Saturday, December 28, 2019

UW-Madison Swindles Taxpayers Again

It's the old bait-and-switch con.

In 2014, Christopher Coe was awarded $440,094 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) to develop and test a “medicinal food” to treat anemia in children and young women of childbearing age. Coe is the director of the Harlow Primate Laboratory which is adjacent to the Wisconsin National Primate Research Center. He has yet to report on the development or to test such a food.

Coe says that his research is addressing a public health concern:
PUBLIC HEALTH RELEVANCE: Nutritional deficiencies compromise the wellbeing and developmental health of infants worldwide, including many infants in the United States. Our project will determine the value of an innovative medical food, nutritional yeast modified to express human ferritin, for treating anemia. The core hypothesis is that ferritin will outperform the traditional treatment with ferrous sulfate for delivering iron to the brain, and thus provide a more effective approach to managing iron deficiency and preventing the adverse neurodevelopmental effects of untreated anemia.

He has repeated this statement every year for the past five years and has so far received $2,132,528 in tax dollars from NICHD. In his grant abstract, he explained his goal and how he would test the food’s efficacy:
Our primary goal is to investigate the benefits of a new medical food supplement for treating anemia. We will establish the utility and safety of providing iron in yeast biotechnically modified to express human ferritin. One advantage of this modification is that yeast can acquire therapeutic levels of iron in a bioavailable form without significant change in texture or palatability. In addition, ferritin is a highly conserved protein enabling us to provide a natural tissue storage form of iron using yeast as the delivery vehicle. To test its efficacy, we take advantage of a well-characterized nonhuman primate model of infant anemia. Three studies will be conducted in young rhesus monkeys under controlled laboratory conditions, empirically verifying the value of this yeast-ferritin complex in infants, a likely target population in humans. We will directly compare its benefits to a common standard of care: oral treatment with ferrous sulfate.

It seems that he planned to genetically modify yeast to produce an iron-containing protein that could be added to foods. Once the modified yeast was produced, he would feed some anemic young monkeys the special yeast and treat some anemic young monkeys with the standard treatment, and then compare the results.

Over the five years of the grant he has published five papers, which on its Research Portfolio Online Reporting Tools website, the NIH lists as the results of the project.

Here are the titles and a few pull-outs from those papers:

1. “Metabolomic analysis of CSF indicates brain metabolic impairment precedes hematological indices of anemia in the iron-deficient infant monkey.” [Nutritional neuroscience. 2018 Jan; 21 (1) :40-48]

Objectives: Iron deficiency anemia leads to long-term neurodevelopmental deficits by altering iron-dependent brain metabolism. The objective of the study was to determine if iron deficiency induces metabolomic abnormalities in the cerebrospinal fluid (CSF) in the preanemic stage and to ascertain the aspects of abnormal brain metabolism affected.

2. “Maternal Perceived Stress during Pregnancy Increases Risk for Low Neonatal Iron at Delivery and Depletion of Storage Iron at One Year.” [The Journal of pediatrics. 2018 09; 200 :166-173.e2]

Objective: To investigate the impact of maternal stress during pregnancy on newborn iron and Stage 1 iron deficiency (ID) at one year of age.

3. “Social Influences on Prevotella and the Gut Microbiome of Young Monkeys.” [Psychosomatic medicine. 2017 Oct; 79 (8) :888-897]

Objective: Our aim was to evaluate the bacterial profiles of young monkeys as they were weaned into peer groups with a particular focus on Prevotella, an important taxon in both human and nonhuman primates. The weaning of infants and increased social contact with peers is a developmental stage that is likely to affect the gut microbiome.

... Typically, in a natural troop, this progressive movement away from the mother is gradual and takes place over several months, but in captive settings, such as a laboratory, it is common to re-house an entire group of weanlings on the same day. This social transition in young monkeys results in a period of behavioral agitation and activates stress physiology for several days followed by recovery as they become familiar with the new environment and with peers.

4. “Gestational Timing of Prenatal Disturbance and Fetal Sex Determine the Developmental Outcomes.” [Neonatology. 2016; 109 (4) :314-20]

Objective: To determine the impact of a delimited period of moderate maternal stress on infant growth, emotional reactivity and neurobehavioral maturity in a nonhuman primate model.

Methods: Eighty-three infant rhesus monkeys were generated from disturbed pregnancies, either Early or Late Gestation, and compared with 51 Undisturbed infants. Maternal stress was induced with an acoustical startle protocol for 25% of gestation. Infant weights, anthropometrics, and neurobehavioral data were obtained. Analyses focused on differential effects of prenatal stress on male and female infants.

... Female rhesus monkeys were exposed to controlled stress lasting 5-6 weeks, either early or late during their 24-week pregnancy. The immediate impact was assessed by determining maternal cortisol levels at the end of the daily manipulations.

5. “Maternal Obesity Affects Inflammatory and Iron Indices in Umbilical Cord Blood.” [The Journal of pediatrics. 2016 05; 172 :20-8]

Objective: To determine the impact of maternal obesity and gestational weight gain across pregnancy on fetal indices of inflammation and iron status.

