Dr. Andy

Reflections on medicine and biology among other things

Friday, July 29, 2005

Life span and infectious disease

Sorry if this image is hard to read, I had trouble converting from the .pdf file.
This is a view of life-span over time, showing almost no change from the paleolithic era until the mid-19th century (this data is apparently based on data from skeleltons at excavated sites but some assumptions needed to be made about survival in early childhood since very few skeletons of young children were found). The article it comes from notes that only about 1/3 made it to age 40 in the UK even at the end of the 19th century, indicating just how far we've come in the last 100 years. And the reason is infectious; very few people in the paleolitic era died of cancer or heart disease.

The article points out just how ineffective the human immune system is. As a clinical immunologist in the 21st century, it is easy for me to see how well it works aided by vaccines, hygeine and powerful antibiotics availabe at any pharmacy. In fact, until recently most deaths were caused by infections.

This perspective also helps explain the complexity of the human immune system and the amount of "energy" (from both an organismal and genetic/evolutionary perspective) devoted to immunity. Because that is what killed people:
In mid–19th century England, 60% of deaths were due to infectious diseases and this proportion was even higher in previous centuries, especially during epidemics
So the human (and, in general) mammalian immune system is complex and costly, but not very effective. So why do we have it? As brilliantly discussed in this (different) article, the answer is because we need it. Kids with SCID (severe combined immune deficiency, what used to be called the bubble-boy disease) die in infancy of infections that don't bother those with intact immune systems.

As the commentary notes, our immune systems can never hope to absolutely protect against infection, as bacteria may have 100,000 generations for each of ours. There ability to evolve quickly is much greater than ours. One idea is that by allowing generation of diversity many times within each organism (i.e. harnessing natural selection in lymphocytes by recombination of T cell receptor and antibodies) we are able to keep up. But the existence of complex, long-lived invertebrates like squids indicates it isn't simply our complexity or life-span that generated the need for such a complex immune system.

So what is the answer? Probably that a better immune system creates a selective advantage in comparison to other humans. In each generation, those individuals who avoid death of disability due to infection are the ones most likely to reproduce.
By selecting for evermore-devious parasites, the immune system is the cause of its own necessity
As our immune systems improve so do the ability of microbes to resist or outwit them:
The proposal here is that contrary to widely held views of practicing immunologists, the immune system is not evolutionarily selected to prevent infection in an absolute sense. Rather, it is selected to make one individual slightly more resistant or at least different than others of the same or related species. The adversary of any individual is not really the world of parasites, they are truly undefeatable, it is his or her neighbor. A zebra doesn't have to outrun the lion, just the slowest member of the herd.

Another way of looking at this is that acquired immunity was not a final solution to the problem of parasitism. There is no final solution. As novel as the acquired immune was, for rapidly multiplying agents, it was just another hurdle. It may have driven parasites to invent new strategies for fitness, but it did not convey invincibility or anything like it. To say the combination of innate and acquired immunity is the optimal defense is a misunderstanding of the evolutionary landscape. I don't believe there is an optimal defense. I don't believe there is a conceivable immune system that could not be obviated once the barriers to infection have been breached. For all animals and their parasites, generation upon generation, it has been evolutionary thrust and parry, until today as it was a million years ago and as it will be a million years hence, each and every species is literally plagued by parasitic microbial agents and viruses.
If you are interested, I strongly recommend reading the entire second article. It is well worth it.


At 11:41 AM, Blogger Brian said...

Great post! I'm not sure if I understood the squid reference though - do they have simple immune systems?

At 8:46 AM, Blogger Dr. Andy said...

Squids don't have an adaptive immune response. That is they can't generate antibodies or T-cells which specifically recognize a given protein; unlike mammals. Yet they are large complex organisms that live long lives

At 4:46 PM, Anonymous Anonymous said...

thanks for this, but your second article link is wrong

i found the article you quoted at:

Immunity. 2004 Nov;21(5):607-15.

The acquired immune system: a vantage from beneath.

Hedrick SM.

University of California, San Diego, La Jolla, CA 92093, USA.


At 5:33 PM, Blogger Disease Index said...

You keep a nice blog. I just started one myself about Diseases. If you know of anyone who could benefit from Diseases information, then please refer them to my Diseasesinformation site. I'll return the favor by referring my friends to your site.

At 6:03 PM, Blogger Disease Index said...

You keep a nice blog. I just started one myself, about Diseases. If you know of anyone who'd benefit from Diseases information, then please refer them to my Diseases information site. I'll return the favor.

Let's put an end to the suffering.
Find A Cure For Any Disease!

At 10:00 PM, Blogger Disease Index said...

You keep a very nice blog. I'm new to the whole blog thingy, but I enjoy reading through other people's blogs.
Let's end the suffering of all Diseases
Find A Cure For Any Disease:


Post a Comment

<< Home