The Loyal Longevity drug for dogs is getting derailed now too… Trump / Elon seem to be decimating the longevity science field… Everyone’s lives will be shortened because of these disruptions and defunding.

Two weeks earlier:

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Source: x.com

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This thread is depressing. I’d think that here, more than anywhere, people would understand the value of legitimate basic research. But, no. All of the sudden, because we can do our own “research” on ChatGPT we think we are as good as scientists who’ve spent 20+ years studying their specific areas of interest.

If this is allowed to continue (and yes, I know several scientists who’ve already been let go) the U.S. will fall behind and people will suffer.

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Turns out billionaires hating each other is more important to them than being rational.

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A well-known Buck Institute Researcher:

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Yes, move fast and break things is just one paradigm in engineering/ systems design. It is not relevant for all contexts — maybe it is good for a startup who are building systems from the scratch, looking to make quick profits, and show VCs growth. It might be more appropriate when it comes to pilot projects / contexts where breaking things has limited impact and can be informative for eventual large scale deployments.

However, as the scale of change increases, it’d be good at the minimum consider some possible unintended consequences. Mao arguably was looking to move fast and break things — the Great Leap Forward seems to have many parallels to the way the current administration is operating.

What may be better for large scale changes is Design Thinking. The first step in this involves talking to stakeholders to even figure out what to optimize for, and getting a sense of how to keep the best of existing systems while getting rid of the worst. I see no signs so far about such a way of operating at the top. Rather, it is very top-down, lacks naunce, and is blind to feedback.

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Most high quality research done at universities around the country are funded in part by NIH. The dog aging project is a great example.

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Here’s a pretty decent article summarizing the situation and describing the hearing today (Feb 21st)

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The MIT Technology Review:

Ever since World War II, the US has been the global leader in science and technology—and benefited immensely from it. Research fuels American innovation and the economy in turn. Scientists around the world want to study in the US and collaborate with American scientists to produce more of that research. These international collaborations play a critical role in American soft power and diplomacy. The products Americans can buy, the drugs they have access to, the diseases they’re at risk of catching—are all directly related to the strength of American research and its connections to the world’s scientists.

That scientific leadership is now being dismantled, according to more than 10 federal workers who spoke to MIT Technology Review, as the Trump administration—spearheaded by Elon Musk’s Department of Government Efficiency (DOGE)—slashes personnel, programs, and agencies. Meanwhile, the president himself has gone after relationships with US allies.

These workers come from several agencies, including the Departments of State, Defense, and Commerce, the US Agency for International Development, and the National Science Foundation. All of them occupy scientific and technical roles, many of which the average American has never heard of but which are nevertheless critical, coordinating research, distributing funding, supporting policymaking, or advising diplomacy.

They warn that dismantling the behind-the-scenes scientific research programs that backstop American life could lead to long-lasting, perhaps irreparable damage to everything from the quality of health care to the public’s access to next-generation consumer technologies. The US took nearly a century to craft its rich scientific ecosystem; if the unraveling that has taken place over the past month continues, Americans will feel the effects for decades to come.

“If you believe that innovation is important to economic development, then throwing a wrench in one of the most sophisticated and productive innovation machines in world history is not a good idea,” says Deborah Seligsohn, an assistant professor of political science at Villanova University who worked for two decades in the State Department on science issues. “They’re setting us up for economic decline.”

In her 2013 book The Entrepreneurial State , Mariana Mazzucato, a leading economist studying innovation at University College London, found that every major technological transformation in the US, from electric cars to Google to the iPhone, can trace its roots back to basic science research once funded by the federal government. If the past offers any lesson, that means every major transformation in the future could be shortchanged with the destruction of that support.

The National Institutes of Health, for example, has since 2015 been running the Precision Medicine Initiative, the only effort of its kind to collect extensive and granular health data from over 1 million Americans who volunteer their medical records, genetic history, and even Fitbit data to help researchers understand health disparities and develop personalized and more effective treatments for disorders from heart and lung disease to cancer. The data set, which is too expensive for any one university to assemble and maintain, has already been used in hundreds of papers that will lay the foundation for the next generation of life-saving pharmaceuticals.

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I think we have benefited greatly from US government supported basic research. Of course, there is always waste. But it takes knowledge to identify waste, and the types of thoughtless cuts that are being made will not make government more efficient or find much waste. Agency inspector generals do find and eliminate waste—but they are now being fired themselves. What Musk is doing has much more to do with attacks on regulation and on experts—the latter part of the culture wars, and the former profits in big business. Musk is not a disinterested party serving the public good here—as a major government contractor he is serving his own interests.

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The best grifters are the kind of grifters who grift while telling you that they’re protecting you from grifters.

Many are suggesting that everyone should wait until there is actual palpable damage before complaining - “give 'em a chance, whatever you may think”. I get it, believe me, and I sympathize.

But… spoiler alert - there never will be a time when everyone sits down and sums up the results after whatever period. Nobody’s mind will be changed. It’ll merely confirm your prior bias. If you think it’s a disaster, well, you’ll remain with that opinion. If you think it’s just what the doctor ordered, you’ll defend the result no matter what. That’s the essence of political conflicts - no side will back down, whether the evidence is there or not.

So right now, people are saying, “hey, sure there are cuts, but I don’t think this means there will be any damage to science - PLEASE WAIT!!”. It reminds me of the guy who jumps off a skyscraper, and falls down passing multiple floor windows and in one of the windows there’s a party, so he waves to them and screams out: “SO FAR SO GOOD!”. And guess what - the party guests are divided. Some say, “gee, don’t you see it’ll be a disaster for the guy!?” while the other guests go “why are you making up your mind already - wait for the result! Don’t prejudge! Too early! So far so good, no damage!”.

