DARPA Seeks to Shield Blood from Fungal and Bacterial Pathogens | Hacker News Reader

DARPA Seeks to Shield Blood from Fungal and Bacterial Pathogens

darpa.mil

156 pointsJPLeRouzic78 comments

There's the theory that a significant reason why mammals superseded reptiles after the Cretaceous-Tertiary (K-T) mass-extinction event is because the cooler, darker planet prevented reptiles from sunning themselves to clear fungal infections. One of the major reasons cold-blooded animals bask on warm rocks in the sun is to artificially induce a 'fever' to raise their body temperature high enough to break down proteins in fungal infections. Warm-blooded mammals had the ability to do that naturally, even during the very long winter after the K-T event. [0]

Yet, increasing global temperatures have been naturally selecting fungi which can survive at higher temperatures... and the average human body temperature has been decreasing in the developed world [1].

[0]: https://journals.plos.org/plospathogens/article?id=10.1371/j...

[1]: https://med.stanford.edu/news/all-news/2020/01/human-body-te...

The world has been MUCH hotter than it is today since mammals have been around (for most of it): https://www.climate.gov/news-features/climate-qa/whats-hotte...

Which isn't to say that all mammals and especially not that humans can therefore cope fine come what may.

I took a climate course or something in undergrad, and pretty much the only thing that stuck with me from that was technically we are still in an ice age? Since it is technically defined as when there is ice on the north and south poles. For millions (billions?) of years it alternates between there being ice and no ice.

I keep wondering if I misremembered since it's so different to the whole global waking narrative

> I keep wondering if I misremembered since it's so different to the whole global waking narrative

I don't see a problem with both being true: we can technically be in an "ice age" and still experience warming that would hurt us greatly in the future.

Yes but climate change narratives imply that we are the primary cause and must force change (even if harmful) to begin to even attempt to prevent some of these effects.

We are the primary cause of change happening at this rate - too fast for species to adapt.

Climate change has always happened too fast for species to adapt.

Exhibit A - dinosaurs.

We are the cause, that‘s not a narrative but concensus.

It's not a consensus...

https://www.aei.org/carpe-diem/there-is-no-climate-emergency...

That’s linking to a think tank website.

That doesn't automatically invalidate it.

Somewhere out there is a guy that doesn't believe in gravity either - to argue therefore that there's no consensus on gravity is silly.

Rate of change matters.

A car will naturally come to a stop if you don't push the accelerator pedal. A car will naturally come to a stop if you hit a brick wall.

What’s the counter-narrative? That the sudden, rapid temperature swing only coincidentally happened after the industrial revolution but were somehow going to happen anyway? That the greenhouse effect is a woke myth?

Correlation doesn't equal causation.

Despite the common narrative to the contrary, there is no actual hard evidence of what degree humans have contributed to climate change and what will fix it. There are many theories and computer models, but no evidence.

The issue is that history has shown many of these models to be extremely inaccurate.

See below where it was predicted on ABC news in 2008 that the world would be doomed by 2015 (you know, 8 years ago)...none of that happened.

https://www.newsbusters.org/blogs/scott-whitlock/2015/06/12/...

So with the constant Chicken Little coming from the climate change alarmists, I think you can understand some people's skepticism on the matter.

https://www.unionleader.com/opinion/oped-global-warming-dish...

Measurements are evidence.

Evidence that climate change itself is occurring, but not of anything else.

> There are many theories and computer models, but no evidence.

Models and theories are what enabled us to develop all our technological progress. Before, there was random chance and tinkering. That changed when we started doing experiments and to model theories that fit the measurements. These theories made predictions which enabled us to see whether the model was actually valid. Data is worthless if you have no model to plug it in to make predictions from it.

Beside that there are desktop experiments that are so simple that you could almost do them at home that show that the ability of an atmosphere to capture heat is influenced by its carbon dioxide content. These experiments were done over a hundred years ago.

You seem very vocal about the topic. What are you trying to achieve?

Just some more reasonable discussion on the topic instead of the usual alarmism and hysteria.

