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A Conversation with Janice Chen, CTO of Mammoth Biosciences

Janice Chen, CTO of Mammoth Biosciences, spoke to Inside Precision Medicine at the recent Hello Tomorrow conference in Paris about her inspirations, challenges…

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Janice Chen is very inspiring. At the age of 30, she has not only completed a PhD. with recent Nobel prize winner Jennifer Doudna at the University of California, Berkeley, but co-founded Mammoth Biosciences together, where she serves as its CTO.

Janice Chen
CTO, Mammoth Biosciences

Mammoth recently announced it had raised $195 million in financing, bringing its valuation up to more than $1 billion and allowing it to achieve ‘unicorn’ status, an impressive feat considering the young age of the company and the ongoing COVID-19 pandemic.

Chen spoke to Inside Precision Medicines’s Senior Editor, Helen Albert, at the recent Hello Tomorrow conference in Paris about her inspirations, challenges she has overcome and her hopes and plans for Mammoth and CRISPR gene editing in the future.

 

Q: What was it like to do a PhD. with Jennifer Doudna?

It was very cool. Jennifer is a really fantastic scientist and mentor. And I think she’s been able to attract some of the best scientists in her lab. So being not just in the forefront of CRISPR technology, but also working alongside some very talented people. As you know, the CRISPR field is very competitive. I think being able to have the opportunity to continue to push the field forward, that was really remarkable. The other great thing about working in Jennifer’s lab is that if you wanted to collaborate with anyone, you could simply send a cold email, and say, ‘Hey, I’m from Jennifer’s lab’, and they would always respond. So, things that I didn’t have expertise in, I could simply ask ‘is there someone else to collaborate with?’

 

Q: It’s very impressive that you went straight from doing that to co-founding a company with her. Can you tell me a little bit about that journey?

Early on in my PhD. Career, we had been working on more traditional Cas9 enzymes, and then I formed a really great collaboration with my lab mate, Lucas Harrington, who’s also a co-founder at Mammoth. We had been working very closely, he was focused on discovering a new enzyme, I was more focused on the mechanism and application of those. We’ve always been just amazed that how much there is to uncover with CRISPR. But I think what really sparked our imagination to start a company was the ability to use CRISPR, for detection or diagnostics. This was a new area for CRISPR, we felt there was just no better time to push this forward. So, with Jennifer’s support we decided to go all in, and we ended up partnering with our colleague from Stanford, Trevor Martin, who’s also the CEO. In the early stages, it’s sort of what you might imagine, we were just figuring things out.

 

Q: It must have been quite a big lead from being a Ph.D  student to suddenly being CTO. How did you manage that?

You just have to accept that there’s so much that you don’t know and you have to constantly learn very quickly. I think part of what was absolutely critical is being able to adapt quickly, be flexible, but also bring in really, really good people. The best way to scale a company is to bring in people who are smarter than you, have done this before, and have much greater expertise in particular areas to help you take these new ideas, and bring them into the company. We also had really fantastic mentors and advisors, not just our investors and our board members, but also scientific advisors, general advisors on the business strategy who really helped us formulate where we could take Mammoth.

 

Q: How did you find the people management side?

It’s a challenge. Organizations are people and people are human. We all have our own aspirations and goals. The really fun part is building a team that is really aligned on a mission, but it also comes with challenges because especially as a new, young manager you’re learning all this in real time. You develop a skill in grad school, and you think ‘this is my expertise, I am in control’, but sometimes when you’re in an organization and managing people, sometimes there’s things outside of your control. There are other factors at play that you have just never experienced. So, it’s been a learning curve. But it’s also been rewarding to work with people that are just so talented and can move things forward.

 

Q: What are you trying to achieve at Mammoth?

