Thursday, May 27, 2021

ME Research - Mind expanding on AC



AC means air conditioning. It is basic to development. Tall buildings are normally sealed against outside air. It also concentrates disease starters, virii and bacteria1A FAVORITE ARM CHAIR RESEARCH OF MINE EXPLAINS THE VAST COVID-19 LOSS IN DEVELOPED WORLD AS UNJUST REWARDS OF AC!



As an international collaboration of researchers from institutions in the U.S., Canada, Europe and Singapore, we developed a simple, cheap, scalable solution to keeping people comfortable without regulating indoor air temperature.


What's ME about this? Forever, I Thought of AC as comfortable temperature of Air. It is not, never mind thermostat and likes! Heat flows by conduction, convection and radiation. If you are in a surrounding with hot inner surfaces, then radiation is the first mode. Trivial to me, the inventor of generic triage!, only excusable by rec ency effects That is how you feel warm in winter air in sun!

So the point is to only do AC on surfaces, flowing air freely to natural state! You can run AC with windows open! Cost 50% energy! If that ain't ME, nothing is! This is century 21!

Now triage has another ME application. Why do Ramdev medicine (essentially ayurvedic cocktail of antiseptics), HIV cocktail of drugs and latest cure for Covid-19 (that uses cocktail of two monoclonal antibodies) work? In each case. The target disease is partially cured by each component, but removing just 1 cause simply means the disease depends on other paths. Testing will not certify each component as cure. But it will a cocktail!



Tuesday, May 25, 2021

Return to attributed Grammars

 


This is likely my "joy of living" as an elder away from youth indiscretions who have accepted a new stage in life but do not admit to limitations of unbeliever in shastra! Why would a 66-year-old person return to his youth roots?

1 He wishes to make, expected anonymous, significant in his terms, to vitaDAO, the magic company that will research in only central meaningful subject in his existence - extension of healthy life , to be a NFT IMM smart DAO, original development to become the guiding light of next human paradigm, which will value contributions from the only motive other than money; self application of the research. There is a joy similar to discovery of religion by still agnostic me. It is being done on blockchain with artifacts to make even origination DAO provably corruption free DAO, uses essential attributed grammars and can use the meta-compiler like Yacc to develop corruption-free.


2 He has new ideas to try, extending grammars in context-sensitive ways without introducing null production which make the result undecidable.


3 benefit from the magic insight of context sensitivity by still becoming decidable when null productions are introduced by making null derivation only one non-terminal and at the end only! This gives decidable deterministic translations, essential to upgrading crispr cas9 upgrades to DNA with proven limit of DNA sub string replaced.


4 Planet does not have tools to instantiate and use meta-compilers for building GUI, context-sensitive attributed grammars with inherited and synthesized attributes don't exist, nor do event based languages for concurrent programming like internals of UNIX, or methods to record and design genetic manipulations. Provides me with an achievable target for the rest of my life.


5 I am an engineer, not a scientist and have the luxury of a design in my mind. If little is known about a subject, paradigm shift happens, A sub paradigm on the other hand imposes a new hitherto unknown method for solution of a sub problem only, talked down by the supposed wise.


Stephen C. Johnson was my boss who rarely but incisively explained the story of Yacc, I consider it as important to spread of UNIX and textbook example of conversion of concurrent programming to linear form that all languages apply. Concurrency is easy to see, there is limited conflict between concurrent parsing of whole program, bottom-up in concurrent fashion.


If one represents the currently applicable context free production with a dot to mark the separation by the Parser seen on the left and still to be seen on the right, called an item, then the state of the compiler is a list of items. The next parser action depends on the bottom-most item. Depending on the look ahead which is the first of the non-terminal in the RHS, something that can be precomputed. The parser action can be shifted for some possibilities or reduce when a complete RHS has been seen. If more than one action then a conflict - shift/shift is just shift, reduce/reduce is bad grammar, shift/reduce can be done by semantics in many cases. Synthesized attributes are best considered as results, inherited as arguments or common position dependent values on the stack like merging of fields in language inheritance.


The result is incorporation of semantics in grammar itself without getting the full power of attributes but sufficient to solve every real problem. The metacompiler emits errors on shift-reduce conflicts, but these can be solved in actions. By adding conflict productions to the item being scanned, these errors will not show in the result.


index ::= expr {...} {+type = $expr..type} #- stack has 2 elements $expr and $type.

vitaDAO


 

 VitaDAO Whitepaper V0.1
Tyler Golato1, Paul Kohlhaas1
Draft open for public and community comment
Abstract
VitaDAO is a new cooperative vehicle for community-governed and decentralized drug development.
Our core mission is the acceleration of R&D in the longevity space and the extension of human lifeand
health-span. To achieve this, VitaDAO utilizes a combination of novel governance frameworks
and decentralized autonomous organizations (DAOs), non-fungible tokens (NFTs), and financial
engineering tools such as algorithmic automated market makers (AMMs) that run via the Ethereum
blockchain. Today, the biopharma industry is booming with unprecedented late-stage investment
inflows, particularly in the longevity space. However, critical early-stage funding is severely lacking
and incentives between patients, researchers and industry are misaligned.
At its core, biopharma value creation is composed of intellectual property rights and research data.
Research and development has become prohibitively expensive and siloed, partially due to how
intellectual property business models work in monopolizing innovation through patent portfolios.
These mechanisms prevent the open sharing of research data, inherently disincentivizing collaboration
and transparency. They prevent the public and patients from having any real ownership in therapeutic
IP, even though their tax dollars fund much of the early-stage development. Outside of grants to fund
basic research, early-stage funding for drug development is extremely limited, and when drugs do
finally make it to market, there are strong incentives for price gouging.
VitaDAO is an open cooperative that anyone can join and support. Its goal is to acquire, support, and
finance new therapeutics and research data in the longevity space. The collective will directly hold
legal IP rights to novel early-stage projects and may develop a growing portfolio of both IP and data
assets represented as NFTs. These data assets can be made available and monetized in novel data
marketplace structures such as Ocean Marketplace, promoting both open science and novel business
models.
Ownership and governance of the VitaDAO is relegated through VITA tokens. The token can be
obtained by contributing resources, work, or funds to VitaDAO. Ownership of tokens allows its holder
to engage in decision-making and governance of VitaDAO’s research, signal support for specific
initiatives, and govern its data repositories and IP portfolio.


