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A Roadmap to Create Synthetic Multicellular Life:
Applications: Protocols to cure cancer, tissue regeneration,
network-designed heterosis-hybrid vigor
Eric Werner ∗
Oxford Advanced Research Foundation
email: eric.werner@oarf.org
Website: https://oarf.org
Abstract
A synthetic living cell has been created with a designed genome and booted up to start di-
viding. Scientists have designed a genome on the computer then generated the molecular
DNA and inserted it into a cell replacing its own previous genome. They then jump-started
it with a spark and it began to divide. The technology uses a bacterial genome and a bac-
terial cell. Bacteria are single celled organisms. We, however, are multicellular creatures.
A method is presented to design and synthesize multicellular life. Through rapid recent
developments in biotechnology this method has become a pragmatically and technologi-
cally feasible. A step-by-step roadmap is presented to create synthetic multicellular life.
Except for one, all the steps in the roadmap have been technologically realized. The steps
that require wet-lab work been been achieved. The one remaining step requires intense
software and hardware research. Application of the technology: Network designed het-
erosis (hybrid vigor) for food production. Tissue regeneration using designed stem cell
networks. A meta-protocol is presented for curing cancer by editing cancer networks us-
ing multicellular-CAD software in combination with CRISPR-like genome editing. This
opens a path to cure cancer without surgery, drugs or radiation by digital and molec-
ular genome editing using multicellular-CAD software together with CRISPR-Cas style
genome editing. Unfortunately, ignorant use of CRISPR could also create cancers. New
regulations of are called for1.
Key words:Multicellular Computer Aided Design CAD, genome design, genome editing, CRISPR/Cas,
genome control architecture, developmental control networks, CENES, CENOME, genetically modified organ-
isms, GMO, design of synthetic multicellular systems, embryogenesis, heterosis, hybrid vigor, tissue regener-
ation, organ regeneration
∗Oxford Advanced Research Foundation (https://oarf.org)). ©Eric Werner 2017 All rights reserved.
1Much of this article was written while I was at University of Oxford in the Department of Physiology, Anatomy
and Genetics and the Balliol Graduate Centre. I thank my Oxford University, Balliol College, and WIMM col-
leagues and students for 11 years of stimulating discussions
Eric Werner: Roadmap to create multicellular life (Preprint v1.0 Comments Welcome!) 2
Contents
1 Introduction 3
2 Roadmap to create synthetic multicellular life 3
3 Achieved all steps except Step 2 4
4 Genome design 4
5 Cracking the network code of multicellular life 4
5.1 History of a hierarchy of genome codes . . . . . . . . . . . . . . . . . . . . . . 4
5.2 The translation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
6 Cancer diagnosis and cure 6
7 Meta-protocol to cure cancer 6
8 Network search and edit replace drugs 8
9 Future possible disruptive technologies and industries 8
10 Networks, cenes, genes, GMOs and a regulatory vacuum 9
11 A cautionary note 9
Eric Werner: Roadmap to create multicellular life (Preprint v1.0 Comments Welcome!) 3
1 Introduction
A synthetic living cell has been created with a designed genome and booted up to start
dividing[10, 12, 13]. Scientists have designed a genome on the computer then generated the
molecular DNA and inserted it into a cell replacing its own previous genome. They then jump-
started it with a spark and it began to divide. The technology uses a bacterial genome and
a bacterial cell. Bacteria are single celled organisms. We, however, are multicellular crea-
tures.
Our goal is to design and synthesize minimal multicellular life in order to understand the fun-
damental properties of multicellular animals and plants. For details on minimal multicellular
genomes see [28]. Through rapid recent developments in biotechnology this goal has become
possible2.
A method is presented to design and synthesize multicellular life. Through rapid recent devel-
opments in biotechnology this method has become a pragmatically and technologically feasi-
ble. A step-by-step roadmap is presented to create synthetic multicellular life. All the steps
in the roadmap have been technologically realized except one. The steps that require wet-lab
work been been achieved. The one remaining step requires intense software and hardware re-
search. An application of the technology: A meta-protocol is presented for curing cancer by
editing cancer networks using cancer-CAD software in combination with CRISPR-like genome
editing. This opens a path to cure cancer without drugs or radiation by digital and molecular
genome editing using multicellular-CAD software together with CRISPR-Cas style genome
editing.