When we founded the company, we were focused on diagnostics, because again, this was kind of opening up a new world of molecular detection. There are the incumbent technologies, PCR testing, antigen tests, but really, we felt like there wasn’t a good solution to take really high accurate testing into decentralized environments. And so CRISPR was able to make that possible. But as we’ve been developing the diagnostics piece, we also recognize a core competency of Mammoth was the fact that we had this ability to discover new CRISPR enzymes and that was kind of the heart of how this all came about. So, we said, ‘Okay, well, as part of building Mammoth into a really great company, we needed to leverage this whole discovery piece that can be the engine for new applications.’ Diagnostics is a key focus area. And then as we’ve grown the company, we also been really focused on the therapeutic space. That’s recently been announced as part of our series D, and also with a partnership with Vertex Pharma to actually develop new enzymes [eg. Cas14]. These are extraordinarily exciting for delivery, because of their size.

 

Q: Are we now moving on to the next generation of CRISPR gene editing?

I think for a lot of technology that is developed there’s a period where you’re just trying to understand how does this technology work? How can we use it? Cas9 has been extremely successful, but Cas9 was the first enzyme that the field discovered in development. Our approach is let’s see this funnel of enzymes and pick the best tool for the right job. Depending on the application, you can have different enzymes with different properties. It all comes down to making sure that your solution is not going to create more risk than benefit.

 

Q: What do you think have been the key findings in the field of CRISPR, since CRISPR-Cas9 was first discovered?

First of all, I think the clinical trials and the data that’s coming out from things like treating sickle cell disease in patients, I think that’s been remarkable. That’s really what the field is moving towards. And that’s where all these new systems will help enable the other areas since Cas9, which are new iterations of using CRISPR. Some of the technologies like CRISPRi or CRISPRa, the ability to transiently turn on and off genes, for certain cases is going to be more critical than permanently cutting or editing that locus. And then there’s also new ways of doing editing like base editing and prime editing, different ways you can modify the genome.

 

Q: What are the benefits of the smaller enzymes you have developed compared with cas9?

The smaller enzymes, most critically, are going to help in delivery of the [therapeutic] molecule to specific organs. Right now, there’s two major classes of delivery. Lipid nanoparticles (LNPs) and adeno-associated viral vectors (AAVs). LNPs are pretty nonspecific. When you deliver them to a patient, typically they just congregate in the liver. Then you have AAVs. There are different ‘flavors’ of AAVs that can be programmed to target different organs. The way people deliver it is mostly by directly injecting into organs, but it is not really optimal, because it’s pretty invasive. With these smaller enzymes, we’re not limited to just the liver because we fit into AAVs, we can also now tune the AAVs to target the specific organ of interest and maintain the same level of activity as Cas9. When you really shrink down that CRISPR piece, you can add all these different modules on top of that in a vector, and that essentially opens up the opportunity to use it in a therapeutic.

 

Q: Do you think we need a public dialogue about CRISPR-related gene editing and how it can be used to make next generation therapeutics?

I think we’re really in a critical time. Right now, we have the wave of Cas9 based therapeutics that are showing real progress in patients, but I think that will pave the way not just for the technology, but will also give us more knowledge about how this technology actually functions in patients. With new technologies there’s always fear of how anyone’s going to use that. A couple of years ago, we saw that with the gene editing of the Chinese twins. I think that has kind of sparked the reality that there are going to be people that are going to make decisions about how to use this technology for things that are ethically questionable. CRISPR is going to transform the way we think about genetic medicine. That’s going to happen. And so, all of a sudden, that opens up a Pandora’s box. Once we understand different specific targets and can modify that, anything becomes possible… You’re going to need to engage policymakers, you’re going to have to engage people who may one day use the technology, not just as a researcher, but who might also be on the receiving end, and help them get educated and understand what the technology is and what it can do. There are some boundaries that we don’t want to cross. Clearly, people will still make decisions that are quite shocking. But having a dialogue about the topic and expectations, I think we can all do that at a grassroots level.

 

Q: We can’t really talk today without mentioning COVID-19. Maybe you could talk a bit about how it impacted the company and how you responded to it?

