Category: Entrepreneurship

How Science of the Future is being born before our eyes

« [DeSci] transformed my research impact from a low-impact virology article every other year to saving the lives and limbs of actual human beings » Jessica Sacher, Phage Directory co-founder

In a previous article, one of the very first published on Resolving Pharma, we looked at the problems posed by the centralizing role of scientific publishers, which in addition to raising financial and ethical issues, is a brake on innovation and scientific research. At that time, in addition to making this observation, we proposed ways of changing this model, mainly using NFTs and the Blockchain. For several months now, and thanks to the popularization of Web3 and DAOs, initiatives have been emerging from the four corners of the world in favour of a science that facilitates collective intelligence, redesigns the methods of funding and scientific publication and, ultimately, considerably reduces the path between the laboratory and patients. It is time to explore this revolution, which is still in its infancy, and which is called DeSci for Decentralized Science.

The needed emergence of DeSci

One story that illustrates the inefficiencies of current science is often taken as an example in the DeSci world: that of Katalin Kariko, a Hungarian biochemist who carried out numerous research projects from the 1990s onwards (on in vitro-transcribed messenger RNA) which, a few decades later, would be at the origin of several vaccines against Covid-19. Despite the innovative aspects of Kariko’s research, she was unable to obtain the research grants necessary to pursue her projects because of political rivalry: the University of Pennsylvania, where she was based, had chosen to give priority to research on therapeutics targeting DNA directly. This lack of resources led to a lack of publications, and K. Kariko was demoted in the hierarchy of her research unit. This example shows the deleterious consequences of centralized organization on funding allocation (mainly from public institutions and private foundations) and on the reputation of scientists (from scientific publishers). 

How many researchers spend more time looking for funding than working on research topics? How many applications do they have to fill in to access funding? How many promising but too risky, or unconventional, research projects are abandoned for lack of funding? How many universities pay scientific publishers a fortune to access the scientific knowledge they themselves have helped to establish? How many results, sometimes perverted by the publication logic of scientific journals, turn out to be non-reproducible? With all the barriers to data exchange related to scientific publication, is science still the collective intelligence enterprise it should be? How many scientific advances that can be industrialized and patented will not reach the market because of the lack of solid and financed entrepreneurial structures to support them (although considerable progress has been made in recent decades to enable researchers to create their own start-ups)? 

DeSci, which we could define as a system of Science organization allowing, by relying on Web3 technologies and tools, everyone to finance and take part in research and scientific valorization in exchange for a return on investment or a remuneration, proposes to answer all the problems mentioned above. 

This article will first look at the technical foundations of Decentralized Science and then explore some cases in which decentralization could improve Science efficiency.

Understanding Web3, DAOs and Decentralized Science

In the early days of the Web, there were very high barriers to entry for users wishing to post information: before blogs, forums and social networks, one had to be able to write the code for one’s website or pay someone to do it in order to share content. 

With the advent of blogs and social networks, as we mentioned, Web2 took on a different face: expression became considerably easier. On the other hand, it has been accompanied by a great deal of centralization: social networking platforms now possess the content that their users publish and exploit it commercially (mostly through advertising revenue) without paying them a cent.

Web3 is a new version of the Internet that introduces the notion of ownership thanks to the Blockchain. Indeed, whereas Web2 was built on centralized infrastructures, Web3 uses the Blockchain. Data exchanges are recorded in a Blockchain and can generate a remuneration in cryptocurrencies with a financial value but also giving, in certain cases, a decision-making power on the platforms used by the contributors. Web 3 is therefore a way of marking the ownership of content or easily rewarding a user’s action. Web 3 is without doubt the most creative version of the Internet to this day. 

