Are We Chicken Littles?

[RichPella]

Tested and approved in two months? Full-blown pharmaceuticals take years. I understand the need for quick approval; I don't understand the method.

It seems to me that long-term testing under such conditions is 100% impossible, and most of the objections I've heard about this vaccine center around that point. I'm curious why a scientific mind is willing to accept the safety of this vaccine based on what appears to me to be a leap of faith.

[Dick Macy]

Tested and approved in two months? Full-blown pharmaceuticals take years.

Yes, "full-blown pharmaceuticals" take years. But maybe that's because you're talking about the inception of an idea, or a discovery, that will ultimately lead to a new drug being approved and released to the market. Many trials and errors take place in the labs before the new drug goes for animal testing and eventually to human trials. It's a lengthy process, as it should be.

Vaccine technology is an already-proven field of endeavour, I think. The guys who do this know what they're doing. The tests are standardized (again, I think -- hell, I'm no scientist). But I imagine that they're really just building on established science, and can get it done much faster.

Sue? Am I even close to being right?

[MrKnowItAll]

Originally Posted by Suerreal

Mr K, current vaccine technology is such that the CDC has to commit to which three strains of flu the usual vaccine will cover by January in order for good amounts of vaccine to be available by September/October. Swine flu wasn't even recognized until March, and a vaccine was developed by ~ Jun, and tested and approved by August. That is lightning fast. Vaccine is being distributed worldwide (well Northern Hemisphere mainly) equitably, not just to the highest bidder in contrast to SOP. Sadly, the vaccine is coming too late for some, but hopefully, the vaccine will help limit the spread in the next few months.

I understand that. My point is that the high level of concern back in the spring was probably justified considering the state we're at now going into the flu season.

[MrKnowItAll]

Originally Posted by sangfroid

MrKIA, I tried to find current H1N1 info at the CDC site here, but got lost looking for YTD info. Can you link to the figures you're citing, please? Does the source reference this data relative to "normal" or average infections/deaths?

My figures come from Wikipedia, admittedly not the most thoroughly vetted source, but good enough for government work. It was from the regular H1N1 page, but this page has the updated information specific to the 2009 pandemic. It says there's been 6,021 confirmed deaths, 686 of which came within the last week (474 in North America alone).

[Suerreal]

Originally Posted by RichPella

Tested and approved in two months? Full-blown pharmaceuticals take years. I understand the need for quick approval; I don't understand the method.

It seems to me that long-term testing under such conditions is 100% impossible, and most of the objections I've heard about this vaccine center around that point. I'm curious why a scientific mind is willing to accept the safety of this vaccine based on what appears to me to be a leap of faith.

Rich, the H1N1 vaccine is exactly the same as the seasonal flu vaccine except that it targets a different strain. It is not a new drug. The approval process is the same thing the vaccine makers do year in year out to get each new seasonal vaccine approved. The testing & approval was only slightly compressed for the H1N1 vaccine compared to a standard seasonal one.

Vaccine technology is an already-proven field of endeavour, I think. The guys who do this know what they're doing. The tests are standardized (again, I think -- hell, I'm no scientist). But I imagine that they're really just building on established science, and can get it done much faster.

Dick, a truly new vaccine does take years to gain FDA approval. Recent examples include FluMist (nasal spray attenuated influenza), Gardasil & Cervarix (human papilloma virus responsible for cervical cancer). The flu vaccine uses the same technology every year but different virus to produce different versions of what is essentially the same vaccine.

- Sue

[RichPella]

Sue, if I'm understanding correctly, the first flu vaccine went through a years-long approval process. All of the annual updates enjoy a condensed version because they're just changing the virus inside, not the vaccine itself. Is that a fair summary?

If it is a fair summary, how is that different from approving an entirely new vaccine that goes after an entirely new virus (like the FluMist, Gardasil, and Cervarix you mentioned)? The non-medical mind (read: mine) says, "If it's a different virus, it's a different vaccine." You stated above that it's essentially the same vaccine. Are you able to expand on that a bit and still keep it in terms the layman can grasp?

