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For this week, I would like you to choose a molecular biology article from the popular press that was published during the past three months. This article may be discussing new technology, a discovery from the lab, or a review of available data from the medical field. Taking what you have learned over the past few weeks, respond to the following questions:

List the APA style reference for the article:

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Does the article share the information in an honest and ethical fashion? Is there any bias? Explain your response.

In your opinion, what information, data, or analysis is missing from the article? What could be added to make the article more complete?

Please choose an original topic for your post. Feel free to claim a topic at the beginning of the week. Please make your first post by Wednesday evening and be sure to respond to all posts in your thread. Respond to at least one other student by Sunday evening. Please keep HIPAA guidelines in mind if you want to share work experiences

Science & Society

The long journey towards standards for
engineering biosystems
Are the Molecular Biology and the Biotech communities ready to standardise?

Jacob Beal1, Angel Goñi-Moreno2,3, Chris Myers4 , Ariel Hecht5, María del Carmen de Vicente6,

Maria Parco7, Markus Schmidt8, Kenneth Timmis9, Geoff Baldwin10, Steffi Friedrichs11,

Paul Freemont10, Daisuke Kiga12, Elena Ordozgoiti13, Maja Rennig14, Leonardo Rios15 ,

Kristie Tanner16, Víctor de Lorenzo17 & Manuel Porcar18

S
tandards are the basis of technology:

they allow rigorous description and

exact measurement of properties, reli-

able reproducibility and a common

“language” that enables different communi-

ties to work together. Molecular biology was

in part created by physicists; yet, the field

did not inherit the focus on the quantitation,

the definition of system boundaries and the

robust, unequivocal language that is charac-

teristic of the other natural sciences.

However, synthetic biology (SynBio)

increasingly requires scientific, technical,

operational and semantic standards for the

field to become a full-fledged engineering

discipline with a high level of accuracy in

the design, manufacturing and performance

of biological artefacts. Although the benefits

of adopting standards are clear, the commu-

nity is still largely reluctant to accept them,

owing to concerns about adoption costs and

losses in flexibility.

………………………………………………

“. . . Synthetic Biology (SynBio)
increasingly requires scientific,
technical, operational and
semantic standards for the
field to become a full-fledged
engineering discipline . . .”
………………………………………………

What standards are good for

In science and technology, the terms stan-

dard and standardisation describe different

things: shared semantic and graphical

languages for annotating the nature and the

properties of systems and their components;

the definition of units of relevant properties

and parameters along with methods to

calculate them; specifications of properties

and arrangements for the physical assembly

of the components of a system; and unam-

biguous protocols for the construction of

objects. Such standards enable an abstract

and precise description of a system with a

suitable—also standardised—quantitative

language or equivalent methods of

representation.

Beyond their important role in the natural

sciences, standards were also one of the key

drivers for the industrial revolution as they

enabled a seamless integration of product

design, fabrication of its components and

the final assembly—let alone tracing parts

and helping to sort out matters of safety and

intellectual property. Standards are for

instance imperative for designing electronic

circuits built from well-defined, universal

simple components, such as resistors, diodes

and transistors, or for software engineering

that uses precompiled modules and func-

tions. Standards enabled the rapid rise of the

1 Raytheon BBN Technologies, Cambridge, MA, USA
2 School of Computing, Newcastle University, Newcastle upon Tyne, UK
3 Centro de Biotecnología y Genómica de Plantas, (CBGP, UPM-INIA), Universidad Politécnica de Madrid, Pozuelo de Alarcón, Spain
4 University of Utah, Salt Lake City, UT, USA
5 Ginkgo Bioworks, Inc., Boston, MA, USA
6 European Commission, Directorate General for Research and Innovation, Brussels, Belgium
7 IN Srl, Udine, Italy
8 Biofaction, Wien, Austria
9 Institute of Microbiology, Technical University Braunschweig, Braunschweig, Germany
10 Imperial College, London, UK
11 AcumenIST, Brussels, Belgium
12 Waseda University, Tokyo, Japan
13 Asociación Española de Normalización (UNE), Madrid, Spain
14 Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby, Denmark
15 Institute for Bioengineering and Centre for Synthetic and Systems Biology, University of Edinburgh, Edinburgh, UK
16 Darwin Bioprospecting Excellence, Paterna, Spain
17 Centro Nacional de Biotecnología (CNB) CSIC, Madrid, Spain
18 Institute for Integrative Systems Biology, University of Valencia, Paterna, Spain
DOI 10.15252/embr.202050521 | The EMBO Reports (2020) 21: e50521 | Published online 26 April 2020

ª 2020 The Authors. Published under the terms of the CC BY NC ND 4.0 license EMBO reports 21: e50521 | 2020 1 of 5

https://orcid.org/0000-0002-8762-8444

https://orcid.org/0000-0002-4387-984X

https://orcid.org/0000-0002-6041-2731

personal computer industry in the 1980s and

1990s by interlinking standard components

such as hard discs, memory or keyboards

through standardised interfaces and

protocols.