I went to a conference in late December and heard government representatives saying there’s this strange virus in China, we were still figuring out what was going to happen, while we were all in DC. And then, I came back to San Francisco and it became clear this was a serious situation. I remember the phone call that I had with Charles Chiu at UCSF. He said, look, this is a growing situation, Charles had some of the first clinical samples from patients infected with COVID. And we said, ‘okay, we need to be able to demonstrate that there’s a different way we can detect, SARS-CoV-2 in samples’, and we felt that our platform was in a really great position to be quickly reconfigured to do that. So, it was just 10 days from designing the assays to getting the reagents and testing samples, and it was just such a whirlwind at the time. This was before the shutdown. People were still in the lab, I remember we said, okay, let’s focus this part of the company on COVID. You know, there’s still the other piece of the company on the therapeutic side, we just have to stay the course. It was it was extremely motivating, I think, for us to be able to help.

 

Q: What achievement are you most proud of since you started this journey?

I would say the first discovery of using CRISPR for detecting DNA was just one of those once in a lifetime moments. As a scientist, there’s nothing more fulfilling than to say we have this hypothesis, we followed up on it, and then we saw this is a really robust method and tool. That was extraordinarily exciting. And the other thing, too, is navigating all the challenges throughout the pandemic, and being part of a team that’s just so committed to taking these technologies forward. I think that’s been a very proud moment, for me, leading up that part of it.

 

Q: If you had to give someone who was in your position a couple of years ago some advice, or tips, what would you say?

I would say don’t be afraid to take risks. That was such an important mindset for me. It’s OK to think big, you’ve got to be outside your comfort zone, that I think that’s the kind of message that I think young entrepreneurs should take home.

 

Helen Albert is Senior Editor at Inside Precision Medicine and a freelance science journalist. Prior to going freelance, she was Editor-in-Chief at Labiotech, an English-language, digital publication based in Berlin focusing on the European biotech industry. Before moving to Germany, she worked at a range of different science and health-focused publications in London. She was Editor of The Biochemist magazine and blog, but also worked as a Senior Reporter at Springer Nature’s medwireNews for a number of years, as well as freelancing for various international publications. She has written for New Scientist, Chemistry World, Biodesigned, The BMJ, Forbes, Science Business, Cosmos magazine, and GEN. Helen has academic degrees in genetics and anthropology, and also spent some time early in her career working at the Sanger Institute in Cambridge before deciding to move into journalism.

The post A Conversation with Janice Chen, CTO of Mammoth Biosciences appeared first on Inside Precision Medicine.

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International

United Airlines adds new flights to faraway destinations

The airline said that it has been working hard to "find hidden gem destinations."

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Since countries started opening up after the pandemic in 2021 and 2022, airlines have been seeing demand soar not just for major global cities and popular routes but also for farther-away destinations.

Numerous reports, including a recent TripAdvisor survey of trending destinations, showed that there has been a rise in U.S. traveler interest in Asian countries such as Japan, South Korea and Vietnam as well as growing tourism traction in off-the-beaten-path European countries such as Slovenia, Estonia and Montenegro.

Related: 'No more flying for you': Travel agency sounds alarm over risk of 'carbon passports'

As a result, airlines have been looking at their networks to include more faraway destinations as well as smaller cities that are growing increasingly popular with tourists and may not be served by their competitors.

The Philippines has been popular among tourists in recent years.

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United brings back more routes, says it is committed to 'finding hidden gems'

This week, United Airlines  (UAL)  announced that it will be launching a new route from Newark Liberty International Airport (EWR) to Morocco's Marrakesh. While it is only the country's fourth-largest city, Marrakesh is a particularly popular place for tourists to seek out the sights and experiences that many associate with the country — colorful souks, gardens with ornate architecture and mosques from the Moorish period.

More Travel:

"We have consistently been ahead of the curve in finding hidden gem destinations for our customers to explore and remain committed to providing the most unique slate of travel options for their adventures abroad," United's SVP of Global Network Planning Patrick Quayle, said in a press statement.

The new route will launch on Oct. 24 and take place three times a week on a Boeing 767-300ER  (BA)  plane that is equipped with 46 Polaris business class and 22 Premium Plus seats. The plane choice was a way to reach a luxury customer customer looking to start their holiday in Marrakesh in the plane.