> Despite the common narrative to the contrary, there is no actual hard evidence of what degree humans have contributed to climate change and what will fix it. There are many theories and computer models, but no evidence.

This is blatantly false.

Where is all this hard evidence? All I've ever seen are theories and computer models, many of which end up wrong. If I'm wrong, it should be easy for someone to provide the evidence.

JFGI, it should be easy for you to find unless you have a vested interest in avoiding it.

Gives us a starting point, please.

sure

https://en.wikipedia.org/wiki/Climate_change

So like I said, just theories and computer models.

That’s some pretty flimsy evidence to wreck the middle class financially.

We are the primary cause. To suggest otherwise is unscientific and contrary to empirical facts. You may as well say "round earth narratives imply that spheres are the shape that planets tend to be".

Yea people seem to miss the fact that our species development to what we have was fairly dependent on stable conditions within an ice age and that anything outside those specific conditions have never been conducive to any species achieving anything like we have....

But then that's probably because so many don't view humans as an animal species within the greater web and instead view humans as special, whether due to religion or just plain old supremacist ideology the result is the same.

To me, the simplest explanation for our average drop in temperature is indeed less sick people, which means less feverish people driving the average up.

Interesting , but the problems is that dinosaurs aren't reptiles and are theorized to have been warm blooded. So probably a better comparison would be to birds

However as far as I understand birds are found in artict/polar climates while dinosaurs were only at high latitudes during warm periods. It feels like there must be some fundamental physiological difference from birds other than flight - but I'm not clear what.

Would be curious to hear an expert opinion

Arctic

Birds and dinosaurs are/were reptiles in the modern cladistic sense. They're both archosaurs, making them kinds of reptiles.

I love speculating about the similarity of hives/nests and cells, bees raise the temperature of the hive if under attack as do mammals for pathogens. Some ants and termites actually farm fungi, called ant–fungus mutualism, which probably regulates temperature and humidity in the nest as well as providing nutrients.

> preventive treatments for warfighters who suffer trauma from gunshot or blast wounds, or burns

Re the burns, thats why the muscles are catabolised quickly, the creatine in muscle becomes creatinine which has Gram + & - antibiotic properties.

Taurine, is a form of sulfonic acid, and sulfonic acid are precursors to sulfonamides, which were the first anti bacterial drugs, developed by a German scientist, whose work ironically helped save the lives of Winston Churchill and Roosevelts son [1].

Just two examples of many of the chemicals we can find in our diet which can have extremely useful properties for our health.

https://www.chm.bris.ac.uk/motm/sulfanilamide2/sulfanilamide...

Huh, I did not know they were related to sulfonamides like that. If you (or someone else) might like a book that goes into the history of sulfonamides, I'd recommend "The Demon Under The Microscope" by Hager (https://www.amazon.com/Demon-Under-Microscope-Battlefield-Ho...). It was an interesting read.

They're not. The structures are quite different.

Ha, yes. The "sulfonamide" name may make it sound like just an OH acid/amine swap, but the buried part is that all such antibiotics have a big benzene ring hanging off the other end. The prototype is instead sulfanilamide.

I don't see any merit to this antimicrobial hypothesis, honestly. Muscle catabolism happens whenever protein is needed: what's the microbial threat when a body is starting to starve and disassembles some muscles to get gluconeogenesis going?

This is incorrect. Taurine is structurally quite different from sulfonamide antibiotics and isn't converted into them.

Best ignore this study then...

https://pubmed.ncbi.nlm.nih.gov/24262485/ "A case study involving allergic reactions to sulfur-containing compounds including, sulfite, taurine, acesulfame potassium and sulfonamides"

Imagine holding some study that can't even read a structural formula as the holy grail. The big R on any sulfonamide means that there's no "common SO3" as mentioned in the abstract.

Disregarding that, just pull up any sulfonamide antibiotic and tell me where you plan to magick the benzene ring from. Or tell me why an also "sulfonamide" diabetes drug is not antibacterial.