Table of Contents
Abstract 0
Table of Contents 1
1 Introduction and Problem Statement 2
1.1 Intellectual Property in Biopharma 2
1.2 The Evolution of Pharma and the Valley of Death 2
1.3 Longevity Will Transform Our Approach To Medicine 3
2 Solution 4
3 Core Architecture 5
3.1 Organization and Governance 5
3.2 Genesis Bootstrapping & Liquidity 6
4 Holding and Managing IP and Data Assets 6
4.1 Intellectual Property Rights 6
4.2 Data Assets 7
5 Staking & Signalling 7
6 Genesis & First Project Lifecycle 8
7 Exit Scenarios and IP Commercialisation 8
8 Open Research Questions 9
9 Conclusion 9
References 10
1
1 Introduction and Problem Statement
Current biopharma business models carry severe limitations and R&D inefficiencies at the cost of
those who should be the core stakeholders: patients in need of medication and researchers discovering
these molecules.
1.1 Intellectual Property in Biopharma
Fundamentally, value creation in biopharma is driven by two core assets: intellectual property (IP) and
research and development (R&D) data (Saha, 2011). When companies explore a use case for a new
therapeutic, they patent their discoveries to gain IP. This enables them to secure future revenue and
recoup the high costs of R&D. As companies invest billions of dollars into generating data to bring
therapeutics to market, they offset this by selling equity ownership or royalty rights (Olivier, 2020).
While IP is designed to incentivize innovation in theory, intellectual property ownership as a business
model has barely evolved in the past century and is largely analog, operating through extensive legal
contracts and bureaucratic complexities. Today, IP is one of the most valuable asset classes but
remains largely illiquid, hard to transfer, and rigid.
Moreover, the need for monopolistic IP ownership of both patents and data within biopharma
companies creates secrecy, centralization and disincentivizes much-needed collaboration and open
research in the scientific community, which could bring down the rising cost of drug development
(Bookbinder, 2020). Perfectly good drug candidates often fall to the wayside for organizational,
political, or competitive reasons. This concentration of research efforts leads to the high R&D cost
and long time-to-market that pharma is known for today. Pharma tends to only share positive R&D
data -- companies waste enormous resources ignorantly repeating each others’ failures. Under the
current system, incentives for open science, collaboration, and data sharing are severely lacking
(Ali-Khan, 2017).
On a macroscopic scale, this model leads to incentive misalignment and information asymmetry. IP
owners and sellers seeking to monopolize commercial value are not incentivized to report negative
research data. This creates a principal-agent dilemma and, in part, leads to a phenomenon coined the
“reproducibility crisis” (Sherkow, 2017). Thus, side effects or indicators of lower effectiveness of the
owned compounds are downplayed in favor of profit maximization, and valuable research findings are
“lost” for the broader scientific community and not considered during patient treatment. More
democratic, open, and transparent models are needed with a wider inclusion of stakeholders.
Lastly, the current financing and investment landscape centralizes and restricts access and
participation to early-stage biopharma from its most important stakeholders: patients and researchers.
In the US, only accredited investors may finance early-stage ventures. The market is opaque, and no
singular or efficient marketplace exists to discover or access these opportunities in a transparent
fashion.
1.2 The Evolution of Pharma and the Valley of Death
The process of drug development in the pharmaceutical industry is undergoing a significant shift in its
industrial organization. Increasingly, smaller biotech firms leverage recent academic research in the
life sciences to develop new drugs, which are then acquired by pharmaceutical giants using their
2
access to low-cost capital to purchase expertise (Lo, 2021). The number of biotech startup companies
formed due to technology licensing has shifted dramatically in recent years - from 145 in 1994 to 278
in 2000 and 1,024 in 2016. Of the 30 top-selling drugs worldwide in 2000, only five were traceable to
universities; the remaining 25 were developed by big pharma. By 2018, more than one-half of the top
30 drugs were sourced from academia (Lo, 2021). Thus, biotech universities are increasingly proving
to be untapped goldmines of valuable IP, yet often these assets are not investable until a startup is
spun out.
Assets from universities that are not out-licensed or spun out into startups remain in a difficult limbo,
known as The Valley of Death, where they often fail to move forward (Seyhan, 2019). Many of these
technologies are extremely valuable to patients, and because of this system, they will ultimately never
serve the populations they were intended to. These assets require investment and capital injections at
an earlier stage, and new open commercialization models are desperately needed to incentivize their
development.
1.3 Longevity Will Transform Our Approach To Medicine
The longevity field has the power to transform our global healthcare system completely. Age-related
diseases are among the most significant contributors to our global health burden and are responsible
for the highest costs incurred by healthcare systems (WHO, 2020).
The longevity space is experiencing a tremendous boom, in part because of its ability to address this
problem. The space is evolving rapidly in terms of understanding the aging process and its capacity to
develop health- & life-extending therapeutics (Scheibye-Knudsen, 2020). It is now a routine
procedure to reverse the aging of human cells in the laboratory dish. Correspondingly, the economics
of investing in longevity are more attractive than ever. There are 100s of new companies and funds
dedicated to research and product development in the fields of senolytics, telomeres, stem cells,
mitochondria, and gene editing (Pfleger, 2021). These are some of the core domains from which
therapies that increase lifespan will emerge.
The rush of investment into the field has the potential to rapidly accelerate these developments but
also comes with distinct problems. The “centralization” of aging research by large institutions and
billionaires has the potential to create the same problems and pitfalls that plague the pharmaceutical
industry: intransparency, restricted access, and concentrated control over therapeutics that should be
made widely available to anyone at an affordable price.
We believe the future of health- and life-extension should be open, collaborative, and
community-owned. We see longevity as an entirely new approach to medicine, one that has the
potential to prevent, as opposed to treat or intervene. This approach will completely change the way
the world approaches medical care and will profoundly impact society.
3
2 Solution
We propose the creation of VitaDAO: the first fully open and community-owned, transparent
intellectual property collective in longevity.
Members of the public can become co-owners of VitaDAO and its IP by purchasing VITA through
contributing funds, valuable research data, IP assets or performing services for VitaDAO. Ownership
and governance of VitaDAO is relegated through VITA tokens. VITA enables its holder to engage in
decision-making and governance of VitaDAO’s research, signal support for specific initiatives and
govern its data repositories and IP portfolio.
VitaDAO will acquire intellectual property rights, data and commission research to further develop
those assets. Further, it will monetize its intellectual property. In summary, VitaDAOs core assets can
consists of:
1. Intellectual property, patents and licenses to therapeutic research projects.
2. Data assets generated by funding R&D around its research projects.
3. Funds stored in its treasury, as well as unissued VITA tokens.
Intellectual property and data assets will be virtualized and represented as Non-Fungible Tokens
(NFTs), which are explained in more depth in Section 4.
In order to acquire and finance specific research proposals, VitaDAO members may elect to issue
tokens on a continuous or per-project basis, using automatic market makers (AMMs) like Balancer
Liquidity Bootstrapping Pools that enable a fair and transparent participation for prospective
members.
4
3 Core Architecture
3.1 Organization and Governance
VitaDAO will be a non-incorporated partnership that consists of several core components of law and
novel smart contract architecture, including:
1. VitaDAO’s governance smart contract architecture, instituting a legally binding agreement
between all participants, modelled after Moloch DAO and the LAO.
2. VitaDAO’s contribution and liquidity bootstrapping mechanism utilising Balancer Liquidity
Bootstrapping Pools (LBPs) on a continuous basis (Balancer Labs, 2020).
3. VitaDAO’s NFT-based intellectual property holdings and data assets.
VitaDAO’s smart contract architecture enables members, which hold VITA to freely engage in
governance decisions pertaining to the assets and funds held by the collective. At its core, Vita will be
member-managed and rely on a Dapp and related smart contracts to facilitate the purchase, funding
and management of IP and data assets.
VitaDAO will rely on service providers (initially Molecule GmbH, legal advisors and other web3
development teams) to facilitate various administrative, legal and development functions pertaining to
the purchase and transfer of IP from universities, updating and maintaining the Dapp, validating and
formatting information selected by members and handling other interactions that may emerge over its
initial genesis and lifecycle.
The collective will not only govern over its existing structure, but its members will also propose and
vote on how to refine its governance processes. It is thus bestowed with the hard-coded ability to
rectify any shortcomings with a majority vote and to incorporate future progress in governance
developments in its system governance.
VitaDAO members are fully in control of all governance decisions by voting on VitaDAO proposals.
Proposals consist of several types, including governance proposals, project proposals, funding
proposals, data monetization proposals, and IP proposals. The types of proposals to be considered can
be expanded on an as-needed basis determined by members.
To provide the level of industry expertise required to be able to effectively and thoroughly evaluate
therapeutics projects, VitaDAO will elect a council of 3-6 industry experts to review its projects, data
and IP. This council assists in defining executive proposals to the VitaDAO members.
The initial goal of VitaDAO is to mimic successful execution patterns in the biotech industry, while
improving on those that do not work well. Over time, we expect further governance mechanisms to
emerge around VitaDAO.
In summary:
1. VitaDAO members are fully in control of all governance decisions by voting on VitaDAO
proposals.
2. VitaDAO will elect a council of 6 industry experts to review its projects, data and IP. This
council assists in defining executive proposals to the VitaDAO members. Furthermore,
5
VitaDAO may elect to dedicate an individual executive for the community as a whole, or to
individual research projects.
3. VitaDAO may engage service providers spanning patent attorneys, contract research firms or
third party experts.
4. Our initial goal is to mimic successful execution patterns in the biotech industry. Over time,
we expect further governance mechanisms to emerge around VitaDAO.
3.2 Genesis Bootstrapping & Liquidity
For its initial Genesis, VitaDAO will deploy a Balancer Liquidity Bootstrapping Pool (Balancer Labs,
2020) to enable interested participants to contribute funds to its treasury and join the collective. As
VitaDAO grows, members may elect to create additional LBPs to onboard further projects.
We anticipate that the initial genesis will operate as follows:
1. VitaDAO will allocate a small amount of its fixed token supply into a Balancer Liquidity
Bootstrapping Pool (LBP) with the goal to raise suf ficient funds to finance the first
project for two years, as well as provide funds for ongoing operations to refine system
dynamics and source additional projects. The community will decide on the full fundraising
budget and structure pending simulations and crypto economic modeling using cadCAD.
2. The LBP allows the community to contribute funds and join VitaDAO for the first time.
Simultaneously, the pool acts as an important first price discovery mechanism. Individuals
