The reason why I write this blog

Just spotted this headline in a Canadian online news aggregator:

“Severe reactions to H1N1 shot: one death probed”

Then, almost at the very end of the article:

“On the issue of serious adverse reactions to the H1N1 vaccine, Butler-Jones said the rate of anaphylactic events was about 0.32 cases for every 100,000 doses of vaccine delivered - a figure that's within the norm for mass vaccination efforts.”

I just got my shot.

Do we really need two to tango?

It’s not easy finding an adequate male for reproduction. He needs to be manly, but not macho. He needs to be funny, but not immature. He needs to be romantic, but not needy. Ever wonder why we bother to go through the whole finding-a-mate dance when some species can just self-fertilize? Many animals and plants reproduce like us by outcrossing (which means two parents), but there are also a number of selfing species (meaning self-fertilizing or asexual reproduction). Oddly, when you look at the numbers, outcrossing doesn’t make a lot of sense. When selfing organisms (for example, aphids) reproduce, 100% of the offsprings can make more offsprings. When outcrossing organisms reproduce, we end up producing a variable proportion of those pesky boys (50% in the case of humans), who really are no good when it comes to having babies (except maybe for this guy). For many years, scientists have been speculating as to the evolutionary benefit of this numerical disadvantage. Recently, researchers tackled the question in a new way: by recreating evolution experimentally.

First, an important term to define: evolution. For the sake of this post, let’s use a simple definition: evolution is the change in the genetic material (genes, made from DNA) of a population of organisms from one generation to the next. Variations in the genetic material can occur in a few different ways, but a main one is mutations. Mutations can arise due to different factors: for example, a mistake can be made when the DNA is being copied during cell division, or the DNA can be damaged due to exposure to radiation or chemicals.

The study, published recently in the journal Nature, looks at a type of worm, C. elegans. Populations of this worm are composed of males and hermaphrodites, meaning this worm can reproduce both by selfing (hermaphrodites) or by outcrossing with males. The researchers were able to genetically engineer these worms to make two different populations: one that is only able to reproduce by selfing, and one that is only able to reproduce by outcrossing. This created a very valuable tool to look at how these populations deal with various evolutionary hurdles.

The researchers took both populations of worms (the selfing worms and the outcrossing worms) and exposed them to a chemical that increases the rate of mutations (a way to mimic a “sped up” evolution). They also created an environment where each population, in order to reach their food, needs to go over a worm-scale obstacle course. These two steps were important because they both impose a strong selection. Once the experiment was set-up, all the researchers did was let the worms reproduce through 50 generations and looked at which population did better.

Male readers, you’re safe! Even with all the hurdles, the outcrossing population of worms managed to maintain their fitness (or their evolutionary health) over the course of the experiment. The selfing populations of worms, however, showed a significant decline in fitness. To make sure this effect was not just a fluke, the researchers tried a different hurdle: they exposed both populations of worms to a disease-inducing bacteria. Initially, this bacteria caused an 80% mortality rate in both the outcrossing and the selfing worms. This means that the worms quickly had to learn to either avoid the bacteria or become resistant to it. This experiment confirmed what the researchers saw previously: the outcrossing population adapted rapidly to the bacteria and showed a significant increase in fitness over 40 generations, the selfing population did not manage to adapt.

This experiment may seem like a no-brainer (if we didn’t need males, they probably wouldn’t be around anymore, so they must be useful for *something*), it represents the first experimental test of the selective pressures that favor the evolution and maintenance of outcrossing. By digging into the genetics of the worms, the researchers were able to come up with two explanations for the usefulness of outcrossing. The first explanation is that outcrossing reduces the effect of harmful mutations. For example, if part of my DNA is damaged, it can be compensated for in my children if my partner’s DNA is intact. If I wasn’t mixing my DNA with someone else’s, my offspring would inevitably inherit my defective DNA, and this would weaken the population. The second reason is that in selfing organisms, mutations (good or bad) are trapped in a single genetic background. This means that a beneficial mutation can never combine with another that may have occurred in a different genetic background. Therefore, beneficial mutations can never add up or even synergize. This results in stalling evolutionary fitness.

So while it’s sometimes hard to find Mr. Dreamy, it seems like in the long run, it’s worth it.