Along with the new Morocco route, United is also launching a flight between Houston (IAH) and Colombia's Medellín on Oct. 27 as well as a route between Tokyo and Cebu in the Philippines on July 31 — the latter is known as a "fifth freedom" flight in which the airline flies to the larger hub from the mainland U.S. and then goes on to smaller Asian city popular with tourists after some travelers get off (and others get on) in Tokyo.

United's network expansion includes new 'fifth freedom' flight

In the fall of 2023, United became the first U.S. airline to fly to the Philippines with a new Manila-San Francisco flight. It has expanded its service to Asia from different U.S. cities earlier last year. Cebu has been on its radar amid growing tourist interest in the region known for marine parks, rainforests and Spanish-style architecture.

With the summer coming up, United also announced that it plans to run its current flights to Hong Kong, Seoul, and Portugal's Porto more frequently at different points of the week and reach four weekly flights between Los Angeles and Shanghai by August 29.

"This is your normal, exciting network planning team back in action," Quayle told travel website The Points Guy of the airline's plans for the new routes.

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Walmart launches clever answer to Target’s new membership program

The retail superstore is adding a new feature to its Walmart+ plan — and customers will be happy.

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It's just been a few days since Target  (TGT)  launched its new Target Circle 360 paid membership plan. 

The plan offers free and fast shipping on many products to customers, initially for $49 a year and then $99 after the initial promotional signup period. It promises to be a success, since many Target customers are loyal to the brand and will go out of their way to shop at one instead of at its two larger peers, Walmart and Amazon.

Related: Walmart makes a major price cut that will delight customers

And stop us if this sounds familiar: Target will rely on its more than 2,000 stores to act as fulfillment hubs. 

This model is a proven winner; Walmart also uses its more than 4,600 stores as fulfillment and shipping locations to get orders to customers as soon as possible.

Sometimes, this means shipping goods from the nearest warehouse. But if a desired product is in-store and closer to a customer, it reduces miles on the road and delivery time. It's a kind of logistical magic that makes any efficiency lover's (or retail nerd's) heart go pitter patter. 

Walmart rolls out answer to Target's new membership tier

Walmart has certainly had more time than Target to develop and work out the kinks in Walmart+. It first launched the paid membership in 2020 during the height of the pandemic, when many shoppers sheltered at home but still required many staples they might ordinarily pick up at a Walmart, like cleaning supplies, personal-care products, pantry goods and, of course, toilet paper. 

It also undercut Amazon  (AMZN)  Prime, which costs customers $139 a year for free and fast shipping (plus several other benefits including access to its streaming service, Amazon Prime Video). 

Walmart+ costs $98 a year, which also gets you free and speedy delivery, plus access to a Paramount+ streaming subscription, fuel savings, and more. 

An employee at a Merida, Mexico, Walmart. (Photo by Jeffrey Greenberg/Universal Images Group via Getty Images)

Jeff Greenberg/Getty Images

If that's not enough to tempt you, however, Walmart+ just added a new benefit to its membership program, ostensibly to compete directly with something Target now has: ultrafast delivery. 

Target Circle 360 particularly attracts customers with free same-day delivery for select orders over $35 and as little as one-hour delivery on select items. Target executes this through its Shipt subsidiary.

We've seen this lightning-fast delivery speed only in snippets from Amazon, the king of delivery efficiency. Who better to take on Target, though, than Walmart, which is using a similar store-as-fulfillment-center model? 

"Walmart is stepping up to save our customers even more time with our latest delivery offering: Express On-Demand Early Morning Delivery," Walmart said in a statement, just a day after Target Circle 360 launched. "Starting at 6 a.m., earlier than ever before, customers can enjoy the convenience of On-Demand delivery."

Walmart  (WMT)  clearly sees consumers' desire for near-instant delivery, which obviously saves time and trips to the store. Rather than waiting a day for your order to show up, it might be on your doorstep when you wake up. 

Consumers also tend to spend more money when they shop online, and they remain stickier as paying annual members. So, to a growing number of retail giants, almost instant gratification like this seems like something worth striving for.

