Malaria
This page describes the organizational forces that limit change.  It explains how to overcome them when necessary. 

Power& tradition holding back progress
This page uses an example to illustrate how:
  • A business can gain focus from targeting key customers,
  • Business planning activities performed by the whole organization can build awareness, empowerment and coherence. 
  • A program approach can ensure strategic alignment. 
Be responsive to market dynamics
This page uses the example of HP's printer organization freeing itself from its organizational constraints to sell a printer targeted at the IBM pc user. 
The constraints are described. 
The techniques to overcome them are implied. 
Overcome reactionaries
Primary Navigation

The malarial arms race

Summary
Sonia Shah reviews the millennia old (500,000 years) malarial
This page reviews the strategy of setting up an arms race.  At its core this strategy depends on being able to alter, or take advantage of an alteration in, the genome or equivalent.  The situation is illustrated with examples from biology, high tech and politics. 
arms race
between Humanity, Anopheles mosquitoes and Plasmodium.  250 - 500 million people are infected each year with malaria and one million die. 
The Fever
In Sonia Shah's book 'The Fever' she introduces Plasmodium, a human and mosquito parasite is a long term relationship between the parasite and its host where the resources of the host are utilized by the parasite without reciprocity.  Often parasites include schematic adaptations allowing the parasite to use the hosts modeling and control systems to divert resources to them.   which developed from a single cell plant like an algae.  She postulates that in that form it found itself cohabiting on ponds with mosquitoes.  Eventually it was introduced into animal blood streams and thrived.  But it is only certain of the Anopheles among the many types of mosquito that Plasmodium survives successfully. 

Plasmodium has a complex life cycle with about seven stages.  It replicates rapidly and generates huge numbers of offspring.  There are a number of species, including malariae, vivax and falciparum.  Plasmodium spends part of its life within humans.  Introduced into the blood stream with the secretions of a feeding female Anopheles, they must avoid destruction by the immune system has to support and protect an inventory of host cell types, detect and respond to invaders and maintain the symbiont equilibrium within the microbiome.  It detects microbes which have breached the secreted mucus barrier, driving them back and fortifying the barrier.  It culls species within the microbiome that are expanding beyond requirements.  It destroys invaders who make it into the internal transport networks.  As part of its initialization it has immune cells which suppress the main system to allow the microbiome to bootstrap.  The initial microbiome is tailored by the antibodies supplied from the mother's milk while breastfeeding.  The immune system consists of two main parts the older non-adaptive part and the newer adaptive part.  The adaptive part achieves this property by being schematically specified by DNA which is highly variable.  By rapid reproduction the system recombines the DNA variable regions in vast numbers of offspring cells which once they have been shown not to attack the host cell lines are used as templates for interacting with any foreign body (antigen).  When the immune cell's DNA hyper-variable regions are expressed as y-shaped antibody proteins they typically include some receptor like structures which match the surfaces of the typical antigen.  Once the antibody becomes bound to the antigen the immune system cells can destroy the invader. 
, and find the liver is an emergent cellular system providing metabolic: Dietary compound metabolism and signalling: After gorging on sugar-rich foods the liver releases FGF21 hormone to dampen further eating activity; Detoxification, Regulation of glucose through glycogen storage (asprosin signalling from white adipose tissue); clotting, immune, exocrine and endocrine functions.  It is supplied with oxygen-rich blood via the hepatic artery and blood rich in semi-processed foodstuffs from the intestines & spleen via the hepatic portal vein.  It is constructed from: Hepatocytes which swim in the blood to process it, BECs, Stromal cells, Hepatic stellate cells, Kupffer cells, and blood vessels.  The embryonic endoderm cells invade the mesoderm to form the liver bud.  Subsequently the liver bud vascularizes and is colonized by hematopoietic cells.  The liver operates on a daily cycle allowing it time to recover from the stress of processing toxic substances.  There are over 100 disorders of the liver.  Obesity and diabetes are associated with increased prevalence of these liver disorders worldwide. 
.  Here they breed and transform into a form that can enter red blood cells.  Hiding in dead liver is an emergent cellular system providing metabolic: Dietary compound metabolism and signalling: After gorging on sugar-rich foods the liver releases FGF21 hormone to dampen further eating activity; Detoxification, Regulation of glucose through glycogen storage (asprosin signalling from white adipose tissue); clotting, immune, exocrine and endocrine functions.  It is supplied with oxygen-rich blood via the hepatic artery and blood rich in semi-processed foodstuffs from the intestines & spleen via the hepatic portal vein.  It is constructed from: Hepatocytes which swim in the blood to process it, BECs, Stromal cells, Hepatic stellate cells, Kupffer cells, and blood vessels.  The embryonic endoderm cells invade the mesoderm to form the liver bud.  Subsequently the liver bud vascularizes and is colonized by hematopoietic cells.  The liver operates on a daily cycle allowing it time to recover from the stress of processing toxic substances.  There are over 100 disorders of the liver.  Obesity and diabetes are associated with increased prevalence of these liver disorders worldwide. 
cells they invade the blood stream.  Most are destroyed by the immune system, but a few survive to enter red blood cells where they feed on hemoglobin.  Animals respond by destroying the infected blood cells in the spleen.  This gives rise to the typically distended spleens of infected humans.  With their oxygen supply diminished and toxic products of the hemoglobin breakdown present, humans with malaria are weak and suffer fevers.  Children and old people especially may die. 

