Marker discovery

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Governance of Molecular Breeding
Marker discovery
How does the way this is structured and organised

Marker-assisted selection(Molecular
plant-breeding)
New crop varieties
affect the characteristics and value of these?
Farmers
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Outline

• Molecular breeding plant breeding that is helped
  by the use of molecular markers
• Also commonly known as marker-assisted selection
• Molecular markers
• What are they?
• Why are they useful?
• How are they discovered?
• Governance issues in marker discovery
• Global or local relevance?
• Appropriate performance indicators
• Organisational issues
• Marker application in practice an Indian seed
  company
• Products depend on commercial criteria, and IP
  context
• Commercial management of breeders
• Germplasm commodity or common heritage?

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What are molecular markers?

• They are identifiable DNA sequences, found at
  specific locations of the genome, and transmitted
  by the standard laws of inheritance from one
  generation to the next.
• Their presence can be detected by DNA assay and
  predicts the presence of the genes with which
  they are associated

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Why are MMs useful in plant breeding?

• MAS can extend traditional breeding by providing
  solutions when phenotypic screening is
• Technically difficult and so expensive
• Testing a plant for pest resistance involves
  maintaining a pest population, and exposing
  plants to a standard pest attack
• Impossible
• Breeding for disease resistance in a country
  where the disease is not present
• Pyramiding several different genes for
  resistance to the same pest into a single plant

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• MAS can increase the efficiency of traditional
  breeding programs by
• speeding up the time of varietal release,
• lowering plant population requirements,
• eliminating costly field evaluation.
• Many valuable traits are only expressed by mature
  plants, but since the associated DNA is present
  in seedlings, there is no longer any need to grow
  a large population in order to find the few
  plants with the desired trait.

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Marker discovery

• A plant with the trait of interest is crossed
  with another that does not have the trait
• Their progeny are examined to see whether they
  display the trait, and their DNA is examined to
  identify differences between the DNA of those
  that do and those that do not have the trait
• This costs up to US50,000 per marker, depending
  on the equipment available
• Markers discovered in this way may or may not
  apply to other varieties of the same species, or
  indeed to plants of other species
• Before using a marker in a variety different from
  that in which it was discovered, it is necessary
  to test whether it applies in the new variety,
  that is, to validate it

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Marker discovery global or local relevance?

• Since marker discovery is expensive, it should
  concentrate on traits that are important to large
  numbers of farmers
• China (university department) the dean explained
  that the problems addressed were well-known, so
  there was no need to consult farmers nor study
  local contexts
• He supported the choice of problems by quoting
  aggregate statistics for China as a whole

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Context matters in marker discovery evidence
from Vietnam

• An institute in Vietnam has discovered markers
  for genes that protect rice from blast (most
  serious disease of rice)
• And also from Brown Plant Hopper (BPH), most
  serious insect pest of rice
• Very similar criticisms of these projects were
  made by pathologists and by entomologists working
  in the same institute

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Rice blast the need to take account of context

• Vietnamese pathologists argued that
• The fungus that causes blast occurs in different
  forms
• Resistance genes that are effective against one
  form may fail against another
• Therefore, to protect rice in a given region it
  is necessary to
• Find out which forms of the fungus are present in
  the region in question,
• Then list the rice resistance genes that are
  effective against all forms of the fungus present
  in that region,
• Focus research efforts (marker discovery, then
  breeding) on the resistance genes that are
  relevant to that region
• In other words, they argued that marker discovery
  needs to be
• Context-specific, and
• Interdisciplinary (since pathology has a part in
  defining the project)
• Entomologists presented a similar argument, since
  BPH occurs in a number of different biotypes,
  each sensitive to different R-genes

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Importance of context in marker discovery

• Resistance to rice blast
• Resistance to BPH (rice)
• India a scientist working in the public sector
  identified markers for resistance to gall midge
  (damages rice)
• These markers were patented, with help from
  Company A
• Company A then found that they were ineffective
  against the gall midge biotypes that were
  important in their main markets

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Performance indicators for marker discovery

• Marker discovery is close to basic science, so
  is often judged by scientific criteria
• China the scientists interviewed were mainly
  rewarded for publishing research in high-impact
  journals
• Vietnam research on blast was financed by
  Rockefeller Foundation
• Payment/rewards to scientists were only weakly
  linked to user benefits
• India scientist (gall-midge markers) was
  rewarded for having a patent on his work
• The practical value of this work was irrelevant

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Some organisational issues in marker discovery

• Links with users and local contexts
• How strong should these links be?
• How locally focussed?
• Links with experts inside and outside the
  research institute
• Vietnam role of pathologists or entomologists in
  defining project direction
• China relationship between university
  departments and seed companies (who have a
  different technological agenda)