"Penicillin I and IV have no characteristic u.v. absorption, but penicillin II and III show clearly the fine structure of a benzene ring." https://www.nobelprize.org/uploads/2018/06/chain-lecture.pdf

Not all antibiotics will have a benzene ring, besides benzene is carcinogenic, and some penicillin's will be metabolised into penicillamine which depletes the body of metals including copper, useful for treating Wilsons Disease. https://en.wikipedia.org/wiki/Penicillamine#History

Low copper leads to lower levels of interleukin 6, which is a particularly useful part of the immune system for targeting some cancers, ergo some antibiotics with their benzene ring and copper chelating properties, increases the risk of cancer...

I assume you refer to the Hypoglycaemic Sulfonamides? https://pubmed.ncbi.nlm.nih.gov/9463023/#:~:text=As%20a%20fu...(

I know antibiotics are a hot topic for a variety of reasons, including the fact that livestock fed antibiotics increase muscle mass, perhaps this is why here in the UK Redbull and other taurine rich energy drinks are banned to under 16yr olds on the pretence the caffeine is the greater enemy, because they dont want stacked as in muscular teenagers running around. https://en.wikipedia.org/wiki/Effect_of_psychoactive_drugs_o...

I think this also shows that what constitutes an antibiotic varies enormously, unless the definition of an antibiotic is one that includes the carcinogenic benzene ring?

Surprised you haven't mentioned how vitamin K1 disrupts bacterial biofilms, and is particularly useful for tackling pseudomonas, a particularly nasty and stubborn bacteria. Of course its not classed as an antibiotic, its classed as a vitamin, but even the definition of vitamins are being called into doubt when considering pathways that exist in the body, they werent known when the definition of vitamin or "vital amine" were agreed, so maybe the medical profession need to update their terminology in order to not mislead the public en-masse?

https://www.researchgate.net/figure/The-kynurenine-pathway-T...

The program will be divided into three phases. The first phase will show proof-of-concept studies for safety and efficacy in in vitro studies. The second phase seeks to validate these findings with either fungal or bacterial infections in animal models, while the final phase aims to increase survival in animals exposed to both fungal and bacterial pathogens simultaneously.

Correct me if I'm wrong, but it sounds like this is just an idea and they still are looking for basic proof of concept as step one.

Good to see this issue is making someone's radar but I'm a little eh on the proposed solution.

That’s DARPA’s bread and butter. They’re a research org, not a productization org.

Has anyone here ever done any work at DARPA, and if so how was the experience?

Also, I'm assuming you need some kind of background related to the projects you apply to work on right?

Like most government agencies I assume most of the work is done by some form of defence contractor.

That being said, I'd like to hear stories from anyone who has worked there as well.

I've never worked at DARPA, but yeah, they are a funding agency mostly so there's director-types who set research directions and create grant opportunities, admin-types who push money around and track status, and most the work is done by those who submit successful proposals. I've had a couple smallish tasks for DARPA while I was at a gov lab.

They have a nice model. The program managers (those who set research directions) are fixed-term IIRC, so they have very little incentive to politic, and instead can focus on seeing their pet program through to completion in the given time / funding.

One of their main "jobs" (aside from above), is to be an advocate for emerging tech among the military and civilian industrial partners to make sure it actually "becomes something".

To work at DARPA in this capacity usually requires a lot of successful R&D program management experience and some sense of grand vision. To work in a lesser, administrative capacity, including interacting with research partners, requires just a tad less, but on the average they've been exceptional, intelligent, and responsive partners for all the work we've done for them.

Program Managers are fixed term - up to 3 2 year terms (though Director Tompkins generally doesn’t like PMs to be around longer than 4 years - see section 1101 of the Strom Thurmond NDAA for more details about the hiring authority).

I don’t know about the admin vs director types split you’re talking about (at least in the PM ranks). Office directors generally provided top cover and some very sweeping research directions, but as a PM it was your job to come up with research programs that were roughly compatible, convince the office director it was, and then manage the technical execution with the performers and doing dog and pony shows when the pentagon called.

How ironic that Strom Thurmond had anything to do with any limits on tenure for such posts...