Meet C. elegans, evolutionary tool extraordinaire

Reference: Mutation load and rapid adaptation favour outcrossing over self-fertilization. (2009) Morran LT, Parmenter MD, Phillips PC. Nature, 462(7271):350-2.

The fine print

Don’t you just hate it when you sign up for a new telephone/internet/cable plan thinking the offer is such a good deal, only to find out three months later that after the “introductory period” you are actually charged way more? You typically only make that mistake once and then learn to read the pesky fine print. In science, just like in advertising, the claims and the fine print need to be scrutinized. And typically, the bolder the claim, the more attention is paid to the fine print. For example, if I’m going around boasting that I discovered that a molecular component Y of the protein X interacts with a sub-component of the peptide Z, chances are, no one will really care enough to read about it (ah, the joys of the PhD thesis). But, if I’m going around claiming that I have a vaccine that prevents AIDS, you can be sure people will read the fine print.

In September of this year, a press conference was held to announce the results of the largest AIDS-vaccine study ever conducted. The study, funded in part by the US Army and having cost a whopping $105 million, was a “first success” in the research for an AIDS vaccine, a “yes we can” moment. However, not unlike the story about the Darwininan fossil, this press conference came before the findings were published in a peer-reviewed journal. When the paper came out in October and the fine print was read by all, the excitement dropped significantly: as it turns out, many results from the study were negative, and the positive results showed that the vaccine only protects a third of the people who got get it, and only for a short while.

The actual article presents the results from three different analyses. The first analysis looked at all the participants in the study (over 16, 000 people). For this group, the vaccine had 26% efficacy. Sounds like a good start, right? The problem is that the p value for this effect was 0.08. This means that there’s an 8% chance that this effect is just due to chance. This is quite a bit over the golden scientific standard of 5%, and should be considered not significant. The second study started with the same amount of participants (16, 000), then excluded around 4000 people because they didn’t follow the protocol exactly (for example, they didn’t get the vaccine at the correct time). Logically, the results should look better. Interestingly, they don’t. In this case, the vaccine still showed a modest protective effect, but the p value was now 0.16, meaning there’s an even bigger chance this is just a fluke. Finally, the third study looked at the initial 16, 000 people minus 7 who turned out to have been infected with HIV before the study even started. In that case, the vaccine still showed a similar effect (about 30% efficacy), but this time, the p value was under the cutoff at a less-than-impressive 0.04. Phew! Something to brag about during the press conference!

The negative, statistically insignificant results combined with a few other issues (for example, the short-term protection offered by the vaccine –only about a year) have drawn a number of criticisms not necessarily of the study, but of the bragging. As for the study itself, opinions are divided. Some see it as a glimpse of hope and an encouraging start, many see it as a weak effect, mostly not statistically significant, and possibly a waste of (a lot of) money.

With all the vaccine controversies and conspiracy theories going around these days, all I have to say is throw this new one in the mix.

Image from Scientific American

Reference: Vaccination with ALVAC and AIDSVAX to Prevent HIV-1 Infection in Thailand. (2009) Rerks-Ngarm S. et al. New Engl J Med. [Epub ahead of print]

To panic or not to panic: An interview with the swine flu (part II)

When the H1N1 story erupted in the media a little while back, I wrote a short Q and A post to give a scientific perspective on the topic. After that I really didn’t give much thought to the H1N1 flu. Since I don’t have a television at home and never listen to the radio, I live in a kind of media void. It’s glorious in there, let me tell you. Unfortunately, I was recently at a relative’s place and watched the news. I was shocked to see an endless stream of panic-inducing warnings and news about the H1N1, so the microbiologist in me decided to revive the topic here on Scientific Chick with the latest scientific information. So here you have it, a second exclusive interview with Mr. Swine Flu himself.

Scientific Chick: Mr. Flu, thanks for accepting to come back on Scientific Chick. How have you been? It seems you are gaining in strength and giving more severe illnesses.

Swine Flu: I’ve been well, thank you, but please notice that I’ve changed my name to H1N1. As you know, we are now in the regular flu season, so I am quite busy going around and infecting people. However, unfortunately for my plans to dominate the Earth, I have not been inducing an increasingly severe flu. It may seem so because with more people infected, the percentage of seriously ill patients becomes more apparent, but I’m still the same guy.