Related: Veteran fund manager picks favorite stocks for 2024

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President Biden Delivers The “Darkest, Most Un-American Speech Given By A President”

President Biden Delivers The "Darkest, Most Un-American Speech Given By A President"

Having successfully raged, ranted, lied, and yelled through…

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President Biden Delivers The "Darkest, Most Un-American Speech Given By A President"

Having successfully raged, ranted, lied, and yelled through the State of The Union, President Biden can go back to his crypt now.

Whatever 'they' gave Biden, every American man, woman, and the other should be allowed to take it - though it seems the cocktail brings out 'dark Brandon'?

Tl;dw: Biden's Speech tonight ...

  • Fund Ukraine.

  • Trump is threat to democracy and America itself.

  • Abortion is good.

  • American Economy is stronger than ever.

  • Inflation wasn't Biden's fault.

  • Illegals are Americans too.

  • Republicans are responsible for the border crisis.

  • Trump is bad.

  • Biden stands with trans-children.

  • J6 was the worst insurrection since the Civil War.

(h/t @TCDMS99)

Tucker Carlson's response sums it all up perfectly:

"that was possibly the darkest, most un-American speech given by an American president. It wasn't a speech, it was a rant..."

Carlson continued: "The true measure of a nation's greatness lies within its capacity to control borders, yet Bid refuses to do it."

"In a fair election, Joe Biden cannot win"

And concluded:

“There was not a meaningful word for the entire duration about the things that actually matter to people who live here.”

Victor Davis Hanson added some excellent color, but this was probably the best line on Biden:

"he doesn't care... he lives in an alternative reality."

*  *  *

Watch SOTU Live here...

*   *   *

Mises' Connor O'Keeffe, warns: "Be on the Lookout for These Lies in Biden's State of the Union Address." 

On Thursday evening, President Joe Biden is set to give his third State of the Union address. The political press has been buzzing with speculation over what the president will say. That speculation, however, is focused more on how Biden will perform, and which issues he will prioritize. Much of the speech is expected to be familiar.

The story Biden will tell about what he has done as president and where the country finds itself as a result will be the same dishonest story he's been telling since at least the summer.

He'll cite government statistics to say the economy is growing, unemployment is low, and inflation is down.

Something that has been frustrating Biden, his team, and his allies in the media is that the American people do not feel as economically well off as the official data says they are. Despite what the White House and establishment-friendly journalists say, the problem lies with the data, not the American people's ability to perceive their own well-being.

As I wrote back in January, the reason for the discrepancy is the lack of distinction made between private economic activity and government spending in the most frequently cited economic indicators. There is an important difference between the two:

  • Government, unlike any other entity in the economy, can simply take money and resources from others to spend on things and hire people. Whether or not the spending brings people value is irrelevant

  • It's the private sector that's responsible for producing goods and services that actually meet people's needs and wants. So, the private components of the economy have the most significant effect on people's economic well-being.

Recently, government spending and hiring has accounted for a larger than normal share of both economic activity and employment. This means the government is propping up these traditional measures, making the economy appear better than it actually is. Also, many of the jobs Biden and his allies take credit for creating will quickly go away once it becomes clear that consumers don't actually want whatever the government encouraged these companies to produce.

On top of all that, the administration is dealing with the consequences of their chosen inflation rhetoric.

Since its peak in the summer of 2022, the president's team has talked about inflation "coming back down," which can easily give the impression that it's prices that will eventually come back down.

But that's not what that phrase means. It would be more honest to say that price increases are slowing down.

Americans are finally waking up to the fact that the cost of living will not return to prepandemic levels, and they're not happy about it.

The president has made some clumsy attempts at damage control, such as a Super Bowl Sunday video attacking food companies for "shrinkflation"—selling smaller portions at the same price instead of simply raising prices.

In his speech Thursday, Biden is expected to play up his desire to crack down on the "corporate greed" he's blaming for high prices.

In the name of "bringing down costs for Americans," the administration wants to implement targeted price ceilings - something anyone who has taken even a single economics class could tell you does more harm than good. Biden would never place the blame for the dramatic price increases we've experienced during his term where it actually belongs—on all the government spending that he and President Donald Trump oversaw during the pandemic, funded by the creation of $6 trillion out of thin air - because that kind of spending is precisely what he hopes to kick back up in a second term.