Finally, we cannot talk about Web3 without talking about Decentralized Autonomous Organizations (DAOs). These organizations are described by Vitalik Buterin, the iconic co-founder of the Ethereum blockchain, as: “entities that live on the Internet and have an autonomous existence, while relying on individuals to perform the tasks it cannot do itself”. In a more down-to-earth way, they are virtual assemblies whose rules of governance are automated and transparently recorded in a blockchain, enabling its members to act collectively, without a central authority or trusted third party, and to take decisions according to rules defined and recorded in smart contracts. Their aim is to simplify and make collective decisions-making and actions more secure, transparent and tamper-proof. DAOs have not yet revealed their full potential, but they have already shown that they can operate as decentralized and efficient investment funds, companies or charities. In recent months, science DAOs have emerged, based on two major technological innovations.

The technological concepts on which DeSci relies on: 

To understand the inner workings of DeSci and especially its immense and revolutionary potential, it is important to clarify two concepts, which are rather uncommon in the large and growing Web3 domain, but which lie at the heart of a number of DeSci projects:

• IP-NFTs: The concept of IP-NFTs was developed by the teams of the company Molecule (one can find their interview on Resolving Pharma). It is a meeting point between IP (intellectual property) and NFTs (non-fungible tokens): it allows scientific research to be tokenized. This means that a representation of a research project is placed on the Blockchain in the form of an exchangeable NFT. A legal agreement is automatically made between the investors (buyers of the NFT) and the scientist or institution conducting the research. The owners of the NFT will be entitled to remuneration for licensing the intellectual property resulting from the research or creating a start-up from this intellectual property.

Figure 1 – Operating diagram of the IP-NFT developed by Molecule (Source: https://medium.com/molecule-blog/molecules-biopharma-ipnfts-a-technical-description-4dcfc6bf77f8)

• Data-NFTs: Many Blockchain projects are concerned with Data ownership , but one of the most successful project is Ocean Protocol.  A Data-NFT represents a copyright (or an exclusive licence) registered in the Blockchain and relating to a data set. Thus, it is possible for a user to exploit its data in several ways: by charging other users for temporary licences, by selling its datasets or by collectivizing them with other datasets in a “Data Union”.

These two concepts make it possible to make intellectual property liquid, and thus to create new models of financing and collaboration. To take a simple example, a researcher can present a project and raise funds from investors even before a patent is filed. In exchange, the investors have an IP-NFT that allows them to benefit from a certain percentage of the intellectual property and revenues that will potentially be generated by the innovation. 

Let’s now turn to some DeSci examples.

Transforming scientific reviewing

When researchers want to communicate to the scientific community, they write an article and submit it to scientific publishers. If the publishers accept the research topic, they will seek out other researchers who verify the scientific validity of the article, and a process of exchange with the authors ensues: this is called peer-reviewing. The researchers taking part in this process are not paid by the publishers and are mainly motivated by their scientific curiosity.

This system, as it is currently organized – centrally, gives rise to several problems:

• It takes a long time: in some journals, it takes several months between the first submission of an article and its final publication. This avoidable delay can be very damaging to the progress of science (but we will come back to this later in the article!). Moreover, given the inflation in the number of scientific articles and journals, the system based on volunteer reviewers is not equipped to last in the future.
• The article is subject to the bias of the editor as well as the reviewers, all in an opaque process, which makes it extremely uncertain. Studies have shown that by resubmitting a sample of previously published papers and changing the names and institutions of the authors, 89% of them were rejected (without the reviewers noticing that the papers were already published)
• The entire process is usually opaque and unavailable to the final reader of the paper.

Peer-reviewing in Decentralized Science will be entirely different. Several publications have demonstrated the possibility of using thematic scientific DAOs to make the whole process more efficient, fair and transparent. We can thus imagine that decentralization could play a role in different aspects: 

• The choice of reviewers would no longer depend solely on the editor , but could be approved collectively.
• Exchanges around the article could be recorded on the blockchain and thus be freely accessible.
• Several remuneration systems, financial or not, can be imagined in order to attract quality reviewers. We can thus imagine that each reviewer could earn tokens allowing them to register in a reputation system (see below), to participate in the DAO’s decision-making process but also to participate in competitions with the aim of obtaining grants. 

