

MIT Scientists Develop a Drug to Fight Any Viral Infection - schintan
http://healthland.time.com/2011/08/11/mit-scientists-develop-a-drug-to-fight-any-viral-infection/

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fauigerzigerk
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 :-)

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briggsbio
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.

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

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briggsbio
That depends on the cancer and depends on the approach (structural, genetic,
or immunological).

The difficulty in cancer treatment is that you're dealing with a natural
biological process gone awry. It's not like viral or bacterial infections,
where you're fighting something off. You're dealing with aggregations of
unwanted mutations and cellular proliferation (over simplification warning).

Chemotherapy is less trying to alter a process than it is dropping a bomb in
the body and hoping that you kill the cancer before killing the patient. There
are some incredibly effective chemotherapy agents that will never make it to
market because they are just too toxic.

Gene therapy approaches are making promising moves, but it is very early.

There are some pretty cool structural approaches, such as protein conjugated
nanotubes that lyse cancer cells under infrared light (Stanford and Oklahoma
researchers), but these too are early, and for only specific tumor types.

Cancer is a huge problem that takes a multifaceted, case-by-case approach.
Lots of tools in the tool shed, and it's growing every year. I feel in my
heart that one day in the future, cancer will be called "the biggest problem
of the last generation." But there is much work to be done.

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geoffschmidt
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?

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michaelcampbell
> 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.

~~~
geoffschmidt
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.

~~~
michaelcampbell
Sure, it's all possible, but evolution isn't an optimum-finding strategy; it's
just a "good enough to be better than the last one". And, it's random, so even
if a "6" on a dice roll is better than a "5", it's still possible to roll 1
through 5 ten-billion times in a row. And even if I do roll a 6, it's possible
no one would see it, or I die immediately afterwords and can't take whatever
advantage such a roll would invoke.

So the question of "Why didn't evolution come up with this?" is, to me,
somewhat nonsensical.

But reasonable people disagree, and I'm no expert.

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

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brimpa
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).

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

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leoh
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?

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

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AshleysBrain
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
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.

~~~
maayank
"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.

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hammock
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?

~~~
eru
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.

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logjam
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
Yep, here was the previous article.

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

