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SCIENCE KOLKATA WEDNESDAY 26 MAY 2010 10

‘It’s a whole new paradigm’ Parthenogenetic

protocol
Steve Connor speaks to scientist Craig
Venter, head of the team that created
the first synthetic living cell
CRAIG Venter first gained notoriety in
the 1980s when he left the publicly funded
human genome project in the USA to set up a
privately financed initiative in direct
competition with the government research
programme. He developed a “shotgun” method
of decoding the genome by splitting the DNA
into thousands of fragments that could be
decoded simultaneously. This technique was
faster than the more laborious, but somewhat
more accurate, method used by the public
project.
A former Vietnam veteran and beach bum,
Venter became interested in medical science
when he witnessed soldiers dying from a single
bullet wound and others surviving horrific
injuries. He went back to college to make up
for his lost education and quickly made a
name for himself, as well as some enemies on
the way.
He completed a draft of the human genome
and agreed to share the publicity platform
with scientists leading the publicly funded
initiative. He shook hands with his arch-rivals
in a White House ceremony presided over by
Bill Clinton. He claims he was depicted
wrongly by the media as a scientist more
interested in financial gain than furthering the
boundaries of scientific knowledge.
His first big breakthrough in the field of
synthetic life probably occurred in 1995, when
he led the team that sequenced the genome of
the microbe Mycoplasma genitalium, only the
second free-living organism to have its genome
sequenced at that time. He said that the
decoding of a microbe led him to think about
synthesising a genome from scratch to create a
free-living organism.
In 1999, he announced his intention to start
the “minimal genome project” to find the
smallest set of genes required for life. This led,
in 2008, to the production of a complete
genome of a single-celled microbe, but it
would take several more years for Venter and
his team to get this synthetic genome to control
a living cell.
On 20 May 2010, Venter led the $40-million
study that created the synthetic microbe from
a living cell and an artificially-constructed
chromosome made from a DNA code stored
on a computer. Excerpts from an interview:
What have you done that is new?
This is the first time anyone has built an
entire 1.08-million base pair chromosome,
transplanted that chromosome into a recipient
cell and for that chromosome to take over that
cell, effectively converting it into a new species
defined by the chromosome. So it’s a whole
new paradigm, the first time we have a cell
that is totally controlled 100 per cent by a
synthetic chromosome.
Do you consider this to be synthetic life?
We’re defining it as synthetic life because it’s
totally determined by the synthetic
chromosome. We do start with a living cell but
the synthetic chromosome totally transforms
that living cell to this new synthetic cell.
There are no single elements of the recipient
cell. Our synthetic cell has undergone over a
billion replication events and the only DNA in
it is the synthetic DNA and the only proteins
hard to imagine all the applications of this
technology. Our view is that we’re going from
Tapan Kumar Maitra examines
6.8 billion to nine billion people in the next 30
to 40 years, and we can’t provide the food, the
energy, clean water or medicines for the 6.8
some of the common features of
billion, so we need some radical new asexual reproduction in animals
technology to be able to do that without
destroying the planet for nine billion people. REPRODUCTION by groups of cells, comparable to veg-
are those coded for by the synthetic DNA. We etative reproduction in plants, occurs only among the
don’t make the proteins synthetically, we don’t Are you playing God with life? more primitive invertebrates; but among the normal sex-
make the cells synthetically. All that is dictated We’ve covered this before because it’s almost ual groups parthenogenesis is widespread and can be art-
by the chromosome. a cliché every time there’s a new breakthrough ificially induced in such vertebrates as the turkey and rab-
We do not consider this to be “creating life in science, particularly in biology. Science is bit. Haploid parthenogenesis is both a form of reproduc-
from scratch” but rather we are creating new understanding life at its most basic levels and tion and a means of sex determination. Fertilised eggs
life out of existing life using synthetic DNA to trying to use that knowledge for the develop into diploid females, unfertilised parthenogenetic
reprogramme the cells to form new cells that betterment of humanity, so I think we are part ones into haploid males.
are specified by the synthetic DNA. of the progression of scientific knowledge and The former has evolved independently six or seven times
understanding of the world around us. in the animal kingdom: in the Rotifera, Acarina (mites)
Why did you choose the microbe Mycoplasma and in four orders of insects — the Hymenoptera, Homop-
mycoides to be your guinea pig? Are you concerned that this technology may tera, Coleoptera and Thysanoptera. Oogenesis in these
This is step one, a proof of the paradigm. It be misused? forms is essentially normal. However, because the males
makes sense to us to start with something that We have to be concerned. It’s a powerful are haploid, spermatogenesis cannot follow a normal
we know should be biologically active, if we technology and I’ve proposed new regulations course of events. The first meiotic division is abortive and
can make it accurately. Proving that this is in this field because I feel the existing ones a reduction in chromosome number does not take place.