As is typical in arms races, the combatants have developed
This page introduces a series of asymmetries which encourage different strategic approaches.   
The differences found in business, sexual selection, gamete structure, as well as in chess encourage escalations in the interactions. 
And yet the systems including these asymmetries can be quite stable. 
asymmetric
adaptations in evolutionary biology is a trait that increased the number of surviving offspring in an organism's ancestral lineage.  In Deacon's conception of evolution an adaptation is the realization of a set of constraints on candidate mechanisms, and so long as these constraints are maintained, other features are arbitrary. 
to each other:
  • Plasmodium induces infected female Anopheles to change their behavior.  Because of the risk of death, female Anopheles typically seek blood meals only when ready to breed.  Once infected the females become initially more cautious, giving the Plasmodium time to replicate.  Later the Anopheles seek many blood meals.  Their ability to obtain nutrients from animals is impacted by Plasmodium so they seek more meals helping vector Plasmodium between infected and uninfected animals.  Infected animals are particularly attractive to Anopheles. 
  • Humans developed various mutations, which made it difficult for the Plasmodium that was parasitizing them to attack the hemoglobin.  Duffy-less blood cells, those missing the Duffy chemokine receptor, in biological cells these proteins are able to span the cell membrane and present an active site which is tailored to interact with a specific signal.  When the receptor pairs with its signal, its overall shape changes resulting in changes in the part internal to the cell which can be relayed by the cells signalling infrastructure.  In neuron synapses one type of receptor (fast) is associated with an ion channel.  The other (slow) is associated with a signalling enzyme chain and modulates the neuron's response. 
    , were effective against vivax attack.  Hemoglobin E was harder for the parasite to digest, although Plasmodium falciparum has a mutation that enables it to digest E.  Sickle cell trait can limit the impact of even P. falciparum, although it carries the potential for generating sickle cell anemia. Humans also migrated out of Africa, to climates where Anopheles hibernates during the winter season.  That was too long a period for Africa's Plasmodium to survive initially.  Eventually Plasmodium developed a dormant stage where they could wait out the winter too.  Plasmodium vivax entered southern Europe 2000 years ago and northern Europe in the Middle Ages.  As Europeans sailed to the Americas they acted as a vector for Plasmodium vivax, which found niches in places like Panama, the Carolinas and Virginia.
  • As humans alter the environment around them varieties of local mosquitoes find their relative competitiveness changed.  In Africa, the Bantu created clearings to grow their diet of vegetables.  Without farm animals any mosquitoes in this new environment would have to focus primarily on humans.  Anopheles operate in species complexes which encourage evolution of new sub types.  Anopheles gambiae focused totally on humans improved the infection rate of Plasmodium falciparum.  This created an important advantage for Bantus with the sickle cell mutation when competing with other humans. 
Over time the effects of the arms race would be reduced lethal impacts of the local malaria which became chronic with all the typical attributes of such disease states. 

