The business model for pharma and drug discovery is unfortunately one that requires a lot of upfront investment for research and trials that may or may not pay off as revenue one day.
The technology they invented is incredibly promising for new vaccines and they should be attracting enough investment (through contracts or other deals) to continue innovating and saving lives. Maybe they can license it as a last ditch effort to build revenue, but unfortunately the public perceptions about vaccine efficacy is on the wane and government contracts are no longer there to support this vital work both in the present and as a hedge against future pandemics.
To put some numbers to trying to develop a single therapy (where candidates etc. will fail as you try them)
- Plan to sink $180-500M+ just in R&D
- Factor in failures, regulatory, clinical, recruitment, phase 1/2 trials and you arrive very quickly around $1.3-2.1 BILLION USD per therapy approved.
...there is a 90% chance that you will spend that $1B+ - and it will fail completely.
According to your numbers, Moderna got lucky at a 10% chance of producing the mRNA COVID-19 vaccine in 48 hours of computation? I don't know, but there seems to be more factors at play.
Moderna got lucky in that we know enough about that virus that the chance of a COVID-19 vaccine was a lot more than 10%. The more general case of a drug is a lot more than specific one
> Also, in 2018, just one year before the outbreak in a DARPA grant proposal, Wuhan Institute of Virology and its collaborators proposed to construct genetically modified SARS viruses having a furin cleavage site, a feature associated with increased viral growth and increased transmissibility. They proposed to insert the furin cleavage site at the spike gene S1/S2 border, and to construct the viruses by synthesizing six nucleic acid-building blocks, and assembling them using the reagent BsmB1.
> Fourth, in 2019, a novel SARS virus having a spike with extremely high binding affinity for human SARS receptors, a furin cleavage site inserted at the spike S1/S2 border, and a genome sequence with features enabling assembly from six synthetic nucleic acid building blocks using the reagent BsmB1--a virus having the exact features proposed into 2018 NIH and DARPA proposals--emerged on the doorstep of Wuhan Institute of Virology.
> Taken together, the presence of a spike having an extremely high affinity for human SARS receptors, the presence of a furin cleavage site inserted at the spike S1/S2 border, the genome sequence enabling assembly from six synthetic nucleic acid- building blocks using the reagent BsmB1, and the one-for-one match between these features and the features proposed in the 2018 NIH and DARPA proposals, make an extremely strong case--a smoking gun--for a research origin.
It raises questions that James Comer keeps raising to attack Fauci, but which never seem to get anywhere close to being proven. It's now been four years. The various libels against Fauci remain unsupported.
It's tough to get people to want a vaccine which knocks you off your feet for 3 days and needs to be repeated every 6-12 months. I'm very bullish on mRNA vaccine technology - but it's potentially a poor fit for rapidly changing viruses.
That sucks if that's your experience, but it's not the universal, or even the common, experience.
For reference, I get a sore-ish shoulder the next day, and that's it. Also for reference, when I got Actual Covid, I was knocked on my ass for almost two weeks. So for me, at least, the choice is easy.
It's my unfortunate experience, when I've had covid its a 6-12 hour affair that happens once every 12-24 months. My 3rd vaccine shot had me in bed for 3 days. Leading to continued vaccination being unsustainable. My wife has a similar experience to yours, and gets moderate to severe covid. She gets the vaccine every year to help avoid it - but still gets moderate COVID roughly once per 6 months.
It's unfortunate that the vaccine has such radically different outcomes within a single household, if it was a flu shot like experience I'd happily get it once per year.
COVID is a nasty virus. I need my brain way to much to FAFO.
COVID-19 may Enduringly Impact Cognitive Performance and Brain Haemodynamics in Undergraduate Students - ScienceDirect https://share.google/49ER4VjJUwipGotZO
Flu shot experience varies too. The last several have been very low response, but the first few were a miserable couple days and I stopped getting them because certain misery was worse than a chance of misery that I'd never know if it was flu or not, because testing was inaccessible.
Last year I skipped the flu vac (I had a zillion for tropical diseases so I though come one not another one) and lo, I got a flu about every 4 weeks, so like over 6 the whole season. I'm on a way to get it this year.
At least testably/symptomatically, I'm asthmatic as well - so it's surprising that the impact is so small. My wife gets it for 1-2 weeks whenever she comes down with it.
As a data point, my experience with the shot was a sore arm and chills for a couple days.
When I got Covid later, it was slightly worse chills for 3 days. By the 4th time I got Covid, it was just chills for a day.
If I knew that would be the experience, I'd probably have skipped it. That said, it's completely possible it was having the vaccine that made getting real Covid not so bad.
