Friday, October 12, 2012

Lessons from the Past: The Case of Smallpox

This morning I started reading this interesting book. I was motivated to read it because I believe that understanding the historical example of smallpox (the only disease we have eliminated) will be useful for understanding how we should tackle the diseases of aging in the 21st century.

I've finished the first 3 chapters of the book and want to make some notes here, and will simply update this post in the future for any future points.

Why focus on smallpox? Human populations have always faced significant risks of harm from infectious diseases. It is worth bearing in mind that for 99.9% of our species' existence, average life expectancy at birth did not surpass 30 years (source). Why? Death in early and mid-life was a regular part of life. And infectious diseases were a main (and remain so in developing countries) culprit. Small pox is a special case in this story for a number of reasons.

Firstly, the magnitude of the suffering and death caused by smallpox is beyond what the human mind could possibly comprehend. In the 20th century alone it is estimated that between 300-500 million people died from smallpox. So from the perspective of human suffering and death, smallpox warrants serious attention. Secondly, the World Health Organization declared smallpox was eradicated in 1980. This is an enormous success story worth understanding if we hope to be prepared for the health challenges of the 21st century.

OK, some points of note from the book:

Origins of smallpox: p.3, from the East, recorded in Arabia in 572 AD.

Symptoms of the disease: 1. shivers or convulsions, sharp pain, usually in lower back (lasts 1-2 days) [period of invasion]. 2. Red spots appear on body, become pimples and then blisters containing a pale yellow liquid [period of eruption]. 3. Blisters burst, releasing significant amounts of pus [suppuration], high fever returns.

Mortality caused by smallpox (p.6): 80% of people contracted the disease, mostly as children, and authors in 18th and 19th centuries estimate between 1-10 to 1-7 died from the disease.

What did people think caused the disease? many thought it was innate to humans (p. 4). Others thought it was an infection attributed to menstrual blood or something caused by the putrefaction of the umbilical cord(p. 5).

What did people think could cure it? A host of remedies were proposed at the time, such as special diets and enemas.

First real progress: from the East, came the advice that it was possible to inoculate smallpox in order to protect oneself against it (p. 7). It was realized that someone who developed smallpox and survived would be protected from the disease in the future. In the 18th century this process was called "insertion" as it involved inserting a thread that had been doused in the liquid from a blister into a cut in the healthy person.

The details of some of the early human experiments are both fascinating as well as disturbing. Prisoners from Newgate prison in London, who were destined to hang, were convinced to try the smallpox inoculation. Three men and three women agreed to this and the procedure was successful, after which they were released from prison. Inoculation became fashionable, but then faced setbacks as people inoculated against the disease died from the disease. And many of the unnecessary preparations undertaken at this time, such as strict diets, enemas and taking blood, made things much worse than they needed to be. Only the upper classes pursued inoculations at this time, who could afford to keep their children isolated from others for weeks on end.

Food for thought: I couldn't help but be struck by the important lessons the case of smallpox provides us as we struggle to combat the chronic diseases of late life.

Here are a few points to keep in mind:

1. The health risks associated with senescence are a relatively new problem for human populations, created by civilization's success in combating early and mid-life morbidity and mortality. Nonetheless, senescence is a biological puzzle that ought to be investigated with much vigor, and interventions sought which could slow down the rate of aging so that aging populations can remain healthy for a prolonged period of time.

2. The mortality caused by aging today is also staggering. Unprecedented numbers of people suffer cancer, heart disease, stroke, AD, etc. So retarding the rate of molecular and cellular decline is the health challenge of the 21st century.

3. Like smallpox, many falsely attributed aging to factors that were subsequently shown to be false. For example, many Christians just assume that aging is part of god's plan for humans and, by this logic, I presume other domesticated or protected species, like laboratory mice and rats, pet cats and dogs, and zoo animals, etc. Others believed there was an aging "gene" that programmed us for death, perhaps as part of a group selection design to limit the strains of overpopulation (here is a contemporary proponent of such a view). But biogerontology has demonstrated aging is a product of evolutionary neglect, and that the rate of aging is not immutable.

4. Like a potential aging intervention, small-pox faced tough ethical issues in terms of how one can justifiably experiment on humans to test the safety and efficacy of an intervention. Back in the 18th century there were not the ethical and bureaucratic regulations for clinic trials that there are today.

5. The timeline from Jenner's first experiments with a vaccine to the eradication of smallpox in 1980 is telling for a number reasons. More to follow on this as I get through the book.

6. There is a striking parallel between the plurality of proposed "cures" for smallpox and so-called anti-aging interventions pandered to the public by those looking to make a quick buck. So the fad of special diets and enemas are still with us. It is important to distinguish between those interventions that are demonstrated, empirically, to work and those that are presented as "alternative" medicine (read- not regulated for safety or efficacy).

6. The biggest and most important part of the story-- success against smallpox came when efforts focused on those cases where people were immune to the disease (i.e. those that had previously contracted the disease). This reinforces the point that positive biology ought to be part of our strategic plan to promote health this century. With aging, the real secret to unravel lies in understanding the biology of those with exceptional longevity (like supercentenarians age >110 years). If the thought of developing a drug that activates the longevity genes these people are born with sounds farfetched, just remember Jenner's accomplishment of eradicating smallpox by injecting children with cowpox, a mild viral infection of cows that protected against small pox. Health innovations are not always intuitive, but rather are made by innovative thinkers who are brave enough to try something new and think outside the box.

I expect to update this post as I get further into the book.