………………………………………………

“. . . standards were also one
of the key drivers for the indus-
trial revolution as they enabled
a seamless integration of
product design, fabrication of
its components and the final
assembly. . .”
………………………………………………

From software to nuts and bolts, the

concept of a universally usable toolbox of

parts to assemble more complex systems is

typical for every discipline of engineering:

electronics, software, mechanical design,

architecture, chemical synthesis and so on.

Standards enable people to work together

through interoperability, coordination of

labour, reproducibility and reuse of other

people’s efforts and achievements.

Standards must be reliable, robust and

affordable, but, first and foremost, they must

be agreed on by their users. Indeed, stan-

dardisation—the process of implementing

and developing technical standards—

requires the consensus of many different

parties, such as private and public compa-

nies, organisations and policy makers. Stan-

dardisation can be driven by public

acceptance/market forces (de facto stan-

dards), directly ordained by law (de jure

standards) or, most commonly, arise from

the combination of legal/technical require-

ments and recognition by potential operators

since, in general, the broader the applicabil-

ity of a format, the greater its market [1].

Standards in the life sciences

That said, the core standardisation process in

many scientific and engineering disciplines

took place decades to centuries ago, but it is

still in its infancy in the life sciences. Interest-

ingly, it is still a bottleneck for even well-

developed technologies: smartphones, for

instance, still lack standard key components

such as batteries or electric charger cables (see

e.g. https://ec.europa.eu/info/law/better-re

gulation/initiatives/ares-2018-6427186_en).

In this context, the conceptual frame of

synthetic biology aims to making biology

easier to engineer by applying principles

such as modularity, orthogonality, chain

production and reproducibility. Moreover,

the rapid advances in wet and computa-

tional tools for genome editing, metabolic

design and in silico modelling are opening

new opportunities for genetic programming

that could not have been anticipated even

just a few years ago, and allow engineers to

tackle increasingly complex engineering

objectives. The growing demand for scaling

up such technologies raises the issue of what

is needed to make them work at an indus-

trial scale [2]. Following the path of other

branches of engineering, the establishment

of standards appears among the key objec-

tives of contemporary SynBio—and eventu-

ally of the life sciences as a whole—as a

prerequisite for applications such as biore-

mediation, biomedicine, bioenergy, novel

chemicals, innovative materials and cellular

factories.

Although standards in SynBio have

contributed to successes such as the synthe-

sis of artemisinin or morphine (both in

yeast), the problem of defining common

standards is still far from being resolved.

The reusability patterns of the iGEM parts

database [3], the context dependence of

biological components [4], the variable

behaviour among strains, genetic stability or

even the contested philosophical analogy

between cells and machines are by no

means solved issues at this point. However,

there is no doubt that even partial progress

on standardisation would have major conse-

quences for bioengineering.

One bottleneck is the widespread and

incorrect assumption among many

researchers in the life sciences that stan-

dards may increase interoperability but

necessarily limit flexibility—which is obvi-

ously important for any creative research.

Rather, good standards will increase

people’s flexibility and creativity because it

will make it easier for them to achieve their

scientific objectives. A separate challenge is

identifying specific systems and operations

that need to be standardised, and then navi-

gating the minefield of personal interests

that typically inhibit agreement on a given

format or language. As Murray Gell-Mann

quipped, “a scientist would rather use some-

one else’s toothbrush than someone else’s

nomenclature”. Scientists and engineers will

adopt standards only when they add value

to their efforts to overcome the often steep

costs of adoption.

Standards for engineering biology

While a number of SynBio standards have

already been developed and await adoption

by the broader community of users [5],

others touch on core biological questions

that are by no means solved from a scientific

point of view. There is a legitimate concern

that we still need to know more fundamen-

tal facts before we can describe engineered

biosystems with a formal, unequivocal

language. One typical case involves the

design of genetic circuits, an archetypal

product of SynBio endeavours. Habitual

practices include directly transplanting

toolkit for building electronic logic gates and

related information-processing devices into

the biological domain. However, one must

be honest about how far these abstractions

and their accompanying theoretical frame-

work reflect biological reality. Boolean logic

relies on values that are either true or false.