SC: How do you feel about our new H1N1 vaccine?

H1N1: I find it quite sad. You see, the vaccine is composed of my virus brothers, completely killed and inactivated. When talk of the vaccine started, I had a glimpse of hope that maybe, just maybe we could infect humans through the vaccine, but alas, that’s not possible. There is no chance a vaccine containing my dead relatives will give you flu.

SC: Surely with a vaccine so new, there is some chance of things going awry for us humans?

H1N1: I wish! It is often thought that because this vaccine is new, it is untested and unsafe. Unfortunately, because I am so similar to my seasonal cousin, the H1N1 vaccine has been produced the same way regular flu vaccines are produced every year. Health organizations (like the NIH) around the world have conducted rigorous clinical trials that show the vaccine is both safe and effective. It’s been licensed by all the governmental agencies and even though I tried to be very sneaky showing up unexpectedly like I did, no shortcuts were taken.

SC: At least most formulations of the vaccine contain thimerosal, so if we don’t catch you, you’ll at least have the consolation that we’ll suffer from mercury poisoning and all the associated conditions.

H1N1: Well, that would be nice, but you are grossly exaggerating. While it is tempting to blame thimerosal (a mercury-derived preservative) for a number of conditions, there is just no scientific evidence for any sort of suggestion that thimerosal is unsafe. Since the hypothesis that thimerosal causes autism broke out many years ago, scientists have been working very hard to prove or disprove that link. Interestingly, some of the best, largest, most well-controlled and unbiaised clinical studies came out of this controversy, all concluding that there is no link. The irony is that there is more mercury in a can of tuna than in any vaccine.

SC: So really, if I wanted to give up vaccines for fear of thimerosal, I’d also have to give up ahi tuna tacos? That’s just not a possibility. What about adjuvants in vaccines? How do you feel about those?

H1N1: I like adjuvants, because since they boost your immune response to the vaccine, less inactivated virus is needed per dose, which means less deaths in my family. That being said, whether you receive a vaccine with or without an adjuvant depends on where you live. In the USA, no adjuvants will be used. In Canada and some European countries, the vaccines contain adjuvants. Adjuvants are not new, and they also have a good safety track record. I hear a lot of concerns about squalene being used as an adjuvant, but you find squalene in olive oil.

SC: I hear a lot of discussions about Guillain-Barré Syndrome. Should we worry?

H1N1: Guillain-Barré Syndrome (GBS) occurs when your body’s immune system turns against its own nerve cells, and this leads to paralysis. If caught early enough, it can be reversed. And yes, vaccines are among the many risk factor for GBS, at a rate of about one in a million. Guess what else is a risk factor for GBS? Me! The nasty ol’ flu. Pick your odds.

SC: Are you hiding in my tasty pork tenderloin and bacon?

H1N1: No. You can only catch me through coughing or sneezing droplets from someone who is already infected, or through touching something contaminated and then letting your hands get to your face before they get to a sink to be washed.

SC: Should I wear a mask if I want to avoid you?

H1N1: Also a no. The Public Health Agency of Canada doesn’t recommend wearing surgical masks to avoid catching me. While this may sound counter-intuitive, there is actually scientific evidence that shows that this is not an effective way to prevent flu transmission in the general public. People tend to use the masks incorrectly, contaminate themselves when putting the mask on or taking it off, and increase their risk of infection by trapping me near their mouth. That would really make it too easy for me.

SC: H1N1, thank you. While it was lovely having you, I hope this was the last time.

H1N1: Thank you. Did you want to come closer? I have a secret for you…

This plush H1N1 virus is safe to cuddle with!

References:
Autism and vaccination-the current evidence. (2009) Miller L, Reynolds J. J Spec Pediatr Nurs. 14(3):166-72.

A Novel Influenza A (H1N1) Vaccine in Various Age Groups. (2009) Zhu FC et al. N Engl J Med. Oct 21.

The H1N1 flu pandemic. What you need to know. (2009)
Mayo Clin Womens Healthsource. (11):4-5.

The Centre for Disease Control and Prevention – www.cdc.gov Public Health Agency of Canada – www.publichealth.gc.ca