wishing to join may contribute a multitude of assets, such as ETH, USDC or Ocean and
receive VITA tokens according to the corresponding $ value. The primary currency of the
LBP will be USDC to ensure price stability.
3. After a fixed period, the LBP resolves, forwarding its acquired funds to VitaDAO and kick
starting its operation. Should the LBP fail to reach a specific threshold participants may
withdraw their stakes.
4 Holding and Managing IP and Data Assets
4.1 Intellectual Property Rights
The VitaDAO collective will directly hold legal IP rights to these projects and may develop a growing
portfolio of assets represented as NFTs. In order to achieve this, Molecule is developing a novel IP to
NFT framework, which allows the holder of an existing piece of IP in the form of a license or patent,
to attach said ownership to an NFT and transfer it to a new owner.
When the NFT is created, the creator must sign a cryptographic message which prints their signature
onto an IP licensing agreement. This transaction requires both buyer and seller of the NFT to sign a
message that includes references to the transaction, their respective identities and legal signature,
modelled after the legal Signature Algorithm pioneered by Open Law (OpenLaw, 2019).
6
Initially, VitaDAO will primarily hold licenses to therapeutic research projects. These licenses enable
VitaDAO, or its designated service providers, to file for patents or various forms of market exclusivity
that would grow the value of its underlying assets.
4.2 Data Assets
Besides owning IP rights related to individual projects, VitaDAO will also own any data assets and
research outputs from the work it commissions and funds. VitaDAO will safely store these assets,
make them available to its members and the public at large and monetize them via Ocean Marketplace
(Ocean Protocol Foundation, 2020). Furthermore, VitaDAO could attach these data assets to NFTs,
where useful and applicable. This would drive fluid price discovery and liquidity for each individual
data set, as buyers and sellers engage around individual data sets and curate the most valuable
findings. The overall value of VITA tokens could then be derived through the sum of its individual
priced data assets, IP assets and liquidity pools. The applications around composability and
interoperability here are manifold and will be fully explored once first versions are in production.
Finally, obfuscation of data assets and enabling secure computation on them will be a highly relevant
future use case that could be facilitated by Web3 data protocols such as Ocean Protocol.
Data assets could include, but are not limited to: laboratory updates and reports, processed data,
quarterly updates, western blot data, qPCR data, cell culture experiments, survival analysis, sequence
data, western blot gels, microscopy and cell culture. These data assets could be in the forms of raw
data CSV files, images or PDFs.
The type of data assets and their monetization potential are summarized below:
1. Public Data Assets: all data in these assets are viewable by members, which can vote to list
these data packages on Ocean Marketplace.
2. IP Data Assets: Required for filing of patents or further IP. These assets will be obfuscated as
they could compromise filing of IP. These assets could be uploaded to Ocean Marketplace, as
soon as IP has been filed to protect them.
3. Progress Data Assets: intended to keep DAO members up-to-date on ongoing research
findings and serving as proof of progress. This data has a certain level of obfuscation,
meaning that any information that could compromise the intellectual property itself will be
hidden. Such data would not be relevant for Ocean Marketplace.
Members wishing to engage with the IP, review the data assets directly, or engage with the council,
will need to submit KYC documentation and sign non-compete and confidentiality agreements. This
helps ensure the viability of the IP for all members.
5 Staking & Signalling
VITA tokens may be used to signal long-term support for individual projects. A member may stake
their VITA tokens for a set time period until a project milestone is reached (e.g. 3M/6M/12M). Project
milestones are predetermined by projects and measurable. However, their outcome is uncertain,
meaning members take additional risk by foregoing liquidity.
7
When a milestone is reached, staked tokens are unlocked. In return for locking tokens, VitaDAO pays
out regular signalling rewards to stakers. This process sends valuable signals to the market, as it
showcases the confidence of members in specific projects. Furthermore, it reduces volatility and
creates a circular economy to members, which actively contribute value and review project success.
It is anticipated that signalling will be implemented after the first successful project has run an initial
funding cycle, giving members time to sufficiently model this mechanism and implement it in
VitaDAO V2.
6 Genesis & First Project Lifecycle
The following section details the initial Genesis project acquisition and models out a first potential
project lifecycle. After successful completion of its Genesis Liquidity Bootstrapping and instantiation
of its governance mechanism, VitaDAO members will vote to incorporate the first longevity
therapeutic into its collective. Molecule will propose to attach one of its longevity projects with the
Scheibye-Knudsen Laboratory at the University of Copenhagen to an NFT and sell this to VitaDAO.
Once the sale is complete, members can vote to allocate a first tranche of funding to the University of
Copenhagen to commence research.
The first project lifecycle could operate as follows:
1. Molecule proposes to VitaDAO to purchase the Scheibye-Knudsen Laboratory IP as an NFT.
2. VitaDAO members vote on the proposal and define the project parameters and payment
schedules with the Scheibye-Knudsen Laboratory.
3. The project commences, as VitaDAO completes a first payment to initiate the preclinical
studies.
4. The Scheibye-Knudsen Laboratory begins delivering first data assets consisting of progress
reports, raw data and initial findings.
5. First definitive findings are in, and VitaDAO members, with the support of industry advisors,
decide on how to use the data and further commercialise the asset. This could result in:
a. File for further IP and patents.
b. File for clinical trials and further studies.
c. Monetize the data sets through Ocean Marketplace.
6. Simultaneously, VitaDAO may decide to launch further Liquidity Bootstrapping Pools for
additional projects at any point, which are sourced through its community, or to raise
additional funding for the Scheibye-Knudsen Laboratory.
7 Exit Scenarios and IP Commercialisation
Finally, if the research data surrounding an asset is sufficiently positive and clinical trials attractive,
VitaDAO can license or sell its IP or data to institutional stakeholders, such as pharmaceutical or
biotech companies. Given enough liquidity and governance sophistication, VitaDAO could even
attempt to bring these assets to market itself. Members of VitaDAO decide how to distribute income
generated from successful IP monetization.
Individual IP and NFTs may be spun out into separate refractionalized markets to enable more
granular participation by the public. From a technical perspective, this would entail moving the NFT
8
and associated data sets out of custodianship of VitaDAO into a sub-DAO represented by a new
ERC20 token. Members of VitaDAO may elect to spin out a project to:
1. Enable the project and IP to raise additional funding from a wider community.
2. Create exit scenarios for VitaDAO and further decentralize project ownership.
3. Enable more granular fundability and participation on a project level.
8 Open Research Questions
The mechanics described in this paper are novel, experimental and rely on multiple moving parts,
especially the creation of an active tokenized governance community. Our goal is to tackle these
questions together as a community and through multiple working groups that contain industry experts,
as they will substantially improve the system’s long-term potential.
1. Governance and effective collective decision-making around drug development projects:
can a decentralized community effectively govern and attract the expertise required to
successfully commercialize therapeutics? Will the token-based voting mechanism described
herein succeed in generating positive outcomes?
2. Biopharma business logic: will the biopharma industry be open to purchasing IP and patents
produced by a decentralized collective, as opposed to current business practices? Will
VitaDAO be able to support a sufficient number of projects to become positive sum at scale?
3. Legal and patent law: can VitaDAO successfully file for further patents on the IP assets it
manages or will it have to rely on third parties? In case of patent litigation against VitaDAO,
is it able to protect the validity of the IP as a normal company could?
9 Conclusion
The open IP and data ownership structures presented here could help to alleviate some of the most
severe challenges in the current pharmaceutical and biotech pipeline and help create a future of open
and democratic ownership of longevity therapeutics.
First, IP collectives like VitaDAO could help realign incentives with neglected stakeholder groups -
patients and scientists - by creating alternative democratic research structures that distribute value and
governance more evenly. Imagine research on a new breakthrough insulin treatment funded by
diabetics who believed in it and stand to benefit the most from it. What would this do to access and
pricing?
Second, separating R&D data creation from IP ownership helps overcome a costly principal-agent
dilemma and the current reproducibility crisis. In an openly traded curation market and structure, both
negative and positive data might surface much sooner and the best therapeutics succeed. Third,
transparent financialization of data and open composability with decentralised financial markets
opens up entirely new and accelerated funding models to promising scientists and laboratories across
the globe.
From an industry perspective, we believe that IP cooperatives like VitaDAO could be a win-win
situation for all stakeholders: biopharma, researchers, and patients. It combines traditional industry IP
holding structures with novel tokenized ownership accessible by anyone wishing to contribute to the
research. In doing so, it drives valuable innovation in the biopharma industry.
9
References
1. Saha, C., & Bhattacharya, S. Intellectual property rights: An overview and implications in the
pharmaceutical industry. J Adv Pharm Technol. Res., April 2011
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3217699/
2. Olivier J. Wouters, P. Research and development costs of bringing a new medicine to market.
JAMA, March 2020.
https://jamanetwork.com/journals/jama/fullarticle/2762311
3. Bookbinder, M. Trends in drug development: Improving ROU on R&D. Clinical Research
News, March 2020.
https://www.clinicalresearchnewsonline.com/news/2020/03/05/trends-in-drug-development-i
mproving-roi-on-r-d
4. Ali-Khan, S., Harris, L., & Gold, E. Motivating participation in open science by examining
researcher incentives. eLife, October 2017.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5662284/
5. Sherkow, J. Patent Law’s Reproducibility Paradox. Duke Law Journal, January 2017.
https://scholarship.law.duke.edu/dlj/vol66/iss4/2/
6. Huang, S., Siah, K., Vasileva, D., Chen, S., Nelsen, L., & Lo, A. Life sciences intellectual
property licensing at the Massachusetts Institute of technology, Nature Biotechnology, March
2021.
https://www.nature.com/articles/s41587-021-00843-5
7. Seyhan A. Lost in translation: The valley of death across preclinical and clinical divide –
identification of problems and overcoming obstacles. Biomedcentral, November 2019.
https://transmedcomms.biomedcentral.com/articles/10.1186/s41231-019-0050-7
8. WHO (2020). Global Health and Aging.
https://www.who.int/ageing/publications/global_health.pdf
9. Scheibye-Knudsen, M. ARDD 2020: From aging mechanisms to interventions. Aging, 2020.
https://pubmed.ncbi.nlm.nih.gov/33378272/
10. Pfleger, K. Aging Biotech Info. 2021.
https://agingbiotech.info/
11. Ocean Protocol Foundation, Ocean Marketplace. 2020.
https://oceanprotocol.com/technology/marketplaces
12. Balancer Labs, Balancer Liquidity Bootstrapping Pools. 2020.
https://docs.balancer.finance/guides/smart-pool-templates-gui/liquidity-bootstrapping-pool
13. OpenLaw. OpenLaw Signature Algorithm. 2020.
https://docs.openlaw.io/sign-store/#openlaw-signature-algorithm
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Thursday, May 20, 2021