In electronics, this is readily implemented

using voltage levels that are separated by a

larger amount than the expected noise to

faithfully represent the state of the gate. In

contrast, biological implementations of

circuits tend to have a much higher noise-to-

signal ratio, which makes it difficult to effec-

tively distinguish true and false states and

strongly limits the design of logic circuits.

One way to alleviate this problem is by

redesigning regulatory components to

behave more digitally, but ultimately, we

may need to revisit information processing

in/by biological systems with other formal-

isms, either existing or yet to be developed,

that go beyond Boolean logic [6].
………………………………………………

“Scientists and engineers will
adopt standards only when
they add value to their efforts
to overcome the often steep
costs of adoption.”
………………………………………………

The same theory/implementation conun-

drum might be true for biological metrology,

one of the main tenets of SynBio. Electronic

circuits crucially rely on a clear definition of

potential and current, their description in

volts and amperes, and methods to measure

these. By the same token, it is difficult to

think about genetic circuits without robust

measures of signal transmission through the

regulation of gene expression or other core

cellular processes. The concepts of RNA

2 of 5 EMBO reports 21: e50521 | 2020 ª 2020 The Authors

EMBO reports Jacob Beal et al

https://ec.europa.eu/info/law/better-regulation/initiatives/ares-2018-6427186_en

polymerase per second (PoPS; [7]) and ribo-

some per second (RiPS) as biological coun-

terparts of current were conceptualised early

in the history of SynBio. Alas, very little has

been done to further develop these units as

practicable indicators of genetic circuit

performance, perhaps due to the difficulties

of measuring them accurately.

These examples showcase how developing

standards for biological engineering still

requires addressing a number of core scien-

tific and technological gaps that have been left

behind in the ongoing frenzy of application-

focused development. Yet, such unsolved

issues may strike back when the field contin-

ues to move from largely academic endea-

vours towards industrial realisation.

………………………………………………

“. . .developing standards for
biological engineering still
requires addressing a number
of core scientific and technolog-
ical gaps that have been left
behind in the ongoing frenzy of
application-focused develop-
ment.”
………………………………………………

Key actors in the standards
conversation

International discussions about SynBio stan-

dards, mostly with US and EU stakeholders,

have been going on since before 2010. Under

the umbrella of the BIOROBOOST Project

(http://standardsinsynbio.eu), the conversa-

tion now incorporates key actors of SynBio

from Europe, North America and Asia. Much

of the discussions deal with identifying key

challenges for the development, promulga-

tion and adoption of standards, and identify-

ing stakeholders in academia, industry,

research centres and politics.

The most conspicuous technical chal-

lenges include standardising simple biologi-

cal parts, devices and circuits, chassis,

metrology, descriptive languages (including

graphical representations) and software

tools. But the complexity of the endeavour

also asks for the creation of a network of

SynBio practitioners that share and evolve

these standards together. While this is remi-

niscent of earlier Computational Modeling in

Biology Network (COMBINE, http://co.mb

ine.org/), the focus of these SynBio

networks needs to go beyond academic

interests to include industry and commerce,

and to develop strategies for educating a

new generation of synthetic biologists who

routinely use standards.

From the regulatory, technical and soci-

etal point of view, the challenge is complex.

For example, there are practical questions

such as the level of detail required in a given

biological standard, which can go from light

to very deep. As indicated above, standard

is an umbrella concept, which includes a

number of different approaches to harmoni-

sation. These range from agreeing on metro-

logy units and best practices to measure

them, to developing standardised functional

chassis—specific, formatted biological hosts

for specific applications—to data formats, to

safety criteria for approval by regulatory

agencies and to ISO-approved reports and

technical specifications.

It is necessary to distinguish between

biological standards that could be similar to

physics and engineering counterparts, such as

the PoPS or RiPS units discussed above, and

standard operating procedures (SOPs), which

help users to carry out routine operations

with efficiency, consistent quality and perfor-

mance, and are compliant with regulations.

For instance, the composition and preparation

of the M9 medium would be an SOP, while

the metrics for calculating containment of a

given SynBio agent when released in the envi-

ronment could become a biological standard.

