Knowledge Accumulation and Vaccine Development

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Knowledge Accumulation and Vaccine Development

• Ohid Yaqub
• May 2009

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Vaccines are very desirable

• Have prevented more premature deaths, permanent
  disability and suffering than any other medical
  discovery or intervention (Andre, 2001)
• Prevention rather than treatment
• Cost effective (cgdev.org)
• Promotes health equity (Chairman of WHO, 2000
  Bishai et al., 2003)

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Need for vaccines for big killers

• HIV, TB and malaria account for half of global
  infectious disease burden
• Kills nearly 25,000 people every day

Sources www.unaids.org, www.malaria.org,
www.who.int.
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Explanations for variation

• Market failure
• Overshadowed by big pharma
• Oligopsony
• Liability, regulation
• IPR
• Neglected diseases
• Social resistance
• Political sensitivity.
• Weak understanding of pathogenesis

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Vaccine Innovation Policies

• Pull
• Patents
• Tax credit on sales
• Advance Purchase Commitments (Kramer 2003)

• Push
• Public funding of basic research (Archibugi and
  Bizzari 2003)
• RD Tax credits
• Fast track regulation (Abraham 2008)

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Grandfathers who went beyond push-pull
Demand pull (Schmookler)
Science push (Bush)

• Search routines (NW82), technological regimes
  (NW77)
• Technological paradigms and trajectories
  (Dosi82)
• Technological Knowledge (Pavitt99)

• Specific, complex, sometimes tacit
• Cumulative
• Reliable, robust, shared

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Central argument

• Vaccine innovation requires technological
  knowledge
• Cannot be obtained as-is from science
• It must be generated in a testing regime with a
  social vision.

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Social Visions

• Diagnosis and disease specification bringing
  together previously unrelated phenomena
• Problematising the disease
• Identifying / characterising the agent
• How is the disease caused?
• Cyclical expectations
• Unexpected learning from nature
• How can we intervene reliably?

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Testing Regimes Step-wise knowledge accumulation

• Intermediate conditions
• Instrumentalities
• Institutional Structure

• (learning vs relevance)
• (instruments, skills, capabilities)
• (regime, networks, law, ethics, regulation,
  social norms, policies)

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Increasing indirectness of innovation and
learning process

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Polio diagnosis

• Teething
• Infants
• Morning paralysis
• Tephromyelitis
• Acuta parenchymatose
• Infantile paralysis
• Poliomyelitis
• Clustering of cases

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Vision

• Viral agent discovered
• Public health environment
• Flexner
• Skills shortage for diagnostic testing
• 1916 epidemic 27,000 7,000 dead, 1/3 in NY
• Very conspicuous
• Seasonal occurrence
• Disfiguring nature
• Iron lung
• All social classes
• Quarantine unlikely to work

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• In 1921, Roosevelt changed the way disabled
  people were viewed
• a cripple is detestable in character, a menace
  and burden to society, who is apt only to
  graduate into the mendicant and criminal classes
• Carefully managed PR
• Set up Warm Springs Foundation
• OConnor
• Birthday Balls raised 1m in 1934.

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Brodie-Kolmer failures

• Formalin treated mashed up spinal cord
• Live virus from spinal cord treated with
  chemicals and refridgeration
• A veritable witches brew, kitchen chemistry
• Not tested on many animals
• Killed or paralysed 1000s of children
• Traumatised field

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The National Foundation strengthened the testing
regime

• Renamed from Warm Springs
• finance, lead, direct and unify the fight of
  every phase of this sickness
• 630m between 1938 and 1962
• 1947, OConnor appointed Director of Research
• Conferences and round table discussions
• to encourage communication and
  cross-fertilisation in field notable for its lack
  of both

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• Only an appalling few were really trying to
  solve the problem of polio. If real progress were
  to be made, more exact methods of research would
  have to be clearly defined, procedures and
  techniques developed to permit attaining those
  objectives and individuals would have to
  sacrifice their right to roam the field
• 11point plan

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• Monkey Business
• Sourcing, Housing, Feeding
• Tissue Culturing
• Sourcing, Training, Funding
• Not an electrifying piece of news
• Tighter learning feedback loops
• Better quality virus, safe and clean
• Reduced monkey need
• Standards and criteria for diagnosis
• Virus Typing
• dull and menial drudgery
• Challenge stock
• Multi-year multi-university multi-million dollar
  program using 30,000

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Passive Immunisation trials

• Translation of subjective design aims into
  objective specifications
• Developing capabilities
• How much enough for humans?
• How long do they last?
• Grading severity of paralysis
• Blind controls, dosage, syringes, packaging,
  venue, site on the body.

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Killed trials

• More risky, borne by few sections of society
  low-grade idiots and imbeciles
• Foundation mediated concerns about placebos,
  fetish of orthodoxy
• Foundation mediated rivalries quackery
• Taking calculated risks

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Live vaccine trials

• Scarcity of testing resources
• Does the vaccine cause polio?
• Vaccine as part of a wider health system
• Path dependency

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Policy Conclusions

• Instrumentalities need to be nurtured with
  training from experienced vaccinologists
• Investigator-initiated research for innovation
  can lead to fragmented output so governing
  institutions are needed to accumulate
  technological knowledge
• Slack yet strategic funding for contracted
  research ensures mundane research gets done
• Well developed testing regimes are likely to be
  expensive
• Engage countries where the vaccine is likely to
  be used

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Polio cases by year and milestones
Salk vaccine trials
Roosevelt and OConnors daughter infected
Cutter
Sabin vaccine licensed
Natural Sterilising Immunity trough
Start of co-ordinated RD