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Molecular breeding in practice

• Company A Indian-owned, founded in 1989
• Biotechnology work began in 1999
• Major issues
• Access to markers and germplasm
• Kinds of product that are developed
• Only profitable product types
• Management of breeders

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Access to markers and germplasm

• Markers are generally in the public domain,
  accessible on-line
• Germplasm commodity or common heritage?
• Indian public sector generally shares seeds
  freely
• But becoming more cautious with trend to
  commodification
• Personal contacts are becoming increasingly
  important
• Breeders make strategic use of their own
  germplasm
• Other potential suppliers (e.g. Cornell) demand
  fees that Company A cannot possibly pay
• China exports hybrid seeds but restricts export
  of parental lines and some other material (e.g.
  BPH)
• Company A must validate Cornells markers in
  locally-available germplasm

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Products developed by Company A

• Company A survives by selling seed, so supplies
  only hybrids, not OPVs, to prevent farmers from
  saving seed
• Past experience of selling OPV rice seed, but
  they lost money so will not do that again
• Cotton consensus that OPV cotton performs better
  than hybrid cotton, but in the absence of
  effective IP protection only hybrid cotton seed
  is commercially attractive
• Contrast with North America

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Hybrid rice in South India

• Fragrant rice is not popular in Indias main
  rice-producing region, the South
• Until recently (2000), all materials available
  for producing hybrid rice were fragrant (based on
  basmati)
• This is one reason why only 1 per cent of Indias
  rice area is under hybrid rice!
• Company A began working on non-aromatic hybrid
  rice in 2003 and commercialised it a year later
• Major opportunity responded by trebling the size
  of the rice-breeding function and beginning an
  ambitious programme to develop 50 new hybrids!
• This increased the breeders workload, and
  managements need to maximise breeder productivity

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Management of breeders in Company A

• Breeders are highly skilled (PhD-qualified) and
  highly paid workers
• They retain considerable control over their
  activities at work
• Maintaining their own germplasm collections helps
  them to retain their position
• Provides basis for promises used to negotiate
  improved working conditions, e.g. Dr. R.
• People may be recruited as a means of gaining
  access to their (or their employers) germplasm
• Helps to make their work opaque to management and
  so resist deskilling
• Breeders therefore wish to retain control of key
  breeding materials
• Management has responded by setting ambitious
  targets and making breeders compete against each
  other
• Breeders have a heavy workload, with rewards for
  success

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Ambivalence of breeders towards molecular markers

• Breeders fear that the new technology could
  dilute their control over key materials
• Validating markers in such materials involves
  passing them to the Biotechnology lab, after
  which they would be available to the company as a
  whole
• General fear that the new technology might
  devalue their skills
• However, they recognise that MAS could help them
  to achieve their goals
• Difficulty of introgression into hybrid rice
• Implications for characteristics of products that
  may feasibly be developed?

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Conclusions I

• Molecular breeding offers important benefits to
  plant breeding, and so to all farmers who could
  benefit from new crop varieties
• Suitable governance and management mechanisms are
  needed in order to maximise these benefits
• Since marker discovery and marker application are
  distinct activities that may well be performed in
  different institutions, they require distinct
  forms of governance

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Conclusions II

• Marker discovery is expensive, but offers
  considerable economies of scale.
• Policy-makers have naturally (and rightly)
  concentrated these activities in a small number
  of institutes in order to capture scale
  economies.
• Such concentration may lead to a loss of focus on
  user needs, and a consequent lack of relevance
• To correct this tendency, projects need to begin
  by specifying the geographical area(s) and farmer
  type(s) who are to be helped. Project objectives
  should be defined in the light of generalisations
  that apply to a large proportion of these users
• Forms of governance that might correct this
  problem include appointing a board of trustees
  that includes representatives of organisations
  that
• serve those farmers who are intended to be
  helped, or
• are likely to conduct breeding programmes using
  markers discovered by the project

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Conclusions III

• MAS, like other forms of plant breeding, may be
  carried out in a range of contexts
• Policy-makers tend to see plant-breeding as an
  activity that is best located in the private
  sector, because public-sector agricultural
  research has well-known difficulties in achieving
  client focus
• However, the experience of Company A demonstrates
  that
• Many crop varieties that would be socially
  desirable are not profitable and so do not get
  developed by the private sector
• Forms of management that are widespread in the
  private sector may hinder the introduction of MAS
  and reduce its effectiveness
• The trend to commodify germplasm limits the value
  of MMs that are in the public domain and reduces
  the practical value of germplasm collections.
• However, the introduction of effective IP systems
  could create incentives for the private sector to
  create socially desirable crop varieties