If reelected, the president wants to "revive" parts of his so-called Build Back Better agenda, which he tried and failed to pass in his first year. That would bring a significant expansion of domestic spending. And Biden remains committed to the idea that Americans must be forced to continue funding the war in Ukraine. That's another topic Biden is expected to highlight in the State of the Union, likely accompanied by the lie that Ukraine spending is good for the American economy. It isn't.

It's not possible to predict all the ways President Biden will exaggerate, mislead, and outright lie in his speech on Thursday. But we can be sure of two things. The "state of the Union" is not as strong as Biden will say it is. And his policy ambitions risk making it much worse.

*  *  *

The American people will be tuning in on their smartphones, laptops, and televisions on Thursday evening to see if 'sloppy joe' 81-year-old President Joe Biden can coherently put together more than two sentences (even with a teleprompter) as he gives his third State of the Union in front of a divided Congress. 

President Biden will speak on various topics to convince voters why he shouldn't be sent to a retirement home.

According to CNN sources, here are some of the topics Biden will discuss tonight:

  • Economic issues: Biden and his team have been drafting a speech heavy on economic populism, aides said, with calls for higher taxes on corporations and the wealthy – an attempt to draw a sharp contrast with Republicans and their likely presidential nominee, Donald Trump.

  • Health care expenses: Biden will also push for lowering health care costs and discuss his efforts to go after drug manufacturers to lower the cost of prescription medications — all issues his advisers believe can help buoy what have been sagging economic approval ratings.

  • Israel's war with Hamas: Also looming large over Biden's primetime address is the ongoing Israel-Hamas war, which has consumed much of the president's time and attention over the past few months. The president's top national security advisers have been working around the clock to try to finalize a ceasefire-hostages release deal by Ramadan, the Muslim holy month that begins next week.

  • An argument for reelection: Aides view Thursday's speech as a critical opportunity for the president to tout his accomplishments in office and lay out his plans for another four years in the nation's top job. Even though viewership has declined over the years, the yearly speech reliably draws tens of millions of households.

Sources provided more color on Biden's SOTU address: 

The speech is expected to be heavy on economic populism. The president will talk about raising taxes on corporations and the wealthy. He'll highlight efforts to cut costs for the American people, including pushing Congress to help make prescription drugs more affordable.

Biden will talk about the need to preserve democracy and freedom, a cornerstone of his re-election bid. That includes protecting and bolstering reproductive rights, an issue Democrats believe will energize voters in November. Biden is also expected to promote his unity agenda, a key feature of each of his addresses to Congress while in office.

Biden is also expected to give remarks on border security while the invasion of illegals has become one of the most heated topics among American voters. A majority of voters are frustrated with radical progressives in the White House facilitating the illegal migrant invasion. 

It is probable that the president will attribute the failure of the Senate border bill to the Republicans, a claim many voters view as unfounded. This is because the White House has the option to issue an executive order to restore border security, yet opts not to do so

Maybe this is why? 

While Biden addresses the nation, the Biden administration will be armed with a social media team to pump propaganda to at least 100 million Americans. 

"The White House hosted about 70 creators, digital publishers, and influencers across three separate events" on Wednesday and Thursday, a White House official told CNN. 

Not a very capable social media team... 

The administration's move to ramp up social media operations comes as users on X are mostly free from government censorship with Elon Musk at the helm. This infuriates Democrats, who can no longer censor their political enemies on X. 

Meanwhile, Democratic lawmakers tell Axios that the president's SOTU performance will be critical as he tries to dispel voter concerns about his elderly age. The address reached as many as 27 million people in 2023. 

"We are all nervous," said one House Democrat, citing concerns about the president's "ability to speak without blowing things."

The SOTU address comes as Biden's polling data is in the dumps

BetOnline has created several money-making opportunities for gamblers tonight, such as betting on what word Biden mentions the most. 

As well as...

We will update you when Tucker Carlson's live feed of SOTU is published. 

Tyler Durden Fri, 03/08/2024 - 07:44

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