Rebirth - Triage Rational Skepticism for neochain = BLM NFT DAO smart blockchain

The Latest link


Assumes familiarity with Triage at deep level.

 
I consider self as reborn after my study (vitaDAO and deep linking) convinced me that that it was possible to evolve a DAO (=Decentralized Autonomous Organization) over normal items and NFT (= non-fungible token). Such a DAO could be started on evolution path using AMM (=automated market maker) in blockchain, Complete DAO means all can be assumed to be individual sinners (or maximal bastards in my think) and under 1/3 as a group (impossibly hard to synchronize secretly to 1/3 of population).

DAO, AMM and NFT are common usage of new paradigm you must intern to even read in new earth. One example use is vitaDAO. This company has two greatest human alive starting it - Dr. deGrey of age/health extension and in bit-coin-like blockchain space. To achieve this, VitaDAO utilizes a combination of novel governance frameworks and decentralized autonomous organizations (DAOs), non-fungible tokens (NFTs), and financial engineering tools such as algorithmic automated market makers (AMMs). Their initial experiences will certainly be studied in launch of DAO-NFT-AMM (neochain) to which all earth will evolve to. End of traditional entrepreneurs and startup-companies. This and not communism or socialism, destined to become gali! There is no other way to build truly and always autonomous outfits forever free of abuse by descendants of early investors! The motivation is not money but self-use of the product!

Religion of all kinds and I differ. Every religion assumes 'you are innocent unless proven guilty'. I take the non-stoic view that 'everyone is guilty unless proven innocent' applies to all with any iota of power over me (over-me-power)! Thus, all politicians and inspectors and all others. Unlike real world, failure of corruption, regardless of duration does not prevent corruption for 50 years or 1000 years, alive or dead! With that much cynicism, there is only one open path - cryptography. But my style - all letters can be fraudulent, so can all credentials, unless proven safe. Hard technology solutions are needed and can be seen in my resear4xh Banknotes are largely safe, and that is my minimum level of desired security for all credentials and recommendations and elections and product-quality votes and ...

It has taken me 65 years of life to even imagine a world such as above could exist in reality and could be evolved into. Smart contract blockchains are the essential meaning of truth and autonomy. AMM acts as a DAO. Encapsulated items NFT (and medicine by liposome) permit even abstract entities to be monetized. A music, art piece, medicine as intellectual property of creation etc. can all be NFTed and be on blockchain(by my define smart blockchain with DAO, AMM and NFT). So can all legal documents and insurances. These can all be done by companies totally decentralized by empower in every customer as a proportional owner! A company then can be official less using smart contracts (by my define smart blockchain with DAO, AMM and NFT). Every official and middlemen can be eliminated! Human civilization henceforth is in a new paradigm. All existing religions, ideologies and virtues become redundant. Essential are necessary but insufficient neochain so far.

And no virtuous guides are needed! Evolution and competition are only needed. Evolution will guide us into a new society, far more virtuous as driven solely by Triage Rational Skepticism TRS which will win because of inherent superiority in competitive  situations and partially used by all scientists, so much so that its use can define its user a scientist!

A blockchain is really the truth. It holds despite attempts to lie! This is done several copies of truth and an incentive scheme to pay for its infrastructure.

The whole blockchain scene is new and requires small number of new entrepreneurs. It is too complicated for normal human and there is no shortage of thugs (hackers) who exploit the error of even the virtuous. One deficiency exists which makes the field a playground of the criminals. Logical since crime requires anonymous smart contracts safe from law enforcement and other criminals (honor in thieves is stupid idea, killing is only justice). Even Tor was hacked, new one was needed.

Some things are missing. Three identified (by me) so far are are flaws of government/citizen disbelief (dictatorship-of-stupid), by dictatorship-of-power and dictatorship-of-attorny. All blockchains are evil (dictatorship-of-stupid), useful only for criminals, has been drilled into most Indians. Further neochain outfits have no way to prevent power concentration, giving rise to multi generation dictatorship-of-power, solved by no transmit of power and total extinguish with death. This requires explicit forbid of all transfers of power, achieved by five year halving of power (blockchain votes floored by minimal share for all). Like patents, some incentive is good, but only for some time, and flattening of power by progressive taxation on the very rich is needed. A smart person can set up overlap patents but limited by death! Rich will have some transmission of power but constitutional block necessary. Compare it to tax-free inherited accumulations possible due emfubar subanimal politicians in the USA in some states!

Dictatorship-of-the-attorny is my reaction to my experience of Arya Samaj prior to Agnosticism - members are very interested in detailed conflict rather than good relations and being helpful. Seen since 15 years ago, then I appeared for an exam to law diploma for Cyber Law, happened in Bombay. No one but Baldev Rohra agreed to put me up! That has taught me an unforgettable lesson - disagree but be civilized. BTW I passed to become a diploma-lawyer and never needed to stay as exam was cancelled that date and I flew back before nightfall. Arya Samaj has degenerated into discussion club of skin-the-hair pseudo-lawyers.

