Synthetic Biology is the name given to an emerging scientific discipline which integrates knowledge of biology, genetics, chemistry, computational
science and engineering, and which has the principle objective of producing new or improved life
forms. Unlike traditional biology, which aims to
understand and explain the chemistry and structure
of living beings as a natural phenomenon, synthetic biology, using tools derived from advances in
molecular biology, treats the structures, molecules
and biochemical systems as starting material for the
design of de novo life forms or life forms with new
properties that are absent in nature.
Synthetic Biology promises to revolutionise biotechnology in the years to come, reducing our dependence on fossil fuels with the introduction of cleaner
energy and transforming biomedicine, for example
by developing biosensors that integrate diagnosis
The origin of this discipline goes back to the
70s, with the emergence of the first
breakthroughs in Molecular Biology
(1-4), from which methods and techniques are drawn. The 80s and 90 took advantage of two notable developments,
the arrival of the polymerase chain reaction, and later automatic sequencing
techniques, which allowed the completion of the whole human genome
(Human Genome Project) in 2001 (5,6). In 2010,
the Venter group showed that a new self-replicating
bacterial species could be produced using these
techniques (7). This early study showed the creation of the first self-replicating synthetic genome in
a bacterial cell of a different species, and was the
first time that all the genetic material in a bacterial
cell had been replaced with a synthetic copy of the
genes necessary for its normal functioning. Basically, the research consisted of assembling synthetic
DNA fragments to obtain the complete genome of
one of the most simple bacteria known, Mycoplasma mycoides, which has around 1 million base pairs
(the unit of length of nucleic acids, consisting of
pairing of complementary nucleotides A-T or C-G).
This new set of genes or synthetic genome is rather
like an instruction manual with the message required for the cell to be able to live and divide. This
genome was then used to replace that of a “sister”
bacterium, Mycoplasma capricolum, which without
its instruction manual becomes a useless shell. This
synthetic genome was then able to take charge of
the activity of the bacterial cell and adapt it according to its own instructions, enabling its growth and
As can be clearly seen in the example above, the
basic tools of Synthetic Biology are the standardised
fragments, such as genes, proteins or
chromosome fragments with a known
function, which can be assembled to
program cells and control the function
of the organism. One of the most widely used strategies in Synthetic Biology consists of the use of so-called
Biobricks, more or less complex DNA
fragments that determine a function or
coordinated functions (8), and which can be designed and combined to achieve a new function for the
cell or by extension, for the organism or species.
More recently, there has been a quantum leap with
the synthesis of the first synthetic eukaryotic species (9). In this case, Dr. Moreno of the University of Berne was able to produce a new species of
Instituto de Ciencias de la Vida
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fly by manipulating a small group of known genes,
generating a fly with a different phenotype which
was able to reproduce with those of its own species,
but not with the species from which it
originated, thereby demonstrating for
the first time that the transition between
transgenic and synthetic species is possible.
Venter’s work exemplifies a type of
top-down approach, starting from one
of the simplest forms of cell life and separating each of its genes to observe its
effect on the organism. In contrast, other Synthetic
Biology studies such as those conducted by Murtas
(10) and Luisi (11) exemplify a bottom-up strategy or approach, which aims to create a living being
from totally inert materials. The progress consists
of having produced a species of simple cells which
are, basically, sacs made from adipose membrane
containing purified enzymes and ribosomes, components common to all cells which translate the genetic code into proteins.
Although this is an area in early development,
with numerous limitations, many other biochemical transformation projects have been carried out,
which we can group into four types (12):
-Incorporation of non-native genes to extend the
natural metabolism of the organism.
-Incorporation of complete metabolic pathways
to add their function.
-Creation of new metabolic pathways which never existed before in nature.
-Organisation of metabolic pathways to potentiate their activity (via scaffolds).
This discipline, by applying the techniques and
tools of engineering to biological systems, will advance our basic understanding of how living beings
function, and of the design and production of new
molecules. Some of the most important approaches
on which their development is based are the expansion of the genetic code, the design of genetic circuits with coordinated function and the identification of the self-replicating minimal genome.
In the biomedical field, the main achievement to
date has been the artificial production of the antimalarial drug artimiscinic acid (13). However,
Synthetic Biology will also enable advances to be
made in the biomedical field in the characterisation
of pathogens, analysis of diseases, the
development of new diagnostic tools,
new screening assays and in the production of personalised drugs and vaccines. In the short term, this progress
could result in shorter periods for the
discovery and development of drugs
and improvement of their specificity,
as well as production of cheaper medicines. Similarly, sophisticated sensors are being
designed that can detect changes in metabolites and
pathological conditions, and which have the ability to return abnormalities to a normal status, thus
connecting diagnosis and treatment automatically.
Some recent studies show that this is possible in
animal models of human diseases. However, there is still a long way to go before these Synthetic
Biology-based systems can be used in clinical medicine. One of the major challenges will be to place
these circuits specifically into cells, either based on
genes or on cells, with the certainty that they will
not interfere with the metabolism (14).