By the time it was my turn to get Covid I’d been twice vaccinated. It’s the most exhausted I can remember ever feeling. Let me tell you, the whole time I kept thinking: How much more miserable would this have been without the vaccine to blunt the impact? Felt grateful and humbled
You said: "When I got Covid later, it was slightly worse chills for 3 days. By the 4th time I got Covid, it was just chills for a day. If I knew that would be the experience, I'd probably have skipped it."
I'm saying that's not an apples to apples comparison due to the growing evidence of how much long term damage a COVID infection can cause.
Ah I see, thanks. Yep, it's definitely not apples to apples in either event. As in, not having the vaccine could have made getting it, at least the first time, way way worse to deal with.
It has affected me for at most 16 hours. I have never heard 3 days, though I'm sure there are some rare outliers. And, not being at high risk, I don't "need" it more than once a year. This kind of exaggeration is one of the things that doesn't help public opinion. Especially when there are people actively looking for ways to subvert it.
People have varying immune responses to getting vaccines, but feeling crummy after getting a flu shot has nothing to do with whether the vaccine used mRNA technology or not.
I would say people who end up bedridden for 3 days are in the minority for most vaccines immune responses, but people also need to make peace with the idea that an ounce of prevention is worth a pound of cure.
Quite a lot of the low-hanging fruit from pharma has already been picked. The modern business model for pharma involves coming up with a patentable new drug that does the same thing as an older drug that's now out of patent and available for manufacture as a generic.
Making pharmaceuticals subservient to the whimsy of the stock market is a bad idea. It introduces incentive distortions where none should be.
The incentive many times is to create a scarcity of talent for other tech companies by hiring as many experts as you can. Facebook, Amazon, and many others have been employing this strategy for over a decade, but now that the era of cheap money is over we're seeing a pivot away.
Eh, if this is true then IBM and Intel would still be the kings of the hill. Plenty of companies came from the bottom up out of nothing during the 90s and 2000s to build multi-billion dollar companies that are still dominate the market today. Many of those companies struggled for investment and grew over a long timeframe.
The argument is something like that is not really possible anymore given the absurd upfront investments we're seeing existing AI companies need in order to further their offerings.
Anthropic has existed for a grand total of 4 years.
But yes, there was a window of opportunity when it was possible to do cutting-edge work without billions of investment. That window of opportunity is now past, at least for LLMs. Many new technologies follow a similar pattern.
Regional Rail runs a little on the expensive side. Round trip from Philly back to the suburbs is $17.50. I take that to get to work sometimes. The bus, subway, and trolley are extremely affordable for what they are.
Can't find it right now, but I also remember a study that compared funding for other major metro transit agencies, and SEPTA ranked very highly for offering as many transit options for the amount of riders they handle given their relatively anemic budget (compared to NYC or Chicago).
> Regional Rail runs a little on the expensive side. Round trip from Philly back to the suburbs is $17.50.
Are you paying the surcharge to buy a ticket on board in one of those directions? Normally if you already have tickets, round trip to zone 4 (outer suburbs) is $15 on weekdays or $14 on weekends.
That's quite cheap in my opinion, considering zone 4 goes pretty far. For example Doylestown is 25 miles from Center City Philly as the crow flies.
Compare that to an equivalent trip in northern Jersey on NJ Transit rail: Morristown NJ is about 25 miles from Midtown Manhattan, and a round-trip fare is currently $32.20. And after next week's fare hike, it will be $33.10.
Pennsylvania could be so much more for its residents but we're a state bogged down politically by rural districts that do everything within their power to kneecap the our two major economic hubs/cities: Philadelphia and Pittsburgh.
Our governor backs mass transit, but state reps will not budge on funding as SEPTA only services Philadelphia and the counties immediately adjacent. One politician, Cris Dush who represents the 25th district in the upper most part of the state, released a letter to concerned citizens and characterized the issue as a preferrence for keeping tax dollars in his own district as there's no mass transit available to his constituents. In his view, he's not willing to pay for other people to be "chaffered" around on public transit: http://crossingbroad.com/news/trending/pennsylvania-state-se...
Until Pennsylvania's statehouse can overcome their misguided idea of what it means to levy and collect taxes, PA will continue to lag behind other states in the northeast in terms of basic services and economic competitiveness.
Uneducated question, seems like Philadelphia has around $5B of revenue a year, and the transit deficit is ~$200M. I understand the city has to provide services and a lot of the revenue will be restricted as to what it can be allocated to. But with these orders of magnitude, why is the default expectation not for cities to fund their own transit with city tax revenue?
Much of the service being cut is the regional rail that primarily services the collar counties. Philadelphia will lose bus routes but the core of their transit will survive.
It’s Bucks, Montgomery, and Delaware Counties that will suffer the most from this.
Well that just confuses me more, if the losses are spread out across all these counties each with their own revenue, why isn't that the default place where money is allocated from?