The results of the race are certainly not clear cut: 
  • Plasmodium falciparum is still a devastating killer of more than one million sufferers a year - and it is not known why this subset of infections is lethal. 
  • There are advantages for the chronically infected since human raiders are likely to be killed by the same malaria.  Bantu farmers with chronic malaria were able to overcome all other human groups in Africa.  Similarly European invaders to Africa between 1570 and 1825 were driven back by African malaria.  But as Bantu slaves with falciparum malaria were brought to the new world, malarial infections in the West Indies, Virginia, and the Carolinas made Europeans and natives permanently anemic.  Bantu slaves were not so impacted.  The militarily powerful Europeans found themselves dependent on, and threatened by, 'healthy' Bantu slaves.  In New England the climate, environment and local mosquitoes inhibited Plasmodium infections, until infected soldiers returning from the South provided a reservoir, and water mill deployment altered the ecology encouraging Anopheles species that supported malarial infections.  Once coal replaced water mills as New England's power source malaria disappeared. 
  • But mining, logging and farming typically transform mosquito environments creating access to new niches and destroying others, and wars are powerful catalysts, an infrastructure amplifier.   for malaria when they converge infected humans, and transform environments.  Shah explains that in England from 1400, malaria was endemic to Kent and Essex, with death rates as high as sub-Saharan Africa, but in the 19th century improved drainage and four crop rotation agriculture wiped it out.  Stopping the use of fallow fields, and not killing all the farm animals each winter, reduced the habit for the mosquitos, while leaving animals as targets for the mosquitos reducing the probability of Plasmodium being vectored from one human to another. 
Evolved resistance to plasmodium exists in a variety of species.  Two plants: the Cinchona tree, and the Artemisia wormwood; have developed sophisticated counter measures, quinine and artemisenin, that have been optimized and made robust during the long malarial arms race. 

Quinine
Shah describes how the Dutch used their knowledge of horticulture to isolate Cinchona trees producing high quantities of quinine.  It was a significant achievement, since they had to understand the constrained growing conditions, extraction process and obtain the closely guarded trees from the Spanish Andes.  But having a monopoly on high volume quinine production the Dutch priced the quinine so highly that mass treatment was cost prohibitive.  With the additional confusion about effective dosing most supplies were too weak to provide protection.  Some governments even reserved effective doses for important people.  When effective doses were deployed the patients disliked the dangerous side effects and often refused treatment.  This typically left enough malarially infected humans to sustain the disease. 

Once war demonstrated the threat to America of the loss the Dutch monopoly quinine supply, US is the United States of America.   chemists were tasked with building synthetic quinine equivalents.  These solved the cost problem and the products had limited side effects.  They were deployed prophylactically but they were simplistic attacks.  Plasmodium, which has evolved so as to maintain diverse populations which coexist and rapidly responded to the selection pressure, responded with increased presence of resistant forms.  Scientists were surprised, initially assuming that the target populations were avoiding treatment.  Forced treatments built resentment and anger is an emotion which protects a person who has been cheated by a supposed friend.  When the exploitation of the altruism is discovered, Steven Pinker explains, the result is a drive for moralistic aggression to hurt the cheater. 
as the treatments failed to protect. 

Artemisinin
China, responding to the Vietnam War, isolated Artemisinin.  It was highly effective as a treatment, but its biological basis and initial Chinese identification left it ignored by western health experts for 20 years.  Eventually it was leveraged by Novartis but the price was high and black markets deployed low strength solutions which have allowed Plasmodium to stockpile resistant mutations. 