In the field of environmental science, the main
developments to date have been the production of
bioalcohols as an energy source, the design of photosynthetic algae and hydrogen production (15).
Some of the objectives in this field are the production of renewable energy, increasing energy production and improving its efficiency, and the design of
biological systems that could be useful in bioremediation or that can function as biosensors.
At present, the major limitation for advancement
in this discipline is the inability to predict the behaviour and evolution of the new synthetic biological systems. The extraordinary complexity of gene
expression is evident in recent discoveries on the
function of the genome and the functioning of epigenetic processes (16).
Like any biotechnological advance, synthetic biology is ambivalent, promising enormously useful
discoveries for man on one side, and on the other,
raising far-reaching ethical dilemmas. Some of the
most important are those that could affect the environment, such as the possible threat for biodiversi-
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ty due to the introduction of new synthetic species,
or the possible control of the evolutionary process,
with unpredictable consequences. Another important element to consider is that we are in a setting
where progress in this and other experimental science fields can be made outside university laboratories
and research centres, using sophisticated techniques
that are already considered of routine use, which
increases concern for their possible use in bioterrorism, with a risk ultimately of self-destruction (17).
In addition to the above, advances in this discipline
pose ethical issues arising from what could be an
attempt to overcome the human species in a posthumanist society (18), whilst pushing us towards a
deepening in the meaning of vital phenomenon.
1. Jackson, David D., R. H. Symons, and Paul Berg.
Biochemical Method for Inserting New Genetic Information into DNA of Simian Virus 40: Circular
SV40 DNA Molecules Containing Lambda Phage
Genes and the Galactose Operon of Escherichia
coli. Proc. Natl. Acad. Sci. U.S.A. 1972;69(10):2904-
2. Khorana HG, Agarwal KL, Besmer P, Büchi H,
Caruthers MH, Cashion PJ, et al. Total synthesis
of the structural gene for the precursor of a tyrosine suppressor transfer RNA from Escherichia coli.
1. General introduction. J Biol Chem. 1976 Feb
3. Maxam AM, Gilbert W. A new method for sequencing DNA. Proc. Natl. Acad. Sci. U.S.A. 1977
4. Sanger F, Donelson JE, Coulson AR, Kössel H,
Fischer D. Use of DNA Polymerase I Primed by a
Synthetic Oligonucleotide to Determine a Nucleotide Sequence in Phage f1 DNA. Proc. Natl. Acad.
Sci. U.S.A. 1973;70(4):1209–13.
5. Venter JC, Adams MD, Myers EW, Li PW, Mural
RJ, Sutton GG, et al. The sequence of the human
genome. Science. 2001 Feb 16;291(5507):1304-51.
6. Lander ES, Linton LM, Birren B, Nusbaum C,
Zody MC, Baldwin J, et al. International Human
Genome Sequencing Consortium. Initial sequencing and analysis of the human genome. Nature
2001 Feb 15;409(6822):860-921.
7. Gibson DG, Glass JI, Lartigue C, Noskov VN,
Chuang RY, Algire MA, Benders GA, Montague
MG, Ma L, Moodie MM, Merryman C, Vashee S,
Krishnakumar R, Assad-Garcia N, Andrews-Pfannkoch C, Denisova EA, Young L, Qi ZQ, SegallShapiro TH, Calvey CH, Parmar PP, Hutchison CA
3rd, Smith HO, Venter JC. Creation of a bacterial
cell controlled by a chemically synthesized genome. Science 2010 Jul 2;329(5987):52-6.
9. Moreno E. Design and construction of “synthetic species”. PLoS One.2012;7(7):e39054
10. Murtas G. Artificial assembly of a minimal cell.
Mol Biosyst. 2009 Nov;5(11):1292-7.
11. Luisi PL. Chemical aspects of synthetic biology. Chem Biodivers. 2007 Apr;4(4):603-21.
12. Fritz BR, Timmerman LE, Daringer NM, Leonard JN, Jewett MC. Biology by design: from top
to bottom and back. J Biomed Biotechnol. 2010
Nov. doi: 10.1155/2010/232016
13. Ro DK, Paradise EM, Ouellet M, Fisher KJ,
Newman KL, Ndungu JM, Ho KA, Eachus RA,
Ham TS, Kirby J, Chang MC, Withers ST, Shiba Y,
Sarpong R, Keasling JD. Production of the antimalarial drug precursor artemisinic acid in engineered yeast. Nature. 2006 Apr 13;440(7086):940-3.
14. Weber W, Fussenegger M. Emerging biomedical applications of synthetic biology. Nat Rev Genet. 2011 Nov 29;13(1):21-35.
15. Savage, D.F., Way J., and P.A. Silver. (2008).
Defossiling fuel: How synthetic biology can transform biofuel production. American Chemical Society Chemical Biology 3(1):13-16.
17. Sgreccia E. Manual de bioética. I, fundamentos
y ética biomédica. Madrid: Biblioteca de Autores
Cristianos; 2007. Capítulo II, punto 4 “El método
de investigación en bioética” pp73-74.