There is no mention of yeast in any of the papers.
For decades, it has been possible to diagnose and fully reverse the anemia of iron deficiency at a relatively low cost. Unfortunately, iron deficiency has maintained itself as the most common anemia and nutritional disorder worldwide. This seemingly inexplicable paradox of high prevalence despite effective treatment represents a major challenge to public health efforts. Multiple obstacles involving economics, cultural barriers, and infectious diseases converge and make eradication of this disease more difficult. The additional challenges that are encountered by certain human subpopulations in select geographies need to be overcome to achieve therapeutic success in the global community. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3685880/
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Iron deficiency anemia most commonly affects babies 9 through 24 months old. Breastfed babies need less iron because iron is absorbed better when it is in breast milk. ... Infants younger than 12 months who drink cow's milk rather than breast milk or iron-fortified formula are more likely to have anemia. Medline Plus Feb 19, 2018.

Suppose a scientist asked you for a donation to help them develop a way to increase the amount of iron in yeast to help alleviate iron deficiency in women and children?

An informed response might be something like, how will you get the yeast into the hands of African and Asian mothers, since the prevalence of anemia in infants and young children (birth to 5 years of age) is greatest in Africa, 64.6% and in Asia, 47.7% The prevalence in the North America is only 3.4%. Moreover, according to the NIH National Heart, Lung, and Blood Institute, people with mild or moderate iron-deficiency anemia may not have any signs or symptoms.

But let’s say that you decided to give them a donation. And over the ensuing 5 years, others donated a combined total of $2,132,528. When you learn how much they got, you decide to see how the project is coming along. You find out that the scientist used all the money and has published five papers paid for by those donations, but no where in them is there mention of a new medicinal food for treating anemia.

Where, you might ask, did the claim about wanting to make iron-rich yeast go? Indeed.
Project Number: 5R01HD080201-05 Contact PI / Project Leader: COE, CHRISTOPHER L
Title: NOVEL MEDICAL FOOD FOR TREATING INFANT ANEMIA AND IRON DEFICIENCY IN THE CNS Awardee Organization: UNIVERSITY OF WISCONSIN-MADISON
Abstract Text: DESCRIPTION (provided by applicant): Iron deficiency is the most common micronutrient deficiency worldwide, and is particularly significant for women of child-bearing age and rapidly growing infants. Conventional methods of treating iron deficiency orally are inadequate as evidenced by poor compliance and the periodic need for iron injections. Our primary goal is to investigate the benefits of a new medical food supplement for treating anemia. We will establish the utility and safety of providing iron in yeast biotechnically modified to express human ferritin One advantage of this Modification is that yeast can acquire therapeutic levels of iron in a bioavailable form without significant change in texture or palatability. In addition, ferritin is a highly conserved protein enabling us to provide a natural tissue storage form of iron using yeast as the delivery vehicle. To test its efficacy, we take advantage of a well-characterized nonhuman primate model of infant anemia. Three studies will be conducted in young rhesus Monkeys under controlled laboratory conditions, empirically verifying the value of this yeast-ferritin complex in infants, a likely target population in humans. We will directly compare its benefits to a common standard of care: oral treatment with ferrous sulfate. Beyond traditional hematological tests and iron- related measures in serum, several novel endpoints will be determined in cerebrospinal fluid, including quantitation of iron management proteins and two important protein indices previously identified by proteomic analysis to be abnormal in anemic infants. Prior proteome and metabolome analyses revealed that when infant anemia is not resolved, it impacts functional proteins in the developing CNS, including prostaglandin D2 synthase and amyloid beta A4 protein-like, and impairs brain energetics. In addition to verifying the effectiveness of this innovative treatment, we will determine the safety if an iron-sufficient infant were to consume yeast containing iron, a critical prerequisite for human clinical trials. Measures of the heme and intrathecal compartments will be determined before, during, and after treatment. Based on previously found behavioral differences in anemic Monkeys, emotional reactivity, motor activity, and cognitive performance will be assessed after supplementation. The core hypothesis is that this yeast-ferritin complex will provide iron in a readily absorbed form, and most significantly, that direct provision of ferritin will replenish the iron-deficient CNS more effectively. Using a multi-tiered nutritional and developmental neuroscience approach, several novel aspects of iron delivery and utilization will be investigated. The research has a clear translational relevance with the potential for establishing a new therapeutic modality. It will set the stage for a Phase I/II clinical trial and, at the same time, validate new biomarkers for tracking how anemia and iron supplementation affect the developing brain. Our capacity to carry out this unique inter-disciplinary project is based on a history of collaboration between two laboratories with the essential resources and expertise.

Public Health Relevance Statement:

PUBLIC HEALTH RELEVANCE: Nutritional deficiencies compromise the wellbeing and developmental health of infants worldwide, including many infants in the United States. Our project will determine the value of an innovative medical food, nutritional yeast modified to express human ferritin, for treating anemia. The core hypothesis is that ferritin will outperform the traditional treatment with ferrous sulfate for delivering iron to the brain, and thus provide a more effective approach to managing iron deficiency and preventing the adverse neurodevelopmental effects of untreated anemia.

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But after five years of separating baby monkeys from their mothers, frightening pregnant monkeys, and reporting on the already known fact that obesity in pregnant humans can have deleterious consequences to their offspring, Coe has yet to provide any evidence that he has spent even a moment trying to make an iron-rich yeast.

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