 What are the basic concepts

The goal must include

DAO Decentralized autonomous organization
AMM automated market maker. Loos simple but very hard and solved by millions of company public-makers by paying outrageous fee of banks.

NFT non-fungible token are essential to blockchain technology to assets like housing papers, insurance, law in general, art, music, government in general etc.!

Blind signature
double-spend
zero-knowledge proof

and these for my enthusiastic support to solutions to

dictatorship-of-stupid
dictatorship-of-power
dictatorship-of-the-attorney requires some laid down principles for treatment of violators. The worst way is to let lawyers and judges make the law.


Tuesday, May 18, 2021

VitaDAO Whitepaper


 VitaDAO Whitepaper V0.1
Tyler Golato1, Paul Kohlhaas1
Draft open for public and community comment
Abstract
VitaDAO is a new cooperative vehicle for community-governed and decentralized drug development.
Our core mission is the acceleration of R&D in the longevity space and the extension of human lifeand
health-span. To achieve this, VitaDAO utilizes a combination of novel governance frameworks
and decentralized autonomous organizations (DAOs), non-fungible tokens (NFTs), and financial
engineering tools such as algorithmic automated market makers (AMMs) that run via the Ethereum
blockchain. Today, the biopharma industry is booming with unprecedented late-stage investment
inflows, particularly in the longevity space. However, critical early-stage funding is severely lacking
and incentives between patients, researchers and industry are misaligned.
At its core, biopharma value creation is composed of intellectual property rights and research data.
Research and development has become prohibitively expensive and siloed, partially due to how
intellectual property business models work in monopolizing innovation through patent portfolios.
These mechanisms prevent the open sharing of research data, inherently disincentivizing collaboration
and transparency. They prevent the public and patients from having any real ownership in therapeutic
IP, even though their tax dollars fund much of the early-stage development. Outside of grants to fund
basic research, early-stage funding for drug development is extremely limited, and when drugs do
finally make it to market, there are strong incentives for price gouging.
VitaDAO is an open cooperative that anyone can join and support. Its goal is to acquire, support, and
finance new therapeutics and research data in the longevity space. The collective will directly hold
legal IP rights to novel early-stage projects and may develop a growing portfolio of both IP and data
assets represented as NFTs. These data assets can be made available and monetized in novel data
marketplace structures such as Ocean Marketplace, promoting both open science and novel business
models.
Ownership and governance of the VitaDAO is relegated through VITA tokens. The token can be
obtained by contributing resources, work, or funds to VitaDAO. Ownership of tokens allows its holder
to engage in decision-making and governance of VitaDAO’s research, signal support for specific
initiatives, and govern its data repositories and IP portfolio.