Probably due to the impossible complexity of coming to an agreement on proper funding allocation between the 7 different counties served by SEPTA, especially since 2 of those counties are not even in Pennsylvania... and then having to re-debate that on a periodic basis as ridership trends shift over time.
SEPTA was formed by the state, and its existence benefits the whole state by enabling economic activity (which then leads to more state-level taxes), reducing congestion on roadways maintained by the state, etc. And if my back-of-the-envelope math is correct, nearly 1/3rd of PA's population lives in counties served by SEPTA.
That's a very unsatisfying while probably correct answer. I wish voters stopped accepting this kind of stuff being "impossibly complex" for government.
I just don't think that's realistic when the number of stakeholders grows too high. How do you accurately determine how much each county should pay? How do you allocate funding for commuters who live in one county but work in another?
When a transit agency serves the state's largest population center and economic center, it seems reasonable for its funding to be a state-level concern. Especially when it also serves other states, and additionally ~40% of the tracks used by SEPTA are owned by Amtrak, which is Federal. County-level officials are just not the best layer to interface with all that.
Isn't it the norm for elected officials to want to keep tax dollars in their district? This Dush guy might be misguided somehow in the larger scheme of things, but wouldn't he just be reflecting his constituents' desire to directly benefit from the taxes they pay?
There are huge benefits derived from economies of scale that can be built at the appropriate levels of government. You can end up wasting a lot of resources by trying to do things too locally or not locally enough.
I live in a rural area and it would bankrupt our county if we had to maintain all the miles of road (far more per taxpayer than urban areas) if the state wasn't doing so much of it. The state uses expensive machines to do much of that work efficiently. It wouldn't make sense for our county to buy that equipment and have it sit unused much of the time. So the county would be less efficient at it. And that's before we get to things like duplication of administrative roles around that work.
Sometimes that means urban areas are helping fund some of my local roads. And sometimes that means I'm helping fund their public transport. When done well, we all get far more for less tax money.
The most affected counties (Bucks, Montgomery, and Delaware) have average incomes twice that of the counties Dush represents (Crawford, Erie, Washington, Greene).
So Dush's voters aren't paying much in the way of taxes.
For a similar situation to Trump bombing Iran and only notifying a few members of Congress:
1983 Granada
1989 Panama
2011 Libya
2012 Syria
The 1990s actions in Yugoslavia were done without fall declaration of war, but Congress was more fully engaged in saying no at least.
The 1991 war against Iraq was approved, in part, because the administration allowed a witness to flat out lie to Congress about the horrors of the Iraq invasion of Kuwait.
The 2003 invasion of Iraq was approved, in part, because the administration lied to Congress about weapons of mass destruction.
I mentioned these last two because they make a mockery of the act itself, or of the US congress, or both...
He didn't add sanctions on Russia, but on people dealing with Russia - that's a different thing.
But notice how people talk now - Trump might say he is "planning" something against Russia and people take it as a proof that he is not an asset. They forget about concept of sacrificing something to gain advantage. If heat turns to much on Trump, they might let him disrupt something and then run propaganda that Trump isn't bent. Until he makes next move massively benefitting Putin.
Seems like they can be doing this over and over and general public will see it as Trump just navigating difficult geopolitical landscape and that we should "trust the process". etc.
I am not sure why you are calling this out seeing how many people are hypothesising what is going to happen in this thread (economy destroyed, USD no longer reserve currency, etc). At least we have actual words to base what I wrote unlike all the other theories being thrown out in this thread.
hmm what could have happened in the last 3-4 years that would impact US life expectancy? also a huge part of that decline is preventable death due to drug overdose.
Like every smart device, the Snoo isn't actually that smart. We have a 1 month old and bought a Snoo second-hand in anticipation and way before they changed the terms of their app.
Where you'd expect the Snoo to dutifully monitor the baby and gently increase the intensity of the motion to soothe the baby, it rapidly goes from a baseline to the highest level of motion and sound within a minute or so, which is both annoying for the parents and stressful for the child.
The motion locking feature was how we got around that poor excuse for engineering, but now that pretty basic feature is now behind the paywall. We just use it as a standard bassinet.
I haven't signed up for the added features yet, our kid is a pretty good sleeper at this point, but those features are a necessity to operate the Snoo properly, so I'll end up paying the premium (begrudgingly). As a parent I know companies are doing everything they can to get my business, so I'm not surprised by this behavior, but it's just a disappointment and annoyance.
The technology they invented is incredibly promising for new vaccines and they should be attracting enough investment (through contracts or other deals) to continue innovating and saving lives. Maybe they can license it as a last ditch effort to build revenue, but unfortunately the public perceptions about vaccine efficacy is on the wane and government contracts are no longer there to support this vital work both in the present and as a hedge against future pandemics.