An effective drug treatment strategy would need to take account of local geographic niches, types of Anopheles, and local human culture is how we do and think about things, transmitted by non-genetic means as defined by Frans de Waal.  CAS theory views cultures as operating via memetic schemata evolved by memetic operators to support a cultural superorganism.  Evolutionary psychology asserts that human culture reflects adaptations generated while hunting and gathering.  Dehaene views culture as essentially human, shaped by exaptations and reading, transmitted with support of the neuronal workspace and stabilized by neuronal recycling.  Sapolsky argues that parents must show children how to transform their genetically derived capabilities into a culturally effective toolset.  He is interested in the broad differences across cultures of: Life expectancy, GDP, Death in childbirth, Violence, Chronic bullying, Gender equality, Happiness, Response to cheating, Individualist or collectivist, Enforcing honor, Approach to hierarchy; illustrating how different a person's life will be depending on the culture where they are raised.  Culture:
  • Is deployed during pregnancy & childhood, with parental mediation.  Nutrients, immune messages and hormones all affect the prenatal brain.  Hormones: Testosterone with anti-Mullerian hormone masculinizes the brain by entering target cells and after conversion to estrogen binding to intracellular estrogen receptors; have organizational effects producing lifelong changes.  Parenting style typically produces adults who adopt the same approach.  And mothering style can alter gene regulation in the fetus in ways that transfer epigenetically to future generations!  PMS symptoms vary by culture. 
  • Is also significantly transmitted to children by their peers during play.  So parents try to control their children's peer group.  
  • Is transmitted to children by their neighborhoods, tribes, nations etc. 
  • Influences the parenting style that is considered appropriate. 
  • Can transform dominance into honor.  There are ecological correlates of adopting honor cultures.  Parents in honor cultures are typically authoritarian. 
  • Is strongly adapted across a meta-ethnic frontier according to Turchin.  
  • Across Europe was shaped by the Carolingian empire. 
  • Can provide varying levels of support for innovation.  
  • Produces consciousness according to Dennet. 
.  A complex research problem, but otherwise the results of drug treatment would, and did, appear chaotic. 

DDT
The initial success and simple method of deployment, of DDT (dichlorodiphenyltrichloroethane) is an organochloride insecticide. 
in destroying the Anopheles vector also diverted interest from solving the many complex research and deployment problems with Plasmodium drug treatments.  Its success drove a global malaria eradication plan.  However, complications soon emerged.  Saved populations death rates fell, but birth rates didn't leaving the recipients countries with exploding populations.  DDT's effect on insect populations caused unpredictable effects.  Its concentration in the food chain was also found to impact primary predators.  US is the United States of America.   funders cut DDT eradication budgets. Anopheles adapted!