Decentralized peer-reviewing systems are still in their infancy and, however promising they may be, there are still many challenges to be overcome, starting with interoperability between different DAOs.

Creating a new reputation system

The main value brought about by the centralized system of science is that of the reputation system of the actors. Why do you want to access prestigious schools and universities, and why are you sometimes prepared to go into debt over many years to do so? Having the name of a particular university on your CV will make it easier for you to access professional opportunities. In a way, companies have delegated some of their recruitment to schools and universities.  Another system of reputation, which we mentioned earlier in this article, is that of scientific publishers. Isn’t the quality of a researcher measured by the number of articles he or she has managed to have published in prestigious journals?

Despite their prohibitive cost (which allows scientific publishers to be one of the highest gross margin industries in the world – hard to do otherwise when you are selling something you get for free!), these systems suffer from serious flaws: does being accepted into a university and graduating accurately reflect the involvement you had during your studies and the skills you acquired through various experiences at the intersection of the academic and professional worlds? Is a scientist’s reputation proportional to his or her involvement in the ecosystem? Jorge Hirsch, the inventor of the H-index, which aims to quantify the productivity and scientific impact of a researcher according to the level of citation of his or her publications, has himself questioned the relevance of this indicator.  Peer-reviews, the quality of courses given, the support of young researchers and the real impact of science on society are not considered by the current system.

Within the framework of DeSci, it will be possible to imagine a system based on the Blockchain that makes it possible to trace and authenticate a researcher’s actions – and not just the fact of publishing articles – in order to reward him or her through non-tradable reputation tokens. The main challenge of this reputation system will be the transversality, the interoperability and  adoption by different DAOs. We can imagine that these tokens could be used to participate in votes (in the organization of conferences, in the choice of articles, etc.) and that they will themselves be allocated according to voting mechanisms (for example, students who have taken a course will be able to decide collectively on the number of tokens to allocate to the professor). 

Transforming the codes of scientific publication to bring out collective intelligence

Science is a collective and international work in which, currently, as a researcher, you can only communicate with other research teams around the world through:

• Publications in which you cannot give access to all the data generated by your research and experiments (it is estimated that about 80% of the data is not published, which contributes to the crisis of scientific reproducibility)
• Publications that other researchers cannot access without paying the scientific publishers (in the case of Open Science, it is the research team behind the publication that pays the publisher so that readers can access the article for free)
• Publications which, because of their form and the problems linked to their access, make it very difficult to use Machine Learning algorithms which could accelerate research 
• Finally, scientific publications which, because of the length of the editorial approval mechanisms, only reflect the state of your research with a delay of several months. Recent health crises such as COVID-19 have shown us how important it can be to have qualitative data available quickly.

The Internet has enabled a major transformation in the way we communicate. Compared to letters, which took weeks to reach their recipients in past centuries, e-mail and instant messaging allow us to communicate more often and, above all, to send shorter messages as we obtain the information they contain, without necessarily aggregating it into a complex form. Only scientific communication, even though most of it is now done via the Internet, resists this trend, to the benefit of scientific publishers and traditional forms of communication, but also and above all at the expense of the progress of science and patients in the case of biomedical research.

How, under these conditions, can we create the collective intelligence necessary for scientific progress? The company flashpub.io thinks it has the solution: micro-publications, consisting of a title designed to be easily exploited by an NLP algorithm, a single figure, a brief description and links giving access to all the protocols and data generated. 

Figure 2 – Structure of a micro-publication (Source: https://medium.com/@flashpub_io) 

This idea of micro-publications, if not directly linked to the Blockchain, will be, since it allows for the rapid and easy sharing of information, a remarkable tool for collective intelligence and certainly the scientific communication modality best suited to the coming era of Decentralised Science. The objective will not be to replace traditional publications but rather to imagine a new way of doing science, in which the narrative of an innovation will be built collectively throughout successive experiments rather than after several years of work by a single research team. Contradictory voices will be expressed, and a consensus will be found, not fundamentally modifying the classic model of science but making it more efficient.

