Biology

Model8.ppt

Principle themes of Darwinian Medicine

Symptoms are often adaptations
Pain to prevent further injury
Morning sickness is adaptive
Evolutionary arms races
Overusing antibiotics
Evolutionary mismatches
A trait that evolved in one environment becomes maladaptive in another environment.
Hygiene hypothesis

"Our study…shows that nausea and vomiting in pregnancy is beneficial by expelling such foods as meat and strong-tasting vegetables that historically and still may contain harmful toxins and microorganisms that could potentially sicken the woman and damage her fetus just when its organs are developing and are most vulnerable to chemicals,"

- Paul Sherman Cornell University

The nausea and vomiting declines after 18 weeks of pregnancy, as the fetus becomes less vulnerable to the effects of chemical disruptions.
Women with the most severe morning sickness have lower rates of spontaneous abortion than other pregnant women.
Historically, meat and strong-tasting vegetables were likely to contain parasites, pathogens and plant toxins; these foods tend to reliably trigger morning sickness symptoms across cultures. Alcohol and cigarette smoke, which also can harm the fetus while organs are forming, also trigger the nausea.
Societies that consume more meats, strong-tasting vegetables and alcohol have higher rates of morning sickness than societies whose staples are bland plant products.
Only humans experience morning sickness, as far as is known, because, the researchers suggest, of their "extraordinary broad diet," compared with other primates and mammals.

This doesn’t work very well

Cancer

Iron is crucial for bacterial growth
Iron is also nutrient limiting in the environment
body sequesters Iron as a form of

nutritional immunity

Skaar, E. P. (2010). The Battle for Iron between Bacterial Pathogens and Their Vertebrate Hosts. PLoS Pathogens, 6(8), e1000949

Wild type

No Siderophore prod

Wild type w/ Gallium

"tumors cannot grow and survive without triggering the growth of new blood vessels to supply them with oxygen and nutrients. Through random genetic changes, cancer cells accidentally discover how to express their genes for the angiogenesis factors that signal the vascular system and trigger the growth of new blood vessels. These angiogenesis factors, and the new blood supply they engender, are public goods initially provided by certain mutant cells that benefit all cancer cells in their vicinity, including themselves."

-John Pepper NCI

Cancer

"Endostatin, a potent angiogenesis inhibitor, was administered to mice bearing Lewis lung carcinoma, T241 fibrosarcoma or B16F10 melanoma. Treatment was stopped when tumours had regressed. Tumours were then allowed to re-grow and endostatin therapy was resumed. After 6, 4 or 2 treatment cycles, respectively, no tumours recurred after discontinuation of therapy. These experiments show that drug resistance does not develop in three tumour types treated with a potent angiogenesis inhibitor."

Too many people think of microbes as germs and that our natural environment is too dangerous, confining us indoors while we watch other animals frolic freely

A 'reference man' (one who is 70 kilograms, 20–30 years old and 1.7 metres tall) contains on average about 30 trillion human cells and 39 trillion bacteria

Ron Milo and Ron Sender Weizmann, Institute of Science in Rehovot, Israel, and Shai Fuchs at the Hospital for Sick Children in Toronto, Canada.

And most of these are necessary

Have we gone too far?

How does your immune learn about its environment?

So what are the downsides to sanitation?

Immune system coevolved with various other species, ‘old friends’.

Immune system may not develop normally without exposure to ‘old friends’.

Innovations in hygiene/sanitation reduced exposure to ‘old friends’

Lead to emergence of modern immune system related diseases such as MS, T1 Diabetes, allergies, inflammatory intestinal diseases.

Hygiene hypothesis: Lower incidence of infection in early childhood may be responsible for the increase in modern immune system related diseases.

This side downregulates that side

allergies

autoimmune

Remission was defined as a decrease in CDAI to less than 150 while a response was defined as a decrease in CDAI of greater than 100

A Darwinian View of the Hygiene or “Old Friends” Hypothesis

When urban living reduced contacts of humans with microbes and worms, it increased our risk for chronic inflammatory disorders

Graham A. W. Rook

CAUSE

Environmental factors such as diet and bacterial antigens play an important role in the onset of Type 1 diabetes. Different self-antigens are suggested to play a role in the development of diabetes. Antibodies against the 60-kDa heat shock protein 60, which have a high homology to bacterial heat shock protein 65, have been found in the circulation at the onset of diabetes in humans and in pre-diabetic NOD-mice. One of the immunodominant epitopes in autoimmune diabetes is p277, a specific peptide of human heat shock protein 60 corresponding to positions 437–460. In this study we investigated whether neonatal oral administration of DiaPep277 (a synthetic peptide analogue of p277) affected the development of diabetes in the BioBreeding-Diabetes Prone (BB-DP) rat, and whether this could potentiate the effect of a protective hydrolysed casein-diet. Short-term neonatal feeding with p277 in early life, combined with diet adaptation, appears to provide a procedure to significantly reduce the development of Type 1 diabetes in later life.

