This is a pretty neat study, though it kinda makes me
cringe. You’ll see why.
Whooping cough is a respiratory infection caused by the
bacterium Bordetella pertussis, though apparently there was a lot of
debate about the pathogen (bacteria or virus?) in the first half of last
century. This study was designed in part to test that.
The other part was testing whether Louis Sauer’s vaccine
made from B. pertussis could protect against the disease (which would be
another indication of its bacterial cause). So how did it go?
H. and E.J. Macdonald, a physician husband and nurse wife
team, intentionally exposed four healthy brothers aged 6 to 9 years to cultures
from a separate whooping cough patient. These boys, it turns out, were their
own sons. Now that’s dedication to science!1
Two of the boys, the 9-year-old and one of the 8-year-old
twins, had been vaccinated by Sauer 5 months before, and the other two (8 and 6
years) had not. None had any previous exposure to pertussis.
The team took a cough plate culture from someone with
typical whooping cough and grew cultures from it on agar, checking under a
microscope to make sure it was a pure culture. Half of the growth on this plate
they suspended in saline solution, and then filtered it through a filter with
pores small enough to remove bacteria from the solution, presumably leaving
only viruses, if there were any. The other half of the growth they suspended in
saline without filtering.
To start, they squirted a little of the filtered solution
into the boys’ nose and throat, then quarantined them in a rural apartment with
their mother (the nurse) for 8 weeks. They didn’t come down with any symptoms
within 18 days, long enough for whooping cough to show up, so it didn’t seem to
be some virus present in the culture.
So then after the 18 days, the team squirted some of the
unfiltered suspension into the boys’ nose and throat. They aimed for about 140
bacteria total per boy. First the vaccinated results: neither of the two
vaccinated boys had any symptoms or sign of whooping cough in the whole period
of 38 days. Cultures from their throats and such were consistently negative.
On the other hand, the unvaccinated boys started coughing
after only 7 days. Cultures were rated as ++++, which seems very positive, even
from the beginning. Over the next few weeks, their fever and coughing increased
in severity, they started whooping and vomiting food and mucus, stopped eating
much, and had headaches. Seems pretty miserable. Then they got better,
fortunately.
After recovering, the team tested the antibodies of all four
boys, as well as two others each that were known to be immune or non-immune,
and found that all were positive except the two known non-immunes.
So what could be concluded from this: as few as 140 cells is
enough to cause an infection. B. pertussis is the agent that causes whooping
cough. Seven days is the incubation period (at least here). Possibly also that
the vaccine works pretty well.
On the other hand, it’s definitely a small sample size (2
patients in each group), and there was no blinding or placebo, but it gave very
distinct results in a very controlled situation. All of them were known to have
been exposed to enough pathogen to cause disease, and none could’ve been
exposed from somewhere else. The populations were pretty matched too: two of
the boys were twins, one vaccinated and one not. But one could argue that it’s
not good enough.
As a minor question, I’m not even sure why they would’ve
thought there would be any virus on the culture plate, unless they thought it
were stuck to and replicating along with the bacteria or something…
And finally, the cringe-y part: this seems so unethical
based on my understanding of standards for medical research these days,
exposing children to a potentially deadly disease, but at least we can benefit
somewhat from the results.
Some others agree with me in some ways and make
observations:
"In...1933 the Macdonald husband-and-wife team performed an experiment on their four sons, from which they concluded that 'a filter-passing virus plays no role in the etiology of pertussis.' The wife, a nurse, sequestered herself with the boys in a rural apartment for eight weeks...Aside from proving that there are hazards in being born into a physician's family, and that B. pertussis could cause whooping cough, the findings did not really exclude the possibility of a direct or indirect role for viruses in the disease. It would have been a hardy virus to survive through two subcultures on agar medium."2 [Though later studies confirm the result.]
"In 1933, Sauer vaccinated 2 of 4 brothers; all 4 brothers were then inoculated in the nose and throat with whooping cough bacillus. The 2 hapless controls (sons of a local physician) developed classic cases of whooping cough while their vaccinated siblings remained healthy."3
 |
| The four boys. Source: National Library of Medicine, and Baker 20003 |
Citations:
1. MacDonald, H. & MacDonald, E. J.
Experimental Pertussis. The Journal of Infectious Diseases 53,
328–330 (1933).
2. Nelson,
J. D. Whooping Cough — Viral or Bacterial Disease? New England Journal of
Medicine 283, 428–429 (1970).
3. Baker,
J. P. Immunization and the American Way: 4 Childhood Vaccines. American
Journal of Public Health 90, 199 (2000).
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