[Surgoshan]

The process for making it is what's important. The process in place had to be vetted to insure that, from year to year, it would reliably produce a vaccine regardless of the current formulation of the virus itself. That's why the basic vaccine gets more or less a by. It's like someone who can make apple pies to perfection; if one day you give him granny smiths instead of macintoshes, he'll still make a damn good pie.*

New medications require a sterner vetting because they have to prove that they make what they claim (the old vaccine already has that) and that they deliver an effective cure (ditto).

"It's a new virus, it's a different vaccine" doesn't really apply because it's not really a new virus. It's the old virus in a slightly different overcoat. "H1N1" is a term that refers to two specific proteins involved in the infection process (just like the old bird flu was H5N1, the first protein was different, the second the same). The proteins are slightly modified from one another, but perform essentially the same function. The trick is making sure our bodies recognize the different formulations and know how to fight them off.

The old vaccine delivers on that reliably, albeit slowly (it takes a few months to make).

http://snafu-ed.blogspot.com/2009/04...h1n1-mean.html

* I am not a baker, nor do I play one on television, I have no idea which apple makes the best pie.

[Ursa Major]

Labs have been turning out updated vaccines every year for the last 50 years. It's not an "entirely new virus" (like HIV was 30 years ago) it's just the same old Influenza-A that we've been vaccinating against since it killed 30 million people after World War I. It's the same species with the genes recombined in different configurations. Over the last century, scientists have become really adept at decoding those sequences and creating the necessary vaccine to combat new strains.

ETA: Surgo beat me to it.

[RichPella]

Okay, I get that explanation (mostly). Here's another thing, though. If the virus has been constantly mutating for 50 years that we've been making vaccines for it--and thousands of years before--why is it not now a completely different virus? Year to year, sure, I get that. Over time, though, shouldn't it mutate to the point where it's completely unrecognizable when compared to the original?

Just asking. Again, I've never studied this stuff. Biology was my least favorite science in school. Although I made an A in the class, I wasn't particularly interested in it.

[Suerreal]

Viruses are tiny packets of genes (made from either RNA or DNA) packed into a protein shell. Most viruses have several different proteins in their shells, and each protein has a different purpose in attacking the virus's preferred cell type - attaching to the cell, fending off the immune response, penetrating inside the cell, helping the viral genes go through the steps of making copies of themselves, and coding for the proteins, and getting the viruses to assemble properly.

Each protein also has a different shape and "texture" of plus and minus charges, that make it unique, so that the immune system has to make a new antibody to target it. In the case of some viral disease, one or more critical proteins are always the same, so that a rubella vaccine will always provoke the immune system to make antibodies that will protect the individual against all infections with the rubella virus.

Other viruses, such as HIV, can make many different versions of their proteins, so that having antibodies to one version will not protect against future infections with viruses with different versions. Influenza is another virus with differing versions of its proteins. There are several different H proteins, and several different N proteins. H1N1 decribes a strain that has type 1 of the H (Hemagglutination) protein, and type 1 of the N (Neuraminidase) protein. This does NOT fully define a strain, as there are subtypes for both H and N proteins that make tham different antigens, meaning that antibodies to one sub-type will not (usually) cross-react with a different subtype of the H or N proteins.