Table of Contents
Abstract 0
Table of Contents 1
1 Introduction and Problem Statement 2
1.1 Intellectual Property in Biopharma 2
1.2 The Evolution of Pharma and the Valley of Death 2
1.3 Longevity Will Transform Our Approach To Medicine 3
2 Solution 4
3 Core Architecture 5
3.1 Organization and Governance 5
3.2 Genesis Bootstrapping & Liquidity 6
4 Holding and Managing IP and Data Assets 6
4.1 Intellectual Property Rights 6
4.2 Data Assets 7
5 Staking & Signalling 7
6 Genesis & First Project Lifecycle 8
7 Exit Scenarios and IP Commercialisation 8
8 Open Research Questions 9
9 Conclusion 9
References 10
1
1 Introduction and Problem Statement
Current biopharma business models carry severe limitations and R&D inefficiencies at the cost of
those who should be the core stakeholders: patients in need of medication and researchers discovering
these molecules.
1.1 Intellectual Property in Biopharma
Fundamentally, value creation in biopharma is driven by two core assets: intellectual property (IP) and
research and development (R&D) data (Saha, 2011). When companies explore a use case for a new
therapeutic, they patent their discoveries to gain IP. This enables them to secure future revenue and
recoup the high costs of R&D. As companies invest billions of dollars into generating data to bring
therapeutics to market, they offset this by selling equity ownership or royalty rights (Olivier, 2020).
While IP is designed to incentivize innovation in theory, intellectual property ownership as a business
model has barely evolved in the past century and is largely analog, operating through extensive legal
contracts and bureaucratic complexities. Today, IP is one of the most valuable asset classes but
remains largely illiquid, hard to transfer, and rigid.
Moreover, the need for monopolistic IP ownership of both patents and data within biopharma
companies creates secrecy, centralization and disincentivizes much-needed collaboration and open
research in the scientific community, which could bring down the rising cost of drug development
(Bookbinder, 2020). Perfectly good drug candidates often fall to the wayside for organizational,
political, or competitive reasons. This concentration of research efforts leads to the high R&D cost
and long time-to-market that pharma is known for today. Pharma tends to only share positive R&D
data -- companies waste enormous resources ignorantly repeating each others’ failures. Under the
current system, incentives for open science, collaboration, and data sharing are severely lacking
(Ali-Khan, 2017).
On a macroscopic scale, this model leads to incentive misalignment and information asymmetry. IP
owners and sellers seeking to monopolize commercial value are not incentivized to report negative
research data. This creates a principal-agent dilemma and, in part, leads to a phenomenon coined the
“reproducibility crisis” (Sherkow, 2017). Thus, side effects or indicators of lower effectiveness of the
owned compounds are downplayed in favor of profit maximization, and valuable research findings are
“lost” for the broader scientific community and not considered during patient treatment. More
democratic, open, and transparent models are needed with a wider inclusion of stakeholders.
Lastly, the current financing and investment landscape centralizes and restricts access and
participation to early-stage biopharma from its most important stakeholders: patients and researchers.
In the US, only accredited investors may finance early-stage ventures. The market is opaque, and no
singular or efficient marketplace exists to discover or access these opportunities in a transparent
fashion.
1.2 The Evolution of Pharma and the Valley of Death
The process of drug development in the pharmaceutical industry is undergoing a significant shift in its
industrial organization. Increasingly, smaller biotech firms leverage recent academic research in the
life sciences to develop new drugs, which are then acquired by pharmaceutical giants using their
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access to low-cost capital to purchase expertise (Lo, 2021). The number of biotech startup companies
formed due to technology licensing has shifted dramatically in recent years - from 145 in 1994 to 278
in 2000 and 1,024 in 2016. Of the 30 top-selling drugs worldwide in 2000, only five were traceable to
universities; the remaining 25 were developed by big pharma. By 2018, more than one-half of the top
30 drugs were sourced from academia (Lo, 2021). Thus, biotech universities are increasingly proving
to be untapped goldmines of valuable IP, yet often these assets are not investable until a startup is
spun out.
Assets from universities that are not out-licensed or spun out into startups remain in a difficult limbo,
known as The Valley of Death, where they often fail to move forward (Seyhan, 2019). Many of these
technologies are extremely valuable to patients, and because of this system, they will ultimately never
serve the populations they were intended to. These assets require investment and capital injections at
an earlier stage, and new open commercialization models are desperately needed to incentivize their
development.
1.3 Longevity Will Transform Our Approach To Medicine
The longevity field has the power to transform our global healthcare system completely. Age-related
diseases are among the most significant contributors to our global health burden and are responsible
for the highest costs incurred by healthcare systems (WHO, 2020).
The longevity space is experiencing a tremendous boom, in part because of its ability to address this
problem. The space is evolving rapidly in terms of understanding the aging process and its capacity to
develop health- & life-extending therapeutics (Scheibye-Knudsen, 2020). It is now a routine
procedure to reverse the aging of human cells in the laboratory dish. Correspondingly, the economics
of investing in longevity are more attractive than ever. There are 100s of new companies and funds
dedicated to research and product development in the fields of senolytics, telomeres, stem cells,
mitochondria, and gene editing (Pfleger, 2021). These are some of the core domains from which
therapies that increase lifespan will emerge.
The rush of investment into the field has the potential to rapidly accelerate these developments but
also comes with distinct problems. The “centralization” of aging research by large institutions and
billionaires has the potential to create the same problems and pitfalls that plague the pharmaceutical
industry: intransparency, restricted access, and concentrated control over therapeutics that should be
made widely available to anyone at an affordable price.
We believe the future of health- and life-extension should be open, collaborative, and
community-owned. We see longevity as an entirely new approach to medicine, one that has the
potential to prevent, as opposed to treat or intervene. This approach will completely change the way
the world approaches medical care and will profoundly impact society.
3
2 Solution
We propose the creation of VitaDAO: the first fully open and community-owned, transparent
intellectual property collective in longevity.
Members of the public can become co-owners of VitaDAO and its IP by purchasing VITA through
contributing funds, valuable research data, IP assets or performing services for VitaDAO. Ownership
and governance of VitaDAO is relegated through VITA tokens. VITA enables its holder to engage in
decision-making and governance of VitaDAO’s research, signal support for specific initiatives and
govern its data repositories and IP portfolio.
VitaDAO will acquire intellectual property rights, data and commission research to further develop
those assets. Further, it will monetize its intellectual property. In summary, VitaDAOs core assets can
consists of:
1. Intellectual property, patents and licenses to therapeutic research projects.
2. Data assets generated by funding R&D around its research projects.
3. Funds stored in its treasury, as well as unissued VITA tokens.
Intellectual property and data assets will be virtualized and represented as Non-Fungible Tokens
(NFTs), which are explained in more depth in Section 4.
In order to acquire and finance specific research proposals, VitaDAO members may elect to issue
tokens on a continuous or per-project basis, using automatic market makers (AMMs) like Balancer
Liquidity Bootstrapping Pools that enable a fair and transparent participation for prospective
members.
4
3 Core Architecture
3.1 Organization and Governance
VitaDAO will be a non-incorporated partnership that consists of several core components of law and
novel smart contract architecture, including:
1. VitaDAO’s governance smart contract architecture, instituting a legally binding agreement
between all participants, modelled after Moloch DAO and the LAO.
2. VitaDAO’s contribution and liquidity bootstrapping mechanism utilising Balancer Liquidity
Bootstrapping Pools (LBPs) on a continuous basis (Balancer Labs, 2020).
3. VitaDAO’s NFT-based intellectual property holdings and data assets.
VitaDAO’s smart contract architecture enables members, which hold VITA to freely engage in
governance decisions pertaining to the assets and funds held by the collective. At its core, Vita will be
member-managed and rely on a Dapp and related smart contracts to facilitate the purchase, funding
and management of IP and data assets.
VitaDAO will rely on service providers (initially Molecule GmbH, legal advisors and other web3
development teams) to facilitate various administrative, legal and development functions pertaining to
the purchase and transfer of IP from universities, updating and maintaining the Dapp, validating and
formatting information selected by members and handling other interactions that may emerge over its
initial genesis and lifecycle.
The collective will not only govern over its existing structure, but its members will also propose and
vote on how to refine its governance processes. It is thus bestowed with the hard-coded ability to
rectify any shortcomings with a majority vote and to incorporate future progress in governance
developments in its system governance.
VitaDAO members are fully in control of all governance decisions by voting on VitaDAO proposals.
Proposals consist of several types, including governance proposals, project proposals, funding
proposals, data monetization proposals, and IP proposals. The types of proposals to be considered can
be expanded on an as-needed basis determined by members.
To provide the level of industry expertise required to be able to effectively and thoroughly evaluate
therapeutics projects, VitaDAO will elect a council of 3-6 industry experts to review its projects, data
and IP. This council assists in defining executive proposals to the VitaDAO members.
The initial goal of VitaDAO is to mimic successful execution patterns in the biotech industry, while
improving on those that do not work well. Over time, we expect further governance mechanisms to
emerge around VitaDAO.
In summary:
1. VitaDAO members are fully in control of all governance decisions by voting on VitaDAO
proposals.
2. VitaDAO will elect a council of 6 industry experts to review its projects, data and IP. This
council assists in defining executive proposals to the VitaDAO members. Furthermore,
5
VitaDAO may elect to dedicate an individual executive for the community as a whole, or to
individual research projects.
3. VitaDAO may engage service providers spanning patent attorneys, contract research firms or
third party experts.
4. Our initial goal is to mimic successful execution patterns in the biotech industry. Over time,
we expect further governance mechanisms to emerge around VitaDAO.
3.2 Genesis Bootstrapping & Liquidity
For its initial Genesis, VitaDAO will deploy a Balancer Liquidity Bootstrapping Pool (Balancer Labs,
2020) to enable interested participants to contribute funds to its treasury and join the collective. As
VitaDAO grows, members may elect to create additional LBPs to onboard further projects.
We anticipate that the initial genesis will operate as follows:
1. VitaDAO will allocate a small amount of its fixed token supply into a Balancer Liquidity
Bootstrapping Pool (LBP) with the goal to raise suf ficient funds to finance the first
project for two years, as well as provide funds for ongoing operations to refine system
dynamics and source additional projects. The community will decide on the full fundraising
budget and structure pending simulations and crypto economic modeling using cadCAD.
2. The LBP allows the community to contribute funds and join VitaDAO for the first time.