This guy was in grifting senate/etc for 48!!!!! YEARS...

https://www.ranker.com/list/facts-about-strom-thurmond/micha... (I do not know if these are true - but its not the first time hearing about some of these allegations)

Yes. Most of the work is not done in the DARPA building. Generally federal contractor sites. The daily work in the building is phone calls, reviewing papers, email, building powerpoint slides, and trying to come up with the next program. In my time, most PMs managed between 3 and 5 programs, some of their own creation, and some inherited from outgoing PMs (term limit + federal contracting timelines means generally the originating PM is not around to see a program through to its conclusion)

I know a fair amount about this and will happily answer additional questions. There are two main ways to work for DARPA. Bid on contracts when they are opened up for public bid. The other way is to work at DARPA to do this you need an incredibly unique idea that solves a particular office director's mandate for their tenure then you apply as a program manager. Most program managers are academics with unique ideas to solve the needs of that particular office head. You can only work as a program manager for a certain amount of time, I believe two years, before you have to rotate out.

If you work as a contractor on a DARPA program, you generally get to keep all IP rights. I've used these programs to fund companies before.

Where find list of said *"needs of.... department head"*?

Well for one they publish them here: https://www.darpa.mil/work-with-us/opportunities

Assuming that you mean working on cool research. You can interview and come in as a DARPA Program manager where you need to bring in a grand vision and would be in charge of revolutionizing a field(s). But what is it that you would do day to day? A DARPA PM doesn't do actual research but instead has access to the network of the best minds in research and uses them to shape a multi-million 5 yr 'program' and arrange for funding and transition paths to DoD and private industry. A PM's tenure is 5 yrs, so most PMs come in with a vision, start 2-5 programs, inherit other programs and then transition out.

You can always look at the latest programs - https://www.darpa.mil/work-with-us/opportunities

The people doing the actual research are independent research labs, universities, and small business. These are a combination of scientists and engineers publishing papers and taking the technology from papers to the field.

Frankly, that sounds awful. Like a honeypot for the smoothest bullshitters ever.

You're more wrong than almost any poster I've ever seen on Hacker News. At least you got a throw away before you posted this ignorant comment.

Source: I said so.

GP wrote in a different comment that they worked with DARPA in the past, so I would assume that they know more about the processes than other people.

https://news.ycombinator.com/item?id=36637805

So, government?

Maybe. Even when a PM is very technical in their field, they are not expected to know the nitty gritty of the broad area they tackle in a program. To come up with realistic programs and execute them successfully, a PM needs to know where are the boundaries of current knowledge, how much $$ is required to push research to transition to real tech... and sniff out bullshit being sold by research labs. Bullshitters or not, they need to be really good at sniffing bullshit!

No, that's crypto. And some parts of AI.

I think you are thinking more of defense contracting than darpa.

Also, darpa has real use-cases and those use-cases tend to be hard to solve ones, they aren't VCs looking for the next trend to vampire like a national security version of the TV show shark tank.

Granted, it is 2023, it is the govt, and it is tech/eng/sci holy trinity of profit so I wouldn't be shocked if I am off the mark with my assessment.

Edit: typo

Submit.

Hear absofuckingloutely nothing back.

Get paid obscene levels of money.

Repeat.

DARPA programs are typically not known for large sums of money, especially compared to other defense sectors.

They give a lot of money to things that are yet to be proven.

I participated in a DARPA brainstorming conference a number of years back. It was not paid, but a fun experience. So in addition to bidding on contract topics they propose, you can get invited onto working committees or symposiums and such (but that usually means you have expertise on the topic and someone involved knows who you are). It's a pretty good gov agency to work for as well from my various friends who have worked there.

uh - is it a legit, say, interview experience - or is participating in such teams, which are unpaid, just a harvesting of free ideas for DARPA?

Or a secret recruiting method to weed-out those who wont pull whatever narrative is rq'd around said *'needs of the department head'*?

What I worked on was more of a community of interest brainstorming conference where all the participants had an interest in seeing a good outcome of a DARPA program. You could call it "free ideas" but everyone knew that going in and it was the point after all. Research and development usually benefit from a free exchange of ideas from stake holders and people with expertise in the field (or adjacent fields).