There are, of course, many grey zones

between these two—for instance, formats for

enabling communication between unrelated

software, cloning methods, CRISPR-based

editing and so on—that will hopefully be

solved through conversations between stake-

holders in the various forums just mentioned.

The question remains, however, whether the

wider community of potential users will see

the value of adopting standards in their daily

practice. Today, SynBio and systems biology

practitioners are widely using the Synthetic

Biology Open Language SBOL [8] and

SBOL

visual for describing vectors and constructs

[9], and there is a great consensus on the

need to go beyond the state of the art and

further advance towards the standardisation

of biological systems [5,10].

Stages of adoption

Is there a take-home lesson from the history

of technology adoption that we can learn

from for popularising biological standards?

In fact, the trajectory of acceptance in the

realm of engineering typically involves

several stages: from an innovator phase to

adoption by even the most recalcitrant

laggards (Fig 1). Using this frame, it seems

that most of the SynBio’s standards develop-

ments are still in the innovator phase.

Many developments, even if critical for

the early years in SynBio, never left the

innovator state and are now outdated;

advances in cloning and DNA synthesis have

for instance replaced BioBricks. Others, such

as SBOL [8] or the Standard European

Vector Architecture (SEVA; [9]) are increas-

ingly successful as interim formats in the

early adopter stage. Yet, these may or may

not become generally adopted depending on

success stories and potential alternative

scientific and technical solutions. Such

progress will be determined by the combina-

tion of a bottom-up demand for interoper-

ability and collaboration and a top-down

implementation and enforcement by official

agencies. Journal editors also have a role to

play as well as reviewers of journal articles

and grant proposals in insisting on the use

of standards to improve reproducibility and

reuse. Generally, it is important to realise

that standards are ultimately social

constructs to represent norms, objects or

procedures, and that they become accepted

by a group of individuals for practical

reasons.

………………………………………………

“. . . standards are ultimately
social constructs to represent
norms, objects or procedures,
and that they become accepted
by a group of individuals for
practical reasons.”………………………………………………

Low-hanging fruits

Despite the difficulties, it should be possible

to come up with science-based standardisa-

tion proposals in SynBio that work across

the biological, the digital and the social

realms. The already existing ones at hand

involve simple biological parts: devices such

as promoters and other regulatory nodes

and simple circuits—for instance, inverters,

basic gates—such as those deposited in the

repository of biological parts and other

curated collections. The next stage involves

definition and adoption of SynBio chassis

ª 2020 The Authors EMBO reports 21: e50521 | 2020 3 of 5

Jacob Beal et al EMBO reports

http://standardsinsynbio.eu

http://co.mbine.org/

other than laboratory bacteria or yeast

strains. Not every species or strain that can

host recombinant DNA can be considered a

chassis, and this effort requires establish-

ment of a map of requirements and func-

tional relationships between industrially

relevant practical applications and different

biological platforms. Finally, standardisation

would need to address the issue of metro-

logy through the gene expression flow

including fundamental units and the tech-

nologies and references to measure them, as

well as computational language and soft-

ware tools for easing collaborations between

different actors. The main efforts to collect

such low-hanging fruits would be greatly

facilitated by biofoundries with good

connections to policy makers with the objec-

tive of making the whole endeavour more

appealing for the industrial sector.

………………………………………………

“.. the key to success is the
merger of technical consistency
and scientific soundness with
legal requirements and consen-
sus among end users.”
………………………………………………

The academic community cannot be a

mere observer of these developments. In

fact, there is much to do for endowing

biological standards with a solid scientific

basis, including the definition of each level

of biological complexity amenable to stan-

dardisation. But the role in promoting

standards is not only technical. There is

ample room for networks of practitioners

involving industrial players, who can

provide information on how biological prop-

erties and processes could improve product

development, manufacturability and

consumer confidence. This could create a

framework for identifying and monitoring

standardisation requirements and maintain-

ing an evolving list of scientific and indus-

trial priorities. Ideally, such priority lists

should also be considered by funding bodies

to help in developing and driving adoption

of standards. Relevant regulatory bodies

should be involved to adapt or ease rules on

the management of GMOs and/or SynBio

agents. The same academic–industrial

networks could also strengthen ongoing

public outreach and citizen involvement to

help overcoming the negative perception of

genetic engineering in general.