possible is no minor feat. It changes the stage don’t go far enough. Because we’re the The second division is normal and only two instead of
from hypothetical, which is where it was two What are you hoping to achieve eventually? inventors and developers of this we want to four spermatids are formed. This type of spermatogenesis
months ago, to real. The purpose is to try to understand the basic see everything that can be done to prevent has been shown to occur even in the rare diploid males of
nature of life, and the minimal sets of genes misuse of this technology. the wasp, Habrobracon, where homologous chromosomes
So is this new form of life a replicating, free- needed for life. We do not know all the gene I’ve proposed regulating the companies that capable of pairing in meiosis are available. In an
living organism? functions in any single cell. We don’t know synthesise DNA, to screen (the DNA being evolutionary sense male haploidy means that every
That is correct, only it is only free-living in what they do, we don’t know how they all synthesised) against harmful agents, and we’ve mutation is immediately exposed to the selective action of
the sense that it grows in the laboratory in a work so we’ve been trying for 15 years to given feedback on improving those screens the environment. The same, of course, is true for any
very rich culture media so it wouldn’t survive come up with ways to be able to define that and being more rigorous. I’ve been briefing the haploid organism. A greater degree of homozygosity and
in the outside environment. Given the right even for simple cells. US Congress on this. We don’t want people far fewer lethals are, therefore, to
nutrients in the laboratory, it is completely self- So that is the key part of the next stage. But taken by surprise. We want to put this be expected in such
replicating on its own. over the years the uses of this technology have breakthrough into context in terms of what it populations as
become much more apparent to us and to means. We’re trying to take every responsible compared to
How difficult was this? others. It’s a powerful technology for actually step we can in that respect. I think this is the those of
At one time there was just one error in over trying to design specific functions into first incidence in science where the extensive normal
a million base pairs, and we found that as a organisms, for example to manufacture new bioethical review took place before the diploids. In
result you don’t get life. So this was very fuels out of carbon dioxide or to create new experiments were done. It’s part of an ongoing this sense, the
difficult. I was predicting for the past three vaccines very rapidly instead of the long process that we’ve been driving, trying to make entire haploid The komodo dragon (Varanus
years that we would achieve this delays we have. sure that the science proceeds in an ethical set of komodoensis) can reproduce naturally
breakthrough, so I’ve learnt not to do I liken it to the 1940s and 1950s when the fashion, that we’re being thoughtful about chromosomes by parthenogenesis.
predictions. There were huge hurdles to electronics revolution was still getting going. what we do and looking forward to the is comparable to the X chromosome of those species,
overcome here. We had to learn and invent The people then building circuits probably had implications to the future. including man, which is exposed in an unprotected state in
new systems to make this possible, so it wasn’t very little notion about BlackBerry phones or males. For example, Drosophila X chromosomes do not
trivial iPhones or personal computers. It’s probably The Independent, London contain the frequency of lethal and deleterious genes
found in autosomes. Somatic parthenogenesis produces
DNA synthesis is rapidly becoming cheaper, so only females from unfertilised eggs. If obligatory, the
What other scientists say this could change, but not soon.” ~ Dr Gos population consists only of females. If incomplete,
Micklem, Department of Genetics, parthenogenesis alternates with sexual reproduction in a
‘CRAIG Venter talks of ‘writing the genetic code’ University of Cambridge. systematic manner.
of a cell which then becomes self-replicating. Obligate parthenogenesis is a closed genetic system,
This is heady stuff which Venter admits has “The applications of this technology (could be) because meiosis and the recombination of genes have been
potential for both good and ill. He is very a key step in the industrialisation of synthetic abolished. Such a group of organisms can be considered a
precise about the possible benefits but not biology, leading to a new clonal line of unvarying genotype and is, consequently, at
about the dangers. This work deserves praise era of biotechnology. It is the mercy of a changing environment. Most forms
and enthusiasm, but only so long as the risks not clear if this approach exhibiting obligatory parthenogenesis are polyploid,
are given attention commensurate with the will work for larger and more complex however, and are thereby provided with a buffered
benefits.” ~ Professor John Harris, Manchester University. genomes or for transplantation in different genotype that can exist and reproduce in more diverse
bacterial cells. Still, this is a landmark step in ecological situations than can their related sexual diploid
“Venter is creaking open the most profound our abilities to produce man-made cells for forms.
