promoter or promoters." The researchers said their study is only possible because of CRISPR-Cas9 advances. "Without these genomic targeting tools, we would have to use other more invasive and disruptive synthetic methods, like knocking out or genetically modifying a regulatory element," Wang said. "Our approaches here make it easier to epigenetically hijack or repurpose native cellular mechanisms to precisely understand and engineer how genes are controlled." Co-authors of the paper include Rice postdoctoral researchers Jing Li and Barun Mahata, graduate students Mario Escobar and Jacob Goell, and undergraduates Spencer Shah and Madeleine Cluck. Hilton is an assistant professor of bioengineering and biosciences, and a CPRIT Scholar in Cancer Research. The Cancer Prevention and Research Institute of Texas (RR170030) and the National Institutes of Health (R35GM143532) supported the research.