2 Roadmap to create synthetic multicellular life
1. Use computer aided design (CAD) software to design the genome of the living synthetic
multicellular system (MCS) and to model and simulate the development of the MCS.
This step generates a digital designed genome encoded in artificial DNA.
2. A translation between the artificial CAD-based network code of artificial DNA in de-
signed virtual genomes and the higher level network code of DNA in natural genomes.
3. Synthesize the digital natural genome into its molecular chromosomal DNA counterpart.
4. Biotechnology to insert that designed chromosome into a eukaryotic cell.
2Some of these ideas were presented in an invited talk at the Steenbock Symposium "Synthetic Genes to Syn-
thetic Life" in honor of Gobind Khorana. The Venter group (Geore Church and Hamilton Smith) presented their
plan to construct a synthetic living cell by constructing a synthetic chromosome. My talk was about the next major
future development if the Venter team was successful, namely, to design and construct a living synthetic multicel-
lular system. Talk: Werner, E. "Synthetic multi-cellular systems biology", 33rd Steenbock Symposium: Synthetic
Genes to Synthetic Life (in honor of Gobind Khorana), July 30-Aug2, 2009. The video of that talk can be found
here: https://www.youtube.com/watch?v=3owYMN3qQ2Y&feature=youtu.be
Eric Werner: Roadmap to create multicellular life (Preprint v1.0 Comments Welcome!) 4
5. Then boot up the cell and let it develop into a corresponding multicellular system that
we designed on the computer.
3 Achieved all steps except Step 2
Except for Step 2, all steps in the Roadmap to synthesize multicellular life have been accom-
plished. The heavy lifting that required tedious time consuming wet-lab research and develop-
ment has already been done: Venter’s group has created living bacteria whose genomes were
designed on the computer. The designed digital DNA was used to generate molecular DNA
and formed into a chromosome. The chromosome was inserted into bacterial cell and made to
grow. Furthermore, the recently discovered and rapidly developing CRISPR-Cas technology
makes genome editing in live cells a reality[3, 25, 4]. Hence, the most difficult technological
advances needed to create synthetic multicellular life (steps II. through IV.) have already been
shown to be a practical reality.
4 Genome design
Step 1 of the Roadmap to create synthetic multicellular life, namely, to design the genome of a
multicellular system has also been achieved. We have Computer Aided Design (CAD) software
called EmboCAD that enables us to design a multicellular system (MCS) on the computer.
EmboCAD automatically generates the artificial genome consisting of digital DNA in real
time as the MCS is being created. The EmboCAD encoding of the DNA is artificial in the
sense that it is not the same as the natural code of natural DNA in extant natural multicellular
life.
5 Cracking the network code of multicellular life
To complete the path to creating synthetic multicellular life we need to complete Step 2 of
the Roadmap. We need to translate the artificial DNA of multicellular systems designed and
generated with EmboCAD into the natural code of natural DNA. To do this we can use the
insights gained by the EmboCAD software and the architecture of the developmental networks
contained in CAD encoded artificial DNA to find the corresponding natural developmental
networks in real natural DNA.
5.1 History of a hierarchy of genome codes
Watson and Crick decoded the alphabet of DNA[27, 26], Nirenberg and Khorana deciphered
the genetic triplet code for proteins[22, 15], still others like Davidson and Carroll decoded
Eric Werner: Roadmap to create multicellular life (Preprint v1.0 Comments Welcome!) 5
protein based, gene regulatory networks (GRNs)[5, 8, 7], Werner showed GRNs cannot gen-
erate complex embryological development and hence are not likely the only source of control
of cancer[35, 37], our present task is to decode the higher level network control code of can-
cer and, more generally, of multicellular life residing in the so called non-coding DNA in
genomes[28, 29, 31, 32].3
5.2 The translation
Finding this translation between artificial DNA and natural DNA while difficult may be surpris-
ingly fast compared to the intense research and time that was and will be required to understand
genes and their interactions. Understanding how to drive a car does not imply we understand
auto mechanics. The 20,000 some genes contained in our human genome take up less than 5%
of that genome. It may take centuries before we fully understand all their functions.
