Most shots in the dark miss. Scientists learn this early in their career – most of the guesses we make as to how things work will turn out to be wrong. In fact, a proper understanding of science requires thorough knowledge of all the ways in which humans deceive themselves into believing things that are not true. In fact, most shots in well-lit conditions (informed by prior knowledge) miss. Ignoring prior knowledge results in chances that are all but hopeless.

Therefore the title of the 1985 book DPT: A Shot in the Dark by Harris Coulter and Barbara Loe Fisher, is perhaps unintentionally ironic. The book sparked the first modern popular concern about the risk of neurological damage from vaccines, in this case the pertussis vaccine that is part of the DTP vaccine.Fisher, of the National Vaccine Information Center (NVIC) still promotes the book and its content, even though the science has progressed in the last 25 years.

At the time the whole cell pertussis vaccine was part of the diptheria, tetanus, pertussis vaccine (DTwP). This combination has been largely replaced with the DTaP vaccine, which contains an acellular pertussis component. This change was partly due to safety issues, rare cases of neurological disease (seizures and encephalopathy) following DTwP being given. DTaP has a lower incidence of fever, seizures, and other side effects.

In the 1980s reports were surfacing of seizure and encephalopathy following DTwP. A 1991 review of these reports concluded that there was a possible association, but there was insufficient data to establish causation. It was also unclear if these reactions were causing any long term consequences. The safety of DTwP was therefore further studied, and as the evidence was examined it did not appear to support an actual link between DTwP and neurological injury. A 1990 review found:

There clearly is an increased risk of a convulsion after diphtheria-tetanus-pertussis immunization but no evidence that this produces brain injury or is a forerunner of epilepsy. Studies have also not linked immunization with either sudden infant death syndrome or infantile spasms.

In 1993 the Institute of Medicine conducted their own review of the evidence and concluded.

The committee concluded that the evidence is insufficient to indicate either the presence or absence of a causal relationship between DTP vaccine and permanent neurological damage.

But a later (1994) extensive population-based case control study found:

This study did not find any statistically significant increased risk of onset of serious acute neurological illness in the 7 days after DTP vaccine exposure for young children.

The DTwP has largely been replaced by the DTaP vaccine, and so there is little research into DTwP safety in the last decade. However, there is still some data from countries other than the US, that continued to use the DTwP after it was abandoned in the US. A 2008 Polish study, for example, compared reported side effects following DTwP and DTaP and found:

Comparisons done in children less then 2-years-old show in general about twice as high incidence of adverse effects following the whole-cell than the acellular vaccine. The biggest rate of proportions (RR = 4,75) was observed for high pitch cry. There was no significant difference in incidence of the most severe reactions, including encephalopathy and nonfebrile seizures, and there was no significant difference in allergic reactions.

So while there were more minor reactions to DTwP, there was no increase in seizures or encephalopathy compared to DTaP, which supports the conclusion that DTwP does not increase the risk of these neurological events. However, a Canadian study found a decrease in hospital admissions for febrile seizures following the transition to DTaP, suggesting that DTwP did increase the risk of febrile seizures. It should be noted, however, that febrile seizures do not generally increase the risk of developing epilepsy or permanent neurological damage.

Researchers are not done with the whole cell pertussis vaccine question. It is the nature of research to continually ask questions, to take shots at the truth (in whatever lighting conditions are available). A 2010 paper argues:

We argue that these reactions may have occurred in metabolically vulnerable children, specifically those with defects in fatty acid oxidation. In these children the combination of anorexia and fever that could be caused by the vaccine may have resulted in hypoglycemic episodes and possibly death. We believe that this association was not detected because these conditions were not recognized at the time and because these conditions are uncommon. Nevertheless, at a population level, enough events could have occurred to cause concern amongst parents.

This is a typical follow up question after negative findings – perhaps the effect (whether good or bad) exists only in a subpopulation and therefore was statistically missed by studies of the general population. This is a common question that can be applied to any negative study, and therefore is a fairly generic alternate hypothesis, which most of the time turns out to be false.


The DTwP story is a fairly typical one in the world of medicine. Anecdotal reports indicated a possible adverse reaction to the whole-cell pertussis vaccine. Researchers therefore looked at the question in various ways and eventually concluded that no significant signal or pattern could be detected. In short, there does appear to be an increased incidence of adverse events, such as irritability and maybe even febrile seizures, but no evidence of long term neurological harm. Never-the-less, a newer safer version of the vaccine, the acellular pertussis vaccine, became available and was adopted because it was probably safer. Even still researchers continue to drill down into the question of pertussis vaccine safety.

It is not possible to ever prove zero risk from any medical intervention. The data will always be limited. But we can demonstrate that the risk must be below certain upper limits, and that benefits outweigh risks – that net outcomes are improved with the intervention.

What we also see in this story is that anti-vaccine activists, like Fisher, froze their opinions about DTwP back in the early stages of anecdotal reports. The book, Shot in the Dark, was written prior to the informative research as to the safety of DTwP. The same appears to be true for those who continue to promote the myth that vaccines (MMR or thimerosal specifically) are associated with autism. The science has spoken even more clearly on this question – there is no detectable link between vaccines or mercury toxicity and autism. But the myth persists.

Posted by Steven Novella

Founder and currently Executive Editor of Science-Based Medicine Steven Novella, MD is an academic clinical neurologist at the Yale University School of Medicine. He is also the president and co-founder of the New England Skeptical Society, the host and producer of the popular weekly science podcast, The Skeptics’ Guide to the Universe, and the author of the NeuroLogicaBlog, a daily blog that covers news and issues in neuroscience, but also general science, scientific skepticism, philosophy of science, critical thinking, and the intersection of science with the media and society. Dr. Novella also contributes every Sunday to The Rogues Gallery, the official blog of the SGU.