MIT Scientists Develop a Drug to Fight Any Viral Infection

http://healthland.time.com/2011/08/11/mit-scientists-develop-a-drug-to-fight-any-viral-infection/

by schintan • 15 years ago

141 40 15 years ago

healthland.time.com

That would be very good news indeed, if it turns out to work on anything but mice.

But after reading a lot of that kind of articles over the past years, I'm starting to wonder what's wrong with mice. Whenever a new treatment is tested in mice it seems to work wonders. It makes them not just a little bit better but orders of magnitude. It's like a miracle. Mice must have an incredibly bad natural constitution. You throw them some homeopathic pill and bang you have cured cancer. You drop some genes on them, whoosh, a new human ear pops up. It's amazing :-)

Confusion2• 15 years ago

I wonder if it could be because they are so small, that the dosage is relatively much larger. Their metabolism is much faster than ours: those larger dosages may also be needed to get any effect?

Sandman• 15 years ago

Don't you think the researchers would take their size and metabolism into account when determining the dosage?

ericb• 15 years ago

Ethically speaking, what are the problems with testing things on human bodies with no brain if that were possible?

The idea is disturbing, but is it any worse than dissection/autopsy--in other words, is the disgust a visceral reaction but nothing more? It would probably put the speed of medical advances on steroids and save a lot of lives.

wazoox• 15 years ago

Genetically engineered mice carrying large parts of the human immune system have been in use for years, and can be a good approximation of "human body sans brain", and much cheaper with that - an anencephalic human costs actually a lot to maintain alive.

DasIch• 15 years ago

There are not that much brain dead bodies available, those that are available are used for organ donations. Do you really want to reduce the number of available organs for medical testing at such an early stage?

I imagine that most of these tests fail whereas a functioning organ has a very high chance of saving a life.

briggsbio4• 15 years ago

Actually overall, in vivo animal testing on vaccines, antivirals, and antibiotics are typically quite predictive from animals to humans. These types of tests are not historically very predictive when moving from in vitro to in vivo animal studies, however. This is typically because the treatments and vaccines are structural and/or expression-based (exploit a bacterial surface protein and poke holes in the cell, use a virus to get into T-cells and inject genetic material to let them identify and kill polio, etc). (yes, oversimplified). But moving from cell culture to a living organism This doesnt always work out. If it does, then it's relatively easy to confirm the effect if it works in animals to humans (virus is gone/never infects, etc). So more antibiotics and vaccines fail from in vitro to in vivo than from animal to human data.

In treating diseases of inflammation, rheumatic disease, pain, etc., it is generally quite predictive when moving from in vitro to in vivo animal studies (e.g. is it down-regulating inflammatory transcription factor NF-kB, or not?). But it becomes much less predictive translating endpoints from animals to humans. That's, very generally, because it is difficult to assess disease measures of improvement in inflammation in animals and translate that to humans (pain, discomfort, edema, these processes may present much differently in rats versus humans, for example). Great animal data may not mean you'll get such a strong effect in human subjects, and thus the failure rate for these drugs in clinical studies is quite high compared to vaccine and antibiotic human trials, because those vaccines were shown to be ineffective earlier in development. This was a very general explanation, to be sure, and I'll dig through my archives for some papers on this and try to add links later.

fauigerzigerk2• 15 years ago

That's very interesting. Do you have an idea in which of these two categories cancer treatments typically fall?

DavidSJ• 15 years ago

In this case, they did successful in vivo tests on mice with H1N1.

asdkl234890• 15 years ago

I'm starting to wonder what's wrong with mice. Whenever a new treatment is tested in mice it seems to work wonders.

Mice are tiny and short lived. They have had no need to evolve a whole host of cancer and disease defense mechanism, which we as very long lived and large animals have.

In fact, many cancer cures in mice are simply applications of things which humans are born with.

Elephants and whales probably would be a better way to study diseases. For example, humans have one copy of an ant-tumor gene, elephants have a dozen: http://blogs.discovermagazine.com/loom/2011/02/28/the-mere-e...

But mice are A LOT easier to study in the lab than large long lived animals would be.

Also, spectacular sounding cure + non-specialized mass publication like Time = Do not believe.