But the networks that control our development are far simpler in structure and organization.
Understanding those networks will allow us to control development without necessarily under-
standing all the details of how they are implemented at the protein-gene level. The networks
utilize and control genes. Sometimes these networks are activated by genes but overall the
networks and not genes determine and dominate embryogenesis[36].
3I am, of course, not the only one saying that the noncoding regions of genomes have essential functions.
Among many, Mattick in particular has also been emphasizing this for years[17, 18, 19, 20]. What is different is that
the EmboCAD and CancerCAD software actually lets us understand the structure and function of the noncoding
genome. Evolutionarily there was a switch in the addressing system when the transcription factor (TF) based
gene regulatory networks (GRNs) where no longer adequate to generate the increasing complexity of multicellular
organisms in the Cambrian Explosion[35, 37]. This switch made the complex developmental control networks
possible. I call these networks CENEs, for control genes[33]. CENEs interact with GRNs to control multicellular
development. Many cancers reside in the CENOME[33] (the entire noncoding control network in the DNA) and
not in the protein coding part of the genome[34]. Unfortunately, most persons in the life sciences see only the gene-
centered view of development and cancer. It is as if they are wearing polarized glasses and filter out a different
dimension of life and how it is controlled.
Eric Werner: Roadmap to create multicellular life (Preprint v1.0 Comments Welcome!) 6
6 Cancer diagnosis and cure
Fig. 1: An exponential cancer networks and its growing tumor in cancer CAD software
Given we unravel the network code of life, then cancer treatment will be revolutionized: Under
Werner’s theory of cancer, developmental networks control cancer cells[36, 34, 38, 29, 30, 32].
Part of the EmboCAD software is CancerCAD that can be used to design cancer networks and
encode them in CAD artificial DNA. The cancers can then be simulated within virtual space-
time (cell physics integrated with regulatory networks) by growing them starting from a single
cancer cell.
7 Meta-protocol to cure cancer
Any cancer can be halted by changing the cancer network back into a healthy non-cancerous
one[39] 4. Thus network transformations cause cancer and can also stop cancer. Hence, once
developmental networks in natural genomes are decoded, via insights gained from artificial
networks encoded in artificial EmboCAD genomes, a natural network in natural DNA can be
translated into an artificial network in artificial DNA. The artificial DNA can then be efficiently
analyzed and searched for cancer networks. Once found the corresponding natural cancer
4See https://www.researchgate.net/publication/321714832_A_Roadmap_to_Cure_Cancer_
Combining_CRISPR_genome_editing_with_cancer_network_editing
Eric Werner: Roadmap to create multicellular life (Preprint v1.0 Comments Welcome!) 7
network can be located and edited in the natural DNA code. This method is a meta-protocol
outlined in Fig 2 where each step involves more detailed protocols.
Fig. 2: Meta-protocol to cure cancer by editing
1. Sequence the molecular genome (mNG) of the cancer cell
2. Translate the digital natural DNA code (dNG) into digital artificial DNA code (dAG) of
the CancerCAD software
3. Analyze, simulate, search and edit the artificial genome network
(a) Find the cancer causing network with its cancer links (dAp)
(b) Edit the cancer network links to transform the cancer network in dAG into a cancer
free network (dAG*)
(c) Link Switching: Replace network cancer link-nodes (pAp) with noncancerous
links (dAp*)
(d) Result the cancerous genome dAG has been transformed into a noncancerous
genome dAG*
4. Reverse translate the transformed link-nodes dAp* written in artificial DNA code into
natural digital DNA code dNp*
5. Synthesize the modified network link dNp* into molecular DNA (mNp*)
Eric Werner: Roadmap to create multicellular life (Preprint v1.0 Comments Welcome!) 8
6. Use CRISPR technology to edit the molecular cancerous genomes mNG of the cancer
cells and replace the cancer links mNp with the modified noncancerous links mNp*
7. Result: Cancer free cells with cancer free genomes mNG* in all edited former cancer
cells.