Community response to malaria
Shah explains that the interaction with malaria varies between communities:
  • Human psychology rates unknown threats more highly than familiar chronic ones.  Endemic malaria sufferers respond with disinterest.  The cause of malaria is far from obvious.  Sufferers often get bitten by mosquitos but seldom get ill.  The West's position of mosquito vectored malaria is consequently doubted.  Western treatments are not taken prophylactically in many 3rd world countries.  Sufferers manage and stockpile treatments.  Different medicines are deployed depending on the severity of any illness.  Light malarial symptoms could be allocated aspirin.  Bad symptoms would get stronger drugs, but only while the symptoms are visible.  In these societies politicians respond to their electorate's priorities by treating malaria as of little significance.  Funding is directed to other medical necessities.  The amplification of other disease effects due to malaria is doubted by the medical establishment. 
  • The complexity, M. Mitchell Waldrop describes a vision of complexity via:
    • Rich interactions that allow a system to undergo spontaneous self-organization
    • Systems that are adaptive
    • More predictability than chaotic systems by bringing order and chaos into
    • Balance at the edge of chaos 
    of the disease also requires high caliber doctors, but such people with the skills seek higher salaries in other countries and fields.  Alignment of first world salaries and proven skills drains resources from a focus on poor malarial sufferers.  Doctors do not see the disease as a good carrier path. 
  • Western malaria treatment regimens are centralized, inflexible, and costly. The doctors focused on the disease rather than the illness.  Only desperate families with the worst symptoms seek their aid.  Centralized treatment ensures amplification of the malarial situation near the clinic.  The result is a poor correlation between western treatment and recovery from malaria.  Malarial bed nets are annoying to use, and misapplied.  Most children suffering from malarial symptoms are taken to local healers.  The high recovery rate of this chronic disease anchors the sufferers faith in the local healers.  
  • West's interest in malaria has often peaked when the disease limited the ambitions of politicians and undermined their armies of conquest.  America justified DDT (dichlorodiphenyltrichloroethane) is an organochloride insecticide. 
    as aid to combat communism. 
Shah describes how Western science struggled to define malaria due to its complex adaptive nature.  A holistic strategy was required to understand the total system and how it emerges.  The
Peter Medawar writes about key historic events in the evolution of medical science. 
traditional scientific method
works poorly in this situation.  Only in countries, such as Italy, where the impact of malaria and the various scientific capabilities: experimentalists, clinicians, naturalists; were all present could authorities and powerful, impacted, businesses focus a
This page discusses the program strategy in a complex adaptive system (CAS).  Programs generate coherent end-to-end activity.  The mechanism is reviewed. 
cross domain strategy
.  But
This page reviews the inhibiting effect of the value delivery system on the expression of new phenotypic effects within an agent. 
phenotypic alignment
in science ensured the individual domains resisted this approach and its discoveries.  Most money was allocated to large research labs in first world cities far from the communities suffering in the third world. 

As the world has become more interconnected, and man has reshaped the environment malaria has benefited.  Eradication strategies ebb and flow, as the financial system cycles.  So far our ability to align the cross field resources to iteratively undermine Plasmodium in key hot spots has been weak.  Shah warns against the ever popular big push currently promoted by the Gates foundation and Jeffrey Sachs.  

Complex adaptive system
This page introduces the complex adaptive system (CAS) theory frame.  The theory is positioned relative to the natural sciences.  It catalogs the laws and strategies which underpin the operation of systems that are based on the interaction of emergent agents. 
John Holland's framework for representing complexity is outlined.  Links to other key aspects of CAS theory discussed at the site are presented. 
(CAS) theory
should apply directly to malarial systems.  The issues Shah identifies are exemplars:

The Fever highlights the adaptive nature of the malarial system and the consequent issues with depending on simplistic approaches and treatments. 






  


Market Centric Workshops
The Physics - Politics, Economics & Evolutionary Psychology
Politics, Economics & Evolutionary Psychology

Business Physics
Nature and nurture drive the business eco-system
Human nature
Emerging structure and dynamic forces of adaptation


integrating quality appropriate for each market
 
This page looks at schematic structures and their uses.  It discusses a number of examples:
  • Schematic ideas are recombined in creativity. 
  • Similarly designers take ideas and rules about materials and components and combine them. 
  • Schematic Recipes help to standardize operations. 
  • Modular components are combined into strategies for use in business plans and business models. 

As a working example it presents part of the contents and schematic details from the Adaptive Web Framework (AWF)'s operational plan. 

Finally it includes a section presenting our formal representation of schematic goals. 
Each goal has a series of associated complex adaptive system (CAS) strategy strings. 
These goals plus strings are detailed for various chess and business examples. 
Strategy
| Design |
This page uses an example to illustrate how:
  • A business can gain focus from targeting key customers,
  • Business planning activities performed by the whole organization can build awareness, empowerment and coherence. 
  • A program approach can ensure strategic alignment. 
Program Management
| Home

Profiles | Papers | Glossary | E-mail us