Simultaneously, the pool acts as an important first price discovery mechanism. Individuals
wishing to join may contribute a multitude of assets, such as ETH, USDC or Ocean and
receive VITA tokens according to the corresponding $ value. The primary currency of the
LBP will be USDC to ensure price stability.
3. After a fixed period, the LBP resolves, forwarding its acquired funds to VitaDAO and kick
starting its operation. Should the LBP fail to reach a specific threshold participants may
withdraw their stakes.
4 Holding and Managing IP and Data Assets
4.1 Intellectual Property Rights
The VitaDAO collective will directly hold legal IP rights to these projects and may develop a growing
portfolio of assets represented as NFTs. In order to achieve this, Molecule is developing a novel IP to
NFT framework, which allows the holder of an existing piece of IP in the form of a license or patent,
to attach said ownership to an NFT and transfer it to a new owner.
When the NFT is created, the creator must sign a cryptographic message which prints their signature
onto an IP licensing agreement. This transaction requires both buyer and seller of the NFT to sign a
message that includes references to the transaction, their respective identities and legal signature,
modelled after the legal Signature Algorithm pioneered by Open Law (OpenLaw, 2019).
6
Initially, VitaDAO will primarily hold licenses to therapeutic research projects. These licenses enable
VitaDAO, or its designated service providers, to file for patents or various forms of market exclusivity
that would grow the value of its underlying assets.
4.2 Data Assets
Besides owning IP rights related to individual projects, VitaDAO will also own any data assets and
research outputs from the work it commissions and funds. VitaDAO will safely store these assets,
make them available to its members and the public at large and monetize them via Ocean Marketplace
(Ocean Protocol Foundation, 2020). Furthermore, VitaDAO could attach these data assets to NFTs,
where useful and applicable. This would drive fluid price discovery and liquidity for each individual
data set, as buyers and sellers engage around individual data sets and curate the most valuable
findings. The overall value of VITA tokens could then be derived through the sum of its individual
priced data assets, IP assets and liquidity pools. The applications around composability and
interoperability here are manifold and will be fully explored once first versions are in production.
Finally, obfuscation of data assets and enabling secure computation on them will be a highly relevant
future use case that could be facilitated by Web3 data protocols such as Ocean Protocol.
Data assets could include, but are not limited to: laboratory updates and reports, processed data,
quarterly updates, western blot data, qPCR data, cell culture experiments, survival analysis, sequence
data, western blot gels, microscopy and cell culture. These data assets could be in the forms of raw
data CSV files, images or PDFs.
The type of data assets and their monetization potential are summarized below:
1. Public Data Assets: all data in these assets are viewable by members, which can vote to list
these data packages on Ocean Marketplace.
2. IP Data Assets: Required for filing of patents or further IP. These assets will be obfuscated as
they could compromise filing of IP. These assets could be uploaded to Ocean Marketplace, as
soon as IP has been filed to protect them.
3. Progress Data Assets: intended to keep DAO members up-to-date on ongoing research
findings and serving as proof of progress. This data has a certain level of obfuscation,
meaning that any information that could compromise the intellectual property itself will be
hidden. Such data would not be relevant for Ocean Marketplace.
Members wishing to engage with the IP, review the data assets directly, or engage with the council,
will need to submit KYC documentation and sign non-compete and confidentiality agreements. This
helps ensure the viability of the IP for all members.
5 Staking & Signalling
VITA tokens may be used to signal long-term support for individual projects. A member may stake
their VITA tokens for a set time period until a project milestone is reached (e.g. 3M/6M/12M). Project
milestones are predetermined by projects and measurable. However, their outcome is uncertain,
meaning members take additional risk by foregoing liquidity.
7
When a milestone is reached, staked tokens are unlocked. In return for locking tokens, VitaDAO pays
out regular signalling rewards to stakers. This process sends valuable signals to the market, as it
showcases the confidence of members in specific projects. Furthermore, it reduces volatility and
creates a circular economy to members, which actively contribute value and review project success.
It is anticipated that signalling will be implemented after the first successful project has run an initial
funding cycle, giving members time to sufficiently model this mechanism and implement it in
VitaDAO V2.
6 Genesis & First Project Lifecycle
The following section details the initial Genesis project acquisition and models out a first potential
project lifecycle. After successful completion of its Genesis Liquidity Bootstrapping and instantiation
of its governance mechanism, VitaDAO members will vote to incorporate the first longevity
therapeutic into its collective. Molecule will propose to attach one of its longevity projects with the
Scheibye-Knudsen Laboratory at the University of Copenhagen to an NFT and sell this to VitaDAO.
Once the sale is complete, members can vote to allocate a first tranche of funding to the University of
Copenhagen to commence research.
The first project lifecycle could operate as follows:
1. Molecule proposes to VitaDAO to purchase the Scheibye-Knudsen Laboratory IP as an NFT.
2. VitaDAO members vote on the proposal and define the project parameters and payment
schedules with the Scheibye-Knudsen Laboratory.
3. The project commences, as VitaDAO completes a first payment to initiate the preclinical
studies.
4. The Scheibye-Knudsen Laboratory begins delivering first data assets consisting of progress
reports, raw data and initial findings.
5. First definitive findings are in, and VitaDAO members, with the support of industry advisors,
decide on how to use the data and further commercialise the asset. This could result in:
a. File for further IP and patents.
b. File for clinical trials and further studies.
c. Monetize the data sets through Ocean Marketplace.
6. Simultaneously, VitaDAO may decide to launch further Liquidity Bootstrapping Pools for
additional projects at any point, which are sourced through its community, or to raise
additional funding for the Scheibye-Knudsen Laboratory.
7 Exit Scenarios and IP Commercialisation
Finally, if the research data surrounding an asset is sufficiently positive and clinical trials attractive,
VitaDAO can license or sell its IP or data to institutional stakeholders, such as pharmaceutical or
biotech companies. Given enough liquidity and governance sophistication, VitaDAO could even
attempt to bring these assets to market itself. Members of VitaDAO decide how to distribute income
generated from successful IP monetization.
Individual IP and NFTs may be spun out into separate refractionalized markets to enable more
granular participation by the public. From a technical perspective, this would entail moving the NFT
8
and associated data sets out of custodianship of VitaDAO into a sub-DAO represented by a new
ERC20 token. Members of VitaDAO may elect to spin out a project to:
1. Enable the project and IP to raise additional funding from a wider community.
2. Create exit scenarios for VitaDAO and further decentralize project ownership.
3. Enable more granular fundability and participation on a project level.
8 Open Research Questions
The mechanics described in this paper are novel, experimental and rely on multiple moving parts,
especially the creation of an active tokenized governance community. Our goal is to tackle these
questions together as a community and through multiple working groups that contain industry experts,
as they will substantially improve the system’s long-term potential.
1. Governance and effective collective decision-making around drug development projects:
can a decentralized community effectively govern and attract the expertise required to
successfully commercialize therapeutics? Will the token-based voting mechanism described
herein succeed in generating positive outcomes?
2. Biopharma business logic: will the biopharma industry be open to purchasing IP and patents
produced by a decentralized collective, as opposed to current business practices? Will
VitaDAO be able to support a sufficient number of projects to become positive sum at scale?
3. Legal and patent law: can VitaDAO successfully file for further patents on the IP assets it
manages or will it have to rely on third parties? In case of patent litigation against VitaDAO,
is it able to protect the validity of the IP as a normal company could?
9 Conclusion
The open IP and data ownership structures presented here could help to alleviate some of the most
severe challenges in the current pharmaceutical and biotech pipeline and help create a future of open
and democratic ownership of longevity therapeutics.
First, IP collectives like VitaDAO could help realign incentives with neglected stakeholder groups -
patients and scientists - by creating alternative democratic research structures that distribute value and
governance more evenly. Imagine research on a new breakthrough insulin treatment funded by
diabetics who believed in it and stand to benefit the most from it. What would this do to access and
pricing?
Second, separating R&D data creation from IP ownership helps overcome a costly principal-agent
dilemma and the current reproducibility crisis. In an openly traded curation market and structure, both
negative and positive data might surface much sooner and the best therapeutics succeed. Third,
transparent financialization of data and open composability with decentralised financial markets
opens up entirely new and accelerated funding models to promising scientists and laboratories across
the globe.
From an industry perspective, we believe that IP cooperatives like VitaDAO could be a win-win
situation for all stakeholders: biopharma, researchers, and patients. It combines traditional industry IP
holding structures with novel tokenized ownership accessible by anyone wishing to contribute to the
research. In doing so, it drives valuable innovation in the biopharma industry.
9
References
1. Saha, C., & Bhattacharya, S. Intellectual property rights: An overview and implications in the
pharmaceutical industry. J Adv Pharm Technol. Res., April 2011
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3217699/
2. Olivier J. Wouters, P. Research and development costs of bringing a new medicine to market.
JAMA, March 2020.
https://jamanetwork.com/journals/jama/fullarticle/2762311
3. Bookbinder, M. Trends in drug development: Improving ROU on R&D. Clinical Research
News, March 2020.
https://www.clinicalresearchnewsonline.com/news/2020/03/05/trends-in-drug-development-i
mproving-roi-on-r-d
4. Ali-Khan, S., Harris, L., & Gold, E. Motivating participation in open science by examining
researcher incentives. eLife, October 2017.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5662284/
5. Sherkow, J. Patent Law’s Reproducibility Paradox. Duke Law Journal, January 2017.
https://scholarship.law.duke.edu/dlj/vol66/iss4/2/
6. Huang, S., Siah, K., Vasileva, D., Chen, S., Nelsen, L., & Lo, A. Life sciences intellectual
property licensing at the Massachusetts Institute of technology, Nature Biotechnology, March
2021.
https://www.nature.com/articles/s41587-021-00843-5
7. Seyhan A. Lost in translation: The valley of death across preclinical and clinical divide –
identification of problems and overcoming obstacles. Biomedcentral, November 2019.
https://transmedcomms.biomedcentral.com/articles/10.1186/s41231-019-0050-7
8. WHO (2020). Global Health and Aging.
https://www.who.int/ageing/publications/global_health.pdf
9. Scheibye-Knudsen, M. ARDD 2020: From aging mechanisms to interventions. Aging, 2020.
https://pubmed.ncbi.nlm.nih.gov/33378272/
10. Pfleger, K. Aging Biotech Info. 2021.
https://agingbiotech.info/
11. Ocean Protocol Foundation, Ocean Marketplace. 2020.
https://oceanprotocol.com/technology/marketplaces
12. Balancer Labs, Balancer Liquidity Bootstrapping Pools. 2020.
https://docs.balancer.finance/guides/smart-pool-templates-gui/liquidity-bootstrapping-pool
13. OpenLaw. OpenLaw Signature Algorithm. 2020.
https://docs.openlaw.io/sign-store/#openlaw-signature-algorithm
10