18. Ballesteros J. Biotecnología y posthumanismo.
Pamplona: Ed. Aranzadi; 2007.
Dr. D. José Miguel Hernández Andreu
Professor of Biochemistry and Molecular Biology
Faculty of Medicine and Odontology
Member of the Bioethics Observatory
“San Vicente Mártir” Catholic University of
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As discussed in Nature Medicine (18; 329, 2012),
South Korea is positioning itself at the forefront of
stem cell commercialisation, having approved three
treatments in the last eight months.
The first was approved in July 2011, when the
Korea Food and Drug Administration (KFDA)
authorised the use of a cell product called Hearticellgram-AMI, for treating heart attacks. It is marketed by the Seoul-based company, Pharmicell.
This therapy uses mesenchymal cells
obtained from the patient’s own bone
marrow, which after being appropriately cultured, are injected into the coronary artery of the damaged cardiac
area. Hearticellgram is the first cell
product that uses adult stem cells for
therapeutic purposes to be authorised
in the world.
The second, approved four months
later by the North American FDA, legalised the first product made in the United States,
using cord blood cells obtained from the New York
Blood Center’s cord blood bank. This cell product
is called Hemacord.Also last January, the KFDA
gave the green light to another two cell products,
one for Medipost’s Cartistem which, using cord
blood stem cells, is aimed at regenerating the cartilage in patients who have undergone knee surgery.
The second (third worldwide) is produced by Anterogen. Known as Cupistem, it uses fat stem cells
from the patient himself and is intended for use in
the treatment of anal fistulas in Crohn’s disease.
It should be noted that the cell products Hearticellgram and Cartistem are the first licensed stem cell
products that use bone marrow or cord blood stem
cells to treat non-blood or immune system diseases.
Of these treatments, Cartistem appears to be the
most promising, since of the 89 patients treated, 26% experienced an
improvement in knee function compared with those who received surgical
treatment only. Similarly, using Hearticellgram in a group of 80 patients,
it could be observed that the group of
patients who received the cell product
improved their cardiac function by
6%, compared to 2% of patients who
received standard treatment, although
these differences were not statistically significant.
Nevertheless, certain experts in this therapeutic
area are somewhat sceptical about the efficacy of
these new products, since to date no results have
been published in quality scientific journals. However, representatives of these companies have stated
that their trials will be published shortly in peer-reviewed journals.
If you access internet, you can find advertisements from clinics offering cell therapy in China for
almost any type of disease or injury, and even to
encourage rejuvenation and increase energy, which
naturally is not proven and can therefore constitute
Due to the way in which the advertising is sent,
it can seem that their offer is real and medically serious, as it can be carried out in clinics directed by
doctors and staffed by nurses; they appear to have
stem cells from different sources and of good quality, which apparently suggests the likelihood that
these clinics can reliably help potential patients.
China is not the only country where these
treatments are offered, as other companies that work
with stem cells also offer cell therapies in developed
countries, even in the United States (Nature 483;
13-14, 2012), although these types of clinics are undoubtedly most widespread in China.
The promoters of these treatments, which are
not subject to medical control, compare them to
previously groundbreaking organ transplant, and
although the directors of these clinics generally state that they cannot guarantee that the stem cells are
used for the therapeutic purpose for which they are
intended, they do state that they can guarantee that
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As we have already discussed in Provida Press
(no. 390), a cloning technique has been developed
which can be used to prevent the transmission of
mitochondrial-linked diseases, diseases therefore only transmissible by
women. So what are mitochondria
and what diseases can be associated
with their alteration?
All human cells contain two genomes: one in the cell nucleus and
another in the mitochondria, small organelles contained in human oocytes
(eggs). The genome of the cell nucleus
inherits the genomic message from the father and
the mother. Mitochondria only inherit the mother’s
genes. The mitochondrial genome contains just 37
genes. Any genetic aberrations are transmitted during cell division (mitosis) and can be passed on to
different generations (this is called heteroplasmy).
Individuals who lack mitochondria (homoplasmy) or with alterations in the mitochondria can inherit diseases linked to mitochondrial DNA.
Although the genetic material in the mitochondria
is only 3% of the cellular genetic material, its alteration is nevertheless the cause of serious diseases,
especially those linked to abnormal
energy production, among which are:
deafness, blindness, diabetes, and
heart and liver failure. Around 1 in
every 400 people suffer from these
types of diseases (BMJ 342; 87-89,
Solving the problem of the transmission of mitochondrial-linked diseases is a major medical problem,
but doing so using human cloning techniques has
unquestionable ethical limitations, in addition to the
fact that at present it is not technically possible to
use these techniques in clinical medicine either.
the methods used by them are safe and do not have
negative side effects.
Despite medical safety constraints in these Chinese clinics, clients continue to arrive, since together
with the medical treatment, they also offer to cover all treatment needs with a great range of prices
according to each patient’s requirements. However,
what they cannot guarantee is that the therapies proposed by them have been subjected to rigorously
tested clinical trials (Nature 484; 141, 2012).