Facilitating the financing of innovation and the creation of biotechnology start-ups

Today, the financing of innovation, particularly in health, faces a double problem: 

• From the point of view of scientists and entrepreneurs: despite the development of numerous funding ecosystems, non-dilutive grants and the maturation of venture capital funds, the issue of fundraising remains essential and problematic for most projects. Many projects do not survive the so-called “Valley of Death”, the period before the start of clinical studies, during which raising funds is particularly complicated. 
• On the investor side: It is particularly difficult for an individual to participate in the financing of research and biotech companies in a satisfactory way. 
• It is possible to be a Business Angel and to enter early in the capital of a promising start-up: this is not accessible to everyone, as a certain amount of capital is required to enter a start-up (and even more so if one wishes to diversify one’s investments to smooth out one’s risk)
• It is possible to invest in listed biotech companies on the stock market: the expectation of gain is then much lower, as the companies are already mature, and their results consolidated
• It is possible to fund research through charities, but in this case, no return on investment is possible and no control over the funded projects can be exercised.
• It is possible to invest through crowdfunding sites, but here again there are structural problems: the choice of companies is limited, and the investors are generally in the position of lenders rather than investors: they do not really own shares in the company and will be remunerated according to a predefined annual rate.

These days, one of the pharmaceutical industry’s most fashionable mantras is to put the patient at the center of its therapeutics, so shouldn’t we also, for the sake of consistency, allow him to be at the center of the systems for financing and developing therapeutics?

DeSci will allow everyone – patients, relatives of patients or simply (crypto)investors wishing to have a positive impact on the world – via IP-NFT, data-NFT or company tokenization systems to easily finance drug development projects whatever their stage, from the academic research of a researcher to a company already established. 

This system of tokenization of assets also makes it possible to generate additional income, both for the investor and for the project seeking to be financed:

• The “Lombard loan” mechanisms present in DeFi will also allow investors to generate other types of income on their shares in projects. Indeed, DeFi has brought collateralized loans back into fashion: a borrower can deposit digital assets (cryptocurrencies, but also NFTs or tokenized real assets (companies, real estate, etc) in exchange for another asset (which represents a fraction of the value they deposited, in order to protect the lender) that they can invest according to different mechanisms specific to Decentralized Finance (we will not develop in this article). Thus, in a classic private equity system, the money invested in a start-up is blocked until the possibility of an exit and does not generate returns other than those expected due to the increase in the company’s value. In the new decentralized system, part of the money you have invested can be placed in parallel in the crypto equivalent of a savings account (let’s simplify things, this site is not dedicated to Decentralized Finance!)
• Furthermore, another possibility for biotech projects, whether they are already incorporated or not, to generate additional revenues is to take advantage of the liquidity of the assets (which does not exist in the traditional financing system): it is quite possible to apply a tax of some % to each transaction of an IP-NFT or a data-NFT.

We are in a world where it is sometimes easier to sell a picture of a monkey for $3 or $4 million than to raise that amount to fight a deadly disease. It’s time to understand this and pull the right levers to get the money where it is – sometimes far off the beaten track. 

Conclusion: a nascent community, a lot of work and great ambitions

Despite the high-potential initiatives presented in this article, and the growing involvement of a scientific community throughout the world, DeSci is still young and has yet to be structured. One of the main ones, apart from the aspects related to the regulatory framework, will undoubtedly be that of education in the broadest sense, which is not yet addressed by the current projects. By using Web3 tools to reinvent the way in which a high-level curriculum can be built and financed (tomorrow you will be paid to take online courses – yes!), the DeSci will give itself the means to integrate the most creative and entrepreneurial minds of its time, in the same way that large incubators or investment funds such as Y Combinator or Tech Stars have relied on education to create or accelerate the development of some of the most impressive companies of recent years. The DeSci Collaborative Universities need to emerge, and the connection between Ed3 (education and learning in the Web3 era) and DeSci has yet to be implemented.