AshleysBrain• 15 years ago

I always think excitement over these kind of articles is overblown. Wouldn't it work like this?:

1. Develop a super-treatment for fighting a broad range of infections

2. Enjoy a few years of low levels of disease

3. The "super-bugs" that are naturally resistant and were naturally selected by the broad application of treatment make a comeback

4. Back to step 1

alextp• 15 years ago

Except with antibiotics history did not quite play out like this, in that there were far more fatal diseases before the invention of antibiotics, and some superbugs can be controlled with different variations on the same basic technology.

Jach• 15 years ago

Also if we could guarantee a period of relatively little disease, it's not like all research just stops. We can probably evolve many different types of "super-bugs" in the lab faster than nature and create advance treatments for them, extending the period of low disease even further and further. I'm also a believer in a general solution to human sickness being discoverable, though I don't have confident time frames.

maayank• 15 years ago

"Except with antibiotics history did not quite play out like this"

Sure it did. In fact, already in the 60s the original penicillin became dangerously ineffective. Around that time we (==humanity) developed semi-synthetic penicillin that enables us to change some core ingredients in the formula every few years and thus avoid saturation by bacterial evolution.

Of course, IANABiologist, so look for more information if it interests you.

p.s. if anyone is around London I highly recommend going to the Alexander Fleming museum. Highly recommended and since (sadly) no one goes there you effectively get a private tour of Fleming's lab.

sliverstorm• 15 years ago

The trick would be to use those few years to eradicate the worst diseases, or at least fight it back enough that it can then slowly be eliminated through quarantine etc.

The common cold is still around, but notice that smallpox is essentially extinct, and influenza is way less common than it used to be. Bubonic plague- also mostly gone.

eru3• 15 years ago

With antibiotics the super-bugs are usually only really good at evading our medicine, not as good as infecting a healthy human as the traditional microbes.

Thus they are mostly a concern for already weakened persons.

geoffschmidt3• 15 years ago

So if it's that easy, why did natural selection not find this solution? It sounds like the cells already have far more sophisticated machinery to detect and respond to dsRNA. Evolutionarily, adding apoptosis to that must have been found to be a net loss.

Maybe it's that we're in a cleaner environment and live longer? Maybe it's that we can selectively administer the drugs?

mynegation• 15 years ago

Natural selection works for viruses too so over time they get better in overcoming immune system. In some way HIV is a frightening but amazing work of evolution.

michaelcampbell2• 15 years ago

> So if it's that easy, why did natural selection not find this solution?

Evolution is still working; who's to say it wouldn't have? Your question should be, "why did not natural selection not find this solution YET?" at which point the answer is obvious.

We're not "evolved", we're just the most recent step in evolution. As long as we (or anything) lives, there's more to go.

I hope I'm not feeding a troll; your question smacks of a thinly veiled "Ha! See?!" type creationist rebuttal.

geoffschmidt3• 15 years ago

Please assume good faith. My question is, "Is it more likely that natural selection didn't find the apoptotic strategy, or that the apoptotic strategy wasn't a net win, in the environment in which the natural selection happened?"

So let's try to get a handle on which it is likely to be.

The Time article says:

> To fight infection, human cells have proteins that attach to dsRNA and trigger a cascade of reactions that stop viruses from copying themselves.

So, what we observe is: - Human cells have a mechanism to detect dsRNA; - Human cells have a set of countermeasures that they can produce to block viral replication; - Human cells have a mechanism to produce those countermeasures when dsRNA is detected (and I'll give you good odds that they have other ways of detecting viral infections that also activate the countermeasures); - Human cells also have an apoptosis pathway (which, as it turns out, the cell is not shy about activating in other circumstances, like if too much DNA damage is detected)

One of the following must be true

(1) All of the existing machinery (dsRNA detection, existing countermeasures, and the linkage between the detector and the countermeasures), taken together, must be much simpler than this little transducer they engineered that connects the existing dsRNA detection signal to the existing apoptosis pathway, so that X years of natural selection was likely to find the existing machinery but unlikely to come up with this new solution (2) Blindly triggering apoptosis when you detect dsRNA is not the way to maximize the amount of sex your children have (3) The only reason viruses exist, and plague mankind, is that we got incredibly unlucky

My money's on (2). (1) seems unlikely because it seems like you have to search a much larger space of DNA base pairs to find this whole complex of dsRNA detectors and virus replication inhibitors, than to find this transducer. (3) is unlikely a priori.