My diet versus Dr. Sinclair diet

 



Dr. Sinclair does not recommend any thing or describes his diet in one go. However, based on patient collections from articles, following appears to be his diet, reservations expressed apply, to me too.. The article overlays the opinions of the writer too. It is amazing to compare it with my diet, and the reasons for it, even though mine was independently derived, with reasons given. Best all can do is compare their own and adjust. I am amazed at how much I am similar to my hero.


my view: Heart quad-bypass,, diabetes, osteoarthritis and osteopenia. No genetic gift, but shooting for wish-death, likely with 20 year bioage reduction.


Nicotinamide Mononucleotide (NMN), 1g per day, in the morning. Will do upgrade to nmnh or MIB-626 (nmn with h2s for nitric oxide) or liposome nmn (defeat liver, raise blood level and defeats BBB). LIposome is generic encapsulation in nanoparticles for all kind of vitamins. glutathione, nmn etc

author view: 1000 mg is a high dose of NMN. 250 to 500 mg is also sufficient to benefit from NMN’s health and longevity promoting effects.

my view: I got hooked due to aggressive marketing (after ad minus) and surprise agreement of Dr. Sinclair. There are two minor and one essential difference (take only 500 mg of nmn, rather than have 1 gm/day betaine, 200mg pterostilbene not 1 gm resveratrol)

Resveratrol, 1g per day, in the morning.

Author view: We are lukewarm about resveratrol. We believe pterostilbene is better.

Resveratrol is a stilbenoid found in the skin of grapes in low amounts. Studies have shown that resveratrol can reduce the risk of heart disease, cancer and neurodegeneration. David Sinclair believes that resveratrol works synergistically with NMN. Resveratrol is needed to activate the sirtuin genes (which protect our DNA and epigenome), while NMN is needed to fuel the sirtuins. However, resveratrol is difficult to be absorbed by the gut, and the little resveratrol that ends up in the body is broken down very quickly. Therefore, pterostilbene is a better alternative.

My view: 200 mg pterostilbene not 1 gm resveratrol

Metformin (prescription drug) 1 gram per day: 500 mg in the morning and 500 mg in the evening.

Author view: We are cautiously optimistic about metformin, keeping in mind some caveats.

My view: required 2 gm/day metformin, 75 mg acarbose). Will add DHEA, if needed.

Vitamin D3

author view: We are positive about this vitamin.

Vitamin D can reduce the risk of various aging-related diseases. Vitamin D deficiency in humans has been associated with an increased risk of heart disease, type 2 diabetes, autoimmune diseases and Alzheimer’s disease. Vitamin D activates many genes that confer important health benefits (R).

The dose of vitamin D that most governments advise is too low (e.g. 400 to 800 IU per day). Most vitamin D experts advise to take at least 2000-4000 IU per day, and get your vitamin D levels checked at least every year.

my view: strong endorsement with k2 , 100 microgm of mk-7 for all Indians. Must for me for osteoarthritis, all Indians have suspect bone strength past 65. Agree 2000-4000 IU/day.

Vitamin K2

author view: We like vitamin K (a lot).

Vitamin K is important not just for bone health, but also vascular and mitochondrial health. Vitamin K also improves skin appearance. You take vitamin D, you ideally also combine it with vitamin K2 (MK-7 is the best form): the two vitamins work synergistic ally.

My view: strong endorsement with k2 , 100 microgm of mk-7 for all Indians. Must for me for osteoarthritis, all Indians have suspect bone strength past 65.

Statin (prescription drug) – taken since his early 20s due to family history of cardiovascular disease.

Author view: We are not big fans.

Statins could lower the risk of heart disease. But there is a lot of discussion about how significant the effect of a statin is on reducing the cardiovascular risk.

Some scientists claim you should take statins if you have an increased risk of getting a heart attack (known as “primary prevention”), while others claim that you should only take statins when you’ve already had a heart attack (as “secondary prevention”).

Other studies suggest that for many people, statins don’t work very well for primary prevention.

This will likely depend on your personal genetic make-up; we see that some people react much better to statins while others derive no effect.

Also, not all statins are the same. Some statins seem to be able to extend lifespan in mice (like simvastatin) while other statins do not have this effect. Also, statins can have side effects, like muscle aches or neuropathy (nerve pain), and some statins more than others. 

My view: Needed for Heart, benefits brain (IE Alzheimer). Atorva not simva, document research continues.

Low-dose aspirin – 83 mg per day

author view: Neutral, but also a bit disappointed.

A low dose aspirin could reduce inflammation, reduce the risk of heart attacks, and perhaps the risk of cancer. Many other studies showing that aspirin could have health and longevity benefits.

My view: Strong endorsement, even non-heart-patients.

Alpha Lipoic Acid

author view: This antioxidant very likely does not extend lifespan in humans. In fact, it may actually even shorten lifespan.

Alpha lipoic acid (ALA) is a strong antioxidant. and scientists have learned that antioxidants could actually accelerate aging. So we would be careful with taking supra physiological doses (much greater than you’d ever find in a healthy diet) of antioxidants.

My view: Don't take it.

Coenzyme Q10

author view: This antioxidant probably cannot extend lifespan in humans. It could possibly even shorten lifespan.

Coenzyme Q10 is an antioxidant that improves mitochondrial functioning. There is insufficient scientific evidence (at least in well-conducted studies with the right disease model mice) that coenzyme Q10 can extend lifespan. We would be cautious about taking strong antioxidants like coenzyme Q10 to extend lifespan.

My view: Too many endorsements, plethora of small benefits

He knows very well that nutrition, exercise, proper sleep and stress reduction are also very important methods to extend lifespan. How does he go about this?

Nutrition

David Sinclair often eats only 2 meals per day instead of 3 meals. He drinks lots of green tea. He eats little (red) meat, and consumes lots of vegetables. Professor Sinclair is a proponent of regular fasting.



My view: Diabetes prohibits fasting. Similar effects by making all dinners 1/4 inch roti never thick and lauki or tori sabji. Visible effects in test every morning (15 year) blood draw for insulin, rarely reading above 120, 5.8 - 6.3 HbA1c. Very high protein breakfast, normal lunch, sparse dinner.

Exercise

Regarding exercise, David Sinclair runs once or twice a week, both in a low intensity and high-intensity way. He also does weight lifting one or twice a week.

My view: Required due to heart and diabetes, gym for 2% loss of muscle mass per year. Otherwise, greatly beneficial too. 2 km/day walk, all weathers. No truancy.


Thursday, April 22, 2021

proven contradiction removal method


The latest link

I consider this as an original philosophical contribution and promise to link all comments.

A proven contradiction removal method in compatible interests is what this note is about. Compatible will eliminate insincere interests, any moron that attempts to cause a failure can and will be eliminated as incompatible (and insincere) interests. At this point, it deals with converting relation with stepson who just emerged from teen years (wanted to be an Egyptologist in teen years, Indian Army also) and ready to face the world on his own respect for me as opposed to real mother.

It is a necessary step to decide on the claimed reasons of the interest. A jury can be given a range of their result, threshold communicated and decision is by median. All values cause the highest and lowest jurists to be permanently replaced from the pool. If the median is under threshold then the party is declared incompatible. Majority matters. Jury pool is always dynamic to exclude extreme opinions.

The basic tool for removal of genuine contradictions in interest is scheduling them linearly in part fulfillment order overseen by a trusted reliable judge whose word is kept regardless. Part fulfillment only ensures required CBM (conflict building measures) in all other groups. The duration of each slice depends on the case, but all interest are broken into 2 or more steps. Trust in the judge is required for the last step(s).

To earn respect, my word is good as gold. Never lie to a person or in front of a person to a third person except with atonement in advance that demonstrably and transparently exceeds the gain of lying and clearly is to protect a fourth person. That is generally possible only by being honest. I have never understood how some enjoy life by unnecessary lying or being forced into such situations. Generally by making punishment proportional to income seems to sharply reduce crime. Increased burden hurts the higher income person proportionally means harder! Imprisonment hurts equally, but a proportional fine must always be added.

I am truly interested in the empirical value of such statements, particularly impact on innocent victims, for I consider current law bias to criminals punishment to be outrageous and correctly criminal even if no law currently forbid it! Absolute forbid of some laws is solely for criminal reasons and judges can always can block the relax of such laws, IE the law must always consider the burden of proof. Innocents so far are free of burden of proof while convicts for some case-basis time must carry the burden, and must prove themselves innocent! This loss of privilege is essentially the end of mollycoddling of violators.