Recruiting is never secret and DARPA, DoD, and the IC are just like the rest of the tech industry and _always_ looking for scarce talent (except they have to pay less than commercial sector thanks to congressional laws).

You seem to have convinced yourself of only negative interpretations as being options, but there really is a lot of overtly beneficial research done by DARPA and a lot of people who really believe in the good they do involved. Not to say that there isn't also occasional bad actors, bad policy, or mercenary transactions, but those are the exceptions, not the norm.

>>*You seem to have convinced yourself of only negative interpretations as being options, but there really is a lot of overtly beneficial research done by DARPA*

I appreciate your reality check on this - I dont exclusively focus on negative, but I am sensitive to efforts which ultimately result in negative (sociallogically - such as deeper surveillance) outcomes, and while darpa does awesome science, and great leaps in tech - every one of these steps /tend/ to feed surveillance-state paradigms.

I worked for a few years for a contractor and we did several DARPA projects.

Pros: work on really exciting stuff. I worked on cutting edge squad-embedded robotics platforms and media forensics to fight fake news. Got to travel a bit for demos. It's very rewarding to know your work is making a real impact.

Cons: they don't call it DARPA-hard for nothing. Timelines are tight, the problems are research heavy with no guaranteed results. I did a lot of work bridging grad student quality code to production systems, which is its own kind of hell.

I worked on the DARPA Urban Challenge (before self driving cars were cool) as part of one of the teams competing, does that count?

My experience with them was positive. They ran that challenge really well and created a good environment for teams to compete. It was fun and memorable.

I once interviewed for memex project but didn't get the job. It was $160K-$250K for global remote and hardest interview I ever did (how would you build google for the hidden web for 2 hours, interviewed by 3 senior engineers). I ended being best of ~100 people in that but failed on the next step with machine learning exercise($80/hour take home exercise). This was ~7 years ago.

I'm currently finishing up working on the 2nd big DARPA grant in my career, as an engineer in one of the labs that got paid money to do the work. DARPA funds a lot of "pie in the sky" ideas where the work is super exploratory in the beginning, which is cool because we get to conduct a lot of basic research and try out weird ideas.

Like someone else said, timelines are tight, budgeting is a mess, and every phase you have to continue to justify your team's existence to bureaucrats or you get cut. The updates are in presentation form as well, but you have to abandon the "show don't tell" because the presentation is sent out to a bunch of people that don't attend the meetings afterward.

Overall it's a lot of money to work on cool stuff but I'm happy I'm not managing any of it.

> you have to abandon the "show don't tell" because the presentation is sent out to a bunch of people that don't attend the meetings afterward

I think there is a misunderstanding about what "show don't tell" means.

In a presentation like that tell means: "Our underwater robot is very stealthy." while show means "Our robot spent 2 weeks trailing a nuclear submarine of ours without the submarine being aware of our presence. Here is a picture we took of the submarine's sail, and here is the statement of the captain saying he had no idea." (Obviously this is a silly example, please don't spook people with the biggest, meanest sticks.)

Show means showing your results and tell means describing how awesome you think you are without evidence. It has nothing to do with whether or not your audience attends the presentation.

This is similar to fiction writing, where tell means that you describe what someone is like, while show is describing how that behaviour/emotion appears. For example tell would be "George was angry", while show would be "George banged on the door with two fists, his veins bulging with barely contained rage."

Hopefully this stimulates further research into cocodriles' blood. They already have something similar to what DARPA is looking for, if I recall correctly.

Looks like it's a combination of strong antimicrobial peptides and good antibodies. (They recently figured out a defensin responsible for the fungus resistance). Not sure about if you can just pop these AMPs into human blood and how long the trial process will be though.

I "foresee" soon a sponsored scientific research proposing to replace blood with bleach!

Seeing SHIELD in a government press release, my first thought was Nick Fury, but not a blood roomba :)

Laser zapping or high precision microwaves intersection to zap the mites could be a way

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