door in humanity’s history. He is not merely man-made purposes.” ~ Professor Paul Certain obligatory forms, however, undergo a regular
copying life artificially, as Ian Wilmut did, or Freemont, co-director of the EPSRC meiosis with the somatic number of chromosomes being
modifying it radically by genetic engineering. Centre for Synthetic Biology, Imperial restored by fusion with one of the polar bodies, or by a
He is going towards the role of a god: creating College London. fusion of the cleavage nuclei, and these have a greater
artificial life that could never have existed possibility for phenotypic and genotypic variation. Even
naturally. We need new standards of safety “The ability to do all of the steps of protein so, the entire range of variability is limited by the degree of
evaluation for this kind of radical research synthesis, from genome to product, to make heterozygosity of the mother. It is not surprising,
and protections from military or terrorist something useful is an important step in therefore, that obligatory parthenogenesis is a sporadic
misuse and abuse.” ~ Professor Julian developing the potential of synthetic biology. occurrence in the animal kingdom and does not
Savulescu, Uehiro Chair in Practical Ethics, University of As we become technically better at doing characterise any entire group. Cyclical parthenogenesis, on
Oxford. synthetic biology, the potential applications the other hand, utilises the advantages of both
open up. Mainly, what it will allow us to do is parthenogenetic and sexual reproduction. Such behaviour
“This is a landmark paper. The group are leaders at synthesising harness useful biological processes so that we characterises many of the aphids, the Tetraneura ulmi
and reassembling large segments of DNA. There is already a can make products that are difficult to being an example.
wealth of simple, cheap, powerful and mature techniques for synthesise with traditional chemistry and
The writer is Associate Professor and Head, Department of
genetically engineering a range of organisms. Therefore, for the physics.” ~ Professor Douglas Kell, CEO, Biotechnology
Botany, Ananda Mohan College, Kolkata
time being, this approach is unlikely to supplant existing methods. and Biological Sciences Research Council, UK.

Helping the environment

The lowly termite is seen to have an important
ecological role, says S Ananthanarayanan
THE complexity of the interdependence of natural systems
repeatedly affirms the importance of preserving biodiversity.
Many species and systems living together make for a uniform
exploitation of resources, with species mutually restoring the
resources consumed by others. Each species then depends on
services of other species and there is a feedback mechanism to
check disproportionate growth of any one strain, which affects
the survival of others, on which the first strain depends.
The interdependence of species is often extended and there
can be distant connections between the welfare of seemingly
unrelated natural systems. The destruction of one species can
endanger the survival of many more or even a whole
ecosystem. And then species that apparently serve no end for
other species are often discovered to be vital to the environment,
in a manner not suspected.
A group of researchers studying the grasslands in central
Kenya report in the journal Biology of the Public Library of
Science the role of the termites in maintaining the flora and
fauna of the region.
The discovery of the termites’ role arose from studies of
geckos and lizards that inhabit the region. This part of Kenya is
dotted with grassy termite mounds made of mud, plant matter,
saliva and faeces, sometimes 10 metres in diameter and spaced
some 60-100 metres apart. A remarkable find was that the
mounds were surrounded by large numbers of lizards. A study
of the overall ecological productivity of the region showed that
there were huge aggregations of plant and animal life forms in
the vicinity of the mounds. Plants grew more rapidly when
nearer a mound and animals reproduced noticeably less when
they moved away. This observation became even more marked
when the network of mounds was viewed from satellites.
Satellite imagery showed that although the mounds were not
a significant feature of the terrain on the ground, they were in
fact each one at the centre of a burst of plants and flowers,
with each burst organised in relation to other bursts, as if in a
checkerboard pattern when seen from the air! The termite
mounds were clearly agents of great ecological significance.
“In essence, the highly regular spatial pattern of fertile
mounds generated by termites
actually increases overall levels of
ecosystem production. And it does so From mother From father
in such a profound way,” says Todd
M Palmer, assistant professor of
biology at the University of Florida
and an affiliate of the Mpala
Research Centre in Nanyuki, Kenya.