So, what would explain (2)? Like I said, several options:

(A) The drug isn't valuable in practice (the cure ends up being worse than the disease) (B) The drug is valuable but has a lot of side effects, so taking it all the time is bad. You only want to take it when you have a really nasty viral infections. The machinery to detect the correct case in a cell is too hard, but now that we have brains, doctors, and the internet, we can make a better decision than a cell could about when dsRNA should be connected to apoptosis than a cell could. (C) Having the linkage was a bad idea for most of the history of mammals, but is a good idea for humans today. Maybe we used to have a lot of immune resistance that we no longer have because of our super clean environment. Maybe we have better nutrition and that somehow makes speculative apoptosis hurt less. Maybe viruses are more dangerous in the dense urban environments where we now live. Maybe it's a bad idea for young people, but a good idea for old people.

These all seem possible to me.

geoffschmidt3• 15 years ago

Now, with a little googling, I learn the following things:

"Most viruses encode proteins that can inhibit apoptosis"

There is actually already cellular machinery for triggering apoptosis when a cell is infected with a virus

Some viruses induce apoptosis themselves, to their own benefit. When the cell falls apart during apoptosis, the virus ends up packaged with bits of the host cell, which stops the immune system from responding to it!

http://www.ncbi.nlm.nih.gov/pubmed/10547702

http://en.wikipedia.org/wiki/Apoptosis

EDIT: here is an article that gives a sense of just how complicated this all is, and how much existing machinery in cells and viruses target it:

http://www.nature.com/cdd/journal/v8/n2/full/4400820a.html

briggsbio4• 15 years ago

Depends on how you look at it: Actually we did evolve this mechanism, we just hadn't evolved a way to exploit it yet. We evolved, physiologically, faster mentally than physically and discovered a synthetic way to leverage this exploit before our bodies found a way to naturally.

ArchD• 15 years ago

The results of 'evolution' are not perfect in the way we understand 'perfect'. Evolution's 'goal' is not that human beings be super-healthy. As long as an organism can stay alive long enough and healthy enough to reproduce effectively, the 'goal' is met. Obviously, human beings have been living long enough and healthy enough so that the world population has kept increasing rapidly for the recorded history of human societies.

colanderman• 15 years ago

According to the article, we do have a way to detect dsRNA. But viruses can block those mechanisms. Fortunately yet viruses can't block physical injection of this drug.

geuis• 15 years ago

Direct paper, submitted 3 days ago. http://news.ycombinator.com/item?id=2870955

csomar• 15 years ago

So, is the HIV virus concerned? And can this cure the AIDS?

brimpa• 15 years ago

Why was this down voted? HIV was my first thought after reading the article.

On another note, does anyone have info on the rate of death by virus world-wide? I'm only curious so we I compare to other major killers (cancer, heart disease, etc).

hammock• 15 years ago

Is there such a thing as a good virus (don't just think of your own body as well, think of ecosystems, symbionts etc)? Couldn't there be some harmful implications of a drug that eliminates ALL viruses?

Zaak• 15 years ago

I'm curious about this as well. For example, during the implantation of a mammal embryo, endogenous retroviruses are produced in large quantities. I don't know if the double-stranded RNA targeted by DRACO is present in that situation, but it's certainly something that would need extensive testing.

eru3• 15 years ago

To compare: There are lots of useful bacteria in your guts, and when you take antibiotics most of them die. But most people survive that, and you can help re-populate your guts with the right mix of microbes.

leoh• 15 years ago

What if lots of critical cells (e.g. bone stem cells, brain cells) are infected? Wouldn't it be better for the body to fight the virus rather than killing those cells?

eru3• 15 years ago

If a virus has infected a cell, the cell is usually beyond hope.

logjam• 15 years ago

We discussed this study previously on HN - an extremely preliminary study based on cell culture and a small number of mice. The first author of the paper is the drug patent holder.

pak• 15 years ago

Yep, here was the previous article.

http://news.ycombinator.com/item?id=2847675

MIT Scientists Develop a Drug to Fight Any Viral Infection

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