And there is evidence that the current H1N1 strain is not NEW. People born in 1956 or earlier seem to have some immunity to the current strain, suggesting it is similar to strain in circulation 50+ years ago. Rich, it is not a completely new virus, because influenza recycles the same proteins over & over again in different combinations. Think about this - 100 years ago a 50 year year return would mean that nearly ALL of the population was at risk. Influenza virus mainly attacks birds, pigs, and humans. All it takes for a new flu strain to emerge is for one individual bird, pig or human to have one cell co-infected with two different flu strains and the proteins to assort themselves randomly into viruses. Some of the new viruses will be better at their job of moving from one individual to another, getting inside cells, and making new virus, and become the dominant new strains. Remember "bird flu", or H5N1 flu from 4-5 years ago? It has a very high mortality rate, but quite low transmissibility rate, at least between humans. The H1N1 "swine flu" has a very high transmissability rate, and a moderate mortality rate. It is the combination of the high transmissability rate and the low baseline immunity in the population that allows a pandemic to occur.
----------------------------------------------------------------------------------
On to the flu vaccine. . .
The current flu vaccine technology (growing influenza virus in chicken eggs, inactiviating it, purifying it, and getting "just right" quantities into an injectable form) was developed in the 1930s, and first approved for use in the military (remember that the military suffered horrific losses from influenza at the close of WW I) in the early 1940s. Every year, the World Health Organization decides in January what 3 strains will be included in the vaccine to be given the following fall. It takes 7-9 months usually to grow sufficient chickens to grow sufficient eggs to grow sufficient quantities of the three strains of virus to produce 100,000,000 doses for the US and to meet global demand. A small amount of the earliest available vaccine is submitted for testing which is largely limited to testing for contamination, checking for viral levels, and very limited testing of effectiveness (would you volunteer to be injected and then deliberately exposed to influenza?) because:
1. The flu vaccine uses the same technology
2. in the same facilities
3. run by the same people
4. using the same equipment
5. and the same type of chickens/eggs
for all three strains and for each year.

In 2009, for the first time, a new strain was identified early enough that vaccine makers could divert some chickens and eggs and incubators and personnel to making an additional vaccine after the seasonal vaccine production was well under way. Think of it as an established newspaper running an "extra edition" when something extremely important happens. This year, vaccine makers released a supplemental vaccine targeting the new H1N1 strain to use in additional to the three-strain seasonal flu vaccine.

If an established vaccine maker wanted to use different technology (inserting genes into bacteria to grow virus particles), or different route of administration (FluMist uses a nasal spray to deliver live, but weakened virus to the respiratory tissue), or a new company wanted to launch an influenza vaccine, all would have to go through MUCH more rigorous testing before getting approved. In the case of H1N1/swine flu, established vaccine makers using established technology in established facilities were alloewed to go through a very slightly compressed testing phase compared to what they ordinarily go through every year with their three-strain vaccine. Part of the speed-up was no doubt due to the fact that the new vaccine only has one viral strain to check on, not three. Part of the speedup was due to a sense of urgency because until there is sufficient vaccine for all, people are dying from this disease. 114 children have died in the US from this disease. The vaccine has been tested using the same standards that are used for new versions of the seasonal flu vaccine every year.

Priority groups to receive the vaccine are:
1. People with an infant in their home under 6 months (who can't get the vaccine him- or herself)
2. Children/young adults age 6 months to 24 years
3. Pregnant women.
4. Health Care Workers.
5. Persons aged 25-64 with chronic underlying health conditions such as asthma, diabetes, HIV, or other conditions that weaken the immune or respiratory systems.

If you belong to one of these groups, please do get the vaccine. If you do not belong to one of these groups, please stay tuned. Vaccine is still being produced, and as quickly as it can be packaged up & shipped out it is making its way to a doctor's office near you.

- Sue

[Surgoshan]

It has to do with the fact that the virus has to do a number of very specific things.

1) It has to get into the host cell. To do so, it needs to use a protein on the envelope of the virus to breach the cell membrane without killing or permanently damaging it.
2) Once inside, the virus needs to integrate its own coding into the host cell's DNA, such that the virus's RNA (viruses don't have DNA) and envelope will be recreated many times over by the host cell.
3) The newly created viruses then need to be able to exit the host cell.

If any one of those steps doesn't work, you don't have a virus.

Because RNA doesn't have proofreading (unlike DNA), viruses like influenza, which use RNA, mutate rapidly. In fact, at least one error is likely to be made for every replica influenza virion made inside a cell, meaning that each one is in a small way a mutant.