And when the guy hits the pavement, the whole party moves down to look at the result, they gather around and discuss. So you think - well, now we have the result and finally we’ll all see who was right and who was wrong!.

Except that’s not what happens. The people who predicted disaster will point at the guy on the pavement and scream: “See, disaster!”. But the people who thought so far so good, it’s a pretty good way of not using the elevator, will have a completely different view - “See, no disaster, perfectly fine! He’s sleeping!” “What?? He’s dead! Why do you think his head is so flat!” “Who says, everyone can have a bad hair day once in a while, he’s perfectly fine, just needs a comb!” And so on. Not a single person will be convinced to change their mind. It’s the parrot sketch from Monty Python:

Thats because when politics enters, facts fly out the window. You are welcome to wait, or not wait, doesn’t matter, the same people will just find another way to defend their preconceived position. Because it’s not about the facts, but ideology. If you buy into it, no amount of argument will convince you otherwise and if you don’t, no matter how successful, you will always claim it’s a failure. Such is human nature. That’s why I try to stick to science, however hard it may be, as we all have our biases.

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People voting how they feel like rather what they deeply think is best is probably part of the problem.

I think a party like the one below we all can get behind, and being highly prestigious.

image

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Fortunately, the judge yesterday kept the injunction in place preventing the proposed huge cuts to the indirect costs part of NIH grants while she reviews the case.

However, as someone in the research biz, I can tell you there are already significant problems with the NIH proposal and grants process (the pipeline). Many study sections where future proposals/grants are peer-reviewed by scientists are being cancelled or delayed (I have experienced this myself firsthand and heard it from my colleagues). Here’s a good snippet/overview from a NYT article:

“This week alone, the N.I.H. had scheduled some 47 meetings for handpicked experts in various fields to weigh grant applications, the first stage of a lengthy review process. But 42 of those meetings were canceled, stalling proposals to study pancreatic cancer, addiction, brain injuries and child health.”

I totally agree there is probably waste that could be trimmed but those study areas of pancreatic cancer, addiction, brain injuries and child health all sound pretty important and at least merit some review. Next week it will be another forty-fifty study sections cancelled, etc.

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Regardless of whether you think the budgetary cuts are deleterious or helpful, I think we can all agree that the current state of affairs is not optimal. Despite decades of research spending going into countless billions, the progress in curing cancer and dementias has resulted in extremely poor return on all that investment and effort. Yes, these are complex diseases, some of the lack of progress can be put down to the inherent difficulty and complexity of the underlying biology, but one cannot help but be shocked by how extremely little progress has been made. We also see how much the research has been distorted by ideological biases, commercial motivations, waste and outright fraud. This really is fuel for those who advocate drastic budget cuts. Because here’s the basic question that is devastating in its implications: how much knowledge about Alzheimer’s Disease would have been lost, had we cut the research budget into that disease by 90% each and every year for the past 30 years? One could easily argue, that we would not know appreciably less than we do now, or been any further from a cure than we are at this moment. So if we could have gone back in time, we could have cut the budgets down to practically nothing and been no worse off - perhaps even better off having spared ourselves metric tons of noise in practically useless papers. The situation in cancer research is not a great deal better.

Bottom line, we desperately need a radical reform of research support.

Why America is losing its 50-year ‘war on cancer,’ according to scientist Nafis Hasan

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Feels a bit hyperbolic. It’s taken ~70 years from Ancel Keys to the point where heart disease is optional for those who wish to aggressively treat it. And he was not the first to begin studying heart disease. Obesity has been growing for as long if not longer, and we only recently devised a strong therapeutic for it. Cancer development is in its infancy comparatively.

Edit: And to add to this, heart disease is still the number one killer. By similar line of though we could easily say all research into heart disease is flawed and we might as well have not done it.

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This is true but the statistic is misleading. Everybody still dies of something. What is the average age of a person who dies of heart disease? Dying of heart disease later is progress.

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Here in Hong Kong, heart disease is not the number one killer, cancer is. Heart disease is number 2, and I still know of many people in their 50s-60s who die of it here.

People who die of CVD tend to die 7.5 years earlier than they normally would. Since 1 in 3 die from CVD, they claim curing CVD would raise life expectancies by 2.5 years. (7.5 years* 1/3)

Across the globe, heart attacks and stroke are usually the earliest killers outside accidents and overdoses. CVD also leads to dementia. Taking it off the table by preventing arteriosclerosis would be a major win for longevity.

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Some interesting breadcrumbs to follow for those who are curious. Somewhat inside baseball from down in the trenches.

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"More than 99% of new drug approvals (2010-2019) were funded by NIH. Why dismantle the engine that made the U.S. a world leader in innovation and drug development ?

Original Investigation

April 28, 2023

Comparison of Research Spending on New Drug Approvals by the National Institutes of Health vs the Pharmaceutical Industry, 2010-2019

Key Points

Question How does National Institutes of Health (NIH) investment in pharmaceutical innovation compare with investment by the pharmaceutical industry?

Findings In this cross-sectional study of 356 drugs approved by the US Food and Drug Administration from 2010 to 2019, the NIH spent $1.44 billion per approval on basic or applied research for products with novel targets or $599 million per approval considering applications of basic research to multiple products. Spending from the NIH was not less than industry spending, with full costs of these investments calculated with comparable accounting.

Meaning The results of this cross-sectional study suggest that the relative scale of NIH and industry investment in new drugs may provide a basis for calibrating the balance of social and private returns from these products.

https://jamanetwork.com/journals/jama-health-forum/fullarticle/2804378?utm_source=twitter&utm_campaign=content-shareicons&utm_content=article_engagement&utm_medium=social&utm_term=022325

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