Naïve immune system

A phase II clinical trial testing the ability of the generic vaccine bacillus Calmette-Guérin (BCG) to reverse advanced type 1 diabetes has received approval from the U.S. Food and Drug Administration (FDA). -2015

Please, by all means, take your sweet time

DOI: 10.1542/peds.2012-3345 ; originally published online May 6, 2013;Pediatrics

Agnes E. Wold Bill Hesselmar, Fei Sjöberg, Robert Saalman, Nils Åberg, Ingegerd Adlerberth and

Pacifier Cleaning Practices and Risk of Allergy Development

http://pediatrics.aappublications.org/content/early/2013/04/30/peds.2012-3345

located on the World Wide Web at: The online version of this article, along with updated information and services, is

of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275. Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 2013 by the American Academy published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point publication, it has been published continuously since 1948. PEDIATRICS is owned, PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly

at Nova Southeastern Univ on March 24, 2014pediatrics.aappublications.orgDownloaded from at Nova Southeastern Univ on March 24, 2014pediatrics.aappublications.orgDownloaded from

http://pediatrics.aappublications.org/content/early/2013/04/30/peds.2012-3345

http://pediatrics.aappublications.org/

DOI: 10.1542/peds.2012-3345

; originally published online May 6, 2013;Pediatrics

Agnes E. Wold

Bill Hesselmar, Fei Sjöberg, Robert Saalman, Nils Åberg, Ingegerd Adlerberth and

Pacifier Cleaning Practices and Risk of Allergy Development

http://pediatrics.aappublications.org/content/early/2013/04/30/peds.2012-3345

located on the World Wide Web at:

The online version of this article, along with updated information and services, is

published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point

publication, it has been published continuously since 1948. PEDIATRICS is owned,

PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly

at Nova Southeastern Univ on March 24, 2014pediatrics.aappublications.orgDownloaded from at Nova Southeastern Univ on March 24, 2014pediatrics.aappublications.orgDownloaded from

DOI: 10.1542/peds.2012-3345 ; originally published online May 6, 2013;Pediatrics

Agnes E. Wold Bill Hesselmar, Fei Sjöberg, Robert Saalman, Nils Åberg, Ingegerd Adlerberth and

Pacifier Cleaning Practices and Risk of Allergy Development

http://pediatrics.aappublications.org/content/early/2013/04/30/peds.2012-3345

located on the World Wide Web at: The online version of this article, along with updated information and services, is

at Nova Southeastern Univ on March 24, 2014pediatrics.aappublications.orgDownloaded from at Nova Southeastern Univ on March 24, 2014pediatrics.aappublications.orgDownloaded from

http://pediatrics.aappublications.org/content/early/2013/04/30/peds.2012-3345

http://pediatrics.aappublications.org/

DOI: 10.1542/peds.2012-3345

; originally published online May 6, 2013;Pediatrics

Agnes E. Wold

Bill Hesselmar, Fei Sjöberg, Robert Saalman, Nils Åberg, Ingegerd Adlerberth and

Pacifier Cleaning Practices and Risk of Allergy Development

http://pediatrics.aappublications.org/content/early/2013/04/30/peds.2012-3345

located on the World Wide Web at:

The online version of this article, along with updated information and services, is

published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point

publication, it has been published continuously since 1948. PEDIATRICS is owned,

PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly

at Nova Southeastern Univ on March 24, 2014pediatrics.aappublications.orgDownloaded from at Nova Southeastern Univ on March 24, 2014pediatrics.aappublications.orgDownloaded from

However, parental cleaning of the paci- fierbysuckingitwasstronglyassociated with the risk of allergy development. Both eczema (OR 0.37; 95% confidence interval [CI] 0.15–0.91; P = .02) and asthma (OR 0.12; 95% CI 0.01–0.99; P = .03) were strongly reduced in children whose parents had this habit. There was also a trend toward lower risk of

sensitization in this group (OR 0.37; 95% CI 0.10–1.27; P = .08) (Fig 1). Fur- thermore, the blood eosinophil count at 18 months of age was also lower in children whose parents sucked on their pacifier than in other pacifier- using children (Fig 2).