Figure 3 – Presentation of the embryonic DeSci ecosystem at the ETH Denver conference, February 17, 2022 (in the last 3 months, the burgeoning ecosystem has grown considerably with other projects)

Web 3.0 and DAOs have the great advantage of allowing people to be rewarded with equity, or the equivalent, for contributing their skills or financial resources to a project at any stage of its development.  Thus, in a decentralized world where skills and research materials are at hand, and where the interests of the individuals involved in a project are more aligned, the time between the emergence of an idea and its execution is significantly shorter than in a centralized world. This model, which can reinvent not only work but also what a company is, applies to all fields but is particularly relevant where collective intelligence is important and where advanced expertise of various kinds is needed, such as scientific research. 

In the same way that we can reasonably expect Bitcoin to become increasingly important in the international monetary system in the coming years and decades, we can expect DeSci, given its intrinsic characteristics and qualities, to become increasingly important in the face of what we may in the next few years call “TradSci” (traditionally organized Science). By allowing a perfect alignment of interests of its different actors, DeSci will probably constitute the most successful and viable large-scale and long-term collaborative tool of Collective Intelligence that Homo Sapiens will ever have. Whether it is the fight against global warming, the conquest of space, the eradication of all diseases, or the extension of human longevity, DeSci will probably be the catalyst for the next few decades of scientific innovation and, in so doing, will positively impact your life. Don’t miss the opportunity to be one of the first to do so!

Further reading: 

• • The first Resolving Pharma article on the problems caused by the centralization of Science:  https://www.resolving-pharma.com/2021/05/09/demanteler-le-cartel-des-editeurs-scientifiques-pour-liberer-linnovation/ 
  • The interview with the Molecule team, published by Resolving Pharma: https://www.resolving-pharma.com/en/2022/01/04/interview-molecule-en/ 

• General information on DeSci: 

• • The DeSci Wiki, with many resources on the subject, and where you can find the landscape used to illustrate this article as well as DeSci projects to explore (and invest in!) https://docs.google.com/document/d/1aQC6zneXflSmpts0XGE7CawbUEHwnL6o-OFXO52PTc/edit# 
  • Ducrée J, Etzrodt M, Bartling S, Walshe R, Harrington T, Wittek N, Posth S, Wittek K, Ionita A, Prinz W, Kogias D, Paixão T, Peterfi I and Lawton J (2021) Unchaining Collective Intelligence for Science, Research, and Technology Development by Blockchain-Boosted Community Participation. Front. Blockchain 4:631648. doi: 10.3389/fbloc.2021.631648 
  • Let’s focus the power of Web3 on science & biotech’s problems:  https://jessbio.substack.com/p/lets-focus-the-power-of-web3-on-science 
  • Why Science 3 matters, New paradigms for pursuing, accumulating, auditing, and sharing knowledge, by Jan Zheng / https://postfuture.substack.com/p/why-science3-matters 
  • A Guide to DeSci, the Latest Web3 Movement by Sarah Hamburg : https://future.a16z.com/what-is-decentralized-science-aka-desci/ 
  • Hamburg S. Call to join the decentralized science movement. Nature. 2021 Dec;600(7888):221. doi: 10.1038/d41586-021-03642-9. PMID: 34876661.
  • Atoms Whitepaper : https://atoms.org/scientiae 
  • DAOs as novelty search engines : https://mirror.xyz/olly.eth/SptJwnUcMMKtvjoD7J-xYCWZZNTBkaksahJ1CH3aWr4?fbclid=IwAR3Bp7a–wgt8vtn5Wyna3KbPfTGI0mchqqP0QeuOD3ekTmMWrgZgY2lq-M

• Understanding DAOs:

• • https ://www.ethereum-france.com/quest-ce-quune-dao/ 
  • https ://underscore.vc/blog/the-future-is-dao-a-primer-on-daos-and-their-explosive-growth/ 
  • https ://www.inc.com/darren-heitner/never-heard-of-a-dao-heres-why-its-going-to-become-hottest-new-type-of-corporation.html 
  • https://future.a16z.com/the-future-of-work-daos-crypto-networks/ 
  • https ://www.thetilt.com/revenue/dao-business-model 
  • https://fortune.com/2021/11/19/dao-decentralized-autonomous-organization-consitutiondao/ 
  • https ://www.frontiersin.org/articles/10.3389/fbloc.2020.00025/full

• Understanding Web3:

• • An enlightening interview with Gavin Wood, one of the co-founders of Ethereum who coined the term “Web3” in 2014: https://www.wired.com/story/web3-gavin-wood-interview/ 
  • An excellent podcast to understand everything about Web3, with one of the French business leaders surfing this wave: https://www.gdiy.fr/podcast/frederic-montagnon/ 
  • Oussama Ammar explains his vision of Web3 in another podcast: https://www.spreaker.com/user/11710728/silicon-carne-web3-le-grand-remplacement 

• On the IP-NFTs concept:

• • Molecule’s Biopharma IPNFTs – A Technical Description: https://medium.com/molecule-blog/molecules-biopharma-ipnfts-a-technical-description-4dcfc6bf77f8 

• On the Data-NFTs concept:

• • What Is a Data NFT? Data NFTs have arrived — what role do they have in Ocean V4? https://blog.oceanprotocol.com/what-is-a-data-nft-5804a2d88671#:~:text=A%20data%20NFT%20represents%20the,this%20the%20%E2%80%9Cbase%20IP%E2%80%9D 

• On the decentralized peer-reviewing:

• • Bianca Trovo and Nazzareno Massari ; Ants-Review: A privacy-oriented Protocol for Incentivized Open Peer Reviews on Ethereum ; Springer Nature Switzerland AG 2021 B. Balis et al. (Eds.): Euro-Par 2020 Workshops, LNCS 12480, pp. 18–29, 2021. https://doi.org/10.1007/978-3-030-71593-9_2  
  • Decentralizing Journals and Peer Review DAOs, the evolution of legitimacy in scientific publishing: https://www.outofpocket.health/p/decentralizing-journals-and-peer-review-daos 
  • Ambar Tenorio-Fornès et al. Decentralizing science: Towards an interoperable open peer review ecosystem using blockchain;  Information Processing and Management 58 (2021) 102724; https://doi.org/10.1016/j.ipm.2021.102724 

• On the micro-publication concept:

• • Smaller, Faster, Smarter publications, a new way to publish scientific discovery, from flashPub : https://medium.com/@flashpub_io/smaller-faster-smarter-publications-b862d9434ed9  

• On the decentralized construction and financing of Biotechs:

• • Introducing BioDAO: a Web 3.0 solution for biotech funding , Entering the era of biotech and Web3.0 : https://medium.com/@biodao/introducing-biodao-a-web-3-0-solution-for-biotech-funding-3f9fb83aa885 
  • A guide to Decentralized Biotech, by Jocelynn Pearl:  https://future.a16z.com/a-guide-to-decentralized-biotech/ 
  • The Emergence of Biotech DAOs, by Tyler Golato : https://medium.com/molecule-blog/the-emergence-of-biotech-daos-407e31748cd4 

• On the ED3:

• • DAOs as University Replacements: A Thought Experiment: https://kassen.substack.com/p/daos-as-university-replacements-a?s=r
  • Web3 x education #1 – aligning learning and work : https://mirror.xyz/olly.eth/ieqSiPnJkDoJMAPmbyLQolKcU-q17m_ucbjdUZ-UNGY 
  • From Web3 to Ed3 – Reimagining Education in a Decentralized World: https://ed3.mirror.xyz/0U3QG8-4K6CD_ltU6SJyKN3-uBD3x6nEFs-YeShzYmk 

Credits for the illustration of the article :

• Background: @UltraRareBio @jocelynnpearl and danielyse_, Designed by @katie_koczera
• Editing: Resolving Pharma