So you have a rapid mutation process, a rapid breeding process, and a strict selection process (the process of reproduction is slightly more nuanced and can break down at more steps).

The end result is that ...

First let me introduce the term "landscape". Imagine, if you will, a contour map, a sand table, with hills and valleys and ridges and gullies. Now say that the bottom of a valley or gully is where evolutionary fitness lies and that the top of a hill is where unfit things can be found. In the course of things, as generations pass, descendants will tend to travel downhill rather than up, if only because creatures at the top of a hill are less fit, will reproduce less, etc.

So we've defined for ourselves the bare bones of a fitness landscape. It might even be possible to model such, though it would take a lot of computational power. You have a parent virion somewhere on the map, and it produces a lot of offspring who will mostly lie elsewhere on the map. Some of them will be a little downhill, some a little uphill. Because mutation is random, some might jump further away. It's possible that multiple copying errors could be made and one offspring might jump halfway across the map.

In general, though, the offspring will mostly sample just the area around the parent. Mutation will splash the offspring up the walls of whatever valley the flu is in, but they'll mostly roll back downhill.

So, in a population of people, the virus will eventually settle on a stable conformation. It evolves from year to year enough that you'll be able to get sick from it again, which tells us that the valley is very large.


So where do really new viruses, like H5N1 and H1N1, come from? The population isn't stable. Not only are there 6 billion people on the planet, many of whom will never meet one another, but who are nevertheless separated by only about 10 or 20 links (I'm 3 links from Joss Whedon. You may touch me.), but many of those people interact with animals. Cows, pigs, sheep, and birds can all get the flu. And they're different enough that they force the virus to seek out new valleys in an entirely different landscape. What just gives a pig a fever makes the leap and then slaughters 50-100 million people in 1918. Then it vanishes for 90 years, reappears in 2009 and makes people really, really nervous.


So, long answer short:

1) Why don't they change much? Because it's not in their interest to do so.
2) Why do they change at all? Because it is very much in their interest to do so.
3) Why do they sometimes change a lot? Because meat is tasty.

[AuraSeer]

My microbiology professor put it this way: the viruses may mutate a lot, but they almost always come back to the same few tricks, because that's what happens to work in the moment. They don't have a memory, so they cannot realize they're doing the exact same thing they did ten minutes ago, or five years ago, or in 1956.

[RichPella]

Wow!

Thank you, Suerreal and Surgoshan, for the detailed yet understandable scientific explanations. Thank you, also, AuraSeer, for the very quick summation. I just learned a bunch.

[RichPella]

Originally Posted by Ursa Major

It's not an "entirely new virus" (like HIV was 30 years ago)

I do not remember where I read it, so I'm unable to provide any kind of source. I apologize in advance.

I read a few years ago that HIV was not a new virus c. 1984, any more than Pluto was a new celestial body in 1930. In both cases, they had been around for a long time and were newly discovered. I'll see if I can track down where I read that. I'm pretty sure it was in a book and not on the 'Net.

[Ursa Major]

Well, I didn't think you were implying that an entirely new virus was one that was the result of spontaneous creation. We refer to recenty discovered animals as entirely new species all the time even if they've just been hiding from us for the last million years.

[RichPella]

I see. I didn't realize you were using the phrase that way. I have heard other people refer to HIV as a "new" virus, by which those people meant that it recently had come into existence. Apologies for assuming you meant it in the same context.

[Dick Macy]

Was it Shakespeare who said, "There's nothing new under the sun"?

[MrKnowItAll]

Originally Posted by Dick Macy

Was it Shakespeare who said, "There's nothing new under the sun"?

Actually, it's from Ecclesiastes.

[Dick Macy]

You know, I had wondered if it wasn't from Ecclesiastes.

Thanks, MKIA.

[Osmooms]

Quite a good read to settle some of the hysteria, I think.

http://www.newscientist.com/special/swine-flu-myths-that-could-endanger-your-life

[Matt Holck]

creating inactive strains started with rabies by Pasteur in 1885