8. We have cured the cancer not with drugs but with DNA editing.
Once a library of natural cancer networks has been formed the above indirect search of cancer
networks by way of artificial digital DNA can possibly be skipped. However, we still have
to directly search and find the cancer networks in the natural digital DNA. Then we can di-
rectly search and edit the natural cancer network nodes using the already existing CRISPR-Cas
technology[3, 25, 4, 14, 24]. The editing can either delete or inactivate the cancer network or
reverse the deleterious mutations that resulted in the cancer network.
8 Network search and edit replace drugs
Hence the future of cancer diagnosis and therapy will be a precise network based search and
editing process analogous to those already being developed and used today in the most ad-
vanced antiviral and antibiotic CRISPR research[1, 2, 4, 6, 9, 11, 16, 21, 23]. And just like the
antibiotic CRISPR approach this new network search and edit approach to cancer diagnosis
and therapy is disruptive revolutionary technology.
9 Future possible disruptive technologies and industries
Multicellular synthetic biology opens up an amazing new world of technologically unprece-
dented possibilities:
1. Cancer network search, diagnosis, editing and cure
2. Stem cell network editing and programming
3. Tissue and organ generation
4. Tissue regeneration by editing networks in charge
5. Dental industry for tooth regeneration using dental stem cell network programming
6. Agra industry by crop design and network engineering to produce designer crops for
increase in heterosis, plant quality, and quantity5
5For example, by modifying the developmental networks of a simulated multicellular structure, I was able to get
an increase in heterosis (as measured by cell number) of over 1000%. Normally an increase in heterosis or hybrid
vigor of just 10% is considered remarkable. By using dna-CAD software the degree of heterosis can be designed
on the computer and then using CRISPR-like technologies, the plant genome and its networks can be modified. Or
the entire genome and its chromosomes can be constructed based on the CAD network we designed.
Eric Werner: Roadmap to create multicellular life (Preprint v1.0 Comments Welcome!) 9
7. Meat industry for designer animals and meat production
8. Pharmaceutical industry for network diagnosis and therapy of other multicellular dis-
eases
9. Designed bio-live sensor tissues and neuronal control systems (mini-brains) that inter-
face with digital technologies
10. Bio-robotics with bio-live robot subsystems
10 Networks, cenes, genes, GMOs and a regulatory vacuum
In the cancer meta-protocol CRISPR is used to edit cancer control networks (also called
CENEs[33]) and not necessarily the protein coding genes. More generally, CRISPR can edit
other noncoding DNA which includes the all important non-cancerous developmental control
networks (DCNs or CENEs[33]). Because unmodified genes are only activated but not mod-
ified by such higher level networks to molecularly implement their cell directives, one can
change the network without changing the genes. Hence, we do not need to produce geneti-
cally modified crops, for example. For example, we can direct the growth of the plant and its
morphology without changing its genetic makeup. Less 5% of the human genome is made of
protein coding genes. So too for plants.
Hence, food production could be significantly enhanced by network computer aided design
(CAD) without genetic modification. At the same time, to the plant may look and behave very
differently as it develops from a seed. Because current regulation of GMOs is based on the
dominant but soon to be out-dated gene-centered paradigm, we are entering a vast regulatory
vacuum.
11 A cautionary note
Clearly these new technological capabilities would have to be carefully monitored and regu-
lated. Noncoding Network Modified Organisms (NNMOs) or CENEtically Modified Organ-
isms (CMOs) will have to be regulated. This article is a report of what is possible, both good
and bad, given these technologies. We can potentially cure cancer but it can also be created.
For example, the use of CRISPR editing on the noncoding genome without understanding it
can have disastrous consequences, such as creating a cancer network[34]. Therefore, to avoid
disastrous use of CRISPR we need to complete Step 2 in any case.
In spite of the benefits and dangers, like it or not, the discovery of the hidden code in Step 2
is both necessary and inevitable. Therefore, it is important to be informed and be prepared for
the next revolution in the life sciences, namely, the design of multicellular life and the pur-
poseful or inadvertent editing of the as yet hidden networks (the CENEs[33]) in the noncoding
genome.
Eric Werner: Roadmap to create multicellular life (Preprint v1.0 Comments Welcome!) 10
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