In sum, we argue that the promise of

SynBio for the benefit of global society

and industry will only be met if significant

advances are achieved on the standardisa-

tion front. To this end, it is not only

essential to overcome national/political

barriers and particular interests of given

research groups, but also to gather key

players in a permanent forum with the

aim of making biological standards one of

the ingredients of the 4th Industrial Revolu-

tion. Standards in biology will be used

provided that they have intrinsic properties

such as robustness, ease of use and

context independence. But the key to

success is the merger of technical

consistency and scientific soundness with

legal requirements and consensus among

end users. This goes beyond the realm of

research and tackles sociological and

cultural issues that have been traditionally

alien to the conversation. If this can be

achieved, the benefits for SynBio and for

society at large will be great.

Acknowledgements
Mireia Alonso is gratefully acknowledged for help

in formatting the different versions of this manu-

script. This work was funded by the European

Union through the BioRoboost Project, H2020-

NMBP-TR-IND-2018-2020/BIOTEC-01-2018 (CSA),

Project ID 820699. Jake Beal was also supported

in part by NSF Expeditions in Computing

Program Award #1522074. This document does

not contain technology or technical data

controlled under either US International Traffic in

Arms Regulation or US Export Administration

Regulations. The information and views set out

in this article are those of the authors and do

not necessarily reflect the official opinion of the

European Commission.

References
1. Dan SM (2019) How interface formats gain

market acceptance: the role of developers

and format characteristics in the develop-

ment of de facto standards. Technovation 88:

102054

2. Beal J, Haddock-Angelli T, Farny N, Reggberg

R (2018) Time to get serious about measure-

ment in synthetic biology. Trends Biotechnol

36: 869 – 871

3. Vilanova C, Porcar M (2014) IGEM 2.0–refoun-

dations for engineering biology. Nat Biotech-

nol 32: 420 – 424

4. Carr SB, Beal J, Densmore DM (2017) Reduc-

ing DNA context independence in bacterial

promoters. PLoS ONE 12: e0176013

5. de Lorenzo V, Schmidt M (2018) Biological

standards for the knowledge-Based BioEcon-

omy: what is at stake. New Biotechnol 40:

170 – 180

6. Grozinger L, Amos M, Gorochowski TT, Carbo-

nell P, Oyarzún DA, Stoof R, Fellermann H,

Zuliani P, Tas H, Goñi-Moreno A (2019) Path-

ways to cellular supremacy in Biocomputing.

Nat Com 10: 5250

7. Endy D (2005) Foundations for engineering

biology. Nature 438: 449 – 453

8. Galdzicki M, Clancy K, Oberortner E, Pocock

M, Quinn J, Rodriguez C, Roehner N, Wilson

M, Adam L, Anderson JV et al (2014) SBOL: a

community standard for communicating

Innovators Earlyadopters
Early

majority
Late

majority Laggards

BioBricks

Plate
calibration

SYNTHETIC BIOLOGY

Cytometry
calibration

SEVA

SBOL

CRISPR editing

Gibson assembly

MoClo

M
B

Figure 1. Adoption curve of/for biological standards.
Illustrative examples of the position of SynBio standards along the technology adoption curve: SynBio standards
are largely still in the innovator phase but with a few examples having progressed to the early adopters or early
majority segments. SBOL, Synthetic Biology Open Language; SEVA, Standard European Vector Architecture;
MoClo, modular cloning.

4 of 5 EMBO reports 21: e50521 | 2020 ª 2020 The Authors

EMBO reports Jacob Beal et al

designs in synthetic biology. Nat Biotechnol

32: 545 – 550

9. Martínez-García E, Goñi-Moreno A, Bartley B,

McLaughlin J, Sánchez-Sampedro L, Pascual

Del Pozo H, Prieto Hernández C, Marletta AS,

De Lucrezia D, Sánchez-Fernández G et al

(2020) SEVA 3.0: An update of the Standard

European Vector Architecture for enabling

portability of genetic constructs among

diverse bacterial hosts. Nucleic Acids Res 8:

D1164 – D1170

10. Schreiber F, Sommer B, Bader GD, Gleeson P,

Golebiewski M, Hucka M, Keating SM, König

M, Myers C, Nickerson D et al (2019) Specifi-

cations of standards in systems and synthetic

biology: status and developments in 2019. J

Integr Bioinform 16: 20190035

License: This is an open access article under the

terms of the Creative Commons Attribution-

NonCommercial-NoDerivs 4.0 License, which

permits use and distribution in any medium,

provided the original work is properly cited, the use

is non-commercial and no modifications or adapta-

tions are made.

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