Parental Pacifier Sucking and Respiratory Infections in the Child

Respiratoryinfectionsinthechild’sfirst 6 months were recorded by parents and reported at the 6-month telephone interview. On average, 1.5 respiratory infections per child were noted by the parents (CI 1.3–1.7). This frequency did not differ between children whose parents sucked their pacifier (1.4) and other pacifier-using children (1.5; ANOVA, P = .75).

Analysis of Confounding Factors

We analyzed the relationship between parental pacifier sucking and possible confounding factors. Parents of vagi- nally delivered infants were signifi- cantly more likely to suck the child’s pacifier than parents of infants de- livered by cesarean (Fisher’s exact test, P = .02; Table 4). Conversely, mothers with a university-level degree tended to be less likely to suck the child’s pacifier, although this association was not significant (Table 4). After logistic regression to adjust for delivery mode and mother’s education, the protective

effect of parental pacifier sucking on eczema development during the child’s first 18 months of life remained (OR 0.27, 95% CI 0.086–0.819; P = .02). The protective effect on asthma could not be analyzed in this way because of the low number of cases.

We speculated that delivery via the vaginal route, which exposes the infant to the maternal vaginal microbiota, and parent/infant pacifier sharing, which leads to exposure to parental oral microbiota,mayconferadditiveprotective effects against allergy development by exposure to a variety of commensal microbes. We thus stratified the cohort into 3 groups: (1) vaginally delivered infants with pacifier-sucking parents; (2) cesarean-delivered infants whose parentsdidnotsucktheirpacifiers;and (3) infants who were either vaginally delivered or exposed to parents’ oral microbiota by pacifier sharing. We then compared the prevalence of eczema in infants at 18 months of age in these 3 groups (Fig 3). The group exposed to both maternal vaginal and parental oral microbiota had the lowest preva- lence of eczema (20%), whereas infants exposed to neither maternal vaginal or parental oral microbiota had the highest prevalence (54%). The group of children who were either vaginally delivered or whose parents sucked their pacifiers had an intermediate eczema prevalence (31%) (Fig 3).

Parental Pacifier Sucking and Allergy During the Child’s First 36 Months of Life

The childreninthe cohort were followed up at 36 months of age. Kaplan-Meier curves were calculated for eczema, asthma, and sensitization (Fig 4). De- velopment of eczema up to 36 months of age was significantly less likely in infants whose parents sucked on their pacifiers during their first 6 months of life, as compared with other pacifier- using children (P = .04). The protective effect of parental pacifier sucking on

TABLE 2 Pacifier Cleaning Practices Among the 136 Infants Using a Pacifier During the First 6 mo of Life

Technique No. of children

Rinsing in tap water 113 83 Boiling 74 54 Parental sucking of the pacifier

65 48

Not reported 13 10 Total 136 100

Techniques for cleaning the pacifier were reported in a telephone interview when the infant was 6 mo old.

TABLE 3 Allergic Diseases and Sensitization at 18 and 36 mo of Age

Disease No. of children (%)

At 18 mo (n = 184)

At 36 mo (n = 174)

Eczema 46 (25) 40 (23) Asthma 10 (5) 14 (8) Sensitization 25 (15)c 26 (15)d

Phadiatopa 3 (2)c 3 (2)d

Food-mixb 25 (15)c 26 (15)d

a Immunoglobulin E antibodies to birch, timothy grass, mugwort, cat, dog, horse, Dermatophagoides pteronyssi- nus and Dermatophagoides farinae, and mold. b Immunoglobulin E antibodies to cow’s milk, egg, fish, wheat, soy, and peanut. c n = 169. d n = 171.

FIGURE 1 The relationship between atopy or allergy in children at 18 months of age and in relation to pacifier use and different pacifier cleaning practices. ORs are given for pacifier versus no pacifier use. For children usingapacifier,thewayofcleaningthepacifierwascomparedwiththosenotusingthatspecificcleaning method. Ns, not significant.

4 HESSELMAR et al at Nova Southeastern Univ on March 24, 2014pediatrics.aappublications.orgDownloaded from

http://pediatrics.aappublications.org/