“Seen from above, the gridwork of
termite mounds in the savanna is not
just a pretty picture. The over-
dispersion, or regular distribution of
these termite mounds, plays an
important role in elevating the
services this ecosystem provides.”
The water connect
TERMITE mounds seem either to
come up over places where there is
groundwater, or they help
groundwater to collect. Varah Mihira,
sixth century astronomer and
mathematician of the Ujjain court,
writes in his treatise on water divining
that “sweet groundwater would be
found near a termite mound located
east of a Jambu tree”.
The observation has scientific basis,
to cite an extract from Hydrology in
Ancient India,published in 1990 by
the National Institute of Hydrology,
Roorkee, India: Without exception the
water requirements of the insects are
generally very high, and they need to
Termites
Termites are insects, classified along with ants, bees and wasps,
and they show highly developed social organisation. This group
of insects has a peculiar form of heredity, in that fertilised eggs
which have a set of chromosomes from each parent develop
into females. But unfertilised eggs which have only one set of
chromosomes, from the mother, develop into males. Female
siblings thus share 50 per cent of the mother’s genes but all of
the father’s genes, or they have 75 per cent of genes in common.
It is thus more effective, in so far as the objective of passing on
the most genes to the next
All from generation, that reproduction be the
mother province of one queen, the common
mother, as females share more genes
Female Male with their sisters than with their
daughters. The females are thus
unusually cooperative with their
sisters, which makes for remarkable
social organisation and order. In the
case of termites, it results in gigantic
mounds built by millions of
cooperating workers over centuries.
Sisters are genetically closer than The termite mounds are elaborate
offspring structures made of mud, chewed
protect themselves against fatal ground
desiccation by living and working surface,
within the climatically sealed under
environment of their nest or within condition
earth covered galleries. According to of severe
present level of research, the climatic
atmosphere within the nest has to be stress, they
maintained practically saturation can and
moisture level ( 99-100 per cent they
humidity). It is a matter of common probably
observation that whenever a termite do
nest or runway is damaged, the insects descend to
immediately rush to the breach and the water Pattern of termite mounds
repair it with wet soil brought up from table, no seen from the sattelite
within the nest. From an overall matter how deep it may be. Hence, a
consideration of the evidence it seems well-developed, active, permanent
to be safe to conclude that, while colony of mound-building termites
normally the insects use every readily can be taken as an indication of
available source of water close to the underground springs in proximity.
wood/cellulose, saliva and faeces. The mound serves many
functions — a protected living space, to collect water through
condensation, reproductive chambers and some species even
cultivate fungal gardens which are fed on collected plant matter
to generate nutritious victuals for the colony. The mounds
consist of a maze of tunnel-like galleries that provide movement
of air and control the CO2/O2 balance. The mounds can stand
nine metres high and extend underground.
In some parts of the African savanna, a high density of
above-ground mounds dominates the landscape. For instance, in
some parts of the Busanga Plain area of Zambia small mounds
of about one metre in diameter with a density of about 100 per
hectare can be seen on grassland between larger tree- and bush-
covered mounds about 25 metres in diameter with a density of
around one per hectare, and both show up well on high-
resolution satellite images taken in the wet season.
Role in ecology
How the termite mound helps other plant and animal species
is complex. Robert M Pringle, a research fellow at Harvard
University, and Todd M Palmer believe termites bring in soil of
rougher texture and alter the water-retaining property and
stability of the otherwise fine soil. The mounds also show higher
levels of nutrients like phosphorus and nitrogen. The action
affects the chemical and moisture content of the soil in the
region and makes for growth of plants and grass. The mound
structure itself is a haven for many kinds of insects and animals
and even a welcome, above-water-level refuge when there is
rain. The termites themselves are food for different predators.
The result is an interplay of different factors that mutually
ensure each others’ welfare and the creation of a network that
has survived droughts and floods for centuries. “Termites are
typically viewed as pests, and as threats to agricultural and
livestock production,” Pringle says. “But productivity – of both
wild and human-dominated landscapes – may be more
intricately tied to the pattern-generating organisms of the larger
natural landscape than is commonly understood.”
The findings have important implications for conservation,
Palmer says. “As we think about restoring degraded ecosystems,
as we think about restoring coral reefs, or restoring plant
communities, this over-dispersed pattern is teaching us
something. It’s saying we might want to think about doing our
coral restoration or plant restoration in a way that takes
advantage of this ecosystem productivity enhancing
phenomenon.”
The